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Volume 102-B, Issue SUPP_6 July 2020 The Canadian Orthopaedic Association (COA) and The International Combined Orthopaedic Research Societies (ICORS) Meeting, Montreal, Canada, June 2019.

L. Xiong Y. Hu F. Ding Z. Shao W. Wang G. Liu X. Cai

The purpose of this study was to evaluate whether AGEs induce annulus fibrosus (AF) cell apoptosis and to further explore the mechanism by which this process occurs.

AF cells were treated with various concentrations of AGEs for 3 days. Cell proliferation was measured by the Cell Counting Kit-8 (CCK-8) and EdU incorporation assays. Cell apoptosis was examined by the Annexin V/PI apoptosis detection kit and Hoechst 33342. The expression of apoptosis-related proteins, including Bax, Bcl-2, cytochrome c, caspase-3 and caspase-9, was detected by western blotting. In addition, Bax and Bcl-2 mRNA expression levels were detected by RT-PCR. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) production of AF cell were examined by JC-1 staining and DCFH-DA fluorescent probes, respectively.

Our results indicated that AGEs had inhibitory effects on AF cell proliferation and induced AF cell apoptosis. The molecular data showed that AGEs significantly up-regulated Bax expression and inhibited Bcl-2 expression. In addition, AGEs increased the release of cytochrome c into the cytosol and enhanced caspase-9 and caspase-3 activation. Moreover, treatment with AGEs resulted in a decrease in MMP and the accumulation of intracellular ROS in AF cells. The antioxidant N-acetyl-L-cysteine significantly reversed AGE-induced MMP decrease and AF cell apoptosis.

These results suggest that AGEs induce rabbit AF cell apoptosis and mitochondrial pathways may be involved in AGE-mediated cell apoptosis, which may provide a theoretical basis for diabetic IVD degeneration.


Z. Ali A. Sahgal E. David E. Chow S. Burch B. Wilson A. J.M. Yee C. Whyne J. Detsky C. Fisher

The spine is a common site of metastasis. Complications include pathologic fracture, spinal cord compression, and neurological deficits. Vertebroplasty (VP) and Balloon Kyphoplasty (KP) are minimally invasive stabilization procedures used as a palliative treatment to improve mechanical stability, quality of life, and reduce pain. Photodynamic therapy (PDT) is a tumour-ablative modality that may complement mechanical stability afforded by VP/KP. This first-in-human study evaluates PDT safety when applied in conjunction with VP/KP.

This dose escalation trial involved one light only control group and four light-drug doses (50,100,150,200J;n=6) delivered at 150mW from a 690nm diode laser by 800-micron optical fibers prior to KP/VP. Patients eligible for VP/KP in treating pathologic fracture or at-risk lesions at a single level were recruited. Exclusion criteria included spinal canal compromise or neurologic impairment. PDT is a two-step binary therapy of systemic drug followed by intravertebral light activation. Light was applied via bone trochar prior to cementation. This study used a benzoporphyrin derivative monoacid (BPD-MA), Verteporfin (VisudyneTm), as the photosensitizer drug in the therapy. Drug/light safety, neurologic safety, generic (SF-36), and disease-specific outcomes (VAS, EORTC-QLQ-BM22, EORTC-QLQ-C15-PAL) were recorded through six weeks. Phototoxicity and the side effects of the BPD-MA were also examined following PDT use.

Thirty (10 male, 20 female) patients were treated (13 KP, 17 VP). The average age was 61 and significantly different between genders (Male 70yrs vs. Female 57yrs: p 0.05), and tumour status (lytic vs. mixed blastic/lytic: p>0.05). In most cases, fluence rates were similar throughout PDT treatment time, indicating a relatively stable treatment. Twelve (40%) of patients experienced complications during the study, none of which were attributed to PDT therapy. This included two kyphoplasty failures due to progression of disease, one case of shingles, one ankle fracture, one prominent suture, one case of constipation due to a lung lesion, one case of fatigue, and five patients experienced pain that was surgically related or preceded therapy.

Vertebral PDT appears safe from pharmaceutical and neurologic perspectives. KP/VP failure rate is broadly in line with reported values and PDT did not compromise efficacy. The 50J group demonstrated an improved response. Ongoing study determining safe dose range and subsequent efficacy studies are necessary.


J. Bourget-Murray R. Sharma D. Halpenny S. Mahdavi

Limited strong data exists in current literature comparing the 90-day morbidity and mortality following general or spinal anesthetic in patients who underwent total hip or knee arthroplasty, especially between matched cohorts. Because of this, there continues to be an ongoing debate regarding the risks and benefits of using general versus spinal anesthetic for patients undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) for end-stage osteoarthritis.

The Alberta Bone and Joint Health Institute (ABJHI) database was searched to identify all patients who underwent either primary THA or TKA between April 2005 and December 2015. Those identified were matched 1:1 based on age, sex, type of joint replacement (THA or TKA), American Society of Anesthesiologists (ASA) score, and anesthetic type. Patients were stratified into two groups based on whether they received a general anesthesia (GA) or a spinal anesthesia (SA) at the time of their index surgery. Perioperative complications (medical events, mechanical events, deep infection, need for blood transfusion), length of stay (LOS), 30-day readmission, and 90-day mortality were compared between cohorts.

Included in this study are 5,580 patients who underwent THA and 7,712 patient who underwent TKA. All were successfully matched based on similar categorical criteria (THA, 2,790 matched-pairs, TKA, 3,856 matched-pairs). Following stratifications of cohorts, no statistical differences were appreciated between patient baseline demographics. Patients who underwent GA showed a trend towards higher 90-day mortality, however no statistical differences were found between anesthetic type on rates of 90-day mortality following either THA or TKA (THA, p = 0.290, TKA, p = 0.291). Considering this, patients who underwent THA with SA experienced fewer 90-day complications (medical events, p = 0.022, mechanical events, p = 0.017), needed fewer blood transfusions (p < 0 .001), and required shorter LOS (p = 0.038). Moreover, patient who underwent TKA with SA had fewer blood transfusion (p < 0 .001), 30-day readmission rates (p = 0.011), and fewer deep infections (p = 0.030) that required additional surgery compared to those in the GA cohort. Regardless of surgery performed, patients in the SA cohorts were more commonly discharged home without requiring additional support (i.e. home care).

General anesthesia during THA and TKA appears to be associated with increased 90-day morbidity and more frequent need for allogenic blood transfusion. No statistical difference in 90-day mortality is reported between cohorts for either THA or TKA, yet a trend is appreciated favoring SA. Surgeons who commonly perform these surgeries should consider the added benefits of spinal anesthesia for those patients who are candidates.


S. Gautreau M.E. Forsythe O. Gould C. Aquino-Russell W. Allanach A. Clark S. Massoeurs

Total knee arthroplasty (TKA) is considered as one of the most successful and cost-effective medical interventions yet it is consistently reported that up to 20% of patients are dissatisfied with their outcomes. Patient satisfaction is correlated with the fulfillment of expectations and an important aspect of this involves good surgeon-patient communication, which itself is a contributor to TKA satisfaction. The purpose of this study was to develop and test a checklist intended to enhance the quality of surgeon-patient communication by optimizing the surgeon's role in helping patients set (or reset) and manage post-TKA expectations that are realistic, achievable, and most importantly, patient-specific.

In this prospective mixed methods study, a communication checklist was developed from the analysis of interviews with patients who were between six weeks and six months post-TKA. Four orthopaedic surgeons then used the checklist to guide discussions with patients about post-operative expectations and outcomes during follow-up visits between six weeks and six months. A visual analogue scale was used to survey two groups of patients on five measures of satisfaction: the standard of care communication group and the intervention group who had received the checklist. The mean scores of the two groups were compared using independent t-tests. The duration of follow-up visits was also tracked to determine if the checklist took significantly more time in practice.

Themes from the qualitative analysis of eight patient interviews incorporated into the checklist included pain management, medication, physiotherapy, and general concerns and questions. The quantitative study comprised 127 participants, 67 in the standard of care communication group and 60 in the checklist group. There were no significant group differences in gender, BMI, comorbidities, post-operative complications, marital or occupational status, however the standard of care group was older by six years (p < .001). The checklist group reported significantly greater satisfaction on four of the five measures of satisfaction: TKA satisfaction and expectations met (p = .017), care and concern shown by the surgeons (p = .011), surgeons' communication ability (p = .008), and satisfaction with time surgeons spent with patients during follow-up visits (p < .001). Satisfaction with the TKA for relieving pain and restoring function was not significant (p = .064). Although the checklist increased the average clinic visit time by only 1 minute, 51 seconds, it was significantly greater (p = .001). The impact of age and gender on satisfaction was explored using a two-way analysis of variance. No significant effects or interactions were observed.

Checklists have been shown to decrease medical errors and improve overall standards of patient care but no published research to date has used a communication checklist to enhance orthopaedic surgeon-patient communication. The present findings indicate that this simple tool can significantly increase patient satisfaction. This has practical significance because patient satisfaction is a metric that is increasingly used as a key performance indicator for surgeons and health care institutions alike. Increased TKA satisfaction will benefit patients, surgeons, and the health care system overall.


M. Tanzer P. Chuang C. Ngo C. Aponte L. Song K. TenHuisen

Porous surfaces on orthopaedic implants have been shown to promote tissue ingrowth. This study evaluated biological fixation of novel additively manufactured porous implants with and without hydroxyapatite coatings in a canine transcortical model.

Laser rapid manufacturing (LRM) Ti6Al4V cylindrical implants were built with a random interconnected architecture mimicking cancellous bone (5.2 mm diameter, 10mm length, 50–60% porous, mean pore size 450μm). Three groups were investigated in this study: as-built with no coating (LRM), as-built coated with solution precipitated hydroxyapatite (LRM-PA), and as-built coated with a plasma sprayed hydroxyapatite (LRM-PSHA). Implants were press-fit into a 5mm unicortical, perpendicular drill hole in the femoral diaphysis of the left and right femurs in 12 canines. Right femora were harvested for histology (SEM, bone ingrowth into implant within cortical region) and left femora for mechanical push-out testing (shear strength of bone-implant interface) at 4 and 12 weeks (N=6, un-paired Student's t-test, p=0.05).

For mean bone ingrowth, there was no significant difference between groups at 4 weeks (LRM, LRM-PA, LRM-PSHA: 41.5+8.6%, 51+5.5% and 53.2+11%, respectively) or 12 weeks (LRM, LRM-PA, LRM-PSHA: 64.4+2.8%, 59.9+7.6%, 64.9+6.4%, respectively). LRM and LRM-PA implants had more bone ingrowth at 12 weeks than 4 weeks (p < 0 .05). Mean shear strength of all implants at 12 weeks (LRM, LRM-PA, LRM-PSHA: 39.9+3.6MPa, 33.7+4.6MPa, 36+4.1MPa respectively) were greater than at 4 weeks (LRM, LRM-PA, LRM-PSHA: 21.6+2.8MPa, 20.7+1.1MPa, 20.2+2.5MPa respectively) (p < 0 .05). No significant difference was observed between all groups at 4 or 12 weeks.

Overall, this canine study confirmed the suitability of this novel additive manufacturing porous material for biological fixation by bone ingrowth. All implants exhibited high bone ingrowth and mechanical shear strength in this canine model. No difference was observed between uncoated and hydroxyapatite coated implants.


T. Yasuda E. Onishi S. Ota S. Fujita T. Sueyoshi T. Hashimura

Rapidly progressive osteoarthritis of the hip (RPOH) is an unusual subset of osteoarthritis. It is characterized by rapid joint space loss, chondroly­sis, and sometimes marked femoral head and acetabular destruction as a late finding. The exact pathogenetic mechanism is unknown. Potential causes of RPOH include subchondral insufficiency fracture resulting from osteoporosis, increasing posterior pelvic tilt as a mechanical factor, and high serum levels of matrix metalloproteinase (MMP)-3 as biological factors. This study was aimed to identify some markers that associate with the destructive process of RPOH by analyzing the proposed pathological factors of the disease, MMP-3, pelvic tilt, and osteoporosis.

Of female patients who visited our hospital with hip pain from 2012 through 2018, this study enrolled female patients with sufficient clinical records including the onset of hip pain, age and body mass index (BMI) at the onset, a series of radiographs during the period of >12 months from the onset of hip pain, and hematological data of MMP-3 and C-reactive protein (CRP). We found the hip joints of 31 patients meet the diagnostic criteria of RPOH, chondrolysis >two mm in one year, or 50% joint space narrowing in one year. Those patients were classified into two groups, 17 and 14 patients with and without subsequent femoral head destruction in one year shown by computed tomography, respectively. Serum MMP-3 and CRP were measured with blood samples within one year after the hip pain onset. The cortical thickness index (CTI) as an indicator of osteoporosis and pelvic tilt parameters were evaluated on the initial anteroposterior radiograph of the hip. These factors were statistically compared between the two groups. This study excluded male patients because RPOH occurs mainly in elderly females and the reference intervals of MMP-3 are different between males and females.

There was no difference in age at onset or bone mass index between the RPOH patients with and without subsequent femoral head destruction. Serum levels of MMP-3 were significantly higher in the RPOH patients with the destruction (152.1 ± 108.9 ng/ml) than those without the destruction (66.8 ± 27.9 ng/ml) (P = 0.005 by Mann-Whitney test). We also found increased CRP in the patients with femoral head destruction (0.725 ± 1.44 mg/dl) compared with those without the destruction (0.178 ± 0.187 mg/dl) (P = 0.032 by Mann-Whitney test). No difference in the duration between the hip pain onset and the blood examination was found between the two groups. There was no significant difference in CTI or pelvic tilt between the two groups.

The pathological condition that may increase serum MMP-3 and CRP could be involved in femoral head destruction after chondrolysis of the hip in patients with RPOH.


H. Abbasi A. Grant

Obesity is an increasing public health concern associated with increased perioperative complications and expense in lumbar spine fusions. While open and mini-open fusions such as transforaminal lumbar interbody fusion (TLIF) and minimally invasive TLIF (MIS-TLIF) are more challenging in obese patients, new MIS procedures like oblique lateral lumbar interbody fusion (OLLIF) may improve perioperative outcomes in obese patients relative to TLIF and MIS-TLIF.

The purpose of this study is to determine the effects of obesity on perioperative outcomes in OLLIF, MIS-TLIF, and TLIF. This is a retrospective cohort study.

We included patients who underwent OLLIF, MIS-TLIF, or TLIF on three or fewer spinal levels at a single Minnesota hospital after conservative therapy had failed. Indications included in this study were degenerative disc disease, spondylolisthesis, spondylosis, herniation, stenosis, and scoliosis. We measured demographic information, body mass index (BMI), surgery time, blood loss, and hospital stay. We performed summary statistics to compare perioperative outcomes in MIS-TLIF, OLLIF, and TLIF. We performed multivariate regression to determine the effects of BMI on perioperative outcomes controlling for demographics and number of levels on which surgeries were operated.

OLLIF significantly reduces surgery time, blood loss, and hospital stay compared to MIS-TLIF, and TLIF for all levels. MIS-TLIF and TLIF do not differ significantly except for a slight reduction in hospital stay for two-level procedures. On multivariate analysis, a one-point increase in BMI increased surgery time by 0.56 ± 0.47 minutes (p = 0.24) in the OLLIF group, by 2.8 ± 1.43 minutes (p = 0.06) in the MIS-TLIF group, and by 1.7 ± 0.43 minutes (p < 0.001) in the TLIF group. BMI has positive effects on blood loss for TLIF (p < 0.001) but not for OLLIF (p = 0.68) or MIS-TLIF (p = 0.67). BMI does not have significant effects on length of hospital stay for any procedure.

Obesity is associated with increased surgery time and blood loss in TLIF and with increased surgery time in MIS-TLIF. Increased surgery time may be associated with increased perioperative complications and cost. In OLLIF, BMI does not affect perioperative outcomes. Therefore, OLLIF may reduce the disparity in outcomes and cost between obese and non-obese patients.


Y. Marwan J. Karim A. Dawas A. Esmaeel L. Snell

YouTube is one of the main sources for learning clinical skills. This study aims to assess the educational outcomes of medical students from self-directed learning about knee arthrocentesis through searching and using YouTube videos in comparison to traditional supervisor-led sessions.

Seventy-one medical students were randomly assigned in three groups. Group A had a classic supervisor-led clinical session, where the supervisor demonstrated the procedure. Group B students were provided with links to YouTube videos of knee arthrocentesis that were deemed of high educational quality, while group C searched and learned from any YouTube video they found appropriate based on the learning objectives provided. The students' performance pre- and post-feedback was examined using a checklist that was based on the guidelines of the American Academy of Family Physicians on knee arthrocentesis.

Pre-feedback, statistically significant higher mean scores for group A were noted in identification of an appropriate puncture site (p = 0.015), puncture site sterilization (p = 0.046), wearing sterile gloves (p < 0 .001), and direction of needle insertion (p < 0.001). The overall mean scores before feedback for group A, group B and group C were 17.9 ± 1.9, 14.9 ± 2 and 15.4 ± 1.8, respectively (p < 0 .001). None of these scores was below 60% of the total possible score (total score = 21). The overall mean scores after feedback for group A, group B and group C were 21, 20.9 ± 0.3 and 21, respectively (p = 0.037).

Without appropriate feedback to the learners from an instructor, YouTube videos cannot replace traditional supervisor-led sessions in learning knee arthrocentesis.


P. Vendittoli W. Blakeney M. Kiss C. Riviere B. Puliero Y. Beaulieu

Mechanical alignment (MA) techniques for total knee arthroplasty (TKA) may introduce significant anatomic modifications, as it is known that few patients have neutral femoral, tibial or overall lower limb mechanical axes.

A total of 1000 knee CT-Scans were analyzed from a database of patients undergoing TKA. MA tibial and femoral bone resections were simulated. Femoral rotation was aligned with either the trans-epicondylar axis (TEA) or with 3° of external rotation to the posterior condyles (PC). Medial-lateral (DML) and flexion-extension (DFE) gap differences were calculated.

Extension space ML imbalances (3mm) occurred in 25% of varus and 54% of valgus knees and significant imbalances (5mm) were present in up to 8% of varus and 19% of valgus knees. For the flexion space DML, higher imbalance rates were created by the TEA technique (p < 0 .001). In valgus knees, TEA resulted in a DML in flexion of 5 mm in 42%, compared to 7% for PC. In varus knees both techniques performed better. When all the differences between DML and DFE are considered together, using TEA there were 18% of valgus knees and 49% of varus knees with < 3 mm imbalances throughout, and using PC 32% of valgus knees and 64% of varus knees.

Significant anatomic modifications with related ML or FE gap imbalances are created using MA for TKA. Using MA techniques, PC creates less imbalances than TEA. Some of these imbalances may not be correctable by the surgeon and may explain post-operative TKA instability. Current imaging technology could predict preoperatively these intrinsic imitations of MA. Other alignment techniques that better reproduce knee anatomies should be explored.


P. Vendittoli B. Puliero W. Blakeney Y. Beaulieu

Assessing patients' functional outcomes following total hip arthroplasty with traditional scoring systems is limited by their ceiling effects. The Forgotten Joint Score (FJS) has been suggested as a more discriminating option. The actual score in the FJS which constitutes a “forgotten joint”, however, has not been defined. The emerging concept of joint perception led to the development of the Patient's Joint Perception question (PJP) to assess the patient's opinion of their prosthetic joint.

Two hundred fifty-seven THAs were assessed at a mean of 68 months follow-up (range 57–79). Outcomes included the WOMAC, FJS and the PJP. Correlation of the scores as well as the ceiling effects were analysed

The mean FJS was 88.5 (range 27.1–100). PJP was correlated with the FJS and WOMAC (Spearman's rho: −0.510 and 0.465 respectively). Fifty-two percent of the patients felt their hip as a natural joint (FJS CI 95% 93.3–96), 24.1% as an artificial joint with no restriction (FJS CI 95% 83.1–90.5), and 23.3% as an artificial joint with minor restrictions (FJS CI 95% 73.8–82.2). Only 0.8% had major restrictions and none reported a non-functional joint. The ceiling effect was high with both the WOMAC and FJS, with 27.2% and 31.9%. In addition, 28.6% of the patients had a WOMAC >10 and 23.4% a FJS of < 9 0 while reporting having a natural hip. Furthermore, 21.5% with a perfect WOMAC or 21.9% with a perfect FJS, reported having an artificial joint with or without limitation.

A forgotten hip perception corresponds to a FJS >93. In 20–30% of the cases, the WOMAC and FJS failed to identify the forgotten joint, or reached the maximum score when the patients did not feel their hip was natural. The PJP is a simple and reliable tool that enables identification of patients that feel their hip is natural.


P. Vendittoli J. Clément W. Blakeney N. Hagemeister F. Desmeules N. Mezghani Y. Beaulieu

For many years, achieving a neutral coronal Hip-Knee-Ankle angle (HKA) measured on radiographs has been considered a factor of success for total knee arthroplasty (TKA). Lower limb HKA is influenced by the acquisition conditions, and static HKA (sHKA) may not be representative of the dynamic loading that occurs during gait. The primary aim of the study was to see if the sHKA is predictive of the dynamic HKA (dHKA). A secondary aim was to document to what degree the dHKA changes throughout gait.

We analysed the 3-D knee kinematics during gait of a cohort of 90 healthy individuals (165 knees) with the KneeKG™ system. dHKA was calculated and compared with sHKA values. Knees were considered “Stable” if the dHKA remained positive or negative – i.e. in valgus or varus – for greater than 95% of the corresponding phase and “Changer” otherwise. Patient characteristics of the Stable and Changer knees were compared to find contributing factors.

The dHKA absolute variation during gait was 10.9±5.3° [2 .4° – 28.3°] for the whole cohort. The variation was greater for the varus knees (10.3±4.8° [2.4° – 26.3°]), than for the valgus knees (12.8±6.1° [2.9° – 28.3°], p=0.008). We found a low to moderate correlation (r = 0.266 to 0.553, p < 0 .001) between sHKA and the dHKA values for varus knees and no correlation valgus knees. Twenty two percent (36/165) of the knees demonstrated a switch in the dHKA (Changer). Proportion of Changer knees was 15% for varus sHKA versus 39% for valgus sHKA (p < 0.001).

Lower limb radiographic measures of coronal alignment have limited value for predicting dynamic measures of alignment during gait.


D. Axelrod D. Wasserstein T. Zochowski P. H. Marks N. Mahomed A. Veljkovic

The purpose of this study was to define the risk and incidence of eventual ankle arthroplasty or fusion after documented ankle fracture in a large cohort, and compare that rate to matched healthy patients from the general population.

The Ontario health insurance plan (OHIP) physician billing database, Institute for Clinical Evaluative Sciences (ICES) Physician Database, the Canadian Institute for Health Information (CIHI) databases, Discharge Abstract Database (DAD) and Same Day Surgery (SDS) were used to identify patients treated surgically and non-surgically for ankle fractures. Each patient was matched to four individuals from the general population (13.5 million) with no documented prior treatment for ankle fracture, according to age, sex, income, and urban/rural residence. Fusion and replacement incidence was compared using time-to-event analysis (Kaplan-Meier). A Cox Proportional Hazards model was used to explore the influence of patient, provider and surgical factors on time to surgery.

We identified 45,444 (58.8% female, mean age 48.7 years) and 140, 629 (53.9% female, mean age 47.1 years) patients who had undergone open reduction internal fixation (ORIF) or non-operative management of an ankle fracture (NOA), respectively. Among ORIF patients, n=237 (0.5%) and n=69 (0.15%) patients underwent fusion or arthroplasty after a median 2.8 and 6.9 years, respectively. Among non-operatively treated ankle fractures, n=198 (0.14%) and n=36 (0.03%) patients underwent fusion or arthroplasty after a median of 3.2 and 5.6 years, respectively. Surgical treatment (vs. non-operatively treated fracture), older age, greater co-morbidity and a history of infection post fracture significantly increased the risk of eventual fusion or arthroplasty (HR 3.6 (3.1–4.3), p < 0 .001, HR 1.01 (1.01–1.02), p=0.009, HR 1.2 (1.1–1.3), p < 0 .001, HR 11.3 (6.8–18.7), p < 0 .001, respectively). Compared to matched controls, the risk of fusion/arthroplasty was not independent of time, following an exponential decay pattern. ORIF patient risk was 20 times greater than the general population in the first three years post-ORIF, and approached the risk of non-operatively treated patients (HR 4.5 (95CI: 3.5–5.8), p < 0 .0001) by approximately 14 years out from injury on time and comorbidity adjusted KM curves.

Rates of fusion/arthroplasty are very low after ORIF and non-operative treatment of an ankle fracture in the general population of a public healthcare system. Utilization patterns suggest fusion is more common earlier, and arthroplasty remote, which may be a factor of patient age, injury severity, and complications from initial injury/surgery. Patients who underwent ORIF have >20 times the risk of fusion/arthroplasty in the short-term, however, the risk decreases over time eventually approaching that of non-operatively treated patients (∼4.5x the general population) when compared to non-fractured controls.


B. Wildeman N. Bormann E. Beuttel A. Pobloth G. N. Duda

Despite the increasing availability of bone grafting materials, the regeneration of large bone defects remains a challenge. Especially infection prevention while fostering regeneration is a crucial issue. Therefore, loading of grafting material with antibiotics for direct delivery to the site of need is desired. This study evaluates the concept of local delivery using in vitro and in vivo investigations. We aim at verifying safety and reliability of a perioperative enrichment procedure of demineralized bone matrix (DBM) with gentamicin.

DBM (DBMputty, DIZG, Germany) was mixed with antibiotic using a syringe with an integrated mixing propeller (Medmix Systems, Switzerland). Gentamicin, as powder or solution, was mixed with DBM at different concentrations (25 −100 mg/g DBM), release and cytotoxicity was analyzed. For in vivo analysis, sterile drill hole defects (diameter: 6 mm, depth: 15 mm) were created in diaphyseal and metaphyseal bones of sheep (Pobloth et al. 2016). Defects (6 – 8 per group and time point) were filled with DBM or DBM enriched with gentamicin (50 mg/g DBM) or left untreated. After three and nine weeks, defect regeneration was analyzed by µCT and histology.

The release experiments revealed a burst release of gentamicin from DBM independent of the used amount, the sampling strategy, or the formulation (powder or solution). Gentamicin was almost completely released after three days in all set-ups. Eluates showed an antimicrobial activity against S. aureus over at least three days. Eluates had no negative effect on viability and alkaline phosphatase activity of osteoblast-like cells (partially published Bormann et al. 2014). µCT and histology of the drill hole defects revealed a reduced bone formation with gentamicin loaded DBM. After nine weeks significantly less mineralized tissue was detectable in metaphyseal defects of the gentamicin group. Histological evaluation revealed new bone formation starting at the edges of the drill holes and growing into the center over time. The amount of DBM decreased over time due to the active removal by osteoclasts while osteoblasts formed new bone.

Using this mixing procedure, loading of DBM was fast, reliable and possible during surgical setting. In vitro experiments revealed a burst and almost complete release after three days, antimicrobial activity and good biocompatibility of the eluates. Gentamicin/DBM concentration was in the range of clinically used antibiotic-loaded-cement for prophylaxis and treatment in joint replacement (Jiranek et al. 2006). The delayed healing seen in vivo was unexpected due to the good biocompatibility found in vitro. A reduced healing was also seen in spinal fusion where DBM was mixed with vancomycin (Shields et al. 2017), whereas DBM with gentamicin or DBM/bioactive glass with tobramycin had no negative effect on osteoinductivity or femur defect healing, respectively (Lewis et al. 2010, Shields et al. 2016). In conclusion, loading of DBM with gentamicin showed a proper antibiotic delivery over several days, covering the critical phase shortly after surgery. Due to the faster and complete release of the antibiotic compared to antibiotic loaded cement, the amount of antibiotic should be much lower in the DBM compared to cement.


K. Young J. A. Wilson M. J. Dunbar P. Roy S.S.R Abidi

Identifying knee osteoarthritis (OA) patient phenotypes is relevant to assessing treatment efficacy, yet biomechanical variability has not been applied to phenotyping. This study aimed to identify demographic and gait related groups (clusters) among total knee arthroplasty (TKA) candidates, and examine inter-cluster differences in gait feature improvement post-TKA.

Knee OA patients scheduled for TKA underwent three-dimensional gait analysis one-week pre and one-year post-TKA, capturing lower-limb external ground reaction forces and kinematics using a force platform and optoelectronic motion capture. Principal component analysis was applied to frontal and sagittal knee angle and moment waveforms (n=135 pre-TKA, n=106 post-TKA), resulting in a new uncorrelated dataset of subject PCscores and PC vectors, describing major modes of variability throughout one gait cycle (0–100%). Demographics (age, gender, body mass index (BMI), gait speed), and gait angle and moment PCscores were standardized and assessed for outliers. One patient exceeding Tukey's outer (3IQR) fence was removed. Two-dimensional multidimensional scaling followed by k-medoids clustering was applied to scaled demographics and pre-TKA PCscores [134×15]. Number of clusters (k=2:10) were assessed by silhouette coefficients, s, and stability by Adjusted Rand Indices (ARI) of 100 data subsets. Clusters were validated by examining inter-cluster differences at baseline, and inter-cluster gait changes (PostPCscore–PrePCscore, n=105) by k-way ANOVA and Tukey's honestly significant difference (HSD) criterion.

Four (k=4) TKA candidate groups yielded optimum clustering metrics (s = 0.4, ARI=0.75). Cluster 1 was all-males (male:female=19:0) who walked with faster gait speeds (1>2,3), larger flexion angle magnitudes and stance-phase angle range (PC1 & PC4 1>2,3,4), and more flexion (PC2 1>2,3,4) and adduction moment (PC2 & PC3 1>2,3) range patterns. Cluster 1 had the most dynamic kinematics and kinetic loading/unloading range amongst the clusters, representing a higher-functioning (less “stiff”) male subset. Cluster 2 captured older (2>1,3) males (31:1) with slower gait speeds (2 4), and lower flexion angle magnitude (PC1 3 2,3) and less stiff kinematic and kinetic patterns relative to Clusters 2 and 3, representing a higher-functioning female subset. Radiographic severity did not differ between clusters (Kellgren-Lawrence Grade, p=0.9, n=102), and after removing demographics and re-clustering, gender differences remained (p < 0 .04). Pre-TKA, higher-functioning clusters (1&4) had more dynamic loading/un-loading kinetic patterns. Post-TKA, high-functioning clusters experienced less gait improvement (flexion angle PC2, 1,4 < 3, p≥0.004, flexion moment PC2, 4 < 2,3), with some sagittal range patterns decreasing postoperatively.

TKA candidates can be characterized by four clusters, differing by demographics and biomechanical severity features. Post-TKA, functional gains were cluster-specific, stiff-gait clusters experienced more improvement, while higher-functioning clusters experienced less gain and showed some decline. Results suggest the presence of cohorts who may not benefit functionally from TKA. Cluster profiling may support triaging and developing targeted OA treatment strategies, meeting individual function needs.


O. R. Ayeni

Femoroacetabular impingement (FAI) is a condition of the hip where there is a mismatch of the femoral head and hip acetabulum. This mismatch creates abnormal contact between the bones and causes hip pain which can lead to damage, and eventually osteoarthritis of the hip. The diagnosis and treatment of FAI has become one of the most popular clinical scenarios in orthopaedic surgery, with hip arthroscopy procedures increasing exponentially over the past five years. Surgical intervention usually involves correcting the existing deformities by reshaping the ball and socket (“osteoplasty” or “rim trimming”) so that they fit together more easily while repairing any other existing soft tissue damage in the hip joint (e.g. labral repair). Although correction of the misshaped bony anatomy and associated intra-articular soft tissue damage of the hip is thought to appease impingement and improve pain and function, the current evidence is based on small, observational, and low quality studies. A lack of definitive evidence regarding the efficacy of osteochondroplasty in treating FAI fueled the design and execution of the FIRST randomized controlled trial (RCT). FIRST evaluated the impact of surgical correction of the hip impingement morphology with arthroscopic osteochondroplasty versus arthroscopic lavage on pain, function, and quality of life in adults aged 18–50 years diagnosed with non-arthritic FAI at one year.

FIRST was a large definitive RCT (NCT01623843) enrolling patients with FAI requiring surgical intervention across 11 international clinical sites. Participants were randomized to either arthroscopic osteochondroplasty (shaving of bone) or lavage (washing the joint of painful inflammation debris). The primary outcome was patient-reported pain within one year of the initial surgery measured using the Visual Analogue Scale (VAS). Secondary outcomes included function, health utility, and health-related quality of life using several general and hip-centric health questionnaires. An independent, blinded adjudication committee evaluated the quality of surgery, re-operations, and other patient complications. Patients and data analysts were blinded to the treatment groups.

Two-hundred and twenty participants were enrolled into the FIRST trial over a six-year period (pilot phase: N=50, from 2012–2013 and definitive phase: N=170, from 2015–2018) at 11 clinical sites in Canada, Finland, and Denmark. The FIRST results will be released at the ISAKOS annual meeting as follows. The absolute difference in rate of pain reduction between groups was XX (95% CI: YY-YY, p=X). The mean differences of the Short-Form 12 (SF-12, MCS and PCS), Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT-12), and EuroQol 5-Dimensions (EQ-5D) between groups are XX (95% CI: YY-YY, p=X)…, respectively. Reoperations occurred in XX of 220 (X%) patients over the one-year follow up period (OR:XX, 95% CI: YY-YY, p=X) and the patients treated with arthroscopic osteochondroplasty conferred the following risk of reoperation within one-year compared to arthroscopic lavage (RR:XX, 95% CI: YY-YY, p=X).

This RCT represents major international efforts to definitively identify the optimal treatment strategy for FAI. The results of this trial will change practice, being used to prevent chronic hip pain and loss of function caused by hip osteoarthritis.


D. Docheva D. Lin

Tenomodulin (Tnmd) is the best known mature tendon factor for tendon and ligament tissues with reported important regulatory roles1. In addition, Tnmd C-terminal cysteine-rich domain has been descibed to exert anti-angiogenic functions in in vitro angiogenic assays as well as in vivo models of tendon injury and age-associated cardiac valve diseases1, 2. Interestingly, Tnmd expresson in the intervertebral disc (IVD), which is normally avascular tissue, has been also suggested3. Hence, the purpose of this study was first, to map the exact expression pattern of Tnmd during IVD development and aging and second, by implementing Tnmd-knockout mouse model, to examine if Tnmd plays a role in IVD homeostasis.

Histological analyses (hematoxylin/eosin, Safranin O, CD31 for endothelium, TUNEL for apoptosis and type X collagen and Runx2 for hypetrophy) were performed on Tnmd −/−, Tnmd −/− and chondromodulin I Chmd 1 −/− (Tnmd only homolog) double knockout and wild type mice WT (n = three to five) to examine IVD degeneration. Real time PCR was implemented to explore gene expression chnages in annulus fibrous (AF) between Tnmd −/− and WT mice. In addition, outer AF (OAF) cells were isolated from both genotypes to further determine cellular phenotype and assess effects on co-culture with human umbical vein endothelial cells (HUVECs). Statistical differences between two groups were determined with t-test. In multiple comparisons, one-way ANOVA was followed by Bonferroni post-hoc correction.

Tnmd was expressed in a temporal manner in OAF and to very low extent in NP. Tnmd −/− mice exhibited more rapid progression of age-related IVD degeneration. These signs included smaller collagen fibril diameter, reduced multiple IVD- and tendon/ligament-related gene expression, induced angiogenesis and inflamatory cell infiltration in OAF as well as more hypertrophic-like chondrocytes in the NP. In addition, Tnmd−/− Chm1 −/− mice displayes not only accelerated IVD phenotpye, but also ectopic bone formation in the IVD. Lastly, the abscence of Tnmd in OAF-derived cells significantly promoted HUVECs migratory capacity.

These findings provide clear evidence that Tnmd plays a critical role in IVD homeostasis.


A. Badre D. Axford S. Banayan J. Johnson G. J.W. King

The role of anconeus in elbow stability has been a long-standing debate. Anatomical and electromyographic studies have suggested a potential role as a stabilizer. However, to our knowledge, no clinical or biomechanical studies have investigated its role in improving the stability of a lateral collateral ligament (LCL) deficient elbow.

Seven cadaveric upper extremities were mounted in an elbow motion simulator in the varus position. An LCL injured model was created by sectioning of the common extensor origin, and the LCL. The anconeus tendon and its aponeurosis were sutured in a Krackow fashion and tensioned to 10N and 20N through a transosseous tunnel at its origin. Varus-valgus angles and ulnohumeral rotations were recorded using an electromagnetic tracking system during simulated active elbow flexion with the forearm pronated and supinated. During active motion, the injured model resulted in a significant increase in varus angulation (5.3°±2.9°, P=.0001 pronation, 3.5°±3.4°, P=.001 supination) and external rotation (ER) (8.6°±5.8°, P=.001 pronation, 7.1°±6.1°, P=.003 supination) of the ulnohumeral articulation compared to the control state (varus angle −2.8°±3.4° pronation, −3.3°±3.2° supination, ER angle 2.1°±5.6° pronation, 1.6°±5.8° supination).

Tensioning of the anconeus significantly decreased the varus angulation (−1.2°±4.5°, P=.006 for 10N in pronation, −3.9°±4°, P=.0001 for 20N in pronation, −4.3°±4°, P=.0001 for 10N in supination, −5.3°±4.2°, P=.0001 for 20N in supination) and ER angle (2.6°±4.5°, P=.008 for 10N in pronation, 0.3°±5°, P=.0001 for 20N in pronation, 0.1°±5.3°, P=.0001 for 10N in supination, −0.8°±5.3°, P=.0001 for 20N in supination) of the injured elbow. Comparing anconeus tensioning to the control state, there was no significant difference in varus-valgus angulation except with anconeus tensioning to 20N with the forearm in supination which resulted in less varus angulation (P=1 for 10N in pronation, P=.267 for 20N in pronation, P=.604 for 10N in supination, P=.030 for 20N in supination). Although there were statistically significant differences in ulnohumeral rotation between anconeus tensioning and the control state (except with anconeus tensioning to 10N with the forearm in pronation which was not significantly different), anconeus tensioning resulted in decreased external rotation angle compared to the control state (P=1 for 10N in pronation, P=.020 for 20N in pronation, P=.033 for 10N in supination, P=.001 for 20N in supination).

In the highly unstable varus elbow orientation, anconeus tensioning restores the in vitro stability of an LCL deficient elbow during simulated active motion with the forearm in both pronation and supination. Interestingly, there was a significant difference in varus-valgus angulation between 20N anconeus tensioning with the forearm supinated and the control state, with less varus angulation for the anconeus tensioning which suggests that loads less than 20N is sufficient to restore varus stability during active motion with the forearm supinated. Similarly, the significant difference observed in ulnohumeral rotation between anconeus tensioning and the control state suggests that lesser degrees of anconeus tensioning would be sufficient to restore the posterolateral instability of an LCL deficient elbow. These results may have several clinical implications such as a potential role for anconeus strengthening in managing symptomatic lateral elbow instability.


G. Pattappa M. Koch J. Weber S. Lang A. Bohrer B. Johnstone D. Docheva J. Zellner P. Angele J. Krueckel D. Franke

Osteoarthritis (OA) is one of the most prevalent joint diseases involving progressive and degenerative changes to cartilage resulting from a variety of etiologies including post-traumatic incident or aging. OA lesions can be treated at its early stages through cell-based tissue engineering therapies using Mesenchymal Stem Cells (MSCs). In vivo models for evaluating these strategies, have described both chondral (impaction) and osteochondral (biopsy punch) defects. The aim of the investigation was to develop a compact and reproducible defect inducing post-traumatic degenerative changes mimicking early OA. Additionally, a pilot study to evaluate the efficacy of MSC-hydrogel treatment was also assessed.

Surgery was performed on New Zealand white rabbits (male, 5–8 months old) with defects created on medial femoral condyle. For developing an appropriate defect, three approaches were used for evaluation: a biopsy punch (n = three at six and twelve weeks), an impaction device1 (n = three at six and twelve weeks) and a dental drill model (n = six at six and twelve weeks). At stated time points, condyles were harvested and decalcified in 10% EDTA, then embedded in Tissue-Tek and sectioned using a cryostat. Upon identification of region of interest, sections were stained with Safranin-O/Fast green and scored using OARSI scoring system by two blinded observers2. For the pilot study, autologous bone marrow was harvested from rabbits and used to isolate and expand MSCs. The Dental drill model was applied to both knee condyles, left untreated for six weeks at which stage, PKH26 fluorescently labelled MSCs were seeded into a hyaluronic acid hydrogel (TETEC). Repair tissue was removed from both condyles and MSC-hydrogel was injected into the left knee, whilst right knee was left empty. Rabbits were sacrificed at one (n = 1), six (n = 3) and twelve (n = 3) weeks post-treatment, processed as previously described and cartilage regeneration evaluated using Sellers score3.

Impacted condyles exhibited no observed changes histologically (Mean OARSI score = 1 + 1), whereas biopsy punched and dental drilled defects demonstrated equal signs of cartilage erosion (OARSI score = 3 + 1) at assessed time points. However, biopsy punched condyles formed a diffusive defect, whereas dental drilled condyles showed a more defined, compact and reproducible defect. In the pilot study, PKH-labelled MSCs were observed at one and six weeks post-implantation within the defect space where hydrogel was injected. Tissue regeneration assessment indicated no difference between empty (Mean Sellers score = 14 + 2) and MSC treated defects (Sellers score = 16 + 5) at six weeks post-injection. At twelve weeks, MSC treated defects showed improved tissue regeneration with substantial subchondral bone restoration and good integration of regenerative cartilage with surrounding intact tissue (Sellers score = 10 + 1), whereas untreated defects showed no change in regeneration compared to six weeks (Sellers score = 16 + 2).

Dental drill model was found to be the appropriate strategy for investigating early OA progression and treatment. Application of MSCs in defects showed good cartilage regeneration after twelve weeks application, indicating their promise in the treatment of early OA defects.


J. Chang D. Pincus R. Jenkinson D. Wasserstein H. Kreder B. Ravi

Echocardiography is commonly used in hip fracture patients to evaluate perioperative cardiac risk and identify cardiac abnormalities. However, echocardiography that delays surgical repair may be harmful. The objective of this study was to compare mortality, surgical wait times, length of stay (LOS), and health care costs for similar hip fracture patients managed with and without preoperative echocardiography.

A population based, retrospective cohort study of all hip fracture patients (>age 45) in Ontario, Canada was conducted. The primary exposure was pre-operative echocardiography (between hospital admission and surgery). Patients receiving preoperative echocardiography were matched to those without using a propensity score incorporating patient demographic information, comorbidity status, and provider information. Mortality rates, surgical wait times, post-operative length of stay (LOS), and medical costs (expressed as 2013$ CAN) up to one year post-operatively were assessed after matching.

There were 2354 (∼5.6%) of 42,230 eligible hip fracture patients that received preoperative echocardiograghy during the study period. After successfully matching 2298 (∼97.6%) patients, echocardiography was associated with significant increases in mortality at 90 days (20.1% vs. 16.8%, p=0.004) and one year (32.9% vs. 27.8%, p < 0 .001), but not 30-days (11.4% vs. 9.8%, p=0.084). Patients with echocardiography also had an increased (mean ± SD) delay (in hours) from presentation to surgery (68.80 ± 44.23 hours vs. 39.69 ± 27.09 hours, p < 0 .001) and only 38.1% of patients had surgery within 48 hours. Total LOS (in days) (mean 19.49 ± 25.39 days vs. 15.94 ± 22.48 days, p < 0 .001) and total healthcare costs at one year (mean: $51,714.69 ± 54,675.28 vs. $41,861.47 ± 50,854.12, p < 0 .001) were also increased. There was wide variability in echocardiography ordering practice in Ontario, with a range of 0% to 22.97% of hip fracture patients undergoing preoperative echocardiography at different hospital sites.

Preoperative echocardiography for hip fracture patients is associated with increased postoperative mortality. It is also associated with increased surgical delay, post-operative LOS, and total health care costs at one year. Echocardiography should be considered an urgent test when ordered to prevent additional surgical delay, and further research is necessary to clarify indications for this common preoperative investigation.


S. Ge B. Barimani L.M. Epure A. Aoude L. Luo M. Volesky R. E. Chaytor

Recent innovations in total ankle replacement (TAR) have led to improvements in implant survivorship, accuracy of component positioning and sizing, and patient outcomes. CT-generated pre-operative plans and cutting guides show promising results in terms of placement enhancement and reproducibility in clinical studies. The purpose of this study was to determine the accuracy of 1) implant sizes used and 2) alignment corrections obtained intraoperatively using the cutting guides provided, compared to what was predicted in the CT generated pre-operative plans.

This is a retrospective study looking at 36 patients who underwent total ankle arthroplasty using a CT generated pre-operative planning system between July 2015 and December 2017. Personalized pre-operative planning data was obtained from the implant company. Two evaluators took measurements of the angle corrected using pre- and post-operative weight bearing ankle AP X-rays. All patients had a minimum three-month follow-up with weightbearing postoperative radiographs. The actual correction calculated from the radiographic assessment was compared with the predicted angles obtained from pre-operative plans. The predicted and predicted alternative component sizes and actual sizes used were also compared. If either a predicted or predicted alternative size was implanted, we considered it to be accurate.

Average age for all patients was 64 years (range 40–83), with a body mass index of 28.2 ± 5.6. All surgeries were performed by two foot and ankle surgeons. The average total surgical time was 110 ± 23 minutes. Pre-operative alignment ranged from 36.7 degrees valgus to 20 degrees varus. Average predicted coronal alignment correction was 0.8 degrees varus ± 9.3 degrees (range, 18.2 degrees valgus to 29 degrees varus) and average correction obtained was 2.1 degrees valgus ± 11.1 degrees. Average post-op alignment was consistently within 5 degrees of neutral. There were no significant differences between the predicted alignments and the postoperative weightbearing alignments. The predicted tibia implant size was accurate in all cases. The predicted sizes were less accurate for talar implants and predicted the actual talar implant size used in 66% of cases. In all cases of predicted talar size mismatch, surgical plans predicted 1 implant size larger than used.

Preliminary analyses of our data is comparable to previous studies looking at similar outcomes. However, our study had higher pre-operative deformities. Despite that, post-op alignments were consistently within 5 degress of neutral with no significant difference between the predicted and actual corrections. Tibial implant sizes are highly accurate while talar implant sizes had a trend of being one size smaller than predicted. Moreover, this effect seems to be more pronounced in the earlier cases likely reflective of increasing surgeon comfort with the implant with each subsequent case. These results confirm that pre-operative cutting guides are indeed helpful in intra-operative implant selection and positioning, however, there is still some room for innovation.


B. Yew J. Cheng A. Choh A. Yew D.T.T. Lie S.M. Chou

The function of the shoulder joint has traditionally been evaluated based on range of motion (ROM) in predefined anatomical planes and also by using functional scores, which assessed shoulder function based on the ability to conduct certain activities of daily living (ADLs). However, measuring ROM only in terms of flexion-extension, abduction-adduction and internal-external rotation may under-account for the 3-dimensional mobility of the shoulder joint. Furthermore, functional scores, such as the Oxford shoulder score or American shoulder and elbow surgeons (ASES) score, are subjective measures and are not an accurate assessment of shoulder joint function. In this study, we proposed the use of the globe model of the shoulder joint which can be used to provide an objective measure of the global ROM and also function of the shoulder joint – termed the Global and Functional arc of motion (GAM and FAM).

Thirty-three young, healthy male patients (23.7 ± 1.5 years) were recruited and tasked to perform eight ADLs and a full humeral circumduction movement which represented their active global ROM. Reflective markers were placed in accordance to the International Society of Biomechanics (ISB) and optical-based motion capture cameras were used to track relative motion of the dominant humerus with respect to the thorax (i.e. thoracohumeral motion). The GAM and FAM were generated by plotting the thoracohumeral on a spherical coordinate system during global ROM and the eight ADLs respectively. Shoulder joint global ROM and function were quantified by calculating the area enclosed by the closed loop of GAM and FAM respectively.

The spherical coordinate system, or more commonly referred to as the globe model, describes thoracohumeral movement using plane of elevation (POE), angle of elevation (AOE) and rotation. In our model, POE and AOE represents longitude and latitude of the globe respectively, and rotation is depicted using a red-green-blue (RGB) colour scale. Overall, subject's GAM of the shoulder joint covered an area of 4.64 ± 0.48 units2 compared to only 1.12 ± 0.26 units2 for the FAM. Subjects only required 24.4 ± 5.7 % of their global shoulder ROM for basic daily functioning.

Studies that reduced shoulder joint movement into planar movements (i.e. sagittal, coronal and rotation) do not account for the 3-dimensional nature of the joint and doing so may overestimate the requirement of the shoulder joint for ADLs relative to its ROM in each plane. While others have attempted to use the globe model, such studies tend to reduce the globe into its descriptive angles (i.e. POE, AOE and rotation), reducing its intuitiveness. In contrast, by keeping an intact globe, the proposed globe model was more intuitive and yet capable of quantifying both shoulder joint global ROM and function. Doing so, we found that young healthy subjects only required approximately a quarter of their global ROM of the shoulder joint to complete the most common daily tasks, which was significantly less than what was previously reported.


J. Tsang P. Gwynne M. Gallagher H. Simpson

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, with cumulative treatment costs for all prosthetic joint infections estimated to be ∼ $1 billion per annum (UK and North America). Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Low intensity pulsed ultrasound is already licensed for clinical use in fracture management and thus could be translated quickly into a clinical treatment

Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged with gentamicin +/− low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 180 minutes and 20 minutes, respectively. The primary outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. Assessment of cellular metabolism was conducted using a liquid-chromatography-mass spectrometry, as well as a triphenyltetrazolium chloride assay coupled with spectrophotometry.

There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was reduced to 64mg/L. Metabolic activity of biofilm-associated S. aureus was increased by 25% following ultrasound therapy (p < 0 .0001), with identification of key biosynthetic pathways activated by non-lethal dispersal.

Low intensity pulsed ultrasound was associated with a four-fold reduction in the effective biofilm eradication concentration of gentamicin, bringing the MBEC of gentamicin to within clinically achievable concentrations. The mechanism of action was due to partial disruption of the extracellular matrix which led to an increase of nutrient availability and oxygen tension within the biofilm. This metabolic stimulus was responsible for the reversal of gentamicin tolerance in the biofilm-associated S. aureus.


T. Liang Z. Luo

The detailed biomechanical mechanism of annulus fibrosus under abnormal loading is still ambiguous, especially at the micro and nano scales. This study aims to characterize the alterations of modulus at the nano scale of individual collagen fibrils in annulus fibrosus after in-situ immobilization, and the corresponding micro-biomechanics of annulus fibrosus.

An immobilization model was used on the rat tail with an external fixation device. Twenty one fully grown 12-week-old male Sprague-Dawley rats were used in this study. The rats were assigned to one of three groups randomly. One group was selected to be the baseline control group with intact intervertebral discs (n=7). In the other two groups, the vertebrae were immobilized with an external fixation device that fixed four caudal vertebrae (C7-C10) for 4 and 8 weeks, respectively. Four K-wires were fixed in parallel using two aluminum alloy cuboids which do not compress or stretch the target discs. The immobilized discs were harvested and then stained with hematoxylin/eosin, scanned using atomic force microscopy to obtain the modulus at both nano and micro scales, and analyzed the gene expression with real-time quantitative polymerase chain reaction. Significance of differences between the study groups was obtained using a two-way analysis of variance (ANOVA) with Fisher's Partial Least-Squares Difference (PLSD) to analyze the combined influence of immobilization time and scanning region. Statistical significance was set at P≤0.05.

Compared to the control group, the inner layer of annulus fibrosus presented significant disorder and hyperplasia after immobilization for 8 weeks, but not in the 4 week group. The fibrils in inner layer showed an alteration in elastic modulus from 91.38±20.19MPa in the intact annulus fibrosus to 110.64±15.58MPa (P<0.001) at the nano scale after immobilization for 8 weeks, while the corresponding modulus at the micro scale also underwent a change from 0.33±0.04MPa to 0.47±0.04MPa (P<0.001). The upregulation of collagen II from 1±0.03 in control to 1.22±0.03 in 8w group (P = 0.003) was induced after immobilization, while other genes expression showed no significant alteration after immobilization for both 4 and 8 weeks compared to the control group (P>0.05).

The biomechanical properties at both nano and micro scales altered in different degrees between inner and outer layers in annulus fibrosus after immobilization for different times. Meanwhile, the fibril arrangement disorder and the upregulation of collagen II in annulus fibrosus were observed using hematoxylin/eosin staining and real-time RT-PCR, respectively. These results indicate that immobilization not only influenced the individual collagen fibril at the nano scale, but also suggested alterations of micro-biomechanics and cell response. This work provides a better understanding of IVD degeneration after immobilization and benefits to the clinical treatment related to disc immobilization.


R. Galmiche S. Poitras A. Salimian P. Kim R. Feibel W. Gofton H. Abdelbary P. Beaulé

The effectiveness of total hip replacement as a surgical intervention has revolutionized the care of degenerative conditions of the hip joint. However, the surgeon is still left with important decisions in regards to how best deliver that care with choice of surgical approach being one of them especially in regards to the short-term clinical outcome. It is however unclear if a particular surgical approach offers a long-term advantage. This study aims to determine the influence of the three main surgical approaches to the hip on patient reported outcomes and quality of life after 5 years post-surgery.

We extracted from our prospective database all the patients who underwent a Total Hip Replacement surgery for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach. All the pre-operative and post-operative HOOS (Hip disability and Osteoarthritis Outcome Score) and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores were noted. Analysis of covariance (ANCOVAs) were used to study the relationship between amount of change in HOOS and WOMAC subscales (dependant variables) and approach used, by also including confounding factors of age, gender, ASA (American Society of Anaesthesiologists) score, Charnley score and Body Mass Index. A total of 1895 patients underwent a primary total hip arthroplasty during the considered period. Among them, 367 had pre-operative and ≥5 years post operative PROM scores (19.47%)

The mean follow-up for the study cohort was 5.3 years (range 5 to 7 years) with, 277 at 5 years, 63 at 6 years, and 27 at 7 years. In the posterior approach group we had 138 patients (37.60%), 104 in the lateral approach (28.34%) and 125 in the anterior approach (34.06%). There were no significant differences between the 3 groups concerning the Charnley classification, BMI, Gender, ASA score, side and pre-operative functional scores. We did not observe any significant difference in the amount of change in HOOS and WOMAC subscales between the 3 groups. There were no differences either in the post-operative scores in ultimate value.

Our monocentric observational study shows that these three approaches provide predictable and comparable outcomes on HRQL and PROMs at long-term follow-up both in terms of final outcome but also in percent improvement. This study has several limitations. We excluded patients who underwent revision surgery leaving the unanswered question of how choice of surgical approach could lead to different revision rates, which have an impact on the functional outcomes. Moreover, even if we controlled for the most important confounders by a multivariate analysis model, there is still some involved cofounders, which could potentially lead to a bias such as smoking, socio-economical status or femoral head diameter. But we do not have any reason to think that these parameters could be unequally distributed between the three groups. Finally, our study cohort represents of 19.47% of the complete cohort. The fact that not all patients have PROM's was pre-determined as eight years ago we instituted that only 1 in 5 patients that returned their pre-operative questionnaire would get their PROM's at follow-up. Despite this, our statistical power was sufficient.


R. Galmiche P. Beaulé A. Salimian A. Carli

Recently, new metallurgical techniques allowed the creation of 3D metal matrices for cementless acetabular components. Among several different products now available on the market, the Biofoam Dynasty cup (MicroPort Orthopedics® Inc., Arlington, TN, USA) uses an ultraporous Titanium technology but has never been assessed in literature. Coping with this lack of information, our study aims to assess its radiological osteointegration at two years in a primary total hip arthroplasty and compares it to a successful contemporary cementless acetabular cup.

This monocentric retrospective study includes 96 Dynasty Biofoam acetabular components implanted between March 2010 and August 2014 with a minimum 2 years radiographic follow-up. Previous acetabular surgery, any septic issue or re-operation for component malposition were exclusion criteria. They were compared to 96 THA using the Trident PSL matched for age, gender, BMI and follow-up. Presence of radiolucencies and sclerotic lines were described on AP pelvis views using the classification of DeLee and Charnley

There was no statistical difference between the two groups concerning demographics and mean follow-up (p> 0.05). Shell's anteversion was similar but inclination was greater in the biofoam group (p=0.006). 27,17% of the Biofoam shells presented radiolucencies in 2 zones or more and 0% of the Trident shells. 11,96% of Biofoam cups showed radiolucencies in the 3 zones of DeLee comparing to 0% of the Trident cups. There was no statistical difference between the Biofoam group (n=54/96) and the Trident PSL group (n=57/96) in pre-operative functional scores for both WOMAC subscales and SF-12. When evaluating last follow-up PROM's, no significant differences were found comparing the entirety of both groups, 56 Biofoam and 51 Trident PSL. No difference was found either when comparing Biofoam patients with ³ 2 zones of radiolucencies (n=15) to the whole Trident group (n=51).

This study raises concerns about radiologic evidence of osteointegration of the Biofoam acetabular cup. Nevertheless, these radiological findings do not find any clinical correlation considering clinical scores. Thus, it may question the real meaning of these high-rated radiolucencies, which at first sight reflect a poorer osteointegration. The first possible limitation with this study is an overinterpretation of the radiographs. Nevertheless, both observers were blinded regarding the patients groups and clinical outcomes and there was a strong inter-observer reliability. Although both cohorts were matched on their demographics and were similar on the cup anteversion, we noticed a slightly lower abduction angle in the Biofoam population. It could reduce the bone-implant coverage area and hence hinders the bony integration, but this difference was small and both groups remained in the Lewinneck security zone. Furthermore, even if patients were matched on age, gender, BMI and follow-up, other variables can influence early osteointegration (smoke status, osteoporosis) and have not been controlled even though we have no reasons to think their distribution could differ in the 2 groups.

The real clinical meaning of these findings remains unknown but serious concerns are raised about the radiographic osteointegration of the Dynasty Biofoam acetabular components. Concerns are all the more lawful that this implants aim to enhance osteointegration.


T. Lemirre H. Richard J. Janes S. Laverty U. Fogarty C. Girard E. Santschi

Juvenile Osteochondritis dissecans (JOCD) in humans and subchondral cystic lesions (SCL) in horses (also termed radiolucencies) share similarities: they develop in skeletally immature individuals at the same location in the medial femoral condyle (MFC) and their etiology is only partially understood but trauma is suspected to be involved. JOCD is relatively uncommon in people whereas SCLs arise in 6% of young horses leading to lameness. Ischemic chondronecrosis is speculated to have a role in both osteochondrosis and SCL pathogenesis. We hypothesize that MFC radiolucencies develop very early in life following a focal internal trauma to the osteochondral junction. Our aims were to characterize early MFC radioluciencies in foals from 0 to 2 years old.

Distal femurs (n=182) from Thoroughbred horses (n=91, 0–2 years old), presented for post-mortem examination for reasons unrelated to this study, were collected. Radiographs and clinical tomodensitometry were performed to identify lesions defined as a focal delay of ossification. Micro-tomodensitometry (m-CT) and histology was then performed on the MFCs (CT lesions and age-matched subset of controls). Images were constructed in 3D. The thawed condyles, following fixation, were sectioned within the region of interest, determined by CT lesion sites. Hematoxylin eosin phloxin and safran (HEPS) and Martius-Scarlet-Blue (MSB) stains were performed. Histological parameters assessed included presence of chondronecrosis, fibrin, fibroplasia and osteochondral fracture. An additional subset of CT control (lesion-free) MFCs (less 6 months old) were studied to identify early chondronecrosis lesions distant from the osteochondral junction.

One MFC in clinical CT triages controls had a small lesion on m-CT and was placed in the lesion group. All m-CT and histologic lesions (n=23) had a focal delay of ossification located in the same site, a weight bearing area on craniomedial condyle. The youngest specimen with lesions was less than 2 months old. On m-CT 3D image analysis, the lesions seemed to progressively move in a craniolateral to caudomedial direction with advancing age and development. Seventy-four percent (n=17/23) of the lesions had bone-cartilage separation (considered to be osteochondral fractures) confirmed by the identification of fibrin/clot on MSB stains, representing an acute focal bleed. Fibroplasia, indicating chronicity, was also identified (74%, n=17/23). In four cases, the chondrocytes in the adjacent cartilage were healthy and no chondronecrosis was identified in any sections in the lesions. Nineteen cases had chondronecrosis and always on the surface adjacent to the bone, at the osteochondral junction. None of the subset of control specimens, less than 6 months old (n=44), had chondronecrosis within the growth cartilage.

Early subchondral cystic lesions of the medial femoral condyle may arise secondary to focal internal trauma at the osteochondral junction. The presence of fibrin/clot is compatible with a recent focal bleed in the lesion. Medial femorotibial joint internal forces related to geometry could be the cause of repetitive trauma and lesion progression. In the juvenile horse, and potentially humans, the early diagnosis of MFC lesions and rest during the susceptible period may reduce progression and promote healing by prevention of repetitive trauma, but requires further study.


C. Smith G. Athwal L. Ferreira B. Matache

Glenoid replacement is a manual bone removal procedure that can be difficult for surgeons to perform. Surgical robotics have been utilized successfully in hip and knee orthopaedic procedures but there are no systems currently available in the shoulder. These robots tend to have low adoption rates by surgeons due to high costs, disruption of surgical workflow and added complexity. As well, these systems typically use optical tracking which needs a constant line-of-sight which is not conducive to a crowded operating room. The purpose of this work was developing and testing a surgical robotic system for glenoid replacement.

The new surgical system utilizes flexible components that tether a Stewart Platform robot to the patient through a patient specific 3D printed mount. As the robot moves relative to the bone, reaction loads from the flexible components bending are measured by a load cell allowing the robot to “feel” its way around. As well, a small bone burring tool was attached to the robot to facilitate the necessary bone removal. The surgical system was tested against a fellowship-trained surgeon performing standard surgical techniques. Both the robot and the surgeon performed glenoid replacement on two different scapula analogs: standard anatomy and posterior glenoid edge wear referred to as a Walch B2. Six of each scapula model was tested by the robot and the surgeon. The surgeon created a pre-operative plan for both scapula analogs as a target for both methodologies. CT scans of the post-operative cemented implants were compared to the pre-operative target and implant position and orientation errors were measured.

For the standard shoulder analogs the net implant position and orientation errors were 1.47 ± 0.48 mm and 2.57 ± 2.30° for the robot and 1.61 ± 0.29 mm and 5.04 ± 1.92° for the surgeon respectively. For the B2 shoulders, the net implant position and orientation errors were 2.16 ± 0.36 mm and 2.89 ± 0.88° for the robot and 3.01 ± 0.42 mm and 4.54 ± 1.49° for the surgeon respectively.

The new tracking system was shown to be able to match or outperform the surgeon in most metrics. The surgeon tended to have difficulty gauging the depth needed as well as the face rotation of the implant. This was not surprising as the reaming tool used by the surgeon obscures the view of the anatomy and the spherical cutter hinders the ability to index the tool. The robot utilized only one surgical tool, the bone burr, precluding the need for multiple instruments used by the surgeon to prepare the glenoid bone bed. The force-space navigation method can be generalized to other joints, however, further work is needed to validate the system using cadaveric specimens.


Y. Shao X. Chen Z. Luo

Osteoarthritis (OA) is a chronic degenerative joint disease with cartilage degeneration, subchondral bone sclerosis, synovial inflammation and osteophyte formation. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of capsaicin-induced sensory nerve denervation on OA progression in mice.

This study was approved by the Institutional Animal Care and Use Committee. OA was induced via destabilization of the medial meniscus (DMM). Sensory denervation was induced by subcutaneous injection of capsaicin (90mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining with calcitonin gene-related peptide (CGRP)-specific antibodies. Four weeks after DMM, micro-CT scans, histological analysis and RT-PCR tests were performed to evaluate OA progression. Statistical analysis was performed using SPSS 13. P values of less than 0.05 were considered statistically significant.

Subcutaneous injection of capsaicin successfully induced tibial sensory denervation (n=3), which aggravated OA by increasing subchondral bone resorption. The Osteoarthritis Research Society International (OARSI) score of the capsaicin+DMM group (n=8) (11.81±2.92) was significantly higher (P=0.003) than the score of the vehicle+DMM group (n=8) (8.31±1.80). The BV/TV of the tibial subchondral bone in the capsaicin+DMM group (n=8) was 55.67%±3.08, which was significantly lower (P < 0 .001) than in the vehicle+DMM group (n=8) (86.22%±1.92). In addition, the level of expression of somatostatin in the capsaicin+DMM group (n=8) was lower than in the vehicle+DMM group (n=8) (P=0.007).

Capsaicin-induced sensory denervation increased tibial subchondral bone resorption, reduced the expression of somatostatin and eventually exacerbated the existing cartilage degeneration in mice. Despite capsaicin is often used clinically to relieve OA pain, its safety is still controversial according to the OARSI guidelines for the non-surgical management of knee osteoarthritis. The findings of our study suggest that application of capsaicin, although effective in relieving pain, may accelerate the progression of existing OA.


C. A. Tee Z. Yang L. Yin Y. Wu V. Denslin X. Ren C. T. Lim J. Han E. H. Lee

The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture.

Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy.

Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP.

Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects.


J. Kendal A. Singla A. Affan K. Hildebrand A. Al-Ani D. Itani M. Ungrin

Impaired bone healing biology secondary to soft tissue deficits and chemotherapy contribute to non-union, fracture and infection following limb salvage surgery in Osteosarcoma patients. Approved bone healing augments such as recombinant human bone morphogenetic protein-2 (rhBMP-2) have great potential to mitigate these complications. rhBMP-2 use in sarcoma surgery is limited, however, due to concerns of pro-oncogenic signalling within the tumour resection bed. To the contrary, recent pre-clinical studies demonstrate that BMP-2 may induce Osteosarcoma differentiation and limit tumour growth. Further pre-clinical studies evaluating the oncologic influences of BMP-2 in Osteosarcoma are needed. The purpose of this study is to evaluate how BMP-2 signalling affects Osteosarcoma cell proliferation and metastasis in an active tumour bed.

Two Osteosarcoma cell lines (143b and SaOS-2) were assessed for proliferative capacity and invasion. 143b and SaOS-2 cells were engineered to upregulate BMP-2. In vitro proliferation was assessed using a cell viability assay, motility was assessed with a scratch wound healing assay, and degree of osteoblastic differentiation was assessed using qRT-PCR of Osteoblastic markers (CTGF, ALP, Runx-2 and Osx). For in vivo evaluation, Osteosarcoma cells were injected into the intramedullary proximal tibia of immunocompromised (NOD-SCID) mice and local tumour growth and metastases were assessed using weekly bioluminescence imaging and tumour volume measurements for 4–6 weeks. At the experimental end point we assessed radiographic tumour burden using ex-vivo micro-CT, as well as tibial and pulmonary gross and histologic pathology.

SaOS-2 was more differentiated than 143b, with significantly increased expression of the Osteoblast markers Osx (p = 0.004) and ALP (p = 0.035). BMP-2 upregulation did not stimulate an osteoblast differentiation response in 143b, but stimulated an increase in Osx expression in SaOS-2 (p = 0.002). BMP-2 upregulation in 143b cells resulted in increased proliferation in vitro (p = 0.014), faster in vitro wound healing (p = 0.03), significantly increased tumour volume (p = 0.001) with enhanced osteolysis detected on micro-CT, but did not affect rates of lung metastasis (67% vs. 71%, BMP-2 vs. Control). BMP-2 over-expression in SaOS-2 cells reduced in vitro proliferation when grown in osteogenic-differentiation media (p < 0.001), had no effect on in vitro wound healing (p = 0.28), reduced in vivo SaOS-2 tumour burden at 6 weeks (photon counts, p < 0.0001), decreased tumour-associated matrix deposition as assessed by trabecular thickness (p = 0.02), but did not affect rates of lung metastasis (0% vs. 0%).

Our results indicate BMP-2 signalling incites a proliferative effect on a poorly differentiated Osteosarcoma cell line (143b), but conditionally reduces proliferative capacity and induces a partial differentiation response in a moderately-differentiated Osteosarcoma cell line (SaOS-2). This dichotomous effect may be due to the inherent ability for Osteosarcoma cells to undergo BMP-2 mediated terminal differentiation. Importantly, these results do not support the clinical application of BMP-2 in Osteosarcoma limb salvage surgery due to the potential for stimulating growth of poorly differentiated Osteosarcoma cells within the tumour bed. Additional studies assessing the effects of BMP-2 in an immune-competent mouse model are ongoing.


H. Jahr P. Pavanram Y. Li K. Lietaert Y. Kubo H. Weinans J. Zhou T. Pufe A. Zadpoor

Biodegradable metals as orthopaedic implant materials receive substantial scientific and clinical interest. Marketed cardiovascular products confirm good biocompatibility of iron. Solid iron biodegrades slowly in vivo and has got supra-physiological mechanical properties as compared to bone and porous implants can be optimized for specific orthopaedic applications. We used Direct Metal Printing (DMP)3 to additively manufacture (AM) scaffolds of pure iron with fine-tuned bone-mimetic mechanical properties and improved degradation behavior to characterize their biocompatibility under static and dynamic 3D culture conditions using a spectrum of different cell types.

Atomized iron powder was used to manufacture scaffolds with a repetitive diamond unit cell design on a ProX DMP 320 (Layerwise/3D Systems, Belgium). Mechanical characterization (Instron machine with a 10kN load cell, ISO 13314: 2011), degradation behavior under static and dynamic conditions (37ºC, 5% CO2 and 20% O2) for up of 28 days, with μCT as well as SEM/energy-dispersive X-ray spectroscopy (EDS) (SEM, JSM-IT100, JEOL) monitoring under in vivo-like conditions. Biocompatibility was comprehensively evaluated using a broader spectrum of human cells according to ISO 10993 guidelines, with topographically identical titanium (Ti-6Al-4V, Ti64) specimen as reference. Cytotoxicity was analyzed by two-way ANOVA and post-hoc Tukey's multiple comparisons test (α = 0.05).

By μCT, as-built strut size (420 ± 4 μm) and porosity of 64% ± 0.2% were compared to design values (400 μm and 67%, respectively). After 28 days of biodegradation scaffolds showed a 3.1% weight reduction after cleaning, while pH-values of simulated body fluids (r-SBF) increased from 7.4 to 7.8. Mechanical properties of scaffolds (E = 1600–1800 MPa) were still within the range for trabecular bone, then. At all tested time points, close to 100% biocompatibility was shown with identically designed titanium (Ti64) controls (level 0 cytotoxicity). Iron scaffolds revealed a similar cytotoxicity with L929 cells throughout the study, but MG-63 or HUVEC cells revealed a reduced viability of 75% and 60%, respectively, already after 24h and a further decreased survival rate of 50% and 35% after 72h. Static and dynamic cultures revealed different and cell type-specific cytotoxicity profiles. Quantitative assays were confirmed by semi-quantitative cell staining in direct contact to iron and morphological differences were evident in comparison to Ti64 controls.

This first report confirms that DMP allows accurate control of interconnectivity and topology of iron scaffold structures. While microstructure and chemical composition influence degradation behavior - so does topology and environmental in vitro conditions during degradation. While porous magnesium corrodes too fast to keep pace with bone remodeling rates, our porous and micro-structured design just holds tremendous potential to optimize the degradation speed of iron for application-specific orthopaedic implants. Surprisingly, the biological evaluation of pure iron scaffolds appears to largely depend on the culture model and cell type. Pure iron may not yet be an ideal surface for osteoblast- or endothelial-like cells in static cultures. We are currently studying appropriate coatings and in vivo-like dynamic culture systems to better predict in vivo biocompatibility.


M. Perelgut M. Teeter B. Lanting E. Vasarhelyi

Increasing pressure to use rapid recovery care pathways when treating patients undergoing total hip arthroplasty (THA) is evident in current health care systems for numerous reasons. Patient autonomy and health care economics has challenged the ability of THA implants to maintain functional integrity before achieving bony union. Although collared stems have been shown to provide improved axial stability, it is unclear if this stability correlates with activity levels or results in improved early function to patients compared to collarless stems. This study aims to examine the role of implant design on patient activity and implant fixation. The early follow-up period was examined as the majority of variation between implants is expected during this time-frame.

Patients (n=100) with unilateral hip OA who were undergoing primary THA surgery were recruited pre-operatively to participate in this prospective randomized controlled trial. All patients were randomized to receive either a collared (n=50) or collarless (n=50) cementless femoral stem. Patients will be seen at nine appointments (pre-operative, < 2 4 hours post-operation, two-, four-, six-weeks, three-, six-months, one-, and two-years). Patients completed an instrumented timed up-and-go (TUG) test using wearable sensors at each visit, excluding the day of their surgery. Participants logged their steps using Fitbit activity trackers and a seven-day average prior to each visit was recorded. Patients also underwent supine radiostereometric analysis (RSA) imaging < 2 4 hours post-operation prior to leaving the hospital, and at all follow-up appointments.

Nineteen collared stem patients and 20 collarless stem patients have been assessed. There were no demographic differences between groups. From < 2 4 hours to two weeks the collared implant subsided 0.90 ± 1.20 mm and the collarless implant subsided 3.32 ± 3.10 mm (p=0.014). From two weeks to three months the collared implant subsided 0.65 ± 1.54 mm and the collarless implant subsided 0.45 ± 0.52 mm (p=0.673). Subsidence following two weeks was lower than prior to two weeks in the collarless group (p=0.02) but not different in the collared group. Step count was reduced at two weeks compared to pre-operatively by 4078 ± 2959 steps for collared patients and 4282 ± 3187 steps for collarless patients (p=0.872). Step count increased from two weeks to three months by 6652 ± 4822 steps for collared patients and 4557 ± 2636 steps for collarless patients (p=0.289). TUG test time was increased at two weeks compared to pre-operatively by 4.71 ± 5.13 s for collared patients and 6.54 ± 10.18 s for collarless patients (p=0.551). TUG test time decreased from two weeks to three months by 7.21 ± 5.56 s for collared patients and 8.38 ± 7.20 s for collarless patients (p=0.685). There was no correlation between subsidence and step count or TUG test time.

Collared implants subsided less in the first two weeks compared to collarless implants but subsequent subsidence after two weeks was not significantly different. The presence of a collar on the stem did not affect patient activity and function and these factors were not correlated to subsidence, suggesting that initial fixation is instead primarily related to implant design.


Y. Wu V. Denslin X. Ren C. S. Lee F. L. Yap Z. Yang E.H. Lee C.A. Tee

Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and mechanical strength when compared to normal cartilage. The phenotype of cartilage derived from MSCs has been reported to be influenced by the microenvironmental biophysical cues, such as the surface topography and substrate stiffness. In this study, the effect of nano-topographic surfaces to direct MSC chondrogenic differentiation to chondrocytes of different phenotypes was investigated, and the application of these pre-differentiated cells for cartilage repair was explored.

Specific nano-topographic patterns on the polymeric substrate were generated by nano-thermal imprinting on the PCL, PGA and PLA surfaces respectively. Human bone marrow MSCs seeded on these surfaces were subjected to chondrogenic differentiation and the phenotypic outcome of the differentiated cells was analyzed by real time PCR, matrix quantification and immunohistological staining. The influence of substrate stiffness of the nano-topographic patterns on MSC chondrogenesis was further evaluated. The ability of these pre-differentiated MSCs on different nano-topographic surfaces to form zonal cartilage was verified in in vitro 3D hydrogel culture. These pre-differentiated cells were then implanted as bilayered hydrogel constructs composed of superficial zone-like chondro-progenitors overlaying the middle/deep zone-like chondro-progenitors, was compared to undifferentiated MSCs and non-specifically pre-differentiated MSCs in a osteochondral defect rabbit model.

Nano-topographical patterns triggered MSC morphology and cytoskeletal structure changes, and cellular aggregation resulting in specific chondrogenic differentiation outcomes. MSC chondrogenesis on nano-pillar topography facilitated robust hyaline-like cartilage formation, while MSCs on nano-grill topography were induced to form fibro/superficial zone cartilage-like tissue. These phenotypic outcomes were further diversified and controlled by manipulation of the material stiffness. Hyaline cartilage with middle/deep zone cartilage characteristics was derived on softer nano-pillar surfaces, and superficial zone-like cartilage resulted on softer nano-grill surfaces. MSCs on stiffer nano-pillar and stiffer nano-grill resulted in mixed fibro/hyaline/hypertrophic cartilage and non-cartilage tissue, respectively. Further, the nano-topography pre-differentiated cells possessed phenotypic memory, forming phenotypically distinct cartilage in subsequent 3D hydrogel culture. Lastly, implantation of the bilayered hydrogel construct of superficial zone-like chondro-progenitors and middle/deep zone-like chondro-progenitors resulted in regeneration of phenotypically better cartilage tissue with higher mechanical function.

Our results demonstrate the potential of nano-topographic cues, coupled with substrate stiffness, in guiding the differentiation of MSCs to chondrocytes of a specific phenotype. Implantation of these chondrocytes in a bilayered hydrogel construct yielded cartilage with more normal architecture and mechanical function. Our approach provides a potential translatable strategy for improved articular cartilage regeneration using MSCs.


Q. Tan Y. Xie L. Chen

The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation.

Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice.

Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue.

TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation.


I. Tsukamoto K. Yamagishi K. Nakagawa S. Inoue M. Akagi

We proposed the substitute anteroposterior (sAP) line of the tibia for medial unicompartmental knee arthroplasty (UKA), which connects the medial border of the patellar tendon at the articular surface level and the medial intercondylar tubercle of the tibia. However, it has not been shown that referencing this line improves the rotational alignment of the components. Therefore, in this study, we investigated whether the tibial component could be implanted perpendicular to the SEA by referencing the sAP line and whether referencing the sAP line could reduce the rotational mismatch between the femoral and the tibial components.

Postoperative computed tomography datasets from 60 lower limbs in 57 Japanese patients with medial UKA were used. Among these, 30 knees were operated using the sAP line for AP reference and other 30 knees using the medial intercondylar ridge (MIR) line. First, the angle between the AP orientation of the tibial component and the surgical epicondylar axis (SEA) was measured. Then, the rotational mismatch angle between the components was measured.

The tibial and femoral components placed referencing the sAP line were externally rotated 90.7°±3.2° and 91°±7.7° relative to the SEA, respectively, those referencing the MIR line were 94.9°±8.5° and 91.2°±7.7°, respectively. When referencing the sAP line, the orientation of the component was more perpendicular to the SEA (Student t-test, unpaired, P = .016) and rotational variability of the tibial component was significantly smaller (F test, P < 0 .0001). The rotational mismatch angle when referencing the sAP line and the MIR line was 0.3°±8.3°and −3.8°±6.7°, respectively. Referencing the sAP line significantly reduced the rotational mismatch between the components (Student t-test, unpaired, P = .045).

Referencing the sAP line in the medial UKA may be useful to determine the AP orientation of the tibial component.


F. Mahmood J. Clarke P. Riches

The meniscus is comprised largely of type I collagen, as well as fibrochondrocytes and proteoglycans. In articular cartilage and intervertebral disc, proteoglycans make a significant contribution to mechanical stiffness of the tissue via negatively charged moieties which generate Donnan osmotic pressures. To date, such a role for proteoglycans in meniscal tissue has not been established. This study aimed to investigate whether meniscal proteoglycans contribute to mechanical stiffness of the tissue via electrostatic effects.

Following local University Ethics Committee approval, discs of meniscal tissue two millimetres thick and of five millimetres diameter were obtained from 12 paired fresh frozen human menisci, from donors < 6 5 years of age, with no history of osteoarthritis or meniscal injury. Samples were taken from anterior, middle and posterior meniscal regions. Each disc was placed within a custom confined compression chamber, permeable at the top and bottom only and then bathed in one of three solutions − 0.14M PBS (mimics cellular environment), deionised water (negates effect of mobile ions) or 3M PBS (negates all ionic effects). The apparatus was mounted within a Bose Electroforce 3100 materials testing machine and a 0.3N preload was applied. The sample was allowed to reach equilibrium, before being subjected to a 10% ramp compressive strain followed by a 7200 second hold phase. Equal numbers of samples from each meniscus and meniscal region were tested in each solution. Resultant stress relaxation curves were fitted to a nonlinear poroviscoelastic model with strain dependent permeability using FEBio finite element modelling software. Goodness of fit (R2) was assessed using a coefficient of determination. All samples were assayed for proteoglycan content. Comparison of resultant mechanical parameters was undertaken using multivariate ANOVA with Bonferroni adjustment for multiple comparisons.

36 samples were tested. A significant difference (p < 0 .05) was observed in the value of the Young's modulus (E) between samples tested in deionised water compared to 0.14M/3M PBS, with the meniscus found to be stiffest in deionised water (E = 1.15 MPa) and least stiff in 3M PBS (E = 0.43 MPa), with the value of E in 0.14M PBS falling in between (0.68 MPa). No differences were observed in the zero strain permeability or the exponential strain dependent/stiffening coefficients. The viscoelastic coefficient and relaxation time values were not found to improve model fit and were thus held at zero. The mean R2 value was 0.78, indicating a good fit and did not differ significantly between solutions. Proteoglycan content was not found to differ with solution, but was found to be significantly increased in the middle region of both menisci.

Proteoglycans make a significant electrostatic contribution to mechanical stiffness of the meniscus, increasing it by 58% in the physiological condition, and are hence integral to its function. It is important to include the influence of ionic effects when modelling meniscus, particularly where fluid flow or localised strain is modelled. From a clinical perspective, it is critical that meniscal regeneration strategies such as scaffolds or allografts attempt to preserve, or compensate for, the function of proteoglycans to ensure normal meniscal function.


E. Lalone R. Grewal A. Seltser K. Albakri J. MacDermid N. Suh M. Perrin

Scaphoid fractures are a common injury accounting for more than 58% of all carpal bone fractures(1,2). Biomechanical studies have suggested that scaphoid mal-union may lead to altered carpal contact mechanics causing decreased motion, pain and arthritis(1,2). The severity of mal-union required to cause deleterious effects has yet to be established. This limits the ability to define surgical indications or impacts on prevention of posttraumatic arthritis. Computed tomography has been shown to be a useful in determining the 3D implications of altered bony alignment on the joint contact mechanics of surrounding joints. The objective of this study was to report mid-term follow-up image-based outcomes of patients with scaphoid mal-unions to determine the extent to which arthritic changes and decreased joint space is present after a minimum of 4 years following fracture.

Participants (n=14) who had previously presented with a mal-united scaphoid fracture (indicated by a Height:Length Ratio >0.6) between November 2005 and November 2013 were identified and contacted. A short-arm thumb spica case was used to treat X patients and X required surgical management. Baseline and follow-up CT images, were performed with the wrist in radial deviation and positioned such that the long axis of the scaphoid was perpendicular to the axis of the scanner. Three-dimensional inter-bone distance (joint space), a measure of joint congruency and 3D alignment, was quantified from reconstructed CT bone models of the distal radius, scaphoid, lunate, capitate, trapezium and trapezoid from both the baseline and follow-up scans(3). Repeated measures ANOVA was used to detect differences in contact area (mm2) between baseline and follow-up CT's for the radioscaphoid, scaphocapitate and scaphotrapezium-trapezoid joint.

The average age of participants was 43.1 years (16–64 years old). There was significant loss of joint space, indicated by a greater joint contact area 3–4 years post fracture, between baseline and follow-up reconstruction models, at the scaphocapitate (mean difference: 21.5±146mm2, p=0.007) and scaphotrapezoid joints (mean difference: 18.4 ±28.6mm2, 0.042). Significant differences in the measured contact area was not found for the radioscaphoid (0.153) and scaphotrapezium joints (0.72). Additionally, the scaphoid, qualitatively, appears to track in the vorsal direction in the majority of patients following fracture.

Increased joint contact area in the scaphocapitate and scaphotrapezoid joint 3–4 years following fracture results from decreased 3D joint space and overall narrowing. Joint space narrowing, while not significantly different for all joints examined, was reduced for all joints surrounding the scaphoid. Decreased joint space and increased contact area detectable within this short interval might be suggestive of a trajectory for developing arthritis in the longer term, and illustrates the potential value of these measures for early detection. Longer term follow-up and correlation to clinical outcomes are needed to determine the importance of early joint space narrowing, and to identify those most at risk.


E. Lalone N. Suh M. Perrin A. Badre

Distal radius fractures are the most common upper extremity injury, and are increasingly being treated surgically with pre-contoured volar-locking plates. These plates are favored for their low-profile template while allowing for rigid anatomic fixation of distal radius fractures. The geometry of the distal radius is extremely complex, and little evidence within the medical literature suggests that current implant designs are anatomically accurate. The main objective of this study is to determine if anatomic alignment of the distal radii corresponds accurately with modern volar-locking plate designs. Additionally, this study will examine sex-linked differences in morphology of the distal radius.

Segmented CT models of ten female cadaver (mean age, 88.7 ± 4.57 years, range, 82 – 97) arms, and ten male cadaver (mean age, 86 ± 3.59 years, range, 81 – 91) arms were created. Micro CT models were obtained for the DePuy Synthes 2.4mm Extra-articular (EA) Volar Distal Radius Plate (4-hole and 5-hole head), and 2.4mm LCP Volar Column (VC) Distal Radius Plate (8-hole and 9-hole head). Plates were placed onto the distal radii models in a 3D visualization software by a fellowship-trained orthopaedic hand surgeon. The percent contact, volar cortical angle (VCA), border and overlap of the watershed line (WSL) were measured.

Both sexes showed an increase in the average VCA measure from medial to lateral columns which was statistically significant. Female VCA ranged from 28 – 36 degrees, and 38 – 45 degrees for males. WSL overlap ranged from 0 – 34.7629% for all specimens without any statistical significance. The average border distance for females was 2.58571 mm, compared to 3.52411 mm for males, with EA plates having a larger border than VC plates. The border distances had statistically significant differences between the plate types, and was approaching significance between sexes. Lastly, a maximum percent contact of 21.966 % was observed in specimen F4 at a 0.3 mm threshold. No statistical significance between plate or sex populations was observed.

This study investigated the incoherency between the volar cortical angle of the distal radius, and the pre-contoured angle of volar locking plates. It was hypothesized that if the VCA measures between plate and bone were unequal then there would be an increase in watershed line overlap, and decrease in percent contact between the surfaces. Our results agreed with literature, indicating that the VCA of bone was larger than that of the EA and VC pre-contoured plates examined in this study.

With distal radius fracture incidences and prevalence on the rise for elderly female patients, it is a necessity that volar locking plates be re-designed to factor in anatomical features of individual patients with a particular focus on sex differences. New designs should focus on providing smaller head sizes that are more accurately tailored to the natural contours of the volar distal radius. It is recommended that future studies incorporate expertise from multiple surgeons to diversify and further understand plate placement strategies.


N. Mohamed I.D. Castrodad J. Etcheson C. Gwam N. George R. Delanois A. Jetty E. Roadcloud R. Elmallah

Revision total knee arthroplasty (TKA) procedures performed secondary to periprosthetic joint infection (PJI) are associated with significant morbidity and mortality. These poor outcomes may be further complicated by the development of postoperative infection requiring aggressive antibiotic treatment. However, this antibiotic overuse may suppress patients' native bacterial flora, leading to Clostridium difficile infection (CDI). With the increased demand for primary TKAs and expected rise in revision TKA due to PJI, it is important to identify factors contributing to CDI. Therefore, we aimed to study the: 1) incidence, 2) demographics, length of stay (LOS), and total costs, and 3) risk factors and mortality associated with CDI in revision TKA patients.

The National Inpatient Sample database was queried for all individuals diagnosed with PJI and who underwent revision TKA between 2009 and 2013. Patients who developed CDI during their in-patient hospital stay were identified, yielding 83,806 patients (799 with CDI) with a mean age of 65 (S.D.=11.2). Logistic regression analysis was conducted to assess the association between hospital- and patient-specific characteristics and the development of CDI.

During the study period, the overall incidence of CDI after revision TKA was 1%. These patients were significantly older (mean age 69.05 vs. 65.52 yrs), had greater LOS (median 11 vs. 5 days), had greater costs ($30,612.93 vs. 18,873.75), and had higher in-hospital mortality (3.6 vs. 0.5%, p < 0 .001 for all) compared to those without infection. Patients with CDI were more likely to be treated in urban, not-for-profit, medium or large bed-sized hospitals located in the Northeast or Midwest (p < 0 .05 for all). Patients with underlying depression (OR 4.267, p=0.007) or fluid/electrolyte disorders (OR 3.48, p=0.001) were more likely to develop infection.

Although CDI is a rare event following revision TKA, it can have detrimental consequences. Our report demonstrates that CDI is associated with longer LOS, higher costs, and greater in-hospital mortality. With increased legislative pressure to lower healthcare expenditures, it is crucial to identify means of preventing costly complications.


N. Mohamed N. George C. Gwam J. Etcheson I.D. Castrodad A. Passarello R. Delanois C. Gurk-Turner T. Recai

Despite the widespread success of total hip arthroplasty (THA), postoperative pain management remains a concern. Opioids have classically been administered for pain relief after THA, but their side effect profile, in addition to the cognizance of the growing opioid epidemic, has incited a shift toward alternative pain modalities. Although the nonsteroidal anti-inflammatory drug (NSAID) diclofenac is a promising addition, its impact on immediate THA outcomes has not previously been investigated. Thus, in the present study, we evaluate the effects of adjunctive diclofenac on: 1) postoperative pain intensity, 2) opioid consumption, 3) discharge destination, 4) length of stay, and 5) patient satisfaction in primary THA patients.

A retrospective review was performed to identify all patients who underwent primary THA by a single surgeon between May 1 and September 31, 2017. Patients were stratified into a study group (n=25), who were treated with postoperative diclofenac in addition to the standard pain control regimen, and a control group (n=88), who did not receive adjunctive diclofenac. Repeated-measures analysis of variance (ANOVA)/analysis of covariance (ANCOVA) and chi-square/logistic regression analysis were used for continuous and categorical variables, respectively.

Patients receiving adjunctive diclofenac were more likely to be discharged home than to inpatient facilities (O.R. 4.02, p=0.049). In addition, patient satisfaction with respect to how well and how often pain was controlled (p= 0.0436 and p=0.0217, respectively) was significantly greater in the diclofenac group. Finally, patients who received diclofenac had lower opioid consumption on postoperative days one and two (−67.2 and −129 mg, respectively, p=0.001 for both).

The rapid growth of THA as an outpatient procedure has intensified the urgency of improving postoperative pain management. The present study demonstrates that THA patients receiving adjunctive diclofenac were more likely to be discharged home, had reduced opioid consumption, and experienced greater satisfaction. This will, in turn, decrease complications and total hospital costs, leading to a more cost-effective pain control regimen. In order to further investigate the optimal regimen, future studies comprising larger cohort, as well as a comparison of diclofenac to other NSAIDs, are warranted.


M. Monument A. Singla A. Affan F. Jirik K. Hildebrand J. Kendal

Soft tissue sarcomas (STS) have not demonstrated favourable clinical responses to emerging immunotherapies such as checkpoint inhibitors. Studies in carcinomas and melanoma have demonstrated that tumours lacking T-cell infiltrates are associated with poor responses to immunotherapies. It is postulated that STS lack tumour asscoiated lymphocytes which renders these tumours insensitive to checkpoint inhibitors. Our objective was to develop a novel syngeneic mouse model of STS and characterize the immune phenotype of these tumours. Additionally, we sought to evaluate the therapeutic responses of these sarcomas to checkpoint inhibitors and a Type I interferon agonist.

K-ras mutagenesis and p53 deletion was induced using a Lenti-Cre-recombinase injection into the hindlimb of 3 week old C57BL/6 mice. Tumours were harvested and characterized using standard histopathology techniques and whole trascriptome sequencing (RNAseq). Full body necrospy and histopathology was performed to identify metastases. Flow cytometry and immunohistochemistry was used to evaluate tumour immune phenotypes. Tumours were implanted into syngeneic C57BL/6 mice and the therapeutic responses to anti-CTLA4, anti-PD1 and DMXAA (Type I interferon agonist) were performed. Tumour responses were evaluated using bioluminescent imaging and caliper measurements.

Soft tissue sarcomas developed in mice within 2–3 months of Lenti-Cre injection with 90% penetrance. Histologic analyses of tumours was consistent with a high-grade myogenic sarcoma characterized by smooth muscle actin, Desmin and Myogenin D positive immunostaining. Using crossplatform normalization protocols, geneexpression signatures of the mouse tumours most closely correlated with human undifferentiated pleomorphic sarcoma (UPS). Collectively, gene expression signatures of this murine sarcoma correlated with all muscle-derived human sarcomas (ERMS, ARMS, Synovial sarcoma, UPS). No lung or other visceral metastases were observed in all mice who developed spontaneous tumours. Immune phenotyping demonstrated a paucity of tumour-infiltrating lymphocytes (TILs, (TAMs). 50% of identified TILs in these murine sarcomas expressed PD-1, yet tumours were not responsive to anti-PD1 therapy or anti-CTLA4 therapy. A single intra tumoural (i.t.) injection of the Type I interferon agonist, DMXAA resulted in 80–90% tumour necrosis 72 hrs post-injection, decreased tumour viability up to 2 weeks post-injection and a marked infiltration of CD8+ T-cells and anitgen presenting dendritic cells and macrophages. Additional longitudinal experiments demonstrate a sustained and progressive anti-tumour effect in 83% (5/6) mice up to 6weeks following a single i.t. injection of DMXAA. All control treated mice (6/6) reached humane endpoint within 14 days. At 3 months post-DMXAA treatment, 4/6 mice were free of disease. We re-injected UPS tumours into these mice and tumours did not grow, suggesting abscopal effects after DMXAA treatment of primary tumours.

We have characterized a new orthotopic and syngeneic mouse model of a myogenic soft tissue sarcoma. Like most human STS sub-types, these tumours have an immune inert tumour microenvironment and are not sensitive to checkpoint inhibitors. This model, syngeneic to C56BL/6 mice will enable future opportunities to investigate how various branches of the immune system can be targetted or manipulated to unearth new immunotherapeutic strategies for sarcoma. Using this model we have demonstrated that a single, intra-tumoural injection of a Type I interferon agonist can result in anti-tumour effects, recruit cytotoxic lymphocytes and antigen presenting cells with into the the tumour microenvironment. Abscopal tumour rejection after DMXAA treatement suggest adaptive T-cell responses against UPS are active in this model. Future work is needed to determine if upregulation of Type I inferferon pathways can be used as a therapeutic strategy for sarcoma or as a sensitization strategy for checkpoint inhibitors.


H. Diao H. Xin Z. Jin

Cervical spinal arthrodesis is the standard of care for the treatment of spinal diseases induced neck pain. However, adjacent segment disease (ASD) is the primary postoperative complication, which draws great concerns. At present, controversy still exists for the etiology of ASD. Knowledge of cervical spinal loading pattern after cervical spinal arthrodesis is proposed to be the key to answer these questions. Musculoskeletal (MSK) multi-body dynamics (MBD) models have an opportunity to obtain spinal loading that is very difficult to directly measure in vivo.

In present study, a previously validated cervical spine MSK MBD model was developed for simulating cervical spine after single-level anterior arthrodesis at C5-C6 disc level. In this cervical spine model, postoperative sagittal alignment and spine rhythms of each disc level, different from normal healthy subject, were both taken into account. Moreover, the biomechanical properties of facet joints of adjacent levels after anterior arthrodesis were modified according to the experimental results. Dynamic full range of motion (ROM) flexion/extension simulation was performed, where the motion data after arthrodesis was derived from published in-vivo kinematic observations. Meanwhile, the full ROM flexion/extension of normal subject was also simulated by the generic cervical spine model for comparative purpose. The intervertebral compressive and shear forces and loading-sharing distribution (the proportions of intervertebral compressive and shear force and facet joint force) at adjacent levels (C3-C4, C4-C5 and C6-C7 disc levels) were then predicted.

By comparison, arthrodesis led to a significant increase of adjacent intervertebral compressive force during the head extension movement. Postoperative intervertebral compressive forces at adjacent levels increased by approximate 20% at the later stage of the head extension movement. However, there was no obvious alteration in adjacent intervertebral compressive force, during the head flexion movement. For the intervertebral shear forces in the anterior-posterior direction, no significant differences were found between the arthrodesis subject and normal subject, during the head flexion/extension movement. Meanwhile, cervical spinal loading-sharing distribution after anterior arthrodesis was altered compared with the normal subject's distribution, during the head extension movement. In the postoperative loading-sharing distribution, the percentage of intervertebral disc forces was further increased as the motion angle increased, compared with normal subject.

In conclusion, cervical spinal loading after anterior arthrodesis was significantly increased at adjacent levels, during the head extension movement. Cervical spine musculoskeletal MBD model provides an attempt to comprehend postoperative ASD after anterior arthrodesis from a biomechanical perspective.


C. Berkmortel J. A. Johnson G D. Langohr G. J.W. King S. DeDecker

Hemiarthroplasty is a common procedure that is an attractive alternative to total arthroplasty because it conserves natural tissue, allows for quicker recovery, and has a lower cost. One significant issue with hemiarthroplasties is that they lead to accelerated wear of the opposing native cartilage, likely due to the high stiffness of the implant. The purpose of this study was to investigate the range of currently available biomaterials for hemiarthroplasty applications. We employed a finite-element (FE) model of a radial head implant against the native capitellum as our joint model.

The FE model was developed in ABAQUS v6.14 (Dassault Systèmes Simulia Corp., Providence, RI, USA). A solid axisymmetric concave implant with seven different materials and the native radial head were evaluated, six modelled as elastic materials with different Young's moduli (E) and Poisson's Ratios (ν), and one modelled as a Mooney-Rivlin hyperelastic material. The materials investigated were CoCr (E=230 GPa, ν = 0.3), PEEK (E=3.7 GPa, ν = 0.36), HDPE (E=2.7 GPa, ν = 0.42), UHMWPE (E=0.69 GPa, ν = 0.49), Bionate 75D (E=0.288 GPa, ν = 0.39), Bionate 55D (E=0.039 GPa, ν = 0.45), and Bionate 80A (modelled as a Mooney-Rivlin hyperelastic material). A load of 100 N was applied to the radius through the center of rotation representing a typical load through the radius. The variable of interest was articular contact stress on the capitellum.

The CoCr implant had a maximum contact stress over 114% higher than the native radial head. By changing the material to lower the stiffness of the implant, the maximum contact stress was 24%, 70%, 105%, 111%, 113%, and 113% higher than the native radial head for Bionate 80A, Bionate 55D, Bionate 75D, UHMWPE, HDPE, and PEEK respectively.

This work shows that lowering implant stiffness can reduce the contact stress on cartilage in hemiarthroplasty implants. By changing the material below a Young's modulus of ∼100 MPa elevated stresses on the capitellum can be markedly reduced and hence potentially reduce or prevent degenerative changes of the native articulating cartilage. Low stiffness implant materials are not a novel concept, but to date there have been few that investigate materials (such as Bionate) as a potential load bearing material for implant applications. Further work is required to assess the efficacy of these materials for articular bearing applications.


R. Wallace S. Xie H. Simpson

Trabecular bone is a multiscale hierarchical composite material that is known to display time-dependant properties. However, most biomechanical models treat this material as time independent. Time-dependant properties, such as creep and relaxation, are thought to play an important role in many clinically relevant orthopaedic issues: implant loosening, vertebral collapse, and non-traumatic fractures. In this study compressive multiple-load-creep-unload-recovery (MLCUR) tests were applied to human trabecular bone specimens.

15 female femoral heads were harvested, with full ethical approval and patient consent, at the time of total hip replacement. Central cores were extracted and cut parallel under constant irrigation. Specimens were embedded in end caps using surgical cement, an epoxy tube was secured around the end caps and filled with phosphate buffered saline (PBS) to ensure the specimens remained hydrated throughout. Embedded samples were scanned by microCT (SkyScan 1172, Bruker) at a resolution of 17µm to determine microarchitecture. Bone volume fraction (BVF) was used to represent microarchitecture. Specimens had an effective length of 16.37mm (±1.90SD) with diameter of 8.08mm (±0.05SD), and BVF of 19.22% (±5.61SD).

The compressive MLCUR tests were conducted at 5 strain levels, 2000µε, 4000µε, 6000µε, 8000µε and 10000µε. At each strain level, the load required to maintain each strain was held for 200s (creep) then unloaded to 1N for 600s (recovery). The instantaneous, creep, unloading and recovered strains can be easily obtained from the strain-time curves. Stress-strain plots revealed the Young's modulus. Data was modelled using line of best fit with appropriate curve fitting. R2 values were used to indicate association. Mechanical testing demonstrated the expected time independent relationship between BVF and stiffness: higher stiffness was found for specimen with higher BVF and this was consistent for all strain levels.

Creep strain was found to depend on instantaneous strain and BVF. At low levels of instantaneous strain, there was a greater amount of creep strain in low BVF samples (R2 = 0.524). This relationship was no longer apparent at higher strain levels (R2 = 0.058). Residual strain also depended on the applied instantaneous strain and BVF: at low levels of strain, residual strain was similar with all BVF (R2 = 0.108) and at high levels of strain, residual strain was greater in low BVF samples (R2 = 0.319). The amount of instantaneous strain applied to each sample is constant, variations in stiffness result in different applied loads. In low BVF bone, the stiffness is also low, therefore the stress required to reach designed strain is also lower: yet, there is more creep and less recovery.

We have demonstrated that even at loads below recognised yield levels, time-dependence affects the mechanical response and residual strain is present. In cases of low BVF, deflection due to creep, and increased irrecoverable strain could have clinically relevant consequences, such as implant loosening and vertebral collapse. The role of time-dependant properties of bone is seldom considered. This data could be developed into a constitutive model allowing these time-dependant behaviours to be incorporated in finite element modelling, leading to better predictions of implant loosening, especially for lower quality bone.


G.D. Langohr S. DeDecker A. Khayat J. Johnson G. J.W. King J. Medley

Joint hemiarthroplasty replaces one side of a synovial joint and is a viable alternative to total joint arthroplasty when one side of the joint remains healthy. Most hemiarthroplasty implants used in current clinical practice are made from stiff materials such as cobalt chrome or ceramic. The substitution of one side of a soft cartilage-on-cartilage articulation with a rigid implant often leads to damage of the opposing articular cartilage due to the resulting reductions in contact area and increases in cartilage stress. The improvement of post-operative hemiarthroplasty articular contact mechanics is of importance in advancing the performance and longevity of hemiarthroplasty. The purpose of the present study was to investigate the effect of hemiarthroplasty surface compliance on early in-vitro cartilage wear and joint contact mechanics.

Cartilage wear tests were conducted using a six-station pin-on-plate apparatus. Pins were manufactured to have a hemispherical radius of curvature of 4.7 mm using either Bionate (DSM Biomedical) having varying compliances (80A [E=20MPa], 55D [E=35MPa], 75D [E=222MPa], n=6 for each), or ceramic (E=310GPa, n=5). Cartilage plugs were cored from fresh unfrozen bovine knee joints using a 20 mm hole saw and mounted in lubricant-containing chambers, with alpha calf serum diluted with phosphate buffer solution to a protein concentration of 17 g/L. The pins were loaded to 30N and given a stroke length of 10 mm for a total of 50,000 cycles at 1.2 Hz. Volumetric cartilage wear was assessed by comparing three-dimensional cartilage scans before and during wear testing. A two-way ANOVA was used for statistical analysis. To assess hemiarthroplasty joint contact mechanics, 3D finite element modelling (ABAQUS v6.12) was used to replicate the wear testing conditions. Cartilage was modeled using neo-Hookean hyper-elastic material properties. Contact area and peak contact stress were estimated.

The more compliant Bionate 80A and 55D pins produced significantly less volumetric cartilage wear compared with the less compliant Bionate 75D and ceramic pins (p 0.05). In terms of joint contact mechanics, the more compliant materials (Bionate 80A and 55D) had significantly lower maximum contact stress levels compared to the less compliant Bionate 75D and ceramic pins (p < 0 .05).

The results of this study show a relationship between hemiarthroplasty implant surface compliance and early in vitro cartilage wear, where the more compliant surfaces produced significantly lower amounts of cartilage wear. The results of the joint contact mechanics analysis showed that the more compliant hemiarthroplasty materials produced lower maximum cartilage contact stresses than the less compliant materials, likely related to the differences in wear observed. More compliant hemiarthroplasty surfaces may have the potential to improve post-operative cartilage contact mechanics by increasing the implant-cartilage contact area while reducing peak contact stress at the implant-cartilage interface, however, such materials must be resistant to surface fatigue and longer-term cartilage wear/damage must be assessed.


A. Adoungotchodo S. Lerouge Y. Alinejad F. Mwale M. Grant L. Epure J. Antoniou

Intervertebral disc (IVD) degeneration plays a major role in low back pain which is the leading cause of disability. Current treatments in severe cases require surgical intervention often leading to adjacent segment degeneration. Injectable hydrogels have received much attention in recent years as scaffolds for seeding cells to replenish disc cellularity and restore disc properties and function. However, they generally present poor mechanical properties. In this study, we investigated several novel thermosensitive chitosan hydrogels for their ability to mimic the mechanical properties of the nucleus pulposus (NP) while being able to sustain the viability of NP cells, and retain proteoglycans.

CH hydrogels were prepared by mixing the acidic chitosan solution (2% w/v) with various combinations of three gelling agents: sodium hydrogen carbonate (SHC) and/or beta-glycerophosphate (BGP) and/or phosphate buffer (PB) (either BGP0.4M, SHC0.075M-BGP0.1M, SHC0.075M-PB0.02M or SHC0.075M-PB0.04M). The gelation speed was assessed by following rheological properties within 1h at 37°C (strain 5% and 1Hz). The mechanical properties were characterized and compared with that of human NP tissues. Elastic properties of the hydrogels were studied by evaluating the secant modulus in unconfined compression. Equilibrium modulus was also measured, using an incremental stress-relaxation test 24h after gelation in unconfined compression (5% strain at 5%/s followed by 5min relaxation, five steps). Cells from bovine IVD were encapsulated in CH-based gels and maintained in culture for 14 days. Cytocompatibility was assessed by measuring cell viability, metabolism and DNA content. Glycosaminoglycan (GAG) synthesis (retained in the gel and released) was determined using DMMB assay. Finally injectability was tested using human cadaveric discs.

Unconfined compression confirmed drastically enhanced mechanical properties compared to conventional CH-BGP hydrogels (secant Young modulus of 105 kPa for SHC0.075PB0.02 versus 3–6 kPa for BGP0.04). More importantly, SHC0.075PB0.02 and SHC0.075BGP0.1 hydrogels exhibited mechanical properties very similar to NP tissue. For instance, equilibrium modulus was 5.2±0.6 KPa for SHC0.075PB0.02 and 8±0.8 KPa for SHC0.075BGP0.1 compared to 6.1±1.7 KPa for human NP tissue. Rheological properties and gelation time (G′=G″ after less than 15 s at 37°C, and rapid increase of G') of these hydrogels also appear to be adapted to this application. Cell survival was greater than 80% in SHC0.075BGP0.1 and SHC0.075PB0.02 hydrogels. Cells encapsulated in the new formulations also showed significantly higher metabolic activity and DNA content after 14 days of incubation compared to cells encapsulated in BGP0.4 hydrogel. Cells encapsulated in SHC0.075BGP0.1 and SHC0.075PB0.02 produced significantly higher amounts of glycosaminoglycans (GAG) compared to cells encapsulated in SHC0.075PB0.04 and BGP0.4 hydrogels. The total amount of GAG was higher in SHC0.075BGP0.1 hydrogel compared to SHC0.075PB0.02. Interestingly, both the SHC0.075BGP0.1 and SHC0.075PB0.02 hydrogels retained similar amounts of GAG. Injectability through a 25G syringe, filling of nuclear clefts and good retention in human degenerated discs was demonstrated for SHC0.075PB0.02 hydrogel.

SHC0.075BGP0.1 appears to be a particularly promising injectable scaffold for IVD repair by providing suitable structural environment for cell survival, ECM production and mechanical properties very similar to that of NP tissue.


B. Johnstone J. Ryaby N. Zhang E. Waldorff C. Lin P. Punsalan J. Yoo E. Semler

The range of allograft products for spinal fusion has been extended with the development of cellular bone matrices (CBMs). Most of these combine demineralized bone with viable cancellous bone prepared in a manner that retains cells with differentiation potential. The purpose of this study was to compare commercially-available human CBMs in the athymic rat model of posterolateral spinal fusion. The products compared were Trinity ELITE® (TEL, OrthoFix), ViviGen (VIV, DePuy Synthes), Cellentra (CEL, Zimmer Biomet), Osteocel® Pro (OCP, NuVasive), Bio4 (BIO, Stryker) and map3 (MAP, RTI Surgical). Bone from the ilia of syngeneic rats was used as a control to approximate the human gold standard.

All implants were stored, thawed, and prepared per manufacturer's instructions and all implantations occurred within the manufacturer's time allowance for use after preparation. In total, fifteen 9–10 week old male rats were implanted per implant type, with three different lots of each implant used per five rats to account for lot-to-lot variability. Under anesthesia, a posterior midline longitudinal skin and subcutaneous incision was made, followed by bilateral longitudinal paraspinal myofascial incisions to expose the transverse processes at the L4–5 level. Implants (0.3 cc of allograft or freshly harvested syngeneic iliac bone graft) were placed bilaterally. Surgeons were blinded as to CBM implant type. Incisions were closed with sutures and in vivo microCT scans performed within 48 hours of surgery. A second microCT scan was taken at euthanasia, six weeks after surgery, and the lumbar spines harvested. Fusion was evaluated by manual palpation by three independent, blinded reviewers. MicroCT analysis was performed by an independent CRO (ImageIQ, Cleveland OH). Anonymity of implant type was rigorously kept to avoid bias.

By manual palpation, 5/15 (33%) spines of the syngeneic bone group were fused at 6 weeks. The TEL (8/15, 53%) and CEL (11/15, 73%) groups were not significantly different from each other but were from all other CBM groups. Only 2/15 (13%) of VIV-implanted spines fused and none (0/15, 0%) of the OCP, BIO and MAP CBMs produced stable fusion. The mineralized cancellous bone component of the allografts confounded radiographic analysis but microCT analysis indicated bone volume increased over six weeks for all groups except the syngeneic bone (−4.3%). TEL (+65%) and CEL (+73%) were not different from each other but were significantly increased over all other groups (VIV 29%, OCP 37%, BIO 19%, and MAP 45%, respectively).

CBMs have distinct formulations and are likely processed differently. The claimed live cell and stem cell contents differ between products. Additionally, map3 has cells added at the time of surgery, whereas the other CBMs are processed to retain matrix-adherent cells. Given the wide range of formulations, differences in performance were not surprising, and Trinity ELITE and Cellentra did significantly better than other implants at both forming new bone and achieving fusion. The other CBMs did not have greater bone formation than the control and were very poor at forming a solid fusion. These findings suggest more careful consideration of these allograft products is needed at the clinical level.


G. Ng H. El Daou M. Bankes F. Rodriguez y Baena J. Jeffers

Surgical management of cam-type femoroacetabular impingement (FAI) aims to preserve the native hip, restore joint function, and delay the onset of osteoarthritis. However, it is unclear how surgery affects joint mechanics and hip joint stability. The aim was to examine the contributions of each surgical stage (i.e., intact cam hip, capsulotomy, cam resection, capsular repair) towards hip joint centre of rotation and microinstability.

Twelve fresh, frozen cadaveric hips (n = 12 males, age = 44 ± 9 years, BMI = 23 ± 3 kg/m2) were skeletonized to the capsule and included in this study. All hips indicated cam morphology on CT data (axial α = 63 ± 6°, radial α = 74 ± 4°) and were mounted onto a six-DOF industrial robot (TX90, Stäubli). The robot positioned each hip in four sagittal angles: 1) Extension, 2) Neutral 0°, 3) Flexion 30°, and 4) Flexion 90°, and performed internal and external hip rotations until a 5-Nm torque was reached in each direction, while recording the hip joint centre's neutral path of translation. After the (i) intact hip was tested, each hip underwent a series of surgical stages and was retested after each stage: (ii) T-capsulotomy (incised lateral iliofemoral capsular ligament), (iii) cam resection (removed morphology), and (iv) capsular repair (sutured portal incisions). Eccentricity of the hip joint centre was quantified by the microinstability index (MI = difference in rotational foci / femoral head radius). Repeated measures ANOVA and post-hoc paired t-tests compared the within-subject differences in hip joint centre and microinstability index, between the testing stages (CI = 95%, SPSS v.24, IBM).

At the Extension and Neutral positions, the hip joint centre rotated concentrically after each surgical stage. At Flexion 30°, the hip joint centre shifted inferolaterally during external rotation after capsulotomy (p = 0.009), while at Flexion 90°, the hip joint centre further shifted inferolaterally during external rotation (p = 0.005) and slightly medially during internal rotation after cam resection, compared to the intact stages. Consequently, microinstability increased after the capsulotomy at Flexion 30° (MI = +0.05, p = 0.003) and substantially after cam resection at Flexion 90° (MI = +0.07, p = 0.007). Capsular repair was able to slightly restrain the rotational centre and decrease microinstability at the Flexion 30° and 90° positions (MI = −0.03 and −0.04, respectively).

Hip microinstability occurred at higher amplitudes of flexion, with the cam resection providing more intracapsular volume and further lateralizing the hip joint during external rotation. Removing the cam deformity and impingement with the chondrolabral junction also medialized the hip during internal rotation, which can restore more favourable joint loading mechanics and stability. These findings support the pathomechanics of cam FAI and suggest that iatrogenic microinstability may be due to excessive motions, prior to post-operative restoration of static (capsular) and dynamic (muscle) stability. In efforts to limit microinstability, proper nonsurgical management and rehabilitation are essential, while activities that involve larger amplitudes of hip flexion and external rotation should be avoided immediately after surgery.


T. Gascoyne S. Parashin M. Teeter E. Bohm E. Laende M. J. Dunbar T. Turgeon

The purpose of this study was to examine the influence of weight-bearing on the measurement of in vivo wear of total knee replacements using model-based RSA at 1 and 2 years following surgery.

Model-based RSA radiographs were collected for 106 patients who underwent primary TKR at a single institution. Supine RSA radiographs were obtained post-operatively and at 6-, 12-, and 24-months. Standing (weight-bearing) RSA radiographs were obtained at 12-months (n=45) and 24-months (n=48). All patients received the same knee design with a fixed, conventional PE insert of either a cruciate retaining or posterior stabilized design. Ethics approval for this study was obtained.

In order to assess in vivo wear, a highly accurate 3-dimensional virtual model of each in vivo TKA was developed. Coordinate data from RSA radiographs (mbRSA v3.41, RSACore) were applied to digital implant models to reconstruct each patient's replaced knee joint in a virtual environment (Geomagic Studio, 3D Systems). Wear was assessed volumetrically (digital model overlap) on medial and lateral condyles separately, across each follow-up. Annual rate of wear was calculated for each patient as the slope of the linear best fit between wear and time-point. The influence of weight-bearing was assessed as the difference in annual wear rate between standing and supine exams. Age, BMI, and Oxford-12 knee improvement were measured against wear rates to determine correlations.

Weight bearing wear measurement was most consistent and prevalent in the medial condyle with 35% negative wear rates for the lateral condyle. For the medial condyle, standing exams revealed higher mean wear rates at 1 and 2 years, supine, 16.3 mm3/yr (SD: 27.8) and 11.2 mm3/yr (SD: 18.5) versus standing, 51.3 mm3/yr (SD: 55.9) and 32.7 mm3/yr (SD: 31.7). The addition of weight-bearing increased the measured volume of wear for 78% of patients at 1 year (Avg: 32.4 mm3/yr) and 71% of patients at 2 years (Avg: 48.9 mm3/yr). There were no significant (95% CI) correlations between patient demographics and wear rates.

Volumetric, weight-bearing wear measurement of TKR using model-based RSA determined an average of 33 mm3/yr at 2 years post-surgery for a modern, non-cross-linked polyethylene bearing. This value is comparable to wear rates obtained from retrieved TKRs. Weight-bearing exams produced better wear data with fewer negative wear rates and reduced variance. Limitations of this study include: supine patient imaging performed at post-op, no knee flexion performed, unknown patient activity level, and inability to distinguish wear from plastic creep or deformation under load. Strengths of this study include: large sample size of a single TKR system, linear regression of wear measurements and no requirement for implanted RSA beads with this method. Based on these results, in vivo volumetric wear of total knee replacement polyethylene can be reliably measured using model-based RSA and weight-bearing examinations in the short- to mid–term. Further work is needed to validate the accuracy of the measurements in vivo.


T. Gascoyne S. Parashin M. Zarrabian

The purpose of this research was to determine the feasibility of radiostereometric analysis (RSA) as a diagnostic tool for assessing non-union following spinal arthrodesis procedures. Further, to estimate clinical thresholds for precision and accuracy of the proposed method in the cervical and lumbar spine.

A three-level lumbo-sacral and a four-level cervical posterior arthrodesis procedures were performed on an artificial spine model (Sawbones, WA). Using a spring loaded inserter (RSA Biomedical, Sweden), eight to ten RSA markers were placed within each of the L4 and L5 segments in the spinous process (L4 only), lamina, transverse processes, posterior and anterior (down the pedicle) wall of the vertebral body. Eight to ten markers were placed within the proximal sacrum (S1) at the medial and lateral crests, tuberosity, and within the sacral canal wall. Four to eight RSA markers were placed into the C3-C6 lateral masses. Titanium screws and rods were applied to the spinal segments. Identical procedures were then performed on a cadaveric spine using similar bead placement and hardware.

RSA imaging consisted of 12 double exams (24 exams) of the cervical and lumbar regions for both the Sawbones and cadaveric spine to assess precision of measurement under zero-displacement conditions. The most distal vertebrae were considered the datum against which the movement of all other vertebrae was compared.

The artificial spine was then dismantled for accuracy assessment in which the middle vertebrae (L5 and C4-C5) were moved relative to the superior (L4 and C3) and inferior (S1 and C6) vertebrae by known, incremental displacements on an imaging phantom device. Displacements occurred along the superior-inferior, anterior-posterior, and flexion-extension (rotational) axes of motion. RSA images were obtained at each displacement.

Image analysis was performed using model-based software (RSACore v3.41, Leiden, Netherlands) to visualize implanted RSA beads in 3-D space. Precision was defined as the 95% confidence interval of error in measuring zero-displacement. Accuracy was defined as the mean difference (with 95% confidence interval) between the known and measured displacement.

The rate of RSA bead detection was high with 5–8 implanted beads being visible in both the lumbar and cervical regions of the artificial and cadaveric spines.

Translational RSA precision for both spines was better than 0.25 mm and 0.82 mm for the lumbar and cervical regions, respectively. Rotational precision was better than 0.40° and 1.9° for the lumbar and cervical regions, respectively. RSA accuracy for the artificial spine overall demonstrated less than 0.11 mm translational bias (margin < ±0.02 mm) and less than 0.22° rotational bias (margin < ±0.15°).

This study demonstrates that RSA achieves sufficient precision and accuracy to detect intervertebral micromotion for the purpose of assessing arthrodesis. Well dispersed RSA bead placement is critical to achieving sufficient accuracy as well as avoiding occlusion by metal hardware. Cervical bead implantation is particularly sensitive to bead clustering due to small vertebrae size and proximity to critical structures. The results of this work will aid in the development of a clinical study to assess arthrodesis in patients.


K. Vachhani C. Whyne D. Nam J. Wong J. Chou R. Paul

Rotator cuff tears are the most common cause of shoulder disability, affecting 10% of the population under 60 and 40% of those aged 70 and above. Massive irreparable rotator cuff tears account for 30% of all tears and their management continues to be an orthopaedic challenge. Traditional surgical techniques, that is, tendon transfers are performed to restore shoulder motion, however, they result in varying outcomes of stability and complications. Superior capsular reconstruction (SCR) is a novel technique that has shown promise in restoring shoulder function, albeit in limited studies. To date, there has been no biomechanical comparison between these techniques. This study aims to compare three surgical techniques (SCR, latissimus dorsi tendon transfer and lower trapezius tendon transfer) for irreparable rotator cuff tears with respect to intact cuff control using a clinically relevant biomechanical outcome of rotational motion.

Eight fresh-frozen shoulder specimens with intact rotator cuffs were tested. After dissection of subcutaneous tissue and muscles, each specimen was mounted on a custom shoulder testing apparatus and physiologic loads were applied using a pulley setup. Under 2.2 Nm torque loading maximum internal and external rotation was measured at 0 and 60 degrees of glenohumeral abduction. Repeat testing was conducted after the creation of the cuff tear and subsequent to the three repair techniques. Repeated measures analysis with paired t-test comparisons using Sidak correction was performed to compare the rotational range of motion following each repair technique with respect to each specimen's intact control. P-values of 0.05 were considered significant.

At 0° abduction, internal rotation increased after the tear (intact: 39.6 ± 13.6° vs. tear: 80.5 ± 47.7°, p=0.019). Internal rotation was higher following SCR (52.7 ± 12.9°, intact - SCR 95% CI: −25.28°,-0.95°, p=0.034), trapezius transfer (74.2 ± 25.3°, intact – trapezius transfer: 95% CI: −71.1°, 1.81°, p=0.064), and latissimus transfer (83.5 ± 52.1°, intact – latissimus transfer: 95% CI: −118.3°, 30.5°, p=0.400) than in intact controls. However, internal rotation post SCR yielded the narrowest estimate range close to intact controls. At 60° abduction, internal rotation increased after the tear (intact: 38.7 ± 14.4° vs. tear: 49.5 ± 13°, p=0.005). Internal rotation post SCR did not differ significantly from intact controls (SCR: 49.3 ± 10.1°, intact – SCR: 95% CI: −28°, 6.91°, p=0.38). Trapezius transfer showed a trend toward significantly higher internal rotation (65.7 ± 21.1°, intact – trapezius transfer: 95% CI: −55.7°, 1.7°, p=0.067), while latissimus transfer yielded widely variable rotation angle (65.7 ± 38°, intact – latissimus transfer: 95% CI: −85.9°, 31.9°, p=0.68). There were no significant differences in external rotation for any technique at 0° or 60° abduction.

Preliminary evaluation in this cadaveric biomechanical study provides positive evidence in support of use of SCR as a less morbid surgical option than tendon transfers. The cadaveric nature of this study limits the understanding of the motion to post-operative timepoint and the results herein are relevant for otherwise normal shoulders only. Further clinical evaluation is warranted to understand the long-term outcomes related to shoulder function and stability post SCR.


A. Clement C. Whyne M. Hardisty P. Wilkie M. Akens

Quantitative assessment of metastatic involvement of the bony spine is important for assessing disease progression and treatment response. Quantification of metastatic involvement is challenging as tumours may appear as osteolytic (bone resorbing), osteoblastic (bone forming) or mixed. This investigation aimed to develop an automated method to accurately segment osteoblastic lesions in a animal model of metastatically involved vertebrae, imaged with micro computed tomography (μCT).

Radiomics seeks to apply standardized features extracted from medical images for the purpose of decision-support as well as diagnosis and treatment planning. Here we investigate the application of radiomic-based features for the delineation of osteoblastic vertebral metastases. Osteoblastic lesions affect bone deposition and bone quality, resulting in a change in the texture of bony material physically seen through μCT imaging. We hypothesize that radiomics based features will be sensitive to changes in osteoblastic lesion bone texture and that these changes will be useful for automating segmentation.

Osteoblastic metastases were generated via intracardiac injection of human ZR-75-1 breast cancer cells into a preclinical athymic rat model (n=3). Four months post inoculation, ex-vivo μCT images (µCT100, Scanco) were acquired of each rodent spine focused on the metastatically involved third lumbar vertebra (L3) at 7µm/voxel and resampled to 34µm/voxel.

The trabecular bone within each vertebra was isolated using an atlas and level-set based segmentation approach previously developed by our group. Pyradiomics, an open source Radiomics library written in python, was used to calculate 3D image features at each voxel location within the vertebral bone. Thresholding of each radiomic feature map was used to isolate the osteoblastic lesions.

The utility of radiomic feature-based segmentation of osteoblastic bone tissue was evaluated on randomly selected 2D sagittal and axial slices of the μCT volume. Feature segmentations were compared to ground truth osteoblastic lesion segmentations by calculating the Dice Similarity Coefficient (DSC). Manually defined ground truth osteoblastic tumor segmentations on the μCT slices were informed by histological confirmation of the lesions.

The radiomic based features that best segmented osteoblastic tissue while optimizing computational time were derived from the Neighbouring Gray Tone Difference Matrix (NGTDM). Measures of coarseness yielded the best agreement with the manual segmentations (DSC=707%) followed by contrast, strength and complexity (DSC=6513%, 5428%, and 4826%, respectively).

This pilot study using a radiomic based approach demonstrates the utility of the NGTDM features for segmentation of vertebral osteoblastic lesions. This investigation looked at the utility of isolated features to segment osteoblastic lesions and found modest performance in isolation. In future work we will explore combining these features using machine learning based classifiers (i.e. decision forests, support vector machines, etc.) to improve segmentation performance.


C. Taylor T. Waters M. Ries G. Datta E. Davis D. Nathwani P. Sutton A. Trahey I. McNamara

In light of recent regulatory initiatives, medical devices now require additional clinical evidence to prove their safety and efficacy. At the same time, patients' own assessment of their devices' function and performance has gained in importance. The collection of these data allows for a more comprehensive picture of clinical outcomes and complications following total knee arthroplasty (TKA).

These trends have led researchers to search for new methods of acquiring, interpreting and disseminating patient-reported outcome measurements (PROMs). The current study assesses the feasibility of a digital platform for collecting PROMs that was recently adapted for TKA patients. It sought to determine patient engagement, survey completion rates, and satisfaction with this platform.

Eighty-two patients (mean age, 63.7 years, 59% females) scheduled for TKA were enrolled from one US and six UK sites between January 12, 2018 and April 30, 2018. Patients were supplied with a mobile application (app) that collects a variety of PROMs, including four domains based on the Patient-Reported Outcome Information System (PROMIS™): physical function, depression, pain interference and pain behavior. The platform electronically administers questionnaires using computer-adaptive tests (CATs), which reduce the burden on patients by tailoring follow-up questions to account for their previous answers. Satisfaction with the app was assessed in subset of patients who evaluated its ease-of-use (n=45), likelihood that they would recommend it to family/friends (n=35), and whether they successfully used the information it provided during their recovery (n=31). These scores were taken on a 1 to 10 (worst to best) scale.

Patients demonstrated regular engagement with the platform, with 73% using the app at least once a week. Weekly engagement remained high throughout the seven-week post-operative period (Figure 1). There was a 69% completion rate of all PROMIS™ CAT surveys during the study. The four PROMIS™ CAT domains had similar survey completion rates (Figure 2). The subset of patients queried regarding their satisfaction with the app gave it favorable mean scores for ease-of-use (8.8), likelihood to recommend to a family member or friend (8.1), and their success at using its information to improve their recovery (7.4).

Initial results support this digital platform's potential for successfully and efficiently collecting large volumes of PROMs. Patients reported high levels of engagement and satisfaction.

For any figures or tables, please contact authors directly.


P. Vendittoli W. Blakeney M. Kiss B. Puliero Y. Beaulieu

Mechanical alignment (MA) techniques for total knee arthroplasty (TKA) introduces significant anatomic modifications and secondary ligament imbalances. A restricted kinematic alignment (rKA) protocol was proposed to minimise these issues and improve TKA clinical results.

A total of 1000 knee CT-Scans were analyzed from a database of patients undergoing TKA. rKA tibial and femoral bone resections were simulated. rKA is defined by the following criteria: Independent tibial and femoral cuts within ± 5° of the bone neutral mechanical axis and, a resulting HKA within ± 3° of neutral. Medial-lateral (ΔML) and flexion-extension (ΔFE) gap differences were calculated and compared with MA results. With the MA technique, femoral rotation was aligned with either the trans-epicondylar axis (TEA) or with 3° of external rotation to the posterior condyles (PC).

Extension space ML imbalances (>/=3mm) occurred in 33% of TKA with MA technique versus 8% of the knees with rKA (p /=5mm) were present in up to 11% of MA knees versus 1% rKA (p < 0 .001). Using the MA technique, for the flexion space ΔML, higher imbalance rates were created by the TEA technique (p < 0 .001). rKA again performed better than both MA techniques using TEA of 3 degrees PC techniques (p < 0 .001). When all the differences between ΔML and ΔFE are considered together: using TEA there were 40.8% of the knees with < 3 mm imbalances throughout, using PC this was 55.3% and using rKA it was 91.5% of the knees (p < 0 .001).

Significantly less anatomic modifications with related ML or FE gap imbalances are created using rKA versus MA for TKA. Using rKA may help the surgeon to balance a TKA, whilst keeping the alignment within a safe range.


M. M. K. Jalal R. Wallace H. Simpson

Many pre-clinical models of atrophic non-union do not reflect the clinical scenario, some create a critical size defect, or involve cauterization of the tissue which is uncommonly seen in patients. Atrophic non-union is usually developed following high energy trauma leading to periosteal stripping. The most recent reliable model with these aspects involves creating a non-critical gap of 1mm with periosteal and endosteal stripping. However, this method uses an external fixator for fracture fixation, whereas intramedullary nailing is the standard fixation device for long bone fractures.

OBJECTIVES

To establish a clinically relevant model of atrophic non-union using intramedullary nail and (1) ex vivo and in vivo validation and characterization of this model, (2) establishing a standardized method for leg positioning for a reliable x-ray imaging.

Ex vivo evaluation: 40 rat's cadavers (adult male 5–6 months old), were divided into five groups (n=8 in each): the first group was fixed with 20G intramedullary nail, the second group with 18G nail, the third group with 4-hole plate, the fourth group with 6-hole plate, and the fifth group with an external fixator. Tibiae were harvested by leg disarticulation from the knee and ankle joints. Each group was then subdivided into two subgroups for mechanical testing: one for axial loading (n=4) and one for 4-point bending (n=4) using Zwick/Roell® machine. Statistical analysis was carried out by ANOVA with a fisher post-hoc comparison between groups. A p-value less than 0.05 was considered statistically significant.

To maintain the non-critical gap, a spacer was inserted in the gap, the design was refined to minimize the effect on the healing surface area. In vivo evaluation was done to validate and characterize the model. Here, a 1 mm gap was created with periosteal and endosteal stripping to induce non-union. The fracture was then fixed by a hypodermic needle.

A proper x-ray technique must show fibula in both views. Therefore, a leg holder was used to hold the knee and ankle joints in 90º flexion and the foot was placed in a perpendicular direction with the x-ray film. Lateral view was taken with the foot parallel to the x-ray film.

Ex vivo: axial load stiffness data revealed that intramedullary nails are significantly stronger and stiffer than other devices. Bending load to failure showed that 18G nails are significantly stronger than 20G, thus it is used for the in vivo experiments.

In vivo: final iteration revealed 3/3 non-union, and in controls with the periosteum and endosteum intact but with the 1mm non-critical gap, it progressed to 3/3 union.

X-ray positioning: A-P view in supine position, there was an unavoidable degree of external rotation in the lower limb, thus the lower part of the fibula appeared behind the tibia. To overcome this, a P-A view of the leg was performed with the body in prone rather, this arrangement allowed both upper and lower parts of the fibula to appear clearly in both views.

We report a novel model of atrophic non-union, the surgical procedure is relatively simple and the model is reproducible.


D. Tsiapalis A. De Pieri I. Sallent N. Galway D. Zeugolis N. Galway S. Korntner

Cellular therapies play an important role in tendon tissue engineering with tenocytes being described as the most prominent cell population if available in large numbers. However, in vitro expansion of tenocytes in standard culture leads to phenotypic drift and cellular senescence. Recent work suggests that maintenance of tenogenic phenotype in vitro can be achieved by recapitulating different aspects of the native tendon microenvironment. One approach used to modulate the in vitro microenvironment and enhance extracellular matrix (ECM) deposition is macromolecular crowding (MMC). MMC is based on the addition of inert macromolecules to the culture media mimicking the dense extracellular matrix. In addition, as tendon has been described to be a relatively avascular and hypoxic tissue and low oxygen tension can stimulate collagen synthesis and cross-linking, we venture to assess the synergistic effect of MMC and low oxygen tension on human tenocyte phenotype maintenance by enhancing synthesis and deposition of tissue-specific ECM.

Human tendons were kindly provided from University Hospital Galway, after obtaining appropriate licenses, ethical approvals and patient consent. Afterwards, tenocytes were extracted using the migration method. Experiments were conducted at passage three. Optimization of MMC conditions was assessed using 50 to 500 μg/ml carrageenan (Sigma Aldrich, UK). For variable oxygen tension cultures, tenocytes were incubated in a Coy Lab (USA) hypoxia chamber. ECM synthesis and deposition were assessed using SDS-PAGE (BioRad, UK) and immunocytochemistry (ABCAM, UK) analysis. Protein analysis for Scleraxis (ABCAM, UK) was performed using western blot. Gene analysis was conducted using a gene array (Roche, Ireland). Cell morphology was assessed using bright-field microscopy. All experiments were performed at least in triplicate. MINITAB (version 16, Minitab, Inc.) was used for statistical analysis. Two-sample t-test for pairwise comparisons and ANOVA for multiple comparisons were conducted

SDS-PAGE and immunocytochemistry analysis demonstrated that human tenocytes treated with the optimal MMC concentration at 2% oxygen tension showed increased synthesis and deposition of collagen type I, the major component of tendon ECM. Moreover, immunocytochemistry for the tendon-specific ECM proteins collagen type III, V, VI and fibronectin illustrated enhanced deposition when cells were treated with MMC at 2% oxygen tension. In addition, protein analysis revealed elevated dexpression of the tendon-specific protein Sclearaxis, while a detailed gene analysis revealed upregulation of tendon-related genes and downregulation of trans-differentiation markers again when cells cultured with MMC at 2% oxygen tension. Finally, low oxygen tension and MMC did not affect the metabolic activity, proliferation and viability of human tenocytes.

Collectively, results suggest that the synergistic effect of MMC and low oxygen tension can accelerate the formation of ECM-rich substitutes, which stimulates tenogenic phenotype maintenance. Currently, the addition of substrate aligned topography together with MMC and hypoxia is being investigated in this multifactorial study for the development of an implantable device for tendon regeneration.


A. Chevrier M. Hurtig F. Lacasse M. Lavertu H. Potter S. Pownder S. Rodeo M. Buschmann

Surgical reattachment of torn rotator cuff tendons can lead to satisfactory clinical outcome but failures remain common. Ortho-R product is a freeze-dried formulation of chitosan (CS) that is solubilized in platelet-rich plasma (PRP) to form injectable implants. The purpose of the current pilot study was to determine Ortho-R implant acute residency, test safety of different implant doses, and assess efficacy over standard of care in a sheep model.

The infraspinatus tendon (ISP) was detached and immediately repaired in 22 skeletally mature ewes. Repair was done with four suture anchors in a suture bridge configuration (n = 6 controls). Freeze-dried formulations containing 1% w/v chitosan (number average molar mass 35 kDa and degree of deacetylation 83%) with 1% w/v trehalose (as lyoprotectant) and 42.2 mM calcium chloride (as clot activator) were solubilized with autologous leukocyte-rich PRP and injected at the tendon-bone interface and on top of the repaired site (n = 6 with a 1 mL dose and n = 6 with a 2 mL dose). Acute implant residency was assessed histologically at 1 day (n = 2 with a 1 mL dose and n = 2 with a 2 mL dose). Outcome measures included MRI assessment at baseline, 6 weeks and 12 weeks, histopathology at 12 weeks and clinical pathology. MRI images and histological slides were scored by 2 blinded readers (veterinarian and human radiologist, and veterinarian pathologist) and averaged. The Generalized Linear Model task (SAS Enterprise Guide 7.1 and SAS 9.4) was used to compare the different groups with post-hoc analysis to test for pairwise differences.

Ortho-R implants were detected near the enthesis, near the top of the anchors holes and at the surface of ISP tendon and muscle at 1 day. Numerous polymorphonuclear cells were recruited to the implant in the case of ISP tendon and muscle. On MRI, all repair sites were hyperintense compared to normal tendon at 6 weeks and only 1 out 18 repair sites was isointense at 12 weeks. The tendon repair site gap seen on MRI, which is the length of the hyperintense region between the greater tuberosity and tendon with normal signal intensity, was decreased by treatment with the 2 mL dose when compared to control at 12 weeks (p = 0.01). Histologically, none of the repair sites were structurally normal. A trend of improved structural organization of the tendon (p = 0.06) and improved structural appearance of the enthesis (p = 0.1) with 2 mL dose treatment compared to control was seen at 12 weeks. There was no treatment-specific effect on all standard safety outcome measures, which suggests high safety.

Ortho-R implants (2 mL dose) modulated the rotator cuff healing processes in this large animal model. The promising MRI and histological findings may translate into improved mechanical performance, which will be assessed in a future study with a larger number of animals. This study provides preliminary evidence on the safety and efficacy of Ortho-R implants in a large animal model that could potentially be translated to a clinical setting.


D. Hamilton H. Simpson D. Beard K. Barker G. MacFarlane A. Stoddart G. Murray

There is a lack of evidence as to the best way to deliver rehabilitation following TKA. Previous work has suggested that postoperative physiotherapy applied to all patients is not effective at improving one-year post-surgical outcomes. The aim of this study was to target physiotherapy to those at risk of poor outcome following TKA, and to determine if a therapist-led intervention offered superior results compared to a home-exercise based protocol in this ‘at risk’ group.

The Targeted Rehabilitation to Improve Outcomes (TRIO) study was a prospective randomised controlled trial run at 15-centres in the UK. Patients were identified as ‘potential poor outcome’ based on an Oxford Knee Score (OKS) classification at 6-weeks post-surgery and randomised to either therapist-led or home-exercise based protocols. Patients were reviewed by a physiotherapist and commenced 18-exercise sessions over 6-weeks. The therapist-led group undertook a progressive functional protocol (modified weekly in 1-1 contact sessions) in contrast to the static home-exercise based regime. Evaluation took place following rehabilitation intervention, then at 6-months and 1-year post-surgery. Primary outcome was comparative group OKS at 1-year. Secondary outcomes included, ‘worst’ and ‘average’ pain scores, OXS and EQ-5D, and satisfaction questionnaire. Health economic (cost-utility) analysis was undertaken from NHS perspective up to 1-year post-surgery. Incremental cost per Quality Adjusted Life Years (QALYs) were calculated from intervention costs, patient reported primary and secondary care usage, and EQ-5D data.

4264 patients were screened, 1296 were eligible, 334 patients were randomised, 8 were lost to follow-up, therapy compliance was >85%. Clinically meaningful improvement in OKS (between baseline and 1-year) was seen in both arms (p < 0 .001). Between group difference in 1-year OKS was 1.91 (95%CI, −0.17–3.99) points favouring the therapist-led arm (p=0.07). Incorporating all time point data, between group difference in OKS was 2.25 points (95%CI, 0.61–3.90, p=0.008). Small, non-significant reductions (< 5 %) in both worst and average pain scores were observed favouring the therapist-led group. Enhanced satisfaction with pain relief (OR 1.65, p < 0 .02), ability to perform daily functional tasks (OR 1.66, p < 0 .02), and perform heavy functional tasks (OR 1.6, p=0.04) was reported in the therapist-led group. There was a small non-significant difference of 0.02 points (95%CI −0.02–0.06) between groups in EQ-5D, resulting in a £12,125 cost per QALY of delivering the therapist led intervention with a 57% chance of being cost-effective at the standard UK policy threshold of £20,000 per QALY.

TRIO is the largest randomised trial of physiotherapy following TKA, and the first to target rehabilitation to patients at risk of poor outcomes. Both therapist-led and home-exercise based rehabilitation groups made clinically meaningful improvements in outcome by 1-year. We observed a modest difference in OKS in favour of therapist-led rehabilitation compared to the home-exercises which was not statistically significant. The relatively tight confidence intervals suggests that any difference which might exist is too small to be clinically relevant. Patient satisfaction with outcome was however higher in those that received greater physiotherapist contact. While cost per QALY estimates were below UK policy threshold, this result is uncertain and insufficient to make accept-decline recommendations.


Y.N. Chim W. Cheung S. Kwoon-ho Chow

It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as macrophages and the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Therefore, the aim of this study was to investigate the effect of LMFHV treatment on the inflammatory response in osteoporotic fracture healing.

In this study, ovariectomy-induced osteoporotic and sham-operated closed-femoral fracture SD-rats were randomized into three groups: sham control (SHAM), ovariectomized control (OVX-C) or ovariectomized vibration (OVX-V) (n=36, n=6 per group per time point). LMHFV (35Hz, 0.3g) was given 20 min/day and 5 days/week to OVX-V group. SHAM operation and ovariectomy were performed at 6-month and closed femoral fracture was performed at 9-month. Callus morphometry was determined by callus width from weekly radiography. Local expressions of inducible nitric oxide synthase (iNOS) (macrophage M1 marker), CD206 (macrophage M2 marker), TNF-α, IL-6 and IL-10 were detected by immunohistochemistry and quantified by colour threshold in ImageJ, assessed at weeks 1 and 2 post-fracture. Significant difference between groups was considered at p≤0.05 by one-way ANOVA.

Callus formation was higher in OVX-V than that of OVX-C as shown by callus width at weeks 1 and 2 (p=0.054 and 0.028, respectively). Immunohistochemistry results showed that CD206 positive signal and the M2/M1 ratio which indicates the progression of macrophage polarization were significantly higher in OVX-V rats (p=0.053 and 0.049, respectively) when compared to OVX-C at week 1. Area fraction of TNF-α positive signal was significantly higher in SHAM and OVX-V rats at week 1 (p=0.01 and 0.033, respectively). IL-6 signal was also significantly higher in SHAM and OVX-V groups at week 1 (p=0.004 and 0.029, respectively). IL-10 expression was significantly lower in SHAM and OVX-V groups at week 1 (p=0.013 and 0.05, respectively).

Here we have shown that LMHFV treatment promoted the shift from pro-inflammatory stage towards anti-inflammatory stage earlier. It has been reported that the polarization of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 was indicative of the endochondral ossification process in the long bone fracture model. Besides, we found that LMHFV treatment enhanced pro-inflammatory markers of TNF-α and IL-6 and suppressed anti-inflammatory marker of IL-10 at week 1, showing that inflammatory response was enhanced at week 1 post-fracture. These inflammatory cytokines involved in fracture healing were shown to coordinate different fracture healing processes such as mesenchymal stem cell recruitment and angiogenesis. Our previous study has demonstrated that ovariectomized rats exhibit lower levels of inflammatory response after fracture creation. Therefore, we report that LMHFV treatment can modulate macrophage polarization from M1 to M2 at an earlier time-point and partly restore the impaired inflammatory response in OVX bones at the early stage of fracture healing that may lead to accelerated healing of osteoporotic fracture as shown by promoted callus formation.


L. Nowak E. H. Schemitsch

Previous studies have indicated that prolonged surgical time may lead to higher rates of infection following total hip arthroplasty (THA). The purpose of this study was to evaluate the influence of surgical time on 30-day complications following THA and to determine if there was a time interval associated with worse outcomes.

Patients ≥18 years who underwent THA between 2005 and 2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database using procedural codes. Patients with surgical durations >240 minutes were excluded. Patient demographics, operation length, and 30-day major and minor complications were ascertained. Multivariable regression was used to determine if the rate of complications differed depending on length of operation, while adjusting for relevant covariables, and to identify independent predictors of operation length. Covariables of interest included age, sex, American Society of Anaesthesiologists (ASA) class, smoking status, functional status, comorbidities, anesthesia type, and Body Mass Index (BMI).

A total of 131,361 THA patients (average age 65 ±12 years) were identified from the database. Of these, 2,177 (1.64%) experienced a major complication, and 3,504 (2.64%) experienced a minor complication within 30-days of the initial procedure. Average operation length was 91.9 minutes (range 20 – 240 minutes). Independent predictors of prolonged operation length included overweight/obese BMI, male sex, cancer, dependent functional status, epidural anaesthetic, lower pre-operative hematocrit, and ASA class II, III or IV vs. I Alternatively, older age, current smoking, and spinal anaesthetic were associated with shorter surgical durations.

Unadjusted rates of both major and minor complications were significantly higher for patients whose operation lengths were ≥ 120 minutes (P>0.001). Specifically, patients whose operations lasted ≥ 120 minutes had higher rates of septic shock, sepsis, pulmonary embolism (PE), deep vein thrombosis (DVT), urinary tract infection (UTI), renal insufficiency, surgical site infection(SSI) and wound disruption. After covariable adjustment, surgical durations of 90–119 minutes increased the risk of minor complications by 1.2 (95%Confidence interval [95%CI] 1.1–1.3), while surgical durations of 120–179 minutes increased the risk of major complications by 1.4 (95%CI 1.3 – 1.6), and minor complications by 1.4 (95%CI 1.2 – 1.5), and surgical durations ≥180 minutes increased the risk of major complications by 2.1 (95%CI 1.8 – 2.6), and minor complications by 1.9 (95%CI 1.6 – 2.3). There was no difference in the overall risk of complications for operation times lasting 20 – 39, 40 – 59, or 60 – 89 minutes (P>0.05).

In terms of specific complications, operation length ≥90 minutes was determined to be an independent risk factor for deep and superficial incisional SSI, as well as wound disruption, while operation length ≥ 120 minutes was an independent risk factor for sepsis, UTI, and deep, non-incisional SSI and operation length ≥ 180 minutes was an independent risk factor for PE, DVT, and cardiac arrest (p < 0 .05). These data indicate that prolonged surgical durations may be an independent predictor of major and minor complications following THA. This suggests that quality improvements could be made to improve operating room efficiency and surgical times and therefore postoperative outcomes.


L. Nowak E.H. Schemitsch

This study was designed to compare length of hospital stay, and 30-day major and minor complications between patients undergoing total knee arthroplasty (TKA) with general anesthesia, to those undergoing TKA with spinal or epidural anesthesia with or without regional nerve blocks.

Patients 18 years and older undergoing TKA between the years of 2005 and 2016 were identified from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP). Patient demographics, anesthesia type, length of operation and hospital stay, as well as 30-day major and minor complications were collected from the database. Patients with “primary anesthesia technique” codes for either spinal or epidural anesthesia along with “other anesthesia technique” codes for regional anesthesia were assumed to have been given a regional nerve block. Chi square tests, and analysis of variance were utilized to evaluate unadjusted differences in demographics and outcomes between anesthesia types. Multivariable regression was utilized to compare outcomes (length of stay and complications) between anesthesia types, while adjusting for age, American Society of Anesthesiologist (ASA) class, comorbidities, sex, steroid/immunosuppressant use, body mass index (BMI), diabetes, length of operation and smoking status.

A total of 214,665 TKA patients were identified (average age 67 ± 10 years). Of these, 257 (0.12%) underwent epidural anesthesia with a nerve block (EB), while 2,318 (1.08%) underwent epidural anesthesia with no block (E), 14,468 (1.08%) underwent spinal anesthesia with a block (SB), and 85,243 (39.7%) underwent spinal anesthesia with no block (S), and 112,377 (52.4%) underwent general anesthesia (G).

The unadjusted length of stay (LOS) was significantly longer in the E group (3.67 ± 5 days) compared to the G group (3.1 ± 3.9 days), while the unadjusted LOS was significantly shorter in the EB group (2.6 ± 1.2), and both SB and S groups (2.6 ± 3 and 2.9 ± 3, respectively), compared to the G group p < 0 .001. Following covariable adjustment, anesthesia type remained an independent predictor of length of stay. Compared to the G group, patients in the E group stayed 0.56 days longer (95% Confidence interval [95%CI] 0.42 – 0.71 days), while patients in the SB were discharged 0.28 days (95%CI 0.21 – 0.35 days) earlier, and those in the S group were discharged 0.06 days earlier (95%CI 0.02–0.09), (p < 0 .0001).

While the unadjusted rates of major complications were not significantly different between groups, the unadjusted rates of minor complications were higher in the E, EB, and G groups compared to the S and SB groups. Following covariable adjustment, there were no differences between groups in the risk of minor complications.

In conclusion, these data indicate that anesthesia type following TKA is associated with length of hospital stay, but not with 30-day complications. After adjusting for relevant covariables, patients who received epidural anesthesia without a nerve block for TKA were discharged later, while patients who received spinal anesthesia, both with and without a nerve block for TKA were discharged earlier, compared to patients who received general anesthesia for TKA.


L. Nowak M. MacNevin D.W. Sanders A. Lawendy M. D. McKee E.H. Schemitsch R. Walker R. DiGiovanni

This study was designed to compare atypical hip fractures with a matched cohort of standard hip fractures to evaluate the difference in outcomes.

Patients from the American College of Surgeons National Surgical Quality Improvement Program's (NSQIP) targeted hip fracture data file (containing a more comprehensive set of variables collected on 9,390 specially targeted hip fracture patients, including the differentiation of atypical from standard hip fractures) were merged with the standard 2016 NSQIP data file. Atypical hip fracture patients aged 18 years and older in 2016 were identified via the targeted hip fracture data file and matched to two standard hip fracture controls by age, sex, and fracture location. Patient demographics, length of hospital stay, 30-day mortality, major and minor complications, and other hip-specific variables were identified from the database. Binary outcomes were compared using the McNemar's test for paired groups, and continuous outcomes were compared using a paired t-test.

Ninety-five atypical hip fractures were identified, and compared to 190 age, sex, and fracture location matched standard hip fracture controls. There was no statistical difference in body mass index (BMI), race, ASA score, smoking status, timing of fixation, or functional status between the two groups (P>0.05). Thirty-day mortality was significantly higher in the atypical hip fracture group (atypical 7.36%, standard 2.11% p

This is the first study, to our knowledge, that demonstrates an increase in the rate of mortality in atypical hip fractures. Comparing atypical hip fractures with a matched cohort of standard hip fractures revealed a significantly greater 30-day mortality rate with an odds ratio of 3.62 in atypical hip fractures (95% CI 1.03–12.68). Prospective, clinical studies are recommended to further investigate these findings.


J. Zhang G. Zhao F. Li J. H-C. Wang

Tendinopathy is one of the most common orthopaedic pathological conditions characterized by tendon degenerative changes. Excessive mechanical loading is considered as a major causative factor in the development of tendinopathy, but the mechanisms of pathogenesis remain unclear. High mobility group box-1 (HMGB1), a potent inflammatory mediator when released into the matrix, has been identified in the early stage tendinopathy patients. Since the release and contribution of HMGB1 in tendinopathy development due to mechanical overloading is unknown, we investigated the role of HMGB1 in tendinopathy using a mouse intensive treadmill running (ITR) model and injection of glycyrrhizin (GL), a specific inhibitor of HMGB1.

A total of 48 mice were divided into four groups, Cage Control group: The animals were allowed to move freely in their cage, GL group: The animals were received daily IP injection of GL (50 mg/kg body weight) for 24 weeks, ITR group: The animals ran on treadmill at 15 meters/min for three h/ day, five days a week for 12 or 24 weeks, GL+ITR group: The animals ran the same protocol as that of ITR group plus daily IP injection of GL for 12 or 24 weeks. Six mice/group were sacrificed at 12 or 24 weeks and the Achilles and patellar tendon tissues were harvested and used for histochemical staining and immunostaining.

Mechanical overloading induced HMGB1 released from the cell nuclei to the matrix (Fig. 1a, b) caused tendon inflammation (Fig. 1c, d) and led to tendon degenerative changes (Fig. 1e-j). After 12 weeks of ITR, the tendon tissue near the bone insertion site showed typical tendinopathic changes in cell shape, accumulation of glycosaminoglycans (GAG) (Fig. 1e, f), and increase in SOX-9 staining (Fig. 1g-j). After 24 weeks ITR, the distal site of Achilles tendon showed considerable changes in cell shape (Fig. 2A, g, arrows), which is round compared to more elongated in the control and GL groups (Fig. 2A, e, f). However, daily treatment with GL prior to ITR blocked the cell shape change (Fig. 2A, h) and, ITR induced extensive GAG accumulation in ITR group (Fig. 2B, bottom panel). Furthermore, GL inhibited ITR-induced expression of chondrogenic markers (SOX-9 and collagen II) in the tendons (Fig. 3).

Our results showed that mechanical overloading-induced HMGB1 plays a critical role in the development of tendinopathy by initiating tendon inflammation and eventual degeneration characterized by the presence of chondrocyte-like cells, accumulation of proteoglycans, high levels of collagen type II production, and chondrogenic marker SOX-9 expression. These results provide the first evidence for the role of HMGB1 as a therapeutic target to prevent tendinopathy before its onset and block further development at its early inflammation stages. The inhibition of tendinopathy development by GL administration in this study also suggests the putative therapeutic potential of this natural triterpene that is already in clinical use to treat other inflammation-related diseases.

For any figures or tables, please contact authors directly.


K. Lin F. Wong M. Wang K. Y.W. Teo S. J. Chuah X. Ren Y. Wu A. Hassan R. C. Lai S.K. Lim J. H. P. Hui W.S. Toh E.H. Lee S. Zhang

Osteochondral (OC) defects of the knee are associated with pain and significant limitation of activity. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cell (MSC) therapies in treating osteochondral defects. There is increasing evidence that the efficacy of MSC therapies may be a result of the paracrine secretion, particularly exosomes. Here, we examine the effects of MSC exosomes in combination with Hyaluronic Acid (HA) as an injectable therapy on functional osteochondral regeneration in a rabbit osteochondral defect model.

Exosomes were purified from human MSC conditioned medium by size fractionation. A circular osteochondral defect of 4.5 mm diameter and 2.5 mm depth was surgically created in the trochlear grooves of 16 rabbit knees. Thereafter, eight knees received three weekly injections of 200 µg of exosomes in one ml of 3% HA, and the remaining eight knees received three weekly injections of one ml of 3% HA only. The rabbits were sacrificed at six weeks. Analyses were performed by macroscopic and histological assessments, and functional competence was analysed via Young Modulus calculation at five different points (central, superior, inferior, medial and lateral) of the repaired osteochondral defect site.

MSC exosomes displayed a modal size of 100 nm and expressed exosome markers (CD81, TSG101 and ALIX). When compared to HA alone, MSC exosomes in combination with HA showed significantly better repair histologically and biomechanically. The Young Modulus was higher in 4 out of the 5 points. In the central region, the Young Modulus of MSC exosome and HA combination therapy was significantly higher: 5.42 MPa [SD=1.19, 95% CI: 3.93–6.90] when compared to HA alone: 2.87 MPa [SD=2.10, 95% CI: 0.26–5.49], p < 0 .05. The overall mean peripheral region was also significantly higher in the MSC exosome and HA combination therapy group: 5.87 MPa [SD=1.19, 95% CI: 4.40–7.35] when compared to HA alone: 2.70 MPa [SD=1.62, 95% CI: 0.79–4.71], p < 0 .05. The inferior region showed a significantly higher Young Modulus in the combination therapy: 7.34 MPa [SD=2.14, 95% CI: 4.68–10] compared to HA alone: 2.92 MPa [SD=0.98, 95% CI: 0.21–5.63], p < 0.05. The superior region showed a significantly higher Young Modulus in the combination therapy: 7.31 MPa [SD=3.29, 95% CI: 3.22–11.39] compared to HA alone: 3.59 MPa [SD=2.55, 95% CI: 0.42–6.76], p < 0.05. The lateral region showed a significantly higher Young Modulus in the combination therapy: 8.05 MPa [SD=2.06, 95% CI: 5.49–10.61] compared to HA alone: 3.56 MPa [SD=2.01, 95% CI: 1.06–6.06], p < 0.05. The medial region showed a higher Young Modulus in the combination therapy: 6.68 MPa [SD=1.48, 95% CI: 4.85–8.51] compared to HA alone: 3.45 MPa [SD=3.01, 95% CI: −0.29–7.19], but was not statistically significant. No adverse tissue reaction was observed in all the immunocompetent animals treated with MSC exosomes.

Three weekly injections of MSC exosomes in combination with HA therapy results in a more functional osteochondral regeneration as compared to HA alone.


H. Sahak M. Hardisty J. Finkelstein C. Whyne

Spinal stenosis is a condition resulting in the compression of the neural elements due to narrowing of the spinal canal. Anatomical factors including enlargement of the facet joints, thickening of the ligaments, and bulging or collapse of the intervertebral discs contribute to the compression. Decompression surgery alleviates spinal stenosis through a laminectomy involving the resection of bone and ligament. Spinal decompression surgery requires appropriate planning and variable strategies depending on the specific situation. Given the potential for neural complications, there exist significant barriers to residents and fellows obtaining adequate experience performing spinal decompression in the operating room. Virtual teaching tools exist for learning instrumentation which can enhance the quality of orthopaedic training, building competency and procedural understanding. However, virtual simulation tools are lacking for decompression surgery. The aim of this work was to develop an open-source 3D virtual simulator as a teaching tool to improve orthopaedic training in spinal decompression.

A custom step-wise spinal decompression simulator workflow was built using 3D Slicer, an open-source software development platform for medical image visualization and processing. The procedural steps include multimodal patient-specific loading and fusion of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) data, bone threshold-based segmentation, soft tissue segmentation, surgical planning, and a laminectomy and spinal decompression simulation. Fusion of CT and MRI elements was achieved using Fiducial-Based Registration which aligned the scans based on manually placed points allowing for the identification of the relative position of soft and hard tissues. Soft tissue segmentation of the spinal cord, the cerebrospinal fluid, the cauda equina, and the ligamentum flavum was performed using Simple Region Growing Segmentation (with manual adjustment allowed) involving the selection of structures on T1 and/or T2-weighted scans. A high-fidelity 3D model of the bony and soft tissue anatomy was generated with the resulting surgical exposure defined by labeled vertebrae simulating the central surgical incision. Bone and soft tissue resecting tools were developed by customizing manual 3D segmentation tools. Simulating a laminectomy was enabled through bone and ligamentum flavum resection at the site of compression. Elimination of the stenosis enabled decompression of the neural elements simulated by interpolation of the undeformed anatomy above and below the site of compression using Fill Between Slices to reestablish pre-compression neural tissue anatomy.

The completed workflow allows patient specific simulation of decompression procedures by staff surgeons, fellows and residents. Qualitatively, good visualization was achieved of merged soft tissue and bony anatomy. Procedural accuracy, the design of resecting tools, and modeling of the impact of bone and ligament removal was found to adequately encompass important challenges in decompression surgery.

This software development project has resulted in a well-characterized freely accessible tool for simulating spinal decompression surgery. Future work will integrate and evaluate the simulator within existing orthopaedic resident competency-based curriculum and fellowship training instruction. Best practices for effectively teaching decompression in tight areas of spinal stenosis using virtual simulation will also be investigated in future work.


A. Michalek S. Duclos S. Denning

Residual strain development in biological tissue is believed to result from remodeling in response to repetitive loading. This study hypothesized that differences in in-vivo loading between levels of the bovine tail result in differences in intervertebral disc (IVD) annulus fibrosus (AF) microstructural remodeling. The hypothesis was tested by quantifying tail musculature using clinical computed tomography and tissue microstructure using collagen fiber crimp period, which has previously been correlated with residual strain.

Three bovine tail segments (levels c1 through c6) were imaged using a clinical computed tomography (CT) scanner followed by removal of muscle and harvest of IVDs. The discs were frozen, and transverse cryosections were obtained. Additionally, tangential plane cryosections were obtained from the inner and outer zones of the AF.

Transverse CT slices corresponding to each joint level thresholded for both disc and muscle tissue and analyzed in MATLAB. First, the centroid of the disc image was calculated to use as an origin. Then the disc area and moments of inertia about the flexion extension axis and lateral bending axis were calculated. Total muscle area was then calculated, along with muscle moments of inertia relative to the disc centroid. All muscle parameters were normalized by those of the corresponding disc.

Cryosections were imaged using an inverted light microscope equipped with crossed polarizing filters and a digital camera. A MATLAB routine was used to perform Fourier transform analysis on user selected lines of interest in the transverse micrographs, yielding average fiber crimp period in the inner and outer AF. Micrographs from tangential sections were opened in ImageJ, and fiber orientation angles were measured manually.

Muscle moments of inertia were analyzed using a two-way ANOVA with disc level and axis as dependent variables. Normalized muscle area was analyzed with a one-way ANOVA with disc level as a dependent variable. A two-way ANOVA, with disc level and zone (inner versus outer) was used to analyze collagen fiber crimp period and collagen fiber angle.

Normalized muscle moment of inertia showed significant effects of both level and axis (p < 0 .001), decreasing at distal levels, and being lower about the flexion-extension axis than the lateral bending axis. Normalized muscle cross section showed a visible, but not significant (p=0.0721) decreasing trend with disc level. Fiber crimp period had significant effects of both level and zone (p < 0 .001), and was significantly longer in the outer zone than inner at all levels. Significant decrease in crimp period at distal levels were seen in the outer AF, but not the inner. While fiber angle was significantly (p < 0 .001) higher in the inner AF (36±6.6°) than outer AF (24±3.5°)), there was no significant effect of level.

Fiber crimp period in the AF has previously been correlated with residual circumferential strain, with larger crimp period corresponding to increased residual tension. The present study suggests that at proximal levels of the tail, where peak compressive and bending stresses in the AF (as inferred from normalized muscle area and moments of inertia respectively) are greatest, there is more accumulation of residual strain.


A. Michalek D. Nguyen L. Varden

As the intervertebral disc is largely avascular, needle injection is the most practical method for delivery of therapeutic agents used in treatments for degenerative disc disease. Intradiscal pressure increases during injection, and insufficient recovery time prior to needle retraction may result in injectate leakage. In order to determine the maximum pressure and post-injection recovery time for a given injection volume and rate, an analytical model of intradiscal injection was developed and calibrated experimentally.

A governing equation was derived defining intradiscal pressure as a function of effective permeability, initial elastic stiffness, nonlinear stiffness term, and injection rate. The equation was solved using a fourth order Runge-Kutta routine with a 0.05s time step and a ramp-dwell injection.

The model was calibrated by performing controlled intradiscal injections on five bovine caudal intervertebral discs. Three had adjacent vertebrae intact, while two were separated from vertebrae and constrained between porous stainless steel platens. A syringe driven by a linear actuator was used to inject phosphate buffered saline through a 21g hypodermic needle inserted radially into the disc to a depth of one half of the disc diameter. Injection was performed at a rate of 75μL/s to a volume of 250μL followed by a 240s dwell. Fluid pressure was recorded during both the injection phase and subsequent recovery phase. For each experimental pressure vs time trace, model parameters were varied in order to obtain an optimal fit.

The model was run with the average parameter values across a grid of possible injection protocols, with injection volume ranging from 30 to 300μL and injection time ranging from 0.1 to 5s. For each case, peak pressure and time required to reach a 1kPa threshold were recorded.

Experimentally measured peak pressure ranged from 68 to 88kPa. Pressure at the end of the 240s dwell ranged from 49 to 69kPa. There was no apparent difference between discs with and without endplates. Leakage of fluid following needle retraction was observed in all specimens. Experimental data were well fit by the analytical model, which predicted higher peak pressure and longer recovery time with increasing volume, from approximately 1500s at 30μL to nearly 3000s at 300μL. The model was nearly insensitive to injection rate.

The experimental data confirm pressurization of the disc during injection and injectate leakage resulting from insufficient recovery time. The model predicts that the time required to recover to below threshold leakage pressure is impractically long for both laboratory and clinical injection protocols. Similar behavior with and without endplates confirms that fluid flow is limited by permeability of the tissue itself, not the boundary conditions. Slow recovery is likely attributable to the fact that peak injection pressures were lower than the hydraulic swelling pressure of the nucleus pulposus, which has been reported to be approximately 140kPa.

Due to the high swelling pressure of the nucleus pulposus, it is unlikely that intradiscal injection procedures can be performed without substantial injectate leakage following needle retraction.


D. Hall R. Pourzal J. Jacobs R. Urban

Little is known about the relationship between head-neck corrosion and its effect on the periprosthetic tissues and distant organs of patients hosting well-functioning devices. The purpose of this study was to investigate in postmortem retrieved specimens the degree and type of taper damage, and the corresponding histologic responses in periprosthetic tissues and distant organs.

Fifty postmortem THRs (34 primaries, 16 revisions) retrieved after 0.5 to 26 years were analyzed. Forty-three implants had a CoCrMo stem and seven had a Ti6Al4V stem. All heads were CoCrMo and articulated against polyethylene cups (19 XLPE, 31 UHMWPE). H&E sections of joint pseudocapsules, liver, spleen, kidneys and lymph nodes were graded 1–4 for the intensity of various inflammatory cell infiltrates and tissue characteristics. Corrosion damage of the taper surfaces was assessed using visual scoring and quantitated with an optical coordinate measuring machine. SEM analysis was used to determine the acting corrosion mode. Polyethylene wear was assessed optically. The majority of tapers had minimal to mild damage characterized by local plastic deformation of machining line peaks. Imprinting of the stem topography onto the head taper surface was observed in 18 cases. Column damage on the head taper surface occurred in three cases. All taper surfaces scored moderate or severe exhibited local damage features of fretting and/or pitting corrosion.

Moderate or severe corrosion of the head and/or trunnion was present in nine hips. In one asymptomatic patient with bilateral hips, lymphocyte-dominated tissue reactions involving perivascular infiltrates of lymphocytes and plasmacytes were observed. In this patient, mild, focal lymphocytic infiltrates were also present in the liver and kidneys, and there was focal histiocytosis and necrosis of the para-aortic lymph nodes. These two implants, which had been in place for 58.6 and 60.1 months, had severe intergranular corrosion of the CoCrMo trunnion, and column damage and imprinting on the head taper. In the other 41 hips, macrophage responses in the joint pseudocapsule to metallic and/or polyethylene wear particles ranged widely from minimal to marked. Focal necrosis in the pseudocapsules of 12 arthroplasties was related to high concentrations of CoCrMo, TiAl4V, TiO, BaSO4 and polyethylene wear particles. High concentrations of these particles were also detected in para-aortic lymph nodes. Rare to mild macrophages were observed in liver and spleen.

This is a comprehensive study of wear and corrosion within well-functioning postmortem retrieved THRs, and the resulting local and distant tissue reactions. One of eight patients with moderate or severe corrosion did have a subclinical inflammatory response dominated by lymphocytes after five years. To what extent such an inflammatory process might progress to become symptomatic is not known. Ionic and particulate products generated by corrosion disseminated systemically. The minor lymphocytic infiltrate in the liver and kidneys of one subject with bilateral severely corroded head-neck junctions might suggest possible metal toxicity. The diagnosis of adverse tissue reactions to corrosion of modular junctions can be challenging. Postmortem retrieval studies add to our understanding of the nature and progression of lymphocyte-dominated adverse local and potentially systemic tissue reactions to corrosion of modular junctions.


G. Zhai M. Liu P. Rahman A. Furey

While total joint replacement (TJR) is considered as an effective intervention to relieve pain and restore joint function for end-stage osteoarthritis (OA) patients, a significant proportion of the patients are dissatisfied with their surgery outcomes. The aim of this study was to identify genetic factors that can predict patients who do or do not benefit from these surgical procedures by a genome-wide association study (GWAS).

Study participants were derived from the Newfoundland Osteoarthritis Study (NFOAS) which consisted of 1086 TJR patients. Non-responders to TJR was defined as patients who did not reach the minimum clinically important difference (MCID) based on the self administered Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in terms of pain reduction or function improvment. DNA was extracted from the blood samples of the study participants and genotyped by Illumina GWAS genotyping platform. Over two million single nucleotide polymorphisms (SNPs) across the genome were genotyped and tested for assocition with non-responders.

39 non-responders and 44 age, sex, and BMI matched responders were included in this study. Four chromosome regions on chromosomes 5, 7, 8, and 12 were suggested to be associated with non-responders with p < 1 0–5. The most promising one was on chromosome 5 with the lead SNP rs17118094 (p=1.7×10–6) which can classify 72% of non-responders accurately. The discriminatory power of this SNP alone is very promising as indicated by an area under the curve (AUC) of 0.72 with 95% confidence interval of 0.63 to 0.81, which is much better than any previously studied predictors mentioned above. All the patients who carry two copies of the G allele (minor allele) of rs17118094 were non-responders and 75% of those who carry one copy of the G allele were non-responders. The discriminatory ability of the lead SNPs on chromosomes 7 and 12 were comparable to the one on chromosome 5 with an AUC of 0.74, and 88% of patients who carry two copies of the A allele of rs10244798 on chromosome 7 were non-responders. Similarly, 88% of patients who carry two copies of the C allele of rs10773476 on chromosome 12 were non-responders. While the discriminatory ability of rs9643244 on chromosome 8 was poor with an AUC of 0.26, its strong association with non-responders warrants a further investigation in the region.

The study identified four genomic regions harboring genetic factors for non-responders to TJR. The lead SNPs in those regions have great discriminatory ability to predict non-responders and could be used to create a genetic prediction model for clinical unitilty and application.


R. Queen D. Schmitt J. Campbell

Power production in the terminal stance phase is essential for propelling the body forward during walking and is generated primarily by ankle plantarflexion. Osteoarthritis (OA) of the ankle restricts joint range of motion and is expected to reduce power production at that ankle. This loss of power may be compensated for by unaffected joints on both the ipsilateral and contralateral limbs resulting in overloading of the asymptomatic joints. Total ankle arthroplasty (TAA) has been shown to reduce pain and has the potential to restore range of motion and therefore increase ankle joint power, which could reduce overloading of the unaffected joints and increase walking speed. The purpose of this study was to test the hypothesis that ankle OA causes a loss of power in the affected ankle, compensatory power changes in unaffected lower limb joints, and that TAA will increase ankle power in the repaired ankle and reduce compensatory changes in other joints.

One hundred and eighty-three patients (86 men, 97 women with average ages 64.1 and 62.4 years respectively) requiring surgical intervention for ankle OA were prospectively enrolled. Implant selection of either a fixed (INBONE or Salto Talaris) or mobile (STAR) bearing implant was based on surgeon preference. Three-dimensional kinematics and kinetics were collected prior to surgery and one year post-operatively during self-selected speed level walking using an eight-camera motion capture system and a series of force platforms. Subject walking speed and lower extremity joint power during the last third of stance at the ankle, knee, and hip were calculated bilaterally and compared before and after surgical intervention across the entire group and by implant type (fixed vs. mobile), and gender using a series of ANOVAs (JMP SAS, Cary, NC), with statistical significance defined as p < 0 .05.

There were no gender differences in age, walking speed, or joint power. All patients increased walking as a result of surgery (0.87 m/s±0.26 prior to surgery and 1.13 m/s±0.24 after surgery, p < 0 .001) and increased total limb power. Normalized to total power (which accounts for changes in speed and distribution of power production across joints), prior to surgery the affected ankle contributed 19%±10% of total power while the unaffected ankle contributed 42%±12% (P < 0 .001). After surgery, the affected ankle increased to 25%±9% of total power and the unaffected ankle decreased to 38%±9% of total (P < 0.001). Other joints showed no significant power changes following surgery. Fixed bearing implants provide greater surgical ankle power improvement (61% versus 29% increase, p < 0 .002). Much of that change was due to the fact that those that received fixed-bearing implants had significantly lower walking speed and power before surgery.

Ankle OA reduced ankle power production, which was partially compensated for by the unaffected ankle. TAA increases walking speed and power at the affected ankle while lowering power production on the unaffected side. The modifications in power production could lead to increased physical activity and reduced overloading of asymptomatic joints.


M. Mahaffy G. Athwal J. Johnson N. Knowles C. Berkmortel S. Abdic G. Walch

This study examined the regional variations of cortical and cancellous bone density present in superiorly eroded glenoids. It is hypothesized that eroded regions will contain denser bone in response to localized stress. The shift in natural joint articulation may also cause bone resorption in areas opposite the erosion site.

Clinical CT scans were obtained for 32 shoulders (10m/22f, mean age 72.9yrs, 56–88yrs) classified as having E2-type glenoid erosion. The glenoid was divided into four measurement regions - anterior, inferior, posterior, and superior - as well as five depth regions. Depth regions were segmented in two-millimeter increments from zero to 10 millimeters, beginning at the center of the glenoid surface. A repeated-measures multiple analysis of variance (RM-MANOVA) was performed using SPSS statistical software to look for differences and interactions between mean densities in each depth, quadrant, and between genders. A second RM-MANOVA was performed to examine effects of gender and quadrant on cortical to cancellous bone volume ratios. Significance was set at p < 0 .05.

Quadrant and depth variables showed significant multivariate main effects (p 0.147 respectively). Quadrant, depth, and their interaction showed significant univariate main effects for cortical bone (p≤0.001) and cancellous bone (p < 0 .001). The lowest bone density was found to be in the inferior quadrant for cancellous bone (307±50 HU, p < 0 .001). The superior quadrant contained the highest mean density for cortical bone (895±97 HU), however it was only significantly different than in the posterior quadrant (865±97 HU, p=0.022). As for depth, it was found that cortical bone is most dense at the glenoid surface (zero to two millimeters, 892±91 HU) when compared to bone at two to eight millimeters in depth (p < 0 .02). Cancellous bone was also most dense at the surface (352±51 HU), but only compared to the eight to 10 millimeters depth (p=0.005). Cancellous bone density was found to decrease with increasing depth. For cortical-to-cancellous bone volume ratios, the inferior quadrant (0.37±0.28) had a significantly lower ratio than all other quadrants (p < 0 .001)

The superoposterior region of the glenoid was found to have denser cancellous bone and a high ratio of cortical to cancellous bone, likely due to decreased formation of cancellous bone and increased formation of cortical bone, in response to localized stresses. The inferior quadrant was found to have the least dense cortical and cancellous bone, and the lowest volume of cortical bone relative to cancellous bone. Once again, this is likely due to reduction in microstrain responsible for bone adaptation via Wolff's law. The density values found in this study generally agree with the range of values found in previous studies of normal and arthritic glenoids. An important limitation of this study is the sizing of measurement regions. For a patient with a smaller glenoid, a depth measurement of two millimeters may represent a larger portion of the overall glenoid vault. Segments could be scaled for each patient based on a percentage of each individual's glenoid size.


S. Kerslake A. Tucker S. M. Heard G. M.L. Buchko L. A. Hiemstra M. Lafave

The primary purpose of this study was to assess whether patients presenting with clinical graft laxity following primary anatomic anterior cruciate ligament (ACL) reconstruction using hamstring autograft reported a significant difference in disease-specific quality-of-life (QOL) as measured by the ACL-QOL questionnaire.

Clinical ACL graft laxity was assessed in a cohort of 1134/1436 (79%) of eligible patients using the Lachman and Pivot-shift tests pre-operatively and at 12- and 24-months following ACL reconstruction. Post-operative ACL laxity was assessed by an orthopaedic surgeon and a physical therapist who were blinded to each other's examination. If there was a discrepancy between the clinical examination findings from these two assessors, then a third impartial examiner assessed the patient to ensure a grading consensus was reached.

Patients completed the ACL-QOL questionnaire pre-operatively, and 12- and 24-months post-operatively. Descriptive statistics were used to assess patient demographics, rate of post-operative ACL graft laxity, surgical failures, and ACL-QOL scores. A Spearman rho correlation coefficient was utilised to assess the relationships between ACL-QOL scores and the Lachman and Pivot-shift tests at 24-months post-operative.

An independent t-test was used to determine if there were differences in the ACL-QOL scores of subjects who sustained a graft failure compared to the intact graft group. ACL-QOL scores and post-operative laxity were assessed using a one-way analysis of variance (ANOVA).

There were 70 graft failures (6.17%) in the 1134 patients assessed at 24-months. A total of 226 patients (19.9%) demonstrated 24-months post-operative ACL graft laxity. An isolated positive Lachman test was assessed in 146 patients (12.9%), an isolated positive Pivot-shift test was apparent in 14 patients (1.2%), and combined positive Lachman and Pivot-shift tests were assessed in 66 patients (5.8%) at 24-months post-operative.

There was a statistically significant relationship between 24-month post-operative graft laxity and ACL-QOL scores (p < 0.001). Specifically, there was a significant correlation between the ACL-QOL and the Lachman test (rho = −0.20, p < 0.001) as well as the Pivot-shift test (rho = −0.22, p < 0.001). There was no significant difference between the scores collected from the graft failure group prior to failure occurring (mean = 74.38, SD = 18.61), and the intact graft group (mean = 73.97, SD = 21.51). At 24-months post-operative, the one-way ANOVA demonstrated a statistically significant difference between the ACL-QOL scores of the no laxity group (mean = 79.1, SD = 16.9) and the combined positive Lachman and Pivot-shift group (mean = 68.5, SD = 22.9), (p = 0, mean difference = 10.6).

Two-years post ACL reconstruction, 19.9% of patients presented with clinical graft laxity. Post-operative graft laxity was significantly correlated with lower ACL-QOL scores. The difference in ACL-QOL scores for patients with an isolated positive Lachman or Pivot-shift test did not meet the threshold of a clinically meaningful difference. Patients with clinical laxity on both the Lachman and Pivot-shift tests demonstrated the lowest patient-reported ACL-QOL scores, and these results exceeded the minimal clinically important difference.


A. Albiero V. Piombo L. Diamanti M. Birch A.W. McCaskie

Osteoarthritis is a global problem and the treatment of early disease is a clear area of unmet clinical need. Treatment strategies include cell therapies utilising chondrocytes e.g. autologous chondrocyte implantation and mesenchymal stem/stromal cells (MSCs) e.g. microfracture. The result of repair is often considered suboptimal as the goal of treatment is a more accurate regeneration of the tissue, hyaline cartilage, which requires a more detailed understanding of relevant biological signalling pathways. In this study, we describe a modulator of regulatory pathways common to both chondrocytes and MSCs. The chondrocytes thought to be cartilage progenitors are reported to reside in the superficial zone of articular cartilage and are considered to have the same developmental origin as MSCs present in the synovium. They are relevant to cartilage homeostasis and, like MSCs, are increasingly identified as candidates for joint repair and regenerative cell therapy. Both chondrocytes and MSCs can be regulated by the Wnt and TGFβ pathways. Dishevelled Binding Antagonist of Beta-Catenin (Dact) family of proteins is an important modulator of Wnt and TGFβ pathways. These pathways are key to MSC and chondrocyte function but, to our knowledge, the role of DACT protein has not been studied in these cells.

DACT1 and DACT2 were localised by immunohistochemistry in the developing joints of mouse embryos and in adult human cartilage obtained from knee replacement. RNAi of DACT1 and DACT2 was performed on isolated chondrocytes and MSCs from human bone marrow. Knockdown efficiency and cell morphology was confirmed by qPCR and immunofluorescence. To understand which pathways are affected by DACT1, we performed next-generation sequencing gene expression analysis (RNAseq) on cells where DACT1 had been reduced by RNAi. Top statistically significant (p < 0 .05) 200 up and downregulated genes were analysed with Ingenuity® Pathway Analysis software.

We observed DACT1 and DACT2 in chondrocytes throughout the osteoarthritic tissue, including in chondrocytes forming cell clusters. On the non-weight bearing and visually undamaged cartilage, DACT1 and DACT2 was localised to the articular surface. Furthermore, in mouse embryos (E.15.5), we observed DACT2 at the interzones, sites of developing synovial joints, suggesting that DACT2 has a role in cartilage progenitor cells. We subsequently analysed the expression of DACT1 and DACT2 in MSCs and found that both are expressed in synovial and bone marrow-derived MSCs. We then performed an RNAi knockdown experiment. DACT1 knockdown in both chondrocyte and MSCs caused the cells to undergo apoptosis within 24 hours. The RNA-seq study of DACT1 silenced bone marrow-derived MSCs, from 4 different human subjects, showed that loss of DACT1 has an effect on the expression of genes involved in both TGFβ and Wnt pathways and putative link to relevant cell regulatory pathways.

In summary, we describe for the first time, the presence and biological relevance of DACT1 and DACT2 in chondrocytes and MSCs. Loss of DACT1 induced cell death in both chondrocytes and MSCs, with RNA-seq analysis revealing a direct impact on transcript levels of genes involved in the Wnt and TFGβ signalling, key regulatory pathways in skeletal development and repair.


N. Al-Jezani P. Railton J. Powell A. Dufour R. Krawetz

Osteoarthritis (OA) is the fastest growing global health problem, with a total joint replacement being the only effective treatment for patients with end stage OA. Many groups are examining the use of bone marrow or adipose derived mesenchymal stem cells (MSCs) to repair cartilage, or modulate inflammation to promote healing, however, little efficacy in promoting cartilage repair, or reducing patient symptoms over temporary treatments such as micro-fracture has been observed. There is a growing body of literature demonstrating that MSCs derived from the synovial lining of the joint are superior in terms of chondrogenic differentiation and while improvements in clinical outcome measures have been observed with synovial MSCs, results from clinical studies are still highly variable.

Based on our results, we believe this variability in clinical studies with MSCs results in part from the isolation, expansion and re-injection of distinct MSCs subtypes in normal vs. OA tissues, each with differing regenerating potential. However, it remains unknown if this heterogeneity is natural (e.g. multiple MSC subtypes present) or if MSCs are influenced by factors in vivo (disease state/stage). Therefore, in this study, we undertook an ‘omics’ screening approach on MSCs from normal and OA knee synovial tissue. Specifically, we characterized their global proteome and genomic expression patterns to determine if multiple MSC from normal and OA joints are distinct at the protein/gene expression level and/if so, what proteins/genes are differentially expressed between MSCs derived from normal and OA synovial tissue.

Synovium tissue was collected from OA patients undergoing joint replacement and normal cadaveric knees. The in vitro adipogenic, chondrogenic and osteogenic differentiation potential of the MSCs was analyzed via qPCR and histology. Fully characterized MSC populations where then analyzed through an unbiased shotgun proteomics, and microarray analysis.

Synovial MSCs isolated from both OA and normal knees demonstrated similar multipotent differentiation capacity. Likewise, both OA and normal MSCs display the typical MSCs cell surface marker profile in vitro (CD90+, CD44+, CD73+, CD105+).

Using shotgun proteomics, 7720 unique peptides corresponding to 2183 proteins were identified and quantified between normal and OA MSCs. Of these 2183 proteins, 994 were equally expressed in normal and OA, MSCs, 324 were upregulated in OA MSCs (with 50 proteins exclusively expressed in OA MSCs), 630 proteins were upregulated in normal MSCs (with 16 proteins exclusively expressed in normal MSCs). Microarray analysis of normal and OA MSCs demonstrated a similar result in where, 967 genes were differentially expressed between normal and OA MSCs, with 423 genes upregulated in OA, and 544 genes upregulated in normal MSCs.

In this project, we have demonstrated that although normal and OA synovial derived MSCs demonstrate similar multipotent differentiation potential and cell surface markers expression, these cells demonstrated significant differences at the molecular level (protein and gene expression). Further research is required to determine if these differences influence functional differences in vitro and/or in vivo and what drives this dramatic change in the regulatory pathways within normal vs. OA synovial MSCs.


K. Algate M. Cantley T. Fitzsimmons S. Paton F. Wagner A. Zannettino E. Holson D. Fairlie D. Haynes

The inflammatory cascade associated with prosthetic implant wear debris, in addition to diseases such as rheumatoid arthritis and periodontitis, it is shown to drastically influence bone turnover in the local environment. Ultimately, this leads to enhanced osteoclastic resorption and the suppression of bone formation by osteoblasts causing implant failure, joint failure, and tooth loosening in the respective conditions if untreated. Regulation of this pathogenic bone metabolism can enhance bone integrity and the treatment bone loss. The current study used novel compounds that target a group of enzymes involved with the epigenetic regulation of gene expression and protein function, histone deacetylases (HDAC), to reduce the catabolism and improve the anabolism of bone material in vitro.

Human osteoclasts were differentiated from peripheral blood monocytes and cultured over a 17 day period. In separate experiments, human osteoblasts were differentiated from human mesenchymal stem cells isolated from bone chips collected during bone marrow donations, and cultured over 21 days. In these assays, cells were exposed to the key inflammatory cytokine involved with the cascade of the abovementioned conditions, tumour necrosis factor-α (TNFα), to represent an inflammatory environment in vitro. Cells were then treated with HDAC inhibitors (HDACi) that target the individual isoforms previously shown to be altered in pathological bone loss conditions, HDAC-1, −2, −5 and −7. Analysis of bone turnover through dentine resorptive measurements and bone mineral deposition analyses were used to quantify the activity of bone cells. Immunohistochemistry of tartrate resistant acid phosphatase (TRAP), WST-assay and automated cell counting was used to assess cell formation, viability and proliferation rates. Real-time quantitative PCR was conducted to identify alterations in the expression of anti- and pro-inflammatory chemokines and cytokines, osteoclastic and osteoblastic factors, in addition to multiplex assays for the quantification of cytokine/chemokine release in cell supernatant in response to HDACi treatments in the presence or absence of TNFα.

TNFα stimulated robust production of pro-inflammatory cytokines and chemokines by PBMCs (IL-1β, TNFα, MCP1 and MIP-1α) both at the mRNA and protein level (p < 0 .05). HDACi that target the isoforms HDAC-1 and −2 in combination significantly suppressed the expression or production of these inflammatory factors with greater efficacy than targeting these HDAC isoforms individually. Suppression of HDAC-5 and −7 had no effect on the inflammatory cascade induced by TNFα in monocytes. During osteoclastic differentiation, TNFα stimulated the size and number of active cells, increasing the bone destruction observed on dentine slices (p < 0 .05). Targeting HDAC-1 and −2 significantly reduced bone resorption through modulation of the expression of RANKL signalling factors (NFATc1, TRAF6, CatK, TRAP, and CTR) and fusion factors (DC-STAMP and β3-integerin). Conversely, the anabolic activity of osteoblasts was preserved with HDACi targeting HDAC-5 and −7, significantly increasing their mineralising capacity in the presence of TNFαthrough enhanced RUNX2, OCN and Coll-1a expression.

These results identify the therapeutic potential of HDACi through epigenetic regulation of cell activity, critical to the processes of inflammatory bone destruction.


A. Hart W. Rainer M. Taunton T. Mabry D. Berry M. Abdel

Patients who are actively smoking at the time of primary total joint arthroplasty (TJA) are at considerably increased risk of perioperative complications. Therefore, strategies to assist patients with smoking cessation before surgery have become routine practice. A secondary benefit is the theoretical catalyst for long-term smoking cessation. However, questions remain as to whether patients actually cease smoking prior to the procedure, and if so, how long this lasts postoperatively.

Our high-volume, academic institution documents self-reported smoking status at each clinic visit (at 6-month intervals), as well as at the time of surgery through a total joint registry. As such, all patients who underwent TJA from 2007 to 2018 were identified and grouped as: non-smokers, smokers (regularly smoking cigarettes within 1 year from surgery), and former smokers (those who quit smoking within a year before surgery). Thereafter, smoking status in the postoperative period was assessed, with special attention to the former smokers in order to see who remained smoke-free.

From the 28,758 primary TJAs identified, 91.3% (26,244) were non-smokers, 7.3% (2,109) were smokers, and 1.4% (405) had quit smoking before surgery. Among patients who quit smoking before surgery, only 38% were still abstinent at 9 years from surgery. Conversely, 24% of smokers at the time of surgery eventually quit and 3.1% of non-smokers started smoking over the same time period.

Despite a concerted effort to help patients stop smoking before TJA, an important proportion (7.3%) are unsuccessful. Among those patients who do manage to stop smoking, only a minority (38%) remain smoke-free after surgery. Compared to current smokers, patients who managed to quit before surgery are more likely to remain smoke-free after surgery. These findings highlight that smoking remains a tremendous challenge in contemporary TJA practices. Additional strategies targeting smoking cessation before after surgery are needed.


V. M. H. Choy R. M. Y. Wong S. K. Chow W. Cheung J.C.Y. Cheng

Age-related fragility fractures are highly correlated with the loss of bone integrity and deteriorated morphology of the osteocytes. Previous studies have reported low-magnitude high-frequency vibration(LMHFV) promotes osteoporotic diaphyseal fracture healing to a greater extent than in age-matched normal fracture healing, yet how osteoporotic fractured bone responds to the mechanical signal has not been explored. As osteocytes are prominent for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance fracture healing in ovariectomized metaphyseal fracture through morphological changes and mineralisation in the osteocyte Lacuno-canalicular Network(LCN). As most osteoporotic fractures occur primarily at the metaphysis, an osteoporotic metaphyseal fracture model was established.

A total of 72 six-month old female Sprague-Dawley rats (n=72) were obtained(animal ethical approval ref: 16–037-MIS). Half of the rats underwent bilateral ovariectomy(OVX) and kept for 3 months for osteoporosis induction. Metaphyseal fracture on left distal femur was created by osteotomy and fixed by a plate. Rats were then randomized to (1) OVX+LMHFV(20 mins/day and 5 days/week, 35Hz, 0.3g), (2) OVX control, (3) SHAM+LMHFV, (4) SHAM control. Assessments of morphological structural changes, functional markers of the LCN(Scanning Electron Microscopy, FITC-Imaris, immunohistochemistry), mineralization status(EDX, dynamic histomorphometry) and healing outcomes(X-ray, microCT, mechanical testing) were performed at week 1, 2 and 6 post-fracture. One‐way ANOVA with post-hoc test was performed. Statistical significance was set at p < 0.05.

Our results showed LMHFV could significantly enhance the morphology of the LCN. There was a 65.3% increase in dendritic branch points(p=0.03) and 93% increase in canalicular length(p=0.019) in the OVX-LMHFV group at week 2 post-fracture. Besides, a similar trend was also observed in the SHAM+LMHFV group, with a 43.4% increase in branch points and 53% increase in canaliculi length at week 2. A significant increase of E11 and DMP1 was observed in the LMHFV groups, indicating the reconstruction of the LCN. The decreasing sclerostin and increasing FGF23 at week 1 represented the active bone formation phase while the gradual increase at week 6 signified the remodelling phase. Furthermore, Ca/P ratio, mineral apposition rate and bone formation rate were all significantly enhanced in the OVX+LMHFV group. The overall bone mineral density in BV was significantly raised in the OVX+LMHFV group at week 2(p=0.043) and SHAM+LMHFV at week 6(p=0.04). Quantitative analysis of microCT showed BV/TV was significantly increased at week 2 in OVX+LMHFV group(p=0.008) and week 6(p=0.001) in both vibration groups. In addition, biomechanical testing revealed that the OVX+LMHFV group had a significantly higher ultimate load(p=0.03) and stiffness(p=0.02) at week 2.

To our best knowledge, this is the first report to illustrate LMHFV could enhance osteocytes' morphology, mineralisation status and healing outcome in a new osteoporotic metaphyseal fracture animal model. Our cumulative data supports that the mechanosensitivity of bone would not impair due to osteoporosis. The revitalized osteocyte LCN and upregulated osteocytic protein markers implied a better connectivity and transduction of signals between osteocytes, which may foster the osteoporotic fracture healing process through an enhanced mineralisation process. This could stimulate further mechanistic investigations with potential translation of LMHFV to our fragility fracture patients.


G. Atkins D. Yang A. Wijenayaka S. Kidd L.B. Solomon N. Gunn D. Findlay

Periprosthetic joint infection (PJI) is a potentially devastating complication of joint replacement surgery. Osteocytes comprise 90–95% of all cells in hard bone tissue, are long-lived and are becoming increasingly recognised as a critical cell type in the regulation of bone and systemic physiology. The purpose of this study was to examine role of these cells in PJI pathophysiology and aetiology, with the rationale that their involvement could contribute to the difficulty in detecting and clearing PJI. This study examined the ability of human osteocytes to become infected by Staphylococcus aureus and the responses of both the host cell and pathogen in this scenario.

Several S. aureus (MRSA) strains were tested for their ability to infect human primary osteocyte-like cells in vitro and human bone samples ex vivo. Bone biopsies were retrieved from patients undergoing revision total hip arthroplasty for either aseptic loosening associated with osteolysis, or for PJI. Retrieved bacterial colony number from cell lysates and colony morphology were determined. Gene expression was measured by microarray/bioinformatics analysis and/or real-time RT-PCR.

Exposure to planktonic S. aureus (approx. 100 CFU/cell) resulted in intracellular infection of human osteocyte-like cells. We found no evidence of increased rates of osteocyte cell death in bacteria exposed cultures. Microarray analysis of osteocyte gene expression 24h following exposure revealed more than 1,500 differentially expressed genes (fold-change more than 2, false discovery rate p < 0.01). The gene expression patterns were consistent with a strong innate immune response and altered functionality of the osteocytes. Consistent patterns of host gene expression were observed between experimentally infected osteocyte-like cultures and human bone, and in PJI patient bone samples. Internalised bacteria switched to the quasi-dormant small colony variant (SCV) form over a period of 5d, and the ensuing infection appeared to reach a stable state. S. aureus infection of viable osteocytes was also identified in bone taken from PJI patients.

We have demonstrated [1] that human osteocytes can become infected by S. aureus and respond robustly by producing immune mediators. The bony location of the infected osteocyte may render them refractory to clearance by immune cells, and osteocytes may therefore be an immune-privileged cell type. The phenotypic switch of S. aureus to SCV, a form less sensitive to most antibiotics and one associated with intracellular survival, suggests that infection of osteocytes may contribute to a chronic disease state. The osteocyte may therefore serve as a reservoir of bacteria for reinfection, perhaps explaining the high prevalence of infections that only become apparent after long periods of time or recur following surgical/medical treatment. Our findings also provide a biological rationale for the recognised need for aggressive bone debridement in the surgical management of PJI.


A. Padki W. Lim D. Cheng T.S. Howe J.S.B. Koh M. A. Png M.H. Tan

Multiple studies have shown that the symptomatology of knee osteoarthritis weakly correlate to radiographic severity of disease. Current literature however does not have much in the way of comparing functional outcomes of those with OA knees with radiographic severity. Our objective was to compare radiographic measurements of OA knees with self-reported functional outcomes and determine if radiographic severity of OA knees correlated with loss of functional ability.

A retrospective review of prospectively collected registry data of 305 patients with osteoarthritis of the knee was collected. The patient's x-rays were reviewed, and radiographic measurements were taken to include medial, lateral and patellofemoral joint space distance measured in millimetres. The Kellgren and Lawrence, and Ahlback classifications of radiographic knee OA were computed. These were correlated with severity of functional limitations was measured using the SF36, Knee society score (KSS) and Oxford knee scores.

Statistical analysis were conducted with SPSS V22.0 statistical software. Demographic characteristics and functional assessments were analysed using one way ANOVA test. Post-hoc test using Tukey HSD and effect size (partial-eta squared η2) was performed if one-way ANOVA was found to be statistically significant. A p-value of 0.05 or less was considered statistically significant.

Pre-operative patient demographics are shown in table 1. Patients in with Grade 2 osteoarthritis were significantly younger than Grade 4 patients (post-hoc p=0.003). There were no statistically significant differences in age between the other Grades, and there were no differences in BMI or gender or operative site between all grades.

There were significant differences in KSS Function scores between Grade 2 and Grade 3 patients (post-hoc p=0.017) and Grade 2 and 4 patients (post-hoc p < 0 .001). Statistically significant differences were also found between Grade 1 and Grade 4 patients for the KSS Knee score (post-hoc p=0.016). There were significant differences in Oxford knee score (post-hoc p=0.026) and SF- Physical Function (post-hoc p < 0 .001) between Grade 2 and Grade 4 patients too.

The effect size η2 for KSS Function, KSS Knee and Oxford knee score was 0.05, 0.06 and 0.33 respectively. When comparing the loss of joint space with the functional scores, there were no statistically significant correlations. Our study show that the radiological severity of knee osteoarthritis based on the two scoring methods was able to correlate with worsening functional scores. Most notably, the differences in KSS function scores correlated strongly between Grade 2 and Grade 3 patients. Of note, there was no correlation between the loss of joint space and the severity of functional limitations across any of the scoring systems. Our study showed that although both the Kellgren and Lawrence and Ahlback radiological grading of Osteoarthritis were able to correlate with worsening functional scores, this was not due to loss of joint space alone and further studies need to be conducted on the other contributors to the scoring system such as osteophytes and subchondral sclerosis.

Our study show that the radiological severity of knee osteoarthritis based on the two scoring methods was able to correlate with worsening functional scores. Most notably, the differences in KSS function scores correlated strongly between Grade 2 and Grade 3 patients. Of note, there was no correlation between the loss of joint space and the severity of functional limitations across any of the scoring systems. Our study showed that although both the Kellgren and Lawrence and Ahlback radiological grading of Osteoarthritis were able to correlate with worsening functional scores, this was not due to loss of joint space alone and further studies need to be conducted on the other contributors to the scoring system such as osteophytes and subchondral sclerosis.

For any figures or tables, please contact authors directly.


A. Paul S. Basu S. Pacelli J. Wang

A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network.

DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential.

The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment.

A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules.


F. Wang Y. Sun H. Ke

Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass.

Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR.

Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment.

Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons.


A. De Pieri S. Korntner Y. Rochev D. Zeugolis N. Galway

Tissue engineering by self-assembly is a technique that consists of growing cells on surfaces made of thermoresponsive polymers, that allow the production of contiguous cell sheets by simply lowering the temperature below the polymer's low critical solution temperature. In this approach cell-cell junctions and deposited extracellular matrix (ECM) remain intact, which provides a better cell localisation at the site of injury. However, these systems lack the possibility to fabricate multi-layered and three-dimensional cell sheets that would better recapitulate native tissues. Moreover, the fabrication of ECM-rich cell sheets would be highly desirable. This limitation could be overcome by inducing macromolecular crowding (MMC) conditions. Herein we venture to fabricate electrospun thermoresponsive nanofibres to sustain the growth and detachment of ECM-rich tissue substitutes in the presence of a MMC microenvironment.

A copolymer of 85% poly-N-isopropylacrylamide and 15% N-tert-butylacrylamide (pNIPAAm/NTBA) were used for all experiments. To create aligned nanofibers, the polymer was electrospun and collected on a mandrel rotating at 2000 rpm. Human adipose derived stem cells (hADSC) were treated with media containing macromolecular crowders to enhance matrix deposition. Cell viability and morphology were assessed, and immunocytochemistry was conducted in order to estimate matrix deposition and composition. Adipogenic, osteogenic and chondrogenic assays were performed both with and without the presence of MMC. Non-invasive cell detachment was enabled by decreasing the temperature of culture to 10 °C for 20 minutes.

The electrospinning process resulted in the production of pNIPAm/NTBA fibres in the diameter range from 1 to 2 µm and an overall alignment of 80%. Cell viability, proliferation and metabolic activity revealed that hADSCs were able to grow on the thermoresponsive scaffold. The cells were able to detach as an intact cell sheet in presence of MMC. Moreover, it was demonstated that MMC, by a volume extrusion effect, enhances Collagen type I deposition, which is one of the main components of the ECM. Histological analysis revealed that in the presence of MMC the cells were able to self-assembled into three dimensional multi-layers. The cells were able to differentiate towards the osteogenic and adipogenic lineage in the presence of MMC. Interestingly we were able to fabricate three-dimensional chondrogenic cell sheet both with and without MMC. Collectively the pNIPAm/NTBA thermoresponsive fibres were able to sustain the growth and the detachment of ECM-rich multi-layered cell sheets.

The pNIPAm/NTBA fibres were able to successfully sustain growth and detachment of ECM-rich tissue equivalents. We believe that replacement, repair and restoration of tissue function can be accomplished best using cells that create their own tissue-specific extracellular matrix with a precision and stoichiometric efficiency still unmatched by man-made devices.


H. Yao J. Xu L. Qin N. Zheng J. Wang K. Wai Ho

Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs.

Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05.

The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group.

In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy.


D.H.K. Chow L. Qin J. Wang K. Yang P. Wan

Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins.

Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT.

At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12.

Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point.


R. Willing P. Soltanmohammadi

Statistical shape modeling (SSM) and statistical density modeling (SDM) are tools capable of describing the main modes of deviation in the shape and density distribution of the shoulder using a set of uncorrelated variables called principal components (PCs). We hypothesize that the first PC of the SDM, which scales overall density up/down, will be inversely correlated with age and will, on average, be greater for males than females. We also hypothesize that there is a correlation between some PCs of shape and density.

SSM and SDM were developed for scapulae and humeri by segmenting surface meshes from computed tomographic images of 75 cadaveric shoulders. Bones were co-registered and defined by the same surface mesh. Volumetric tetrahedral meshes were defined for one of the specimens serving as base meshes for SDM. Base meshes were morphed to each individual bone's surface and superimposed upon the corresponding CT data to determine image intensity in Hounsfield units at each node. Principal component analysis was performed on the exterior shape and internal density distribution of bones. T-tests were performed to find any differences in PC scores between males and females, and Pearson correlation coefficients were calculated for age and PC scores. Finally, correlation coefficients between each of the PCs of the shape and density models were calculated.

For the humerus, the first three PCs of the SDM were significantly correlated with age (ρ = 0.40, −0.46, and 0.36, all p ≤ 0.007). For the scapula, the first and ninth PCs showed such correlation (ρ = −0.31, and −0.32, all p ≤ 0.02). Statistically significant differences due to sex were found for the second to sixth SDM PCs of the humerus, with differences in average PC scores of 1, 1, −0.7, −0.8, and −0.6 standard deviations, respectively, for males relative to females. For the scapula, the second, fifth and seventh SDM PCs were significantly different between males and females, with average PC scores differing by 1.1, 0.7, and −0.6 standard deviations. Finally, for both bones, the first PC of SSM showed a weak but significant correlation with the second PC of the SDM (ρ = 0.47, p < 0.001 for the humerus, and ρ = 0.39, p < 0.001 for the scapula).

The results of this study suggest that age has a significant influence on the first PC of the SDM, associated with scaling the density in the cortical boundary. Moreover, the negative correlation of age with the second PC of the humerus in SDM which mostly influences the thickness of the cortical boundary implies cortical thinning with age. The second PC of both bones differed significantly between males and females, implying that cortical thickness differs between sexes. Also, there was a significant correlation between the size of the bones and the thickness of the cortical boundary. These findings can help guide the designs of population-based prosthesis components.


N. Ashjaee G. Johnston J. Johnston

Distal radius fractures are the most common osteoporotic fractures among women. The treatment of these fractures has been shifting from a traditional non-operative approach to surgery, using volar locking plate (VLP) technology. Surgery, however, is not without risk, complications including failure to restore an anatomic reduction, fracture re-displacement, and tendon rupture. The VLP implant is also marked by bone loss due to stress-shielding related to its high stiffness relative to adjacent bone. Recently, a novel internal, composite-based implant, with a stiffness less than the VLP, was designed to eradicate the shortcomings associated with the VLP implant. It is unclear, however, what effect this less-stiff implant will have upon adjacent bone density distributions long-term. The objective of this study was to evaluate the long-term effects of the two implants (the novel surgical implant and the gold-standard VLP) by using subject-specific finite element (FE) models integrated with an adaptive bone formation/resorption algorithm.

Specimen: One fresh-frozen human forearm specimen (female, age = 84 years old) was imaged using CT and was used to create a subject-specific FE model of the radius.

Finite element modeling: In order to simulate a clinically relevant (unstable) fracture of the distal radius, a wedge of bone was removed from the model, which was approximately 10 mm wide and centered 20 mm proximal to the tip of the radial styloid.

Bone remodeling algorithm: A strain-energy density (SED) based bone remodeling theory was used to account for bone remodeling. With this approach, bone density decreased linearly when SED per bone density was less than 67.5 µJ/g and increased when it was more than 232.5 µJ/g. When it was in the lazy zone (67.5 to 232.5 µJ/g), no changes in density occurred.

Boundary conditions: A 180 N quasi-static force representing the scaphoid, and a 120 N quasi-static force representing the lunate was applied to the radius. The midshaft of the radius was constrained.

FE outcomes: To examine the effects of stress shielding associated with each implant, the long-term changes of bone density within proximal transverse cross-sections of radius were inspected. The regional density analysis focused on three transverse cross-sections. The transverse cross-sections were positioned proximal to the subchondral plate, and were distanced 50 (cross-section A), 57 (cross-section B), and 64 mm (cross-section C) from the subchondral endplate.

For both implants in all three cross-sections, cortical bone was reserved completely at the volar side. On the dorsal side, the cortical bone was completely resorbed in the VLP model. In all cross-sections, the averaged resultant density was higher for the “novel implant”. The difference ranged from 33% (cross-section A) to 36% (cross-section C) in favor of the “novel implant”. On average, the density values of the novel implant were 34% higher in transverse cross-sections (A, B, and C).

This study showed that the novel implant offered higher density distributions compared to the VLP, which suggests that the novel implant may be superior to the VLP in terms of avoiding stress shielding.


N. Ashjaee G. Johnston J. Johnston

Distal radius fracture is one of the most common fractures in older women (∼70,000 cases annually in Canada). Treatment of this fracture has been shifting toward surgery (mainly volar locking plate (VLP) technology), which significantly enhances surgeon's ability to maintain correction. However, current surgical outcomes are far from perfect. There is a need for an implant which maintains the corrected position (reduction), minimizes soft tissue disruption, and is technically easy to perform. A novel internal, composite-based implant was designed to achieve these ends. It is unclear, however, whether this novel implant offers similar fracture fixation as the VLP. As such, the objective of this research was to evaluate the fracture stability (assessed by calculating change in fracture length) of the novel implant and VLP under cyclic fatigue loading.

Specimens: Seven radius specimens derived from older female cadavers (mean = 82.3 years, SD = 11.3 years) were used for the experiment.

Preparation: A standardized dorsal wedge was removed from the cortex. The distance from the proximal and distal transverse osteotomies was 10 mm and was positioned 20 mm proximal to the tip of the radial styloid. The osteotomy removed all load-bearing capabilities of bone, equivalent to a worst-case-scenario for DRF fixation.

Simulated Loading: The proximal end of the radii was potted (fixed) and positioned in a material testing system. To mimic natural loading conditions, hands were cycled between −30°/30° flexion/extension, at 0.5 Hz, for 2000 cycles, while tension load was applied to the tendons (25-N constant force per tendon, 100-N in total).

Mechanical testing outcomes: A position tracking sensor used to measure change in fracture length. This change, as a function of number of cycles, was used to assess implant resistance to fatigue loading.

Statistical Analysis: A paired student t-test was used to compare the change in fracture length. Level of significance was determined as 5% (p < 0.05).

Changes in fracture fracture-length for both the novel implant and plate is shown in Table 1. The paired t-test indicated significant differences between the two groups in terms of change in fracture length (p = 0.026).

The outcome of the novel implant ranged from very stable (change in fracture-length = 0.01 mm) to highly un-stable (2.88 mm). We believe the reason for this variance, at least in part, originates from the surgical procedures. Presumably, given that one very strong stabilization (0.01 mm) and one acceptable stabilization (0.37 mm) was obtained, future research directed towards surgical procedures may improve fracture stability.

For any figures or tables, please contact authors directly.


I. Sallent D. Zeugolis

Adherent cells are known to respond to physical characteristics of their surrounding microenvironment, adapting their cytoskeleton and initiating signaling cascades specific to the type of cue encountered. Scaffolds mimicking native biophysical cues have proven to differentiate stem cells towards tissue-specific lineages and to maintain the phenotype of somatic cells for longer periods of culture time. Although the characteristic anisotropy of tendon tissue is commonly replicated in scaffolds, relevant physical cues such as tendon rigidity or mechanical loading are often neglected. The objective of this study is to use tendons' main extracellular matrix component, collagen type I, to create scaffolds with an anisotropic surface topography and controlled rigidity, in an effort to engineer functional tendon tissue equivalents, with native organization and strength.

Porcine collagen type I in solution was treated with one of the following cross-linkers: glutaraldehyde, genipin or 4-arm polyethylene glycol (4SP). The resulting mixture was poured on micro-grooved (2×2×2 μm) or planar polydimethylsiloxane (PDMS) molds and dried in a laminar flow hood to obtain 5 mg/ml collagen films. Surface topography and elastic modulus of the final scaffolds were analyzed using SEM/AFM and rheometry, respectively. Human tendon cells were isolated from adult tendon tissue and cultured on micro-grooved/planar scaffolds for 4, 7 and 10 days. Cell morphology, collagen III and tenascin C expression were analyzed by immunocytochemistry.

Among the different cross-linkers used, only the treatment with 4SP resulted in scaffolds with a recognizable micro-grooved surface topography. Precise control over the micro-grooved topography and the rigidity of the scaffolds was achieved by cross-linking the collagen with varying concentrations of 4SP at low pH and temperature. The elastic modulus of the scaffolds cross-linked with the highest concentration of 4SP matched the physiological values reported in developing tendons (∼15 kPa). Around eighty percent of the human tendon cells cultured on the cross-linked collagen films aligned in the direction of the anisotropy for 10 days in culture. At 4 days, tenoyctes cultured on micro-grooved substrates presented a significant higher nuclei aspect ratio than tenocytes cultured on planar substrates for all the 4SP concentrations. Synthesis, deposition and alignment of collagen III and tenascin C, two important tenogenic markers, were up regulated selectively in the rigid micro-grooved scaffolds after 7 days in culture. These results highlight the synergistic effect of matrix rigidity and cell alignment on tenogenic cell lineage commitment.

Collectively, this study provides new insights into how collagen can be modulated to create scaffolds with precise imprinted topographies and controlled rigidities. Gene expression analysis and a replicate study with hBMSCs will be carried out to support the first results and to further identify the optimal biophysical conditions for tenogenic cell lineage commitment. This potentially leads to the design of smart implants that not only restore immediate tendon functionality but also provide microscopic cues that drive cellular synthesis of organized tissue-specific matrix.


K. Chua

Osteosarcoma is the most common primary bone tumour worldwide. This disease presents a formidable challenge to the orthopaedic surgeon, with a mortality rate of 30 per cent, even after surgical clearance. Aberrant Wnt signalling has been implicated in the pathogenesis osteoblastic tumours. The objective of this study is 2 fold- to investigate if osteosarcoma does indeed demonstrate aberrant Wnt signaling, and if so, does osteosarcoma respond to a novel Wnt inhibitor(ETC159). This can potentially lead to the development of a new adjuvant treatment modality for osteosarcoma.

A novel Wnt signaling pathway protein antibody (YJ5) was used in immunihistochemistry staining of clinical osteosarcoma samples. A Wnt high osteosarcoma cell line(SJSA-1) was then implanted subcutaneously in a mouse model. These mice were treated with a novel PORCN inhibitor, ETC 159 for a period of 4 weeks in a two-arm randomised control study. The results of treatment were evaulated by clinical outcome parameters as well as immunohstochemistry.

100 per cent of clinical osteosarcoma samples demonstrated increased WLS expression and Wnt protein expression. SJSA-1 showed no significant decrease in tumour volume after 30 days of drug treatment (3070 SD 625 mm3 vs 3480 SD 433 mm3 p= 0.605 and 2060 SD 209 vs 1677 SD 213 mm3 p=0.219 respectively).

Significantly, SJSA-1 demonstrated increased tumour necrosis in the treatment arm(30–60 percent increase across all samples p < 0 .005) Treated tumours also demonstrated markedly less angiogenesis compared to the non treatment arm.

Osteosarcoma demonstrates aberrant Wnt signaling in a large percentage of cases. The use of a novel PORCN inhibitor ETC 159 for the treatment of Osteosarcoma has a marked effect on tumour necrosis. Our results suggest that ETC159 may cause tumour necrosis by inhibiting angiogenesis within the tumour. Further evaluation and understanding of the mechanism of Wnt singaling in regulating tumour pathogenesis may hold the potential for developing a curative therapeutic drug for this deadly disease.


K. Madden B. Petrisor G. Del Fabbro M. Khan J. Joslin M. Bhandari

Brazilian jiu-jitsu (BJJ) is a grappling-based martial art which can lead to injuries both in training and in competitions. There is a paucity of data regarding injuries sustained while training in Brazilian jiu-jitsu both in competitive and non-competitive jiu-jitsu athletes. Our primary objective was to determine the prevalence of injuries sustained during jiu-jitsu training and competition. Our secondary objectives were to describe the types of injuries, and to determine which participant and injury characteristics are associated with desire to discontinue jiu-jitsu following injury, and characteristics are associated with requiring surgery for an injury.

We conducted a survey of all BJJ participants at one club in Hamilton Ontario. We developed a questionnaire using focus groups, key informants and the previous literature. The questionnaire included questions on demographics, injuries in competition and/or training, treatment received, and whether the participant considered discontinuing BJJ following injury. The primary analysis was descriptive. The secondary analysis consisted of unadjusted logistic regression analyses to evaluate the association between selected demographic and injury patterns and those who considered quitting jiu-jitsu as a result of their injuries as a dependent variable.

Seventy BJJ athletes participated in this study (response rate 85%). The majority of respondents were male (90%), over the age of 30 years (58.6%), and junior trainees (white belts [37.2%] or blue belts [42.9%]). Ninety one percent of participants were injured in training and 60% of competitive athletes were injured in competitions. Significantly more injuries were sustained overall (p < 0 .001) for each body region (p∼0.001) in training in comparison to competition. Two-thirds of injured participants required medical attention, with 15% requiring surgery. Participants requiring surgical treatment were six and a half times more likely to consider quitting compared to those requiring other treatments, including no treatment (OR: 6.50, 95% CI: 1.53–27.60). Participants required to take more than four months off training were five and a half times more likely to consider quitting compared to those who took less time off (OR: 5.48, 95% CI: 2.25–13.38).

We identified that nine out of ten jiu-jitsu practitioners surveyed suffered injury while in training and the most severe injuries for the majority of practitioners occurring during training. The most common injuries identified involved the fingers, neck, knee, and shoulder, with the majority of respondents seeking medical or surgical treatment or requiring physiotherapy or rehabilitation. Potential participants in BJJ should be informed regarding significant risk of injury and instructed regarding appropriate precautions and safety protocols. BJJ practitioners and instructors should be especially cognizant of safety during training, where the majority of injuries occur.


H. Al Farii

to determine the extent of Orthobullets use by orthopaedic residents in academic and clinical settings. We also wanted to determine whether its widespread use is the same in various training programs around the world and so we chose to survey two distinct programs without any academic or institutional ties.

An electronic 9 question survey created using SurveyMonkey was sent to residents in two distinct Orthopaedic residency programs, either via text message or by email. The two programs surveyed were the McGill University Orthopaedic Surgery residency program located in Montreal, Canada, and the Oman Medical Specialty Board (OMSB) Orthopaedic Surgery residency program located in Muscat, Oman.

A total of 36 residents, 20 from McGill and 16 from OMSB, responded to the survey request. In both programs, 89% of all the residents surveyed claimed they use Orthobullets at least 4 times per week, and greater than 95% of them use it during call shifts to obtain information rapidly. Regarding the use of Orthobullets in the context of operating theatre case preparation, over 50% of residents claim to use it often while only 25% claim to rarely use it for this purpose. The use of Orthobullets during clinics seemed to be the least popular among residents as 47% claimed they rarely use it. Cumulatively in both programs, more than 80% of residents indicated that they always use Orthobullets in preparation for an exam especially among senior residents. Approximately two thirds of residents have said they completely trust the information provided on Orthobullets, with the remainder indicating that they trust Orthobullets more than 75% of the time. The proportion of residents who indicated that they completely trust Orthobullets was greater in the OMSB group (75%) and among senior trainees. Over 85% of residents discovered Orthobullets through friends and colleagues, and the rest through the program and faculty members.

Our survey results demonstrate the widespread use of Orthobullets, a popular online orthopaedic resource, among orthopaedic residents of all levels. The settings in which Orthobullets was most used were exam preparation and during call shifts. In addition, with the high amount of confidence residence have Orthobullets, it is questionable as to how many are actually aware that its information is not validated. For the time being however, we do not discourage the use of Orthobullets for exam preparation, however, we recommend that programs warn their residents to abstain from using it in their clinical decision-making until it has demonstrated peer-reviewed approval.


T. Niedermair R. Straub S. Schirner R. Seebröker S. Grässel

Previous studies have described an age-dependent distortion of bone microarchitecture for α-CGRP-deficient mice (3). In addition, we observed changes in cell survival and activity of osteoblasts and osteoclasts isolated from young wildtype (WT) mice when stimulated with α-CGRP whereas loss of α-CGRP showed only little effects on bone cell metabolism of cells isolated from young α-CGRP-deficient mice. We assume that aging processes differently affect bone cell metabolism in the absence and presence of α-CGRP. To further explore this hypothesis, we investigated and compared cell metabolism of osteoblasts and bone marrow derived macrophages (BMM)/osteoclast cultures isolated from young (8–12 weeks) and old (9 month) α-CGRP-deficient mice and age matched WT controls.

Isolation/differentiation of bone marrow macrophages (BMM, for 5 days) to osteoclasts and osteoblast-like cells (for 7/14/21 days) from young (8–12 weeks) and old (9 month) female α-CGRP−/− and WT control (both C57Bl/6J) mice according to established protocols. We analyzed cell migration of osteoblast-like cells out of femoral bone chips (crystal violet staining), proliferation (BrdU incorporation) and caspase 3/7-activity (apoptosis rate). Alkaline phosphatase (ALP) activity reflects osteoblast bone formation activity and counting of multinucleated (≥ 3 nuclei), TRAP (tartrate resistant acid phosphatase) stained osteoclasts reflects osteoclast differentiation capacity.

We counted reduced numbers of BMM from young α-CGRP−/− mice after initial seeding compared to young WT controls but we found no differences between old α-CGRP−/− mice and age-matched controls. Total BMM number was higher in old compared to young animals. Migration of osteoblast-like cells out of bone chips was comparable in both, young and old α-CGRP−/− and WT mice, but number of osteoblast-like cells was lower in old compared to young animals. Proliferation of old α-CGRP−/− BMM was higher when compared to age-matched WT whereas proliferation of old α-CGRP−/− osteoblasts after 21 days of osteogenic differentiation was lower. No differences in bone cell proliferation was detected between young α-CGRP−/− and age-machted WT mice. Caspase 3/7 activity of bone cells from young as well as old α-CGRP−/− mice was comparable to age-matched controls. Number of TRAP-positive multinucleated osteoclasts from young α-CGRP−/− mice was by trend higher compared to age-matched WT whereas no difference was observed in osteoclast cultures from old α-CGRP−/− mice and old WT. ALP activity, as a marker for bone formation activity, was comparable in young WT and α-CGRP−/− osteoblasts throughout all time points whereas ALP activity was strongly reduced in old α-CGRP−/− osteoblasts after 21 days of osteogenic differentiation compared to age-matched WT.

Our data indicate that loss of α-CGRP results in a reduction of bone formation rate in older individuals caused by lower proliferation and reduced activity of osteogenic cells but has no profound effects on bone resorption rate. We suggest that the osteopenic bone phenotype described in aged α-CGRP-deficient mice could be due to an increase of dysfunctional matured osteoblasts during aging resulting in impaired bone formation.


B. Gueorguiev M. Hadzhinikolova I. Zderic D. Ciric D. Enchev A. Baltov L. Rusimov G. Richards M. Rashkov

Distal radius fractures have an incidence rate of 17.5% among all fractures. Their treatment in case of comminution, commonly managed by volar locking plates, is still challenging. Variable-angle screw technology could counteract these challenges. Additionally, combined volar and dorsal plate fixation is valuable for treatment of complex fractures at the distal radius. Currently, biomechanical investigation of the competency of supplemental dorsal plating is scant. The aim of this study was to investigate the biomechanical competency of double-plated distal radius fractures in comparison to volar locking plate fixation.

Complex intra-articular distal radius fractures AO/OTA 23-C 2.1 and C 3.1 were created by means of osteotomies, simulating dorsal defect with comminution of the lunate facet in 30 artificial radii, assigned to 3 study groups with 10 specimens in each. The styloid process of each radius was separated from the shaft and the other articular fragments. In group 1, the lunate facet was divided to 3 equally-sized fragments. In contrast, the lunate in group 2 was split in a smaller dorsal and a larger volar fragment, whereas in group 3 was divided in 2 equal fragments. Following fracture reduction, each specimen was first instrumented with a volar locking plate and non-destructive quasi-static biomechanical testing under axial loading was performed in specimen's inclination of 40° flexion, 40° extension and 0° neutral position. Mediolateral radiographs were taken under 100 N loads in flexion and extension, as well as under 150 N loads in neutral position. Subsequently, all biomechanical tests were repeated after supplemental dorsal locking plate fixation of all specimens. Based on machine and radiographic data, stiffness and angular displacement between the shaft and lunate facet were determined.

Stiffness in neutral position (N/mm) without/with dorsal plating was on average 164.3/166, 158.5/222.5 and 181.5/207.6 in groups 1–3. It increased significantly after supplementary dorsal plating in groups 2 and 3.

Predominantly, from biomechanical perspective supplemental dorsal locked plating increases fixation stability of unstable distal radius fractures after volar locked plating. However, its effect depends on the fracture pattern at the distal radius.


A. Badre D. Axford S. Banayan J. Johnson G. J.W. King

Previous biomechanical studies of lateral collateral ligament (LCL) injuries and their surgical repair, reconstruction and rehabilitation have primarily relied on gravity effects with the arm in the varus position. The application of torsional moments to the forearm manually in the laboratory is not reproducible, hence studies to date likely do not represent forces encountered clinically.

The aim of this investigation was to develop a new biomechanical testing model to quantify posterolateral stability of the elbow using an in vitro elbow motion simulator.

Six cadaveric upper extremities were mounted in an elbow motion simulator in the varus position. A threaded screw was then inserted on the dorsal aspect of the proximal ulna and a weight hanger was used to suspend 400g, 600g, and 800g of weight from the screw head to allow torsional moments to be applied to the ulna. An LCL injured (LCLI) model was created by sectioning of the common extensor origin, and the LCL. Ulnohumeral rotation was recorded using an electromagnetic tracking system during simulated active and passive elbow flexion with the forearm pronated and supinated. A repeated measures analysis of variance was performed to compare elbow states (intact, LCLI, and LCLI with 400g, 600g, and 800g of weight).

During active motion, there was a significant difference between different elbow states (P=.001 pronation, P=.0001 supination). Post hoc analysis showed that the addition of weights did not significantly increase the external rotation (ER) of the ulnohumeral articulation (10°±7°, P=.268 400g, 10.5°±7.1°, P=.156 600g, 11°±7.2°, P=.111 800g) compared to the LCLI state (8.4°±6.4°) with the forearm pronated. However, with the forearm supinated, the addition of 800g of weight significantly increased the ER (9.2°±5.9°, P=.038) compared to the LCLI state (5.9°±5.5°) and the addition of 400g and 600g of weights approached significance (8.2°±5.7°, P=.083 400g, 8.7°±5.9°, P=.054 600g).

During passive motion, there was a significant difference between different elbow states (P=.0001 pronation, P=.0001 supination). Post hoc analysis showed that the addition of 600g and 800g but not 400g resulted in a significant increase in ER of the ulnohumeral articulation (9.3°±7.8°, P=.103 400g, 11.2°±6.2°, P=.004 600g, 12.7°±6.8°, P=.006 800g) compared to the LCLI state (3.7°±5.4°) with the forearm pronated. With the forearm supinated, the addition of 400g, 600g, and 800g significantly increased the ER (11.7°±6.7°, P=.031 400g, 13.5°±6.8°, P=.019 600g, 14.9°±6.9°, P=.024 800g) compared to the LCLI state (4.3°±6.6°).

This investigation confirms a novel biomechanical testing model for studying PLRI. Moreover, it demonstrates that the application of even small amounts of torsional moment on the forearm with the arm in the varus position exacerbates the rotational instability seen with the LCL deficient elbow. The effect of torsional loading was significantly worse with the forearm supinated and during passive elbow motion. This new model allows for a more provocative testing of elbow stability after LCL repair or reconstruction. Furthermore, this model will allow for smaller sample sizes to be used while still demonstrating clinically significant differences. Future biomechanical studies evaluating LCL injuries and their repair and rehabilitation should consider using this testing protocol.


O. R. Ayeni A. Shah J. Kay M. Memon R. Coughlin N. Simunovic S. J. Nho

To assess the current literature on suture anchor placement for the purpose of identifying factors that lead to suture anchor perforation and techniques that reduce the likelihood of complications.

Three databases (PubMed, Ovid MEDLINE, EMBASE) were searched, and two reviewers independently screened the resulting literature. Methodological quality of all included papers was assessed using Methodological Index for Non-Randomized Studies criteria and the Cochrane Risk of Bias Assessment tool. Results are presented in a narrative summary fashion using descriptive statistics.

Fourteen studies were included in this review. Four case series (491 patients, 56.6% female, mean age 33.9 years), nine controlled cadaveric/laboratory studies (111 cadaveric hips and 12 sawbones, 42.2% female, mean age 60.0 years), and one randomized controlled trial (37 hips, 55.6% female, mean age 34.2 years) were included. Anterior cortical perforation by suture anchors led to pain and impingement of pelvic neurovascular structures. The anterior acetabular positions (three to four o'clock) had the thinnest bone, smallest rim angles, and highest incidence of articular perforation. Drilling angles from 10° to 20° measured off the coronal plane were acceptable. The mid-anterior (MA) and distal anterolateral (DALA) portals were used successfully, with some studies reporting difficulty placing anchors at anterior locations via the DALA portal. Small-diameter (< 1 .8-mm) suture anchors had a lower in vivo incidence of articular perforation with similar stability and pull-out strength in biomechanical studies.

Suture anchors at anterior acetabular rim positions (3–4 o'clock) should be inserted with caution. Large-diameter (>2.3-mm) suture anchors increase the likelihood of articular perforation without increasing labral stability. Inserting small-diameter (< 1 .8-mm) all-suture suture anchors (ASAs) from 10° to 20° using curved suture anchor drill guides, may increase safe insertion angles from all cutaneous portals. Direct arthroscopic visualization, use of fluoroscopy, distal-proximal insertion, and the use of nitinol wire can help prevent articular violation.


M. Khan B. Alolabi N. Horner D. Stride J. Wang

Ankle fractures are the fourth most common fracture requiring surgical management. The deltoid ligament is considered the primary stabilizer of the ankle against a valgus force. The management of the deltoid ligament in ankle fractures is currently a controversial topic no consensus exists regarding repair in the setting of ankle fractures. The purpose of this systematic review is to examine the role and indications for deltoid ligament repair in ankle fractures.

A systematic database search was conducted with Medline, Pubmed and Embase for relevant studies discussing patients with ankle fractures involving deltoid ligament rupture and repair. The papers were screened independently and in duplicate by two reviewers. Study quality was evaluated using the MINORs criteria. Data extraction included post-operative outcomes, pain, range of motion (ROM), function, medial clear space (MCS), syndesmotic malreduction and complication rates.

Following title, abstract and full text screening, 10 eligible studies published between 1987 and 2017 remained for data extraction (n = 528). The studies include 325 Weber B and 203 Weber C type fractures. Malreduction rate in studies with deltoid ligament repair was 7.4% in comparison to those without repair at 33.3% (p < 0.05). Eleven (4%) of deltoid ligament repair patients returned for re-operation to have implants removed in comparison to eighty three (42%) of those without repair (p < 0.05). There was no significant difference for pain, function, ROM, MCS and complication rates (p < 0.05). The mean operating time of deltoid ligament repair groups was 20 minutes longer than non-repair groups(p < 0.05).

Deltoid ligament repair offers significantly lower syndesmotic malreduction rates and reduced re-operation rates for hardware removal when performed instead of transsyndesmotic screw fixation. When compared to non-repair groups, there are no significant differences in pain, function, ROM, MCS and complication rates. Deltoid ligament repair should be considered for ankle fracture patients with syndesmotic injury, especially those with Weber C. Other alternative syndesmotic fixation methods such as suture button fixation should be explored. A large multi-patient randomized control trial is required to further examine the outcomes of ankle fracture patients with deltoid ligament repair.


M. Khan E. Y. Liu A. H. Hildebrand G. Athwal B. Alolabi N. Horner

Heterotopic Ossification (HO) is a known complication that can arise after total elbow arthroplasty (TEA). In most cases it is asymptomatic, however, in some patients it can limit range of motion and lead to poor outcomes. The objective of this review was to assess and report incidence, risk factors, prophylaxis, and management of HO after TEA.

A systematic search was conducted using MEDLINE, EMBASE, and PubMed to retrieve all relevant studies evaluating occurrence of HO after TEA. The search was performed in duplicate and a quality assessment was performed of all included studies.

A total of 1907 studies were retrieved of which 45 studies were included involving 2256 TEA patients. HO was radiographically present in 10% of patients and was symptomatic in 3%. Less than 1% of patients went on to surgical excision of HO, with outcomes following surgery reported as good or excellent as assessed by range of motion and Mayo Elbow Performance Scores (MEPS). TEA due to ankylosis, primary osteoarthritis, and posttraumatic arthritis are more likely to develop symptomatic HO.

HO is an uncommon complication following TEA with the majority of patients developing HO being asymptomatic and requiring no surgical management. Routine HO prophylaxis for TEA is not supported by the literature. The effectiveness of prophylaxis in high risk patients is uncertain and future studies are required to clarify its usefulness. The strength of these conclusions are limited by inconsistent reporting in the available literature.


M. Khan B. Alolabi N. Horner O. R. Ayeni A. Bedi M. Bhandari

Shoulder impingement is one of the most common non-traumatic upper limb causes of disability in adults. Often resulting in pain and disability, management remains highly debated. This meta-analysis of randomized trials aims to evaluate the efficacy of surgical intervention in the setting of shoulder impingement in comparison to non-operative or sham treatments.

Two reviewers independently screened MEDLINE, EMBASE, PUBMED and Cochrane databases for randomized control trials published from 1946 through to May 19th, 2018. A risk of bias assessment was conducted for all included studies and outcomes were pooled using a random effects model. The primary outcome was improvement in pain up to two years. Secondary outcomes included functional outcome scores reported at the short term (/=2 years). Heterogeneity was assessed using the I2statistic. Functional outcome scores were presented along with minimal clinically important differences to provide clinical context to findings.

Twelve RCT's (n=1062 patients) were included in this review. Eligible patients were a mean age of 48 (SD +/− 4) years with 45% being male gender. The pooled treatment effect of surgical intervention for shoulder impingement did not demonstrate any benefit to surgery with respect to pain relief (mean difference [MD] −0.07, 95% CI −0.40 to 0.26) or short-term functional outcomes (standardized mean difference [SMD] −0.09, 95% confidence interval [CI] −0.27 to 0.08). Surgical intervention did result in a small statistically significant but clinically unimportant improvement in long term functional outcomes (SMD 0.23, 95% CI 0.06 to 0.41).

Evidence suggests surgical intervention has little, if any, benefit for impingement pathology in the middle-aged patient.


M. El-Husseiny B. A. Masri C. P. Duncan D. Garbuz

High complication rates and poor outcomes have been widely reported in patients undergoing revision of large head metal-on-metal arthroplasty. A previous study from our centre showed high rates of dislocation, nerve injury, early cup loosening and pseudotumor recurrence. After noting these issues, we implemented the following changes in surgical protocol in all large head MOM revisions: One: Use of highly porous shells in all cases. Two: Use of largest femoral head possible. Three: Low threshold for use of dual mobility and constrained liners when abductors affected or absent posterior capsule. Four: Use of ceramic head with titanium sleeve in all cases. Five: Partial resection of pseudotumor adjacent to sciatic and femoral nerves.

The purpose of the present study is to compare the new surgical protocol above to our previously reported early complications in this group of patients

We specifically looked at (1) complications including reoperations, (2) radiologic outcomes, and (3) functional outcomes. Complication rates after (Group 1), and before (Group 2) modified surgical protocol were compared using Chi-square test, assuming statistical significance p < 0 .05.

Major complications occurred in 4 (8.3%) of 48 patients who had modified surgical technique, compared to 12 (38%) of 32 revisions prior to modification (p < 0 .05). Two hips of 48 (4.17%) endured dislocations in Group 1, compared to 9 of 32 (28%) in Group 2 (p < 0 .05). Four patients of 48 had repeat revision in Group 1: 2 for recurrence of pseudotumor, 1 for dislocation, and 1 for infection, compared to 6 patients who had 7 repeat revisions of 32 patients in Group 2: 3 for acetabular loosening, 3 for dislocation, and 1 for recurrence of pseudotumor (p=0.1). None of 48 revisions in Group 1 had acetabular loosening, compared to 4 of 32 in Group 2 (p=0.02). Two patients had nerve injury in Group 2, compared to none in Group 1 (p=0.16). The mean WOMAC pain score was 87.1 of 100 and the function score was 88.4 of 100 in Group 1, compared to a mean WOMAC pain score of 78 of 100 (p=0.6) and a function score of 83 of 100 in Group 2 (p=0.8).

Modification of the surgical techniques described in the introduction has resulted in a significant decrease in complications in revision of large head MOM total hips. We continue to use this protocol and recommend it for these difficult cases.


M. El-Husseiny B. A. Masri C.P. Duncan D. Garbuz

Fully constrained liners are used to treat recurrent dislocations or patients at high risk after total hip replacements. However, they can cause significant morbidities including recurrent dislocations, infections, aseptic loosening and fractures. We examine long term results of 111 patients with tripolar constrained components to assess their redislocation and failure rate.

The purpose of this study was to assess survivorship, complications and functional outcomes at a minimum 10 years after the constrained tripolar liners used in our institute.

We retrospectively identified 111 patients who had 113 revision tripolar constrained liners between 1998 and 2008. Eighty-nine were revised due to recurrent dislocations, 11 for pseudotumor with dysfunctional abductors, and 13 for periprosthetic infection with loss of soft tissue stabilizers. All patients had revision hip arthroplasty before the constrained liner was used: 13 after the first revision, 17 after the second, 38 after the third, and 45 had more than 3 revisions. We extracted demographics, implant data, rate of dislocations and incidence of other complications. Kaplan Meier curves were used to assess dislocation and failure for any reason. WOMAC was used to assess quality of life.

At 10 years, the survival free of dislocation was 95.6% (95%CI 90- 98), and at 20 years to 90.6% (95% CI 81- 95.5). Eight patients (7.1%) had dislocations of their constrained liners: 1 patient had simultaneous periprosthetic infection identified at the time of open reduction, and 1 patient sustained stem fracture 3 months prior to the liner dislocation. At 10 years, the survival to any further surgery was 89.4% (95% CI 82–93.8), and at 20 years, this was 82.5 (95% CI 71.9–89.3). Five patients (4.4%) had deep infection: 4 of these had excision arthroplasty due to failure to control infection, while 1 patient was treated successfully with debridement, exchange of mobile components and intravenous antibiotics. Two patients (1.8%) had dissociated rings that required change of liner, ring and head. Two patients (1.8%) had periprosthetic femoral fractures that were treated by revision stems and exchange of constrained liners. The mean WOMAC functional and pain scores were 66.2 and 75.9 of 100, respectively.

Constrained tripolar liners in our institute provided favourable results in the long term for recurrent dislocation hip arthroplasty with dysfunctional hip stabilizers. Infection in these patients can prove to be difficult to treat due to their poor soft tissue conditions from repeated surgeries. Comparing long terms results from other types of constrained liners is essential to evaluate these salvage liners.


M. Comeau-Gauthier M. Tarchala J. Ramirez-GarciaLuna E. Harvey G. Merle

Bone regeneration includes a well-orchestrated series of biological events of bone induction and conduction. Among them, the Wnt/β-catenin signaling pathway is critical for bone regeneration. Being involved in several developmental processes, Wnt/β-catenin signaling must be safely targeted. There are currently only few specific therapeutic agents which are FDA-approved and already entered clinical trials. A published work has shown that Tideglusib, a selective and irreversible small molecule non-ATP-competitive glycogen synthase kinase 3-β(GSK-3β) inhibitor currently in trial for Alzheimer's patients, can promote tooth growth and repair cavities. [1]Despite some differences, they are some similarities between bone and tooth formation and we hypothesise that this new drug could represent a new avenue to stimulate bone healing.

In this work, we locally delivered Tideglusib (GSK3β inhibitor) in the repair of femoral cortical window defects and investigated bone regeneration. A biodegradable FDA-approved collagen sponge was soaked in GSK-3βinhibitor solution or vehicle only (DMSO) and was implanted in 1 × 2 mm unicortical defects created in femora of 35 adult wild-type male mice. Bone defect repair on control and experimental (GSK-3βinhibitor) groups was assessed after 1 week (n=22), 2 weeks (n=24) and 4 weeks (n=24) with microCT and histological analysis foralkaline phosphatase (ALP, osteoblast activity), tartrate resistant acid phosphatase (TRAP, osteoclasts), and immunohistochemistry to confirm the activation of the Wnt/β-catenin pathway.

Our results showed that Tideglusib significantly enhanced cortical bone bridging (20.6 ±2.3) when compared with the control (12.7 ±1.9, p=0.001). Activity of GSK-3β was effectively downregulated at day 7 and 14 resulting in a higher accumulation of active β-catenin at day 14 in experimental group (2.5±0.3) compared to the control (1.1±0.2, p=0.03). Furthermore, the onset of ALP activity appears earlier in the experimental group (day 14, 1.79±0.28), a level of activity never reached at any end-point by the control defects. At 4 weeks treatment, we observed a significant drop in ALP in the experimental group (0.47±0.05) compared to the control (1.01±0.19, p=0.02) and a decrease in osteoclast (experimental=1.32±0.36, control=2.23±0.67, p=0.04).

Local downregulation of GSK-3β by tideglusib during bone defect repair resulted in significant increase in amount of new bone formation. The early upregulation of osteoblast activity is one explanation of bone healing augmentation. This is likely the effect of upregulation of β-catenin following pharmaceutical inhibition of GSK-3β since β-catenin activation is known to positively regulate osteoblasts, once committed to the osteoblast lineage. As a GSK-3β inhibitor, Tideglusib demonstrates a different mechanism of action compared with other GSK-3β antagonists as treatment was started immediately upon injury and did not interfere with precursor cells recruitment and commitment. This indicates that tideglusib could be used at the fracture site during the initial intraoperative internal fixation without the need for further surgery. This safe and FDA-approved drug could be used in prevention of non-union in patients presenting with high risk for fracture-healing complications.


G. Mosley P. Nasser A. Lai D. Charen T. Evashwick-Rogler J. Iatridis

Low back pain is more common in women than men, yet most studies of intervertebral disc (IVD) degeneration do not address sex differences. In humans, there are sex differences in spinal anatomy and degenerative changes in biomechanics, and animal models of chronic pain have demonstrated sex differences in pain transduction. However, there are few studies investigating sex differences in annular puncture IVD degeneration models. IVD puncture is known to result in progressive biomechanical alterations, but whether these IVD changes correlate with pain is unknown. This study used a rat IVD injury model to determine if sex differences exist in mechanical allodynia, biomechanics, and the relationship between them, six weeks after IVD injury.

Procedures were IACUC approved. 24 male & 24 female four-month-old Sprague-Dawley rats underwent a sham or annular puncture injury surgery (n=12 male, 12 female). In injury groups, three lumbar IVDs were each punctured three times with a needle, and injected with tumor necrosis factor-alpha. Mechanical allodynia was tested biweekly using von Frey filaments. Six weeks after IVD injury, rats were euthanized and motion segments were dissected for non-destructive axial tension-compression and torsional rotation biomechanical testing. Two-way ANOVA with Bonferroni corrections identified statistically significant differences (p < 0 .05) and correlations used Pearson's coefficient.

Annular puncture injury induced a significant increase in mechanical allodynia compared to sham in male but not female rats up to six weeks after injury. There was a significant sex effect on both torque range and torsional stiffness, with males exhibiting greater stiffness and torque range than females. Tensile stiffness, compressive stiffness, and axial range of motion showed no sex difference. Males and females showed similar patterns of correlation between variables when sham and injury groups were analyzed together, but correlations were stronger in males. Most correlations were clustered within testing approach: axial biomechanics negatively correlated, torsional biomechanics positively correlated, and von Frey thresholds positively correlated. Surprisingly, mechanical allodynia did not correlate with any biomechanics after injury, and the axial and torsional biomechanics showed little correlation.

This study demonstrates that males and females respond to IVD injury differently. Given the absence of correlation between pain and biomechanics, pain cannot be attributed completely to biomechanical changes. This may explain why spinal fusion surgery, an intervention limited to the spine, has produced inconsistent results and is controversial for patients with low back pain. Thus, in addressing low back pain, we must consider both spinal tissues and the nervous system. Further, the limited correlation between axial and torsional biomechanics indicates that IVD injury may have distinct effects on nucleus pulposus and annulus fibrosus. Biomechanics did not differ between sham and injury at week six, suggesting healing after injury. It remains possible that acute biomechanical changes may initiate chronic pain pathogenesis. We conclude that the observed sex differences demonstrate the need for inclusion of both males and females in IVD injury and pain studies, and suggest that males and females may require different treatments for conditions that appear similar.


J. Peck D. Pincus D. Wasserstein H. Kreder P. Henry

Rotator cuff repair (RCR) can be performed open or arthroscopically, with a recent dramatic increase in the latter. Despite controversy about the preferred technique, there has been an increase in the number of repairs performed arthroscopically. The purpose of this study was, therefore, to compare revision rates following open and arthroscopic RCR repair.

Adult patients undergoing first-time, primary rotator cuff repair in Ontario, Canada (April 2003-March 2014) were identified using physician billing and hospital databases. Patients were followed for a minimum of two and up to 13 years for the primary outcome, revision rotator cuff repair, and secondary outcome, surgical site infection. The intervention considered was open versus arthroscopic technique. Patient factors (age, gender, residence, socioeconomic status, medical comorbidities) and provider factors (surgical volume, hospital setting, worked night before, year of surgery) were recorded. Standardized mean differences were used for covariate comparison. A Cox Proportional Hazards model was used to compare RCR survivorship between the two groups after adjustment for patient and provider factors, generating hazard ratios with 95% confidence intervals (HR, 95% CIs). Censoring occurred on the first of the primary outcome, death, shoulder arthroplasty or arthrodesis, or the end of the follow-up period (March 2016).

A total of 37,255 patients were included. The overall revision RCR rate was 2.9% (1,096 patients) with a median time to revision of 23 months (IQR 12–52). Revision repair was more common in the arthroscopic group in comparison to the open group (3.2% vs 2.6%, NNT 166.7, p=0.004), with an adjusted HR of 0.72 (0.63–0.83 95% CI, p < 0 .0001). The surgical site infection rate was significantly higher in the open group compared with the arthroscopic group (0.5% vs 0.2%, NNT 333.3, p < 0 .001). Patient and provider covariates had no statistically significant effect on revision rates, aside from increasing age (per 10 year increase, HR 0.85, 0.81–0.90 95% CI, p < 0 .0001).

Revision rotator cuff repair is approximately 30% more common in patients undergoing arthroscopic repair, in comparison to open repair, after adjustment. Surgical site infection is uncommon regardless of surgical technique, however, it is slightly more common following open repair. In the setting of an economic healthcare crisis, trends of increasing arthroscopic RCR may demand scrutiny, as the technique is associated with higher revision rates and higher costs.


S.B. Goodman T. Lin J. Pajarinen Z. Yao

Mesenchymal stem cells (MSCs) are capable of forming bone, cartilage and other mesenchymal tissues but are also important modulators of innate and adaptive immune responses. We have capitalized on these important functions to mitigate adverse responses when bone is exposed to pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), or prolonged pro-inflammatory cytokines. Our goal was to optimize osteogenesis and mitigate persistent undesired inflammation by: 1. preconditioning MSCs by short term exposure to lipopolysaccharide (LPS) and Tumor Necrosis Factor alpha (TNF-α), 2. genetic modification of MSCs to overexpress Interleukin 4 (IL-4) either constitutively, or as NFκB-responsive IL-4 over-expression cells, and 3. training the MSCs (innate immune memory) by repeated stimulation with LPS.

In the first experiment, bone marrow MSCs and macrophages were isolated from femurs and tibias of C57BL/6 mice. MSCs (1×104 cells) were seeded in 24-well transwell plates in the bottom chamber with MSC growth medium. MSCs were treated with 20 ng/ml TNF-α and 1–20 μg/ml LPS for three days. Primary macrophages (2 × 103 cells) were seeded to the insert of a separate transwell plate and polarized into the M1 phenotype. At day four, MSCs and macrophages were washed and the inserts with M1 macrophages were moved to the plates containing preconditioned MSCs at the bottom of the well. Co-culture was carried out in MSC growth medium for 24h.

In the second experiment, bone marrow derived macrophages and MSCs were isolated from femora and tibiae of Balb/c male mice. 5×104 macrophages and 1×104 MSCs were seeded in the bottom well of the 24-well transwell plate. The upper chambers were seeded with unmodified MSCs, MSCs preconditioned with 20 ng/ml TNF-α and 20 mg/ml LPS for 3 days, NFκB-IL4 secreting MSCs (all 5×104 cells), or controls without MSCs. Co-culture was carried out in mixed osteogenic-macrophage media with clinically relevant polyethylene or titanium alloy particles.

In the third experiment, bone marrow MSCs and macrophages were collected from femurs and tibias of C57BL/6 male mice. The MSCs were stimulated by LPS, washed out for five days, and re-stimulated by LPS in co-culture with macrophages.

First, preconditioned MSCs enhanced anti-inflammatory M2 macrophage (Arginase 1 and CD206) expression, decreased pro-inflammatory M1 macrophage (TNF-α/IL-1Ra ratio) expression, and increased osteogenic markers (alkaline phosphatase expression and matrix mineralization) in co-culture. Second, NFκB-IL4 secreting MSCs decreased pro-inflammatory M1 (TNF-α), increased anti-inflammatory M2 (Arg1, IL-1ra) expression, and enhanced the expression of osteogenic factors Runx2 and alkaline phosphatase, in the presence of particles, compared to other groups.

Third, LPS-trained MSCs increased anti-inflammatory (Arginase1 and CD206), and decreased the proinflammatory (TNF-α, IL1b, iNOS, and IL6) marker expression in MSC/macrophage co-culture.

Transforming MSCs via the techniques of preconditioning, genetic modification, or training (innate immune memory) can modulate/convert a potentially injurious microenvironment to an anti-inflammatory pro-reconstructive milieu. These effects are highly relevant for bone healing in the presence of adverse stimuli. These concepts using transformed MSCs could also be extended to other organ systems subjected to potentially damaging agents.


D. Pincus B. Ravi D. Wasserstein R. Jenkinson H. Kreder A. Nathens W. Wodchis

Although wait-times for hip fracture surgery have been linked to mortality and are being used as quality-of-care indicators worldwide, controversy exists about the duration of the wait that leads to complications. Our objective was to use new population-based wait-time data to emprically derive an optimal time window in which to conduct hip fracture surgery before the risk of complications increases.

We used health administrative data from Ontario, Canada to identify hip fracture patients between 2009 and 2014. The main exposure was the time from hospital arrival to surgery (in hours). The primary outcome was mortality within 30 days. Secondary outcomes included a composite of mortality or other medical complications (MI, DVT, PE, and pneumonia) also within 30 days. Risk-adjusted cubic splines modeled the probability of each complication according to wait-time. The inflection point (in hours) when complications began to increase was used to define ‘early’ and ‘delayed’ surgery. To evaluate the robustness of this definition, outcomes amongst propensity-score matched early and delayed patients were compared using percent absolute risk differences (% ARDs, with 95% confidence intervals [CIs]).

There were 42,230 patients who met entry criteria. Their mean age was 80.1 (±10.7) and the majority were female (70.5%). The risk of complications modeled by cubic splines consistently increased when wait-times were greater than 24 hours, irrespective of the complication considered. Compared to 13,731 propensity-score matched patients who received surgery earlier, 13,731 patients receiving surgery after 24 hours had a significantly higher risk of 30-day mortality (N=898 versus N=790, % ARD 0.79 [95% CI 0.23 to 1.35], p = .006) and the composite outcome (N=1,680 versus N=1,383, % ARD 2.16 [95% CI 1.43 to 2.89], p < .001). Overall, there were 14,174 patients (33.6%) who received surgery within 24 hours and 28,056 patients (66.4%) who received surgery after 24 hours.

Increased wait-time was associated with a greater risk for 30-day mortality and other complications. The finding that a wait-time of 24 hours represents a threshold defining higher risk may inform existing hip fracture guidelines. Since two-thirds of patients did not receive surgery within this timeframe, performance improvement efforts that reduce wait-times are warranted.


C. Dion B. Lanting J. Howard M. Teeter R. Willing

During revision total knee arthroplasty (rTKA), proximal tibial bone loss is frequently encountered and can result in a less-stable bone-implant fixation. A 3D printed titanium alloy (Ti6Al4V) revision augment that conforms to the irregular shape of the proximal tibia was recently developed. The purpose of this study was to evaluate the fixation stability of rTKA with this augment in comparison to conventional cemented rTKA.

Eleven pairs of thawed fresh-frozen cadaveric tibias (22 tibias) were potted in custom fixtures. Primary total knee arthroplasty (pTKA) surgery was performed on all tibias. Fixation stability testing was conducted using a three-stage eccentric loading protocol. Static eccentric (70% medial/ 30% lateral) loading of 2100 N was applied to the implants before and after subjecting them to 5×103 loading cycles of 700 N at 2 Hz using a joint motion simulator. Bone-implant micromotion was measured using a high-resolution optical system. The pTKA were removed. The proximal tibial bone defect was measured. One tibia from each pair was randomly allocated to the experimental group, and rTKA was performed with a titanium augment printed using selective laser melting. The contralateral side was assigned to the control group (revision with fully cemented stems). The three-stage eccentric loading protocol was used to test the revision TKAs. Independent t-tests were used to compare the micromotion between the two groups.

After revision TKA, the mean micromotion was 23.1μm ± 26.2μm in the control group and 12.9μm ± 22.2μm in the experimental group. There was significantly less micromotion in the experimental group (p= 0.04). Prior to revision surgery, the control and experimental group had no significant difference in primary TKA micromotion (p= 0.19) and tibial bone loss (p= 0.37).

This study suggests that early fixation stability of revision TKA with the novel 3D printed titanium augment is significantly better then the conventional fully cemented rTKA. The early press-fit fixation of the augment is likely sufficient for promoting bony ingrowth of the augment in vivo. Further studies are needed to investigate the long-term in-vivo fixation of the novel 3D printed augment.


R. Selvam T. Lung D. Sadacharam H. Grant G. Wood

Although the impact of sexual difficulties on quality of life in patients with hip osteoarthritis has been documented in previous literature, recent research has shown that surgeons rarely discuss this sensitive topic with patients. The purpose of this study was to develop an educational tool to address common questions that patients may have regarding returning to sexual activity following their total hip arthroplasty (THA).

The study was conducted in two phases. In Phase 1, patients who underwent a THA between 2013–2017 at a single centre were retrospectively identified and sent an anonymous online survey. This survey was aimed at assessing patient-specific concerns regarding whether they would have liked to receive information about returning to sexual activity, what information they would have liked to know and how they would have liked to receive this information. An educational tool was developed based on the findings of Phase 1. In Phase 2, prospective patients who were scheduled for a unilateral or bilateral THA were provided with the educational tool prior to their surgery. A questionnaire was administered to evaluate the effectiveness of this educational tool. Descriptive statistics and chi-squared tests were used for data analysis.

In Phase 1, the overall response rate was 34.7% (n = 58/167). Out of the total respondents, 51.7% indicated an interest in receiving information on when to return to sexual activity following a THA. Patients selected an informational pamphlet as the most desired method of receiving information (p = .044). In Phase 2, the response rate was 54.5% (n = 30/55). Overall, 90% of patients felt that the pamphlet addressed all their concerns, and 93.3% felt they were provided with adequate information on how they could get more information. The pamphlet addressed questions regarding when it was safe to resume sexual activity following a THA, what positions were safe, and the associated risks.

Individuals undergoing a THA are modestly interested in receiving information regarding when to return to sexual activity following their surgery, especially those who are sexually active preoperatively. This educational pamphlet may be useful in routine clinical practice in addressing concerns regarding returning to sexual activity. Understanding patients' goals and expectations for their postoperative course may help surgeons provide a more comprehensive approach to patient care.


J. Chang K. Bhanot S. Grant A. Fecteau M. Camp

The process of obtaining informed consent is an important and complex pursuit, especially within a paediatric setting. Medical governing bodies have stated that the role of the trainee surgeon must be explained to patients and their families during the consent process. Despite this, attitudes and practices of surgeons and their trainees regarding disclosure of the trainee's participation during the consent process has not been reported in the paediatric setting.

Nineteen face-to-face interviews were conducted with surgical trainees and staff surgeons at a tertiary level paediatric hospital in Toronto, Canada. These were transcribed and subsequently thematically coded by three reviewers.

Five main themes were identified from the interviews. 1) Surgeons do not consistently disclose the role of surgical trainees to parents. 2) Surgical trainees are purposefully vague in disclosing their role during the consent discussion without being misleading. 3) Surgeons and surgical trainees believe parents do not fully understand the specific role of surgical trainees. 4) Graduated responsibility is an important aspect of training surgeons. 5) Surgeons feel a responsibility towards both their patients and their trainees. Surgeons don't explicitly inform patients about the involvement of trainees, believing there is a lack of understanding of the training process. Trainee perspectives reflect this, with the view that families are aware of their participation but likely underestimate their role, and suggest that information is kept purposely vague to reduce anxiety.

The majority of surgeons and surgical trainees do not voluntarily disclose the degree of trainee participation in surgery during the informed consent discussion with parents. An open and honest discussion should occur, allowing for parents to make an informed decision regarding their child's care. Further patient education regarding trainees' roles would help develop a more thorough and patient centred informed consent process.


E. Kowalski M. Lamontagne D. Catelli P. Beaulé

The literature indicates that femoroacetabular impingement (FAI) patients do not return to the level of controls (CTRL) following surgery. The purpose of this study was to compare hip biomechanics during stair climbing tasks in FAI patients before and two years after undergoing corrective surgery against healthy controls (CTRL).

A total of 27 participants were included in this study. All participants underwent CT imaging at the local hospital, followed by three-dimensional motion analysis done at the human motion biomechanics laboratory at the local university. Participants who presented a cam deformity >50.5° in the oblique-axial or >60° in the radial planes, respectively, and who had a positive impingement test were placed in the FAI group (n=11, age=34.1±7.4 years, BMI=25.4±2.7 kg/m2). The remaining participants had no cam deformity and negative impingement test and were placed in the CTRL group (n=16, age=33.2±6.4 years, BMI=26.3±3.2 kg/m2). The CTRL group completed the biomechanics protocol once, whereas the FAI group completed the protocol twice, once prior to undergoing corrective surgery for the cam FAI, and the second time at approximately two years following surgery.

At the human motion biomechanics laboratory, participants were outfitted with 45 retroreflective markers placed according to the UOMAM marker set. Participants completed five trials of stairs task on a three step instrumented stair case to measure ground reaction forces while 10 Vicon MX-13 cameras recorded the marker trajectories. Data was processed using Nexus software and divided into stair ascent and stair descent tasks. The trials were imported into custom written MatLab software to extract peak pelvis and hip kinematics and hip kinetic variables. Non-parametric Kruskal-Wallis tests were used to determine significant (p < 0.05) differences between the groups.

No significant differences occurred during the stair descent task between any of the groups. During the stair ascent task, the CTRL group had significantly greater peak hip flexion angle (Pre-Op=58±7.1°, Post-Op=58.1±6.6°, CTRL=64.1±5.1°) and sagittal hip range of motion (ROM) (Pre-Op=56.7±6.7°, Post-Op=56.3±5.5°, CTRL=61.7±4.2°) than both the pre- and post-operative groups. Pre-operatively, the FAI group had significantly less peak hip adduction angle (Pre-Op=2±4.5°, Post-Op=3.4±4.4°, CTRL=5.5±3.7°) and hip frontal ROM (Pre-Op=9.9±3.4°, Post-Op=11.9±5.4°, CTRL=13.4±2.5°) compared to the CTRL group. No significant differences occurred in the kinetic variables.

Our findings are in line with the Rylander and colleagues (2013) who also found that hip sagittal ROM did not improve following corrective surgery. Their study included a mix of cam and pincer-type FAI, and had a mean follow-up of approximately one year. Our cohort included only cam FAI and they had a mean follow-up of approximately two years, indicating with the extra year, the patients still did not show sagittal hip kinematics improvement. In the frontal plane, there was no significant difference between the post-op and the CTRL, indicating that the postoperative FAI reached the level of the CTRLs. This is in line with recent work that indicates a more medialized hip contact force vector following surgery, suggesting better hip stabilization.


M. Bouchard C. Tipton T.M. Lewis V. Bompadre

The Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) is a validated patient reported outcome tool for paediatric foot and ankle conditions. It includes three domains with a maximum score of 100: physical, school and play, and emotional. The purpose of this cross-sectional study is to examine the differences between self-reported child and parent responses of different age groups, genders, and child-parent combinations.

During a ten-month period, paediatric patients aged eight to 16 years and their parents completed the OxAFQ-C during routine clinic visits, providing a total 116 child-parent questionnaire dyads. Demographics and diagnostic information was obtained through medical record review. Parent and child responses in each domain were compared for concordance and for effect of demographic variables on the results. Means and standard deviations for parent and child questionnaires for each domain were reported and compared using a two-sample Wilcoxon rank-sum test. A multivariate regression model was used to assess the correlation between demographic characteristics with domain scores. Absolute agreement between patient and parent questionnaires was assessed using intra-class correlation coefficients (ICC) with a two-way random effects model.

Seventy patients (60.3%) were female and 46 (39.7%) were male, the majority of parent respondents were mothers (85.3%), followed by fathers (11.2%). Mean patient age was 12.4 (± 2.2) years. Higher scores were reported by the child in every domain, though only the emotional domain score showed statistical significance (p = 0.024) between the parent scores. Male children scored significantly higher than females in school and play domain, (mean 82.38 vs 71.13, p = 0.037) and in the emotional domain (means 90.89 vs79.10, p = 0.002). Parents of males scored significantly higher than parents of females only in the emotional domain (means 86.95 vs 72.67, p = 0.001). Children younger than 13 years old scored significantly higher than older children in the emotional domain (p = 0.004).

Child and parent responses for the OxAFQ-C are statistically concordant in the physical and school and play domains. Though children consistently scored themselves higher than their parents did in all domains, only differences in responses for the emotional domain were significant. The level of agreement between parent and child increases with in patients over 13 years of age. Both females and parents of females report lower scores than males and their male parents. Though the use of OxAFQ-C is supported and confirms parent perception of their child's foot and ankle condition is accurate, further research is needed to better understand gender and age differences on response concordance.


M. Bouchard W. Krengel J. Bauer V. Bompadre

The best algorithm, measurements, and criteria for screening children with Down syndrome for upper cervical instability are controversial. Many authors have recommended obtaining flexion and extension views. We noted that patients who require surgical stabilization due to myelopathy or cord compression typically have grossly abnormal radiographic measurements on the neutral upright lateral cervical spine radiograph (NUL). This study was designed to determine whether a full series of cervical spine images including flexion/extension lateral radiographs (FEL) was important to avoid missing upper cervical instability.

This is a retrospective evaluation of cervical spine images obtained between 2006 and 2012 for the purposes of “screening” children with Down syndrome for evidence of instability. The atlanto-dental interval, space available for cord, and basion axial interval were measured on all films. The Weisel-Rothman measurement was made in the FEL series. Clinical outcome of those with abnormal measurements were reviewed. Sensitivity, specificity, positive and negative predictive values of NUL and FEL x-rays for identifying clinically significant cervical spine instability were calculated.

Two-hundred and forty cervical spine series in 213 patients with Down syndrome between the ages of four months and 25 years were reviewed. One hundred and seventy-two children had a NUL view, and 88 of these patients also had FEL views. Only one of 88 patients was found to have an abnormal ADI (≥6mm), SAC (≤14mm), or BAI (>12mm) on an FEL series that did not have an abnormal measurement on the NUL. This patient had no evidence of cord compression or myelopathy.

Obtaining a single NUL x-ray is an efficient method for radiographic screening of cervical spine instability. Further evaluation may be required if abnormal measurements are identified on the NUL x-ray. We also propose new “normal” values for the common radiographic measurements used in assessing risk of cervical spine instability in patients with Down syndrome.


A. Badre S. Banayan D. Axford J. Johnson G. J. W. King

Hinged elbow orthoses (HEO) are often used to allow protected motion of the unstable elbow. However, biomechanical studies have not shown HEO to improve the stability of a lateral collateral ligament (LCL) deficient elbow. This lack of effectiveness may be due to the straight hinge of current HEO designs which do not account for the native carrying angle of the elbow. The aim of this study was to determine the effectiveness of a custom-designed HEO with adjustable valgus angulation on stabilizing the LCL deficient elbow.

Eight cadaveric upper extremities were mounted in an elbow motion simulator in the varus position. An LCL injured (LCLI) model was created by sectioning of the common extensor origin, and the LCL. The adjustable HEO was secured to the arm and its effect with 0°, 10°, and 20° (BR00, BR10, BR20) of valgus angulation was investigated. Varus-valgus angles and ulnohumeral rotations were recorded using an electromagnetic tracking system during simulated active elbow flexion with the forearm pronated and supinated. We examined 5 elbow states, intact, LCLI, BR00, BR10, BR20.

There were significant differences in varus and ER angulation between different elbow states with the forearm both pronated and supinated (P=0 for all). The LCLI state with or without the brace resulted in significant increases in varus angulation and ER of the ulnohumeral articulation compared to the intact state (P 0.05). The difference between each of the brace angles and the LCLI state ranged from 1.1° to 2.4° for varus angulation and 0.5° to 1.6° for ER.

Although there was a trend toward decreasing varus and external rotation angulation of the ulnohumeral articulation with the application of this adjustable HEO, none of the brace angles examined in this biomechanical investigation was able to fully restore the stability of the LCL deficient elbow. This lack of stabilizing effect may be due to the weight of the brace exerting unintentional varus and torsional forces on the unstable elbow. Previous investigations have shown that the varus arm position is highly unstable in the LCL deficient elbow. Our results demonstrate that application of an HEO with an adjustable carrying angle does not sufficiently stabilize the LCL deficient elbow in this highly unstable position and varus arm position should continue to be avoided in the rehabilitation programs of an LCL deficient elbow.


A. Badre M. Perrin K. Albakri N. Suh E. Lalone

Distal radius fractures are the most common upper extremity fracture. The incidence is significantly higher in elderly females with osteoporotic bone. When surgery is indicated, volar locking plates (VLPs) allow for rigid fixation particularly in comminuted fractures with poor bone quality. Although numerous studies have shown the importance of plate placement to avoid soft tissue complications associated with volar plate fixation, there has been little evidence on the anatomic fit of current VLPs. Moreover, the effect of gender differences in distal radius morphology on anatomic fitting of VLPs has not been studied. The aim of this study was to evaluate the gender difference in distal radius morphology and the accuracy of the fit of a current VLP to CT-based distal radius models.

Segmented CT models of ten female (mean age, 89 ± 5 years), and ten male (mean age, 86 ± 4 years) cadaveric wrists were obtained. Micro-CT models of the DePuy-Synthes 4-hole extra-articular (EA) and 8-hole volar column (VC) distal radius VLPs were created. A 3D visualization software was used to simulate appropriate plate placement on to the distal radius models by a fellowship-trained hand surgeon. Volar cortical angles (VCA) of the medial, middle and lateral portion of the distal radius were measured and compared between genders. The accuracy of the fit of the two VLP designs were quantified using the percentage of the watershed line (WSL) overlapped by the plate (WSL overlap), the distance between the WSL and the most distal aspect of the posterior plate (prominence distance) and the percentage of contact between the plate and bone.

There were statistically significant gender differences in medial, middle and lateral VCAs (p=.003 medial, p=.0001 middle, p=.002 lateral). VCA ranged from 28° to 36° in females and from 38° to 45° in males. The WSL overlap did not show statistically significant gender differences (male: 5.9%, female: 13.6%, p=.174). However, the difference in prominence distance between different genders approached statistical significance (male: 3.5mm, female: 2.6mm, p=.087). Contact mapping between the plate and bone did not demonstrate a perfect contact in any of our specimens. Thus, contact measurements were categorized into 0.1mm, 0.2mm, and 0.3mm threshold contacts. There were no statistically significant gender differences in any of the threshold categories (0.1mm: p=.84, 0.2mm: p=.97, 0.3mm: p=.99).

Our results confirm that there are gender differences in distal radius morphology. Current plate designs incorporate a VCA of 25° which does not match the native VCA of the distal radius in males or females. Although the difference in prominence distance approached statistical significance, there were no statistically significant gender differences in the WSL overlap or the contact threshold values. This lack of statistical significance may be related to the small sample size. This study proposes novel methods of assessing the anatomic fit of current VLPs in a 3D CT-based model that may be used in future studies with a larger sample size. Moreover, this study demonstrated the importance of considering gender differences in distal radius morphology in the design of future generations of implants.


G. Thompson C. Hardesty J. Son-Hing J. Ina P. Tripi C. Poe-Kochert

Intrathecal morphine (IM) is a common adjunct in paediatric spinal deformity surgery. We previously demonstrated with idiopathic scoliosis it provides safe and effective analgesia in the immediate postoperative period. This study represents our 25 year experience with IM in all diagnostic groups.

Our prospective Pediatric Orthopaedic Spine Database (1993–2018) was reviewed to identify all patients undergoing spinal deformity surgery who received IM and who did not. Patients 21 years of age or less who had a posterior spinal fusion (PSF) with segmental spinal instrumentation (SSI), and received 9–19 mcg/kg (up to 1 mg) of IM were included. Early onset scoliosis surgical patients were excluded. We assessed demographics, pain scores, time to first dose of opioids, diagnoses, surgical time, paediatric intensive care unit (PICU) admission and IM complications (respiratory depression, pruritus, nausea/ vomiting).

There were 986 patients who met inclusion criteria. This included 760 patients who received IM and 226 who did not. IM was not used for short procedures (< 3 hrs), respiratory concerns, unsuccessful access of intrathecal space, paraplegia, and anesthesiologist decision. Both groups followed the same strict perioperative care path. The patients were divided into 5 diagnostic groups (IM / non IM patients): idiopathic (578/28), neuromuscular (100/151), syndromic (36/17), and congenital scoliosis (32/21) and kyphosis (14/9). Females predominated over males (697/289). The first dose of opioids after surgery was delayed for a mean of 10.6 hrs in IM group compared to 2.3 hrs in the non-IM group (p=0.001). The postoperative pain scores were significantly lower in the IM groups in the Post Anesthesia Care Unite (p=0.001). Only 17 IM patients (2%) were admitted to the PICU for observation secondary to respiratory depression, none required re-intubation. None of the IM group were re-intubated. Forty-nine patients (6%) experienced pruritus in the IM group compared to 4 of 226 patients (2%) in the non IM group. There were 169 patients (22%) of the IM patients and 21 patients (9%) of the non IM had nausea and vomiting postoperatively. Three patients (0.39%) had a dural leak from the administration of IM but did not require surgical repair. There were no other perioperative complications related to the use of IM. There were no significant group differences.

Pre-incision IM is a safe and effective adjunct for pain management in all diagnostic groups undergoing spinal surgery. The IM patients had lower pain scores and a longer time to first administration of post-operative opioids. Although there is an increased frequency of respiratory depression, pruritus, and nausea/vomiting in the IM group, there were no serious complications.


A. Jhirad G. Wohl

In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis.

All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area.

Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia.

This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss.


S. Kooner C. Hewison S. Sridharan J. Lui G. Matthewson H. Johal M. Clark

It is estimated that a quarter to half of all hospital waste is produced in the operating room. Recycling of surgical waste in the perioperative setting is largely underutilized, despite the fact that many of the materials being discarded can be potentially recycled safely and easily. Given this mounting waste production, recycling programs have become increasingly popular. Therefore, the primary objective of this study is assess the effect of these recent eco-friendly polices by determining the amount of waste and recycling produced in the pre-operative and operative time period for several orthopaedic subspecialties.

Surgical cases were prospectively chosen and assigned to an orthopaedic subspecialty category, which included trauma, arthroplasty, sports, foot and ankle, upper extremity, and paediatrics. The preoperative phase began with the opening of the surgical case carts and concluded with the end of skin preparation. The intraoperative period began after skin preparation was complete, and concluded after the operating room was cleaned. At the end of the preoperative period all surgical waste was weighed and divided into recyclables and non-recyclables. Following the intraoperative period, surgical waste was divided into recyclables, non-recyclables, linens, and biohazardous waste streams. All bags were weighed in a standardized fashion using a portable hand held scale. The primary outcome of interest was the amount of recyclable waste produced per case. Secondary outcomes included the amount of nonrecyclable, biohazardous and total waste produced during the same time intervals. Statistical analysis was then completed using (ANOVA) to detect differences between specialties.

This study included 55 procedures collected over a 1-month period at two hospitals from October 2017 to November 2017. A total of 341 kg of waste was collected with a mean mass of 6.2 kg per case. In terms of primary outcomes, arthroplasty surgery produced a significantly greater amount of recyclable waste per case in the preoperative (2327.9 g)and intraoperative (938.6 g)period. It also produced the greatest amount of total recyclable waste per case, resulting in a significantly greater ratio of waste recycling per case then nearly all other specialties in the preoperative (86.2%) and intraoperative period (14.5%). In terms of secondary outcomes, arthroplasty surgery similarly produced a significantly greater amount of nonrecyclable waste per case then all other specialties (5823.6 g), the majority of which was produced during the intraoperative period (5512.9 g). Arthroplasty surgery also produced a significantly greater amount of biohazardous waste then all other specialties (409.3 g). The majority of surgical waste was produced in the intraoperative period compared to the preoperative period. In the preoperative period an average of 74.4% of waste was recyclable, compared to 7.6% of waste produced during the intraoperative period. In total, the average amount of waste recycled per case was 25.6%. Biohazardous waste only constituted 1.8% of the total waste mass.

Orthopaedic surgery is a significant source of waste production in our hospital system. Among orthopaedic subspecialties, arthroplasty is one of the largest waste producers, but also has the highest potential for recycling of materials. Effective OR recycling programs can significantly reduce our ecological footprint by diverting waste from landfills. In particular, the preoperative period has significant potential for landfill diversion as our study showed that nearly three quarters of all waste in this period can be effectively recycled.


J. Fletcher V. Neumann L. Wenzel G. Richards B. Gueorguiev H. Gill M. Whitehouse E. Preatoni

Nearly a quarter of screws cause damage during insertion by stripping the bone, reducing pullout strength by over 80%. Studies assessing surgically achieved tightness have predominately shown that variations between individual surgeons can lead to underpowered investigations. Further to the variables that have been previously explored, several basic aspects related to tightening screws have not been evaluated with regards to how they affect screw insertion. This study aims to identify the achieved tightness for several variables, firstly to better understand factors related to achieving optimal intraoperative screw purchase and secondly to establish improved methodologies for future studies.

Two torque screwdrivers were used consecutively by two orthopaedic surgeons to insert 60 cortical, non-locking, stainless-steel screws of 3.5 mm diameter through a 3.5 mm plate, into custom-made 4 mm thick 20 PCF sheets of Sawbone, mounted on a custom-made jig. Screws were inserted to optimal tightness subjectively chosen by each surgeon. The jig was attached to a bench for vertical screw insertion, before a further 60 screws were inserted using the first torque screwdriver with the jig mounted vertically, enabling horizontal screw insertion. Following the decision to use the first screwdriver to insert the remaining screws in the vertical position for the other variables, the following test parameters were assessed with 60 screws inserted per surgeon: without gloves, double surgical gloves, single surgical gloves, non-sterile nitrile gloves and, with and then without augmented feedback (using digitally displayed real-time achieved torque). For all tests, except when augmented feedback was used, the surgeon was blinded to the insertion torque. Once the stopping torque was reached, screws were tightened until the stripping torque was found, this being used to calculate tightness (stopping/stripping torque ratio). Screws were recorded to have stripped the material if the stopping torque was greater than the stripping torque. Following tests of normality, Mann-Whitney-U comparisons were performed between and combining both surgeons for each variable, with Bonferroni corrections for multiple comparisons.

There was no significant (p=0.29) difference in the achieved tightness between different torque screw drivers nor different jig positions (p=0.53). The use of any gloves led to significant (p < 0 .001) increases in achieved tightness compared to not using gloves for one surgeon but made no difference for the other (p=0.38–0.74). Using augmented feedback was found to virtually eliminate stripping. For one surgeon average tightness increased significantly (p < 0 .001) when torque values were displayed from 55 to 75%, whilst for the other, this was associated with significantly decreases (p < 0 .001), 72 to 57%, both surgeons returned to their pre-augmentation tightness when it was removed.

Individual techniques make a considerable difference to the impact from some variables involved when inserting screws. However, the orientation of screws insertion and the type of screwdriver did not affect achieved screw tightness. Using visual feedback reduces rates of stripping and investigating ways to incorporate this into clinical use are recommended. Further work is underway into the effect of other variables such as bone density and cortical thickness.


J. Fletcher M. Windolf B. Gueorguiev G. Richards P. Varga

Proximal humeral fractures occur frequently, with fixed angle locking plates often being used for their treatment. However, the failure rate of this fixation is high, ranging between 10 and 35%. Numerous variables are thought to affect the performance of the fixation used, including the length and configuration of screws used and the plate position. However, there is currently limited quantitative evidence to support concepts for optimal fixation. The variations in surgical techniques and human anatomy make biomechanical testing prohibitive for such investigations. Therefore, a finite element osteosynthesis test kit has been developed and validated - SystemFix. The aim of this study was to quantify the effect of variations in screw length, configuration and plate position on predicted failure risk of PHILOS plate fixation for unstable proximal humerus fractures using the test kit.

Twenty-six low-density humerus models were selected and osteotomized to create a malreduced unstable three-part fracture AO/OTA 11-B3.2 with medial comminution which was virtually fixed with the PHILOS plate. In turn, four different screw lengths, twelve different screw configurations and five plate positions were simulated. Each time, three physiological loading cases were modelled, with an established finite element analysis methodology utilized to evaluate average peri-screw bone strain, this measure has been previously demonstrated to predict experimental fatigue fixation failure.

All three core variables lead to significant differences in peri-screw strain magnitudes, i.e. predicted failure risk. With screw length, shortening of 4 mm in all screw lengths (the distance of the screw tips to the joint surface increasing from 4 mm to 8 mm) significantly (p < 0 .001) increased the risk of failure. In the lowest density bone, every additional screw reduced failure risk compared to the four-screw construct, whereas in more dense bone, once the sixth screw was inserted, no further significant benefit was seen (p=0.40). Screw configurations not including calcar screws, also demonstrated significant (p < 0 .001) increased risk of failure. Finally, more proximal plate positioning, compared to the suggested operative technique, was associated with reduced the predicted failure risk, especially in constructs using calcar screws, and distal positioning increased failure risk.

Optimal fixation constructs were found when placing screws 4 mm from the joint surface, in configurations including calcar screws, in plates located more proximally, as these factors were associated with the greatest reduction in predicted fixation failure in 3-part unstable proximal humeral fractures. These results may help to provide practical recommendations on the implant usage for improved primary implant stability and may lead to better healing outcomes for osteoporotic proximal fracture patients. Whilst prospective clinical confirmation is required, using this validated computational tool kit enables the discovery of findings otherwise hidden by the variation and prohibitive costs of appropriately powered biomechanical studies using human samples.


J. Busse D. Heels-Ansdell S. Makosso-Kallyth B. Petrisor K. Jeray T. Tufescu G. Y. Laflamme P. McKay R. McCabe Y. Le Manach M. Bhandari

Persistent post-surgical pain and associated disability are common after a traumatic fracture repair. Preliminary evidence suggests that patients' beliefs and perceptions may influence their prognosis. We sought to explore this association.

We used data from the Fluid Lavage of Open Wounds trial to determine, in 1560 open fracture patients undergoing surgical repair, the association between Somatic PreOccupation and Coping (captured by the SPOC questionnaire) and recovery at 1 year.

Of the 1218 open fracture patients with complete data available for analysis, 813 (66.7%) reported moderate to extreme pain at 1 yr. The addition of SPOC scores to an adjusted regression model to predict persistent pain improved the concordance statistic from 0.66 to 0.74, and found the greatest risk was associated with high SPOC scores [odds ratio: 5.63, 99% confidence interval (CI): 3.59–8.84, absolute risk increase 40.6%, 99% CI: 30.8%, 48.6%]. Thirty-eight per cent (484 of 1277) reported moderate to extreme pain interference at 1 yr. The addition of SPOC scores to an adjusted regression model to predict pain interference improved the concordance statistic from 0.66 to 0.75, and the greatest risk was associated with high SPOC scores (odds ratio: 6.06, 99% CI: 3.97–9.25, absolute risk increase: 18.3%, 95% CI: 11.7%, 26.7%). In our adjusted multivariable regression models, SPOC scores at 6 weeks post-surgery accounted for 10% of the variation in short form-12 physical component summary scores and 14% of short form-12 mental component summary scores at 1 yr.

Amongst patients undergoing surgical repair of open extremity fractures, high SPOC questionnaire scores at 6 weeks post-surgery were predictive of persistent pain, reduced quality of life, and pain interference at 1 yr.


J. Busse Y. Chang S. Kennedy P. Hong N. Chow R. Couban L. Wang R. McCabe P. Bieling

Persistent post-surgical pain affects 10%-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent postsurgical pain and physical impairment.

We searched Medline, PsycINFO, CINAHL, and the Cochrane Central Registry of Controlled Trials to identify relevant RCTs, in any language, from inception of each database to September 1, 2016. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. We pooled treatment effects of perioperative psychotherapy on similar outcomes across eligible trials, focusing on intention-to-treat analysis. We used random effects models to perform all meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence.

Our search found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) −1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) −1.56 to −0.55 cm, risk difference (RD) for achieving no more than mild pain (3 cm or less) 14%, 95% CI 8–21%] and physical impairment [WMD −9.87% on the 0–100% Oswestry Disability Index, 95% CI −13.42 to −6.32%, RD for achieving no more than mild disability (20% or less) 21%, 95% CI 13–29%].

Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. High quality evidence shows no significant effects of perioperative education or psychological support on persistent post-surgical pain or physical impairment compared with usual care. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome.


C. Bolton W. Abuzaiter A. Hallan S. Cartledge D. Warchuk M. Woolfrey

Topically applied vancomycin powder has been used to decrease surgical site infection rates in spinal surgeries, however, randomized controlled trials in total joint arthroplasty are lacking. Application of vancomycin powder topically in the surgical site has theoretical benefit including high local concentration. In this study, we aimed to determine whether intra-operative topical antibiotics are safe and effective as IV antibiotics in preventing post-surgical site infections.

The trial was a randomized controlled, double blind, non-inferiority study. All patients received pre-operative IV antibiotics (cefazolin or vancomycin) within 60 minutes of skin incision. The controlled group received two doses of post-operative IV antibiotics (two grams cefazolin or one gram vancomycin if cefazolin allergy). In the treatment group, the orthopaedic surgeon applied one gram vancomycin powder (500mg applied directly on the prosthesis and 500mg applied above the closed joint capsule). The incidence of acute surgical site infection was defined as positive deep cultures within 42 days of procedure. All patients with evidence of infection underwent joint aspiration for culture.

After one year, 80 patients had received the topical vancomycin treatment and 85 patients had received the standard treatment. In the topical vancomycin group versus the controlled group, the average age was 64 vs 66, average BMI was 35.7 vs 33.4, number of males 33 vs 29, number of females 47 vs 56, and diabetic patients 16 vs 13. The number of infections in the topical vancomycin group was three vs zero in the post-operative IV antibiotic treatment group.

One Tailed Z-test P Value = 0.03. This study statistically demonstrated inferiority of topical vancomycin in comparison to the use of IV antibiotics post-operatively in preventing deep wound infections in TKA. The authors would caution against the sole use of intra-operative vancomycin in TKA to prevent post-operative infection.


A. Hoffer D. Banaszek H. Broekhuyse J. Potter

Distal radius fractures are among the most common fractures seen in the emergency department. Closed reduction can provide definitive management when acceptable radiographic parameters are met. Repeated attempts of closed reduction are often performed to improve the alignment and avoid operative management. However, multiple reduction attempts may worsen dorsal comminution and lead to eventual loss of reduction, resulting in no demonstrable benefit. We hypothesize that compared to one closed reduction attempt, repeated closed reduction of extra-articular, dorsally angulated, displaced distal radius fractures has a low success rate in the prevention of operative fixation and improvement of radiographic parameters.

Initial and post reduction radiographs for all distal radius fractures managed at Vancouver General Hospital between 2015 and 2018 were reviewed. Inclusion criteria were based on the AO fracture classification and included types 23-A2.1, 23-A2.2 and 23-A3. Exclusion criteria included age less than 18, intra-articular involvement with more than two millimeters of displacement, volar or dorsal Barton fractures, fracture-dislocations, open fractures and volar angulation of the distal segment. Distal radius fractures that met study criteria and underwent two or more attempts of closed reduction were matched by age and gender with fractures that underwent one closed reduction. Radiographic parameters including radial height and inclination, ulnar variance and volar tilt were compared between groups.

Sixty-eight distal radius fractures that met study criteria and underwent multiple closed reduction attempts were identified. A repeated closed reduction initially improved the radial height (p = 0.03) and volar tilt (p < 0.001). However, by six to eight weeks the improvement in radial height had been lost (p = 0.001). Comparison of radiographic parameters between the single reduction and multiple reduction groups revealed no difference in any of the radiographic parameters at one week of follow up. By six to eight weeks, the single reduction group had greater radial height (p = 0.01) ulnar variance (p = 0.05) and volar tilt (p = 0.02) compared to the multiple reduction group. With respect to definitive management, 38% of patients who underwent a repeated closed reduction subsequently received surgery, compared to 13% in the single reduction group (p = 0.001).

Repeated closed reduction of extra-articular, dorsally angulated, displaced distal radius fractures did not improve alignment compared to a single closed reduction and was associated with increased frequency of surgical fixation. The benefit of repeating a closed reduction should be carefully considered when managing distal radius fractures of this nature.


S. J.Dixon K. Beaucage M. Nagao G. Lajoie M. Veras D. Fournier D. Holdsworth C. Bailey J. Hammond C. Séguin

Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1-KO) exhibit progressive ectopic calcification of spinal tissues, including the annulus fibrosus (AF) of intervertebral discs (J Bone Miner Res 28:1135–49, 2013, Bone 90:37–49, 2016). Our purpose was twofold: (1) to compare ectopic calcifications in ENT1-KO mice with those in human DISH, and (2) to investigate the molecular pathways underlying pathological calcification in ENT1-KO mice.

Studies were performed with age-matched wild-type (WT) and ENT1-KO mice, as well as human cadaveric vertebral columns meeting radiographic criteria for DISH. Mouse and human specimens were scanned using high-resolution, micro-computed tomography (micro-CT). As well, some samples were decalcified and processed for histological assessment. Calcified lesions in selected specimens were examined using energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). To investigate molecular changes associated with ectopic calcification, we isolated AF tissue from thoracic intervertebral discs of WT and ENT1-KO mice. Tissues were then subjected to transcriptomic and proteomic analyses.

Micro-CT of ENT1-KO mice revealed ectopic calcification of spinal tissues, first appearing in the cervical-thoracic region and extending caudally with advancing age. Histological examination of calcified lesions in mice revealed accumulations of amorphous, eosinophilic, acellular material in paraspinal ligaments and entheses, intervertebral discs, mandibular symphysis, and sternocostal articulations. There was no evidence of inflammation associated with these lesions. EDX of calcified lesions revealed a high content of calcium and phosphorus in a molar ratio of ∼1.6, with hydroxyapatite detected by micro-XRD. Ten human cadaveric spines (three females and seven males, mean age 81 years) that met radiographic criteria for DISH were analysed in detail by micro-CT. Remarkable heterogeneity in the density and morphology of ectopic calcifications was observed. Analyses of calcifications by EDX and XRD again yielded a calcium/phosphorus ratio of ∼1.6 and a crystalline diffraction pattern matching hydroxyapatite. Histological examination of human lesions revealed regions of mature ossification and other areas of irregular amorphous calcification that resembled lesions in ENT1-KO mice. Microarray analysis of AF tissue from WT and ENT1-KO mice showed extensive dysregulation of transcription in affected tissues. Cell cycle-associated transcripts were the most affected, including the E2f family of transcription factors and proliferating cell nuclear antigen. In addition, expression of genes involved in the regulation of mineralization and bone development were dysregulated. Proteomic analyses confirmed transcriptomic changes and revealed alterations in known modulators of biomineralization such as matrix Gla-protein.

Many of the characteristics of ectopic calcification in ENT1-KO mice resemble those of DISH in humans. Human lesions were found to be heterogeneous with regions of pathological ossification and amorphous calcification, the latter resembling lesions in the mouse model. Our studies of the molecular events associated with ectopic calcification in ENT1-KO mice may provide insights into the pathogenesis of DISH in humans. ENT1-KO mice may also be useful for evaluating therapeutics for the prevention of ectopic calcification in DISH and related disorders.


J. Woodmass E. Wagner K. Borque M. Chang K. Welp J.J.P. Warner

Chronic massive irreparable rotator cuff tears represent a treatment challenge and the optimal surgical technique remains controversial. Superior capsular reconstruction (SCR) has been proposed as a means to provide superior stability to the glenohumeral joint, thus facilitating restoration of shoulder function. However, despite the growing use of SCR there is a paucity of data evaluating the outcomes when performed using a dermal allograft. The purpose of this study was to (1) report the overall survival rate (reoperation and clinical failure) of SCR (2) evaluate for pre-operative factors predicting reoperation and clinical failure.

From January 1, 2015 to November 31, 2017, 65 patients were diagnosed with irreparable rotator cuff tears and consented for a superior capsular reconstruction. These surgeries were performed by 6 surgeons, all fellowship trained in either sports or shoulder and elbow fellowships. Outcomes were graded as excellent, satisfactory, or unsatisfactory using the modified Neer scale. An unsatisfactory result was defined as a clinical “failure”. The Kaplan-Meier survival models were created to analyze reoperation-free and failure-free survival for the entire group. The reconstruction was performed using a dermal allograft. There were 31 patients excluded due to insufficient follow-up (< 6 months), leaving 34 included in this study. The mean follow-up was 12 months (range, 6–23). The average number of prior surgeries was 0.91 (range, 0–5), with 52.9% of patients receiving a prior rotator cuff repair and 38.2% of patients with a prior non-rotator cuff arthroscopy procedure.

The one and two-year survival-free of surgery was 64% and 44% and the one and two-year survival free of failure was 34% and 16% following SCR, respectively. For the patients that underwent a reoperation, 62.5% (n= 5/8) underwent reverse shoulder replacements, 25% (n= 2/8) latissimus dorsi tendon transfers, and 12.5% (n= 1/8) a diagnostic arthroscopy. The average period between the primary and revision surgery was 10.2 months (range, 2.1–18.5). All but two patients (75%, n= 6/8) had at least one surgery prior to the SCR. There were 14/34 (41.2%) patients who experienced pain, weakness, and restricted range of motion. These patients were defined as clinical failures with an unsatisfactory grading on Neer's criteria. Previous surgery predicted reoperation (80% vs 43%, p = 0.03). Female gender predicted clinical failure (100% vs 43%, p < 0 .01).

Superior Capsule Reconstruction performed for large to massive rotator cuff tears has a high rate of persistent pain and limited function leading to clinical failure in 65% (n= 22/34) of patients. The rate of failure is increased in revision cases, female gender and increased Goutallier fatty infiltration of the infraspinatus. Narrowed indications are recommended given the surgical complexity and high rate of early failure.


T. Chen M. Camp A. Tchoukanov U. Narayanan J.M. Lee

Technology within medicine has great potential to bring about more accessible, efficient, and a higher quality delivery of care. Paediatric supracondylar fractures are the most common elbow fracture in children and at our institution often have high rates of unnecessary long term clinical follow-up, leading to an inefficient use of healthcare and patient resources. This study aims to evaluate patient and clinical factors that significantly predict necessity for further clinical visits following closed reduction and percutaneous pinning.

A total of 246 children who underwent closed reduction and percutaneous pinning following supracondylar humerus fractures were prospectively enrolled over a two year period. Patient demographics, perioperative course, goniometric measurements, functional outcome measures, clinical assessment and decision making for further follow up were assessed. Categorical and continuous variables were analyzed and screened for significance via bivariate regression. Significant covariates were used to develop a predictive model through multivariate logistical regression. A probability cut-off was determined on the Receiver Operator Characteristic (ROC) curve using the Youden index to maximize sensitivity and specificity. The regression model performance was then prospectively tested against 22 patients in a blind comparison to evaluate accuracy.

246 paediatrics patients were collected, with 29 cases requiring further follow up past the three month visit. Significant predictive factors for follow up were residual nerve palsy (p < 0 .001) and maximum active flexion angle of injured elbow (p < 0 .001). Insignificant factors included other goniometric measures, subjective evaluations, and functional outcomes scores. The probability of requiring further clinical follow up at the 3 month post-op point can be estimated with the equation: logit(follow-up) = 11.319 + 5.518(nerve palsy) − 0.108(maximum active flexion). Goodness of fit of the model was verified with Nagelkerke R2 = 0.574 and Hosmer & Lemeshow chi-square (p = 0.739). Area Under Curve of the ROC curve was C = 0.919 (SE = 0.035, 95% CI 0.850 – 0.988). Using Youden's Index, a cut-off for probability of follow up was set at 0.094 with the overall sensitivity and specificity maximized to 86.2% and 88% respectively. Using this model and cohort, 194 three month clinic visits would have been deemed medically unnecessary. Preliminary blind prospective testing against the 22 patient cohort demonstrates a model sensitivity and specificity at 100% and 75% respectively, correctly deeming 15 visits unnecessary.

Virtual clinics and automated clinical decision making can improve healthcare inefficiencies, unclog clinic wait times, and ultimately enhance quality of care delivery. Our regression model is highly accurate in determining medical necessity for physician examination at the three month visit following supracondylar fracture closed reduction and percutaneous pinning. When applied correctly, there is potential for significant reductions in health care expenditures and in the economic burden on patient families by removing unnecessary visits. In light of positive patient and family receptiveness toward technology, our promising findings and predictive model may pave the way for remote health care delivery, virtual clinics, and automated clinical decision making.


T. Chen J.M. Lee A. Tchoukanov U. Narayanan M. Camp

Paediatric supracondylar fractures are the most common elbow fracture in children, and is associated with an 11% incidence of neurologic injury. The goal of this study is to investigate the natural history and outcome of motor nerve recovery following closed reduction and percutaneous pinning of this injury.

A total of 246 children who underwent closed reduction and percutaneous pinning following supracondylar humerus fractures were prospectively enrolled over a two year period. Patient demographics (age, weight), Gartland fracture classification, and associated traumatic neurologic injury were collected and analyzed with descriptive statistics. Patients with neurologic palsies were separated based on nerve injury distribution, and followed long term to monitor for neurologic recovery at set time points for follow up.

Of the 246 patient cohort, 46 patients (18.6%) sustained a motor nerve palsy (Group 1) and 200 patients (82.4%) did not (Group 2) following elbow injury. Forty three cases involved one nerve palsy, and three cases involved two nerve palsies. No differences were found between patient age (Group 1 – 6.6 years old, Group 2 – 6.2 years old, p = 0.11) or weight (Group 1 – 24.3kg, Group 2 – 24.5kg, p = 0.44). A significantly higher proportion of Gartland type III and IV injuries were found in those with nerve palsies (Group 1 – 93.5%, Group 2 – 59%, p < 0 .001). Thirty four Anterior Interosseous Nerve (AIN) palsies were observed, of which 22 (64.7%) made a full recovery by three month. Refractory AIN injuries requiring longer than three month recovered on average 6.8 months post injury. Ten Posterior Interosseous Nerve (PIN) palsies occurred, of which four (40%) made full recovery at three month. Refractory PIN injuries requiring longer than three month recovered on average 8.4 months post injury. Six ulnar nerve motor palsies occurred, of which zero (0%) made full recovery at three month. Ulnar nerve injuries recovered on average 5.8 months post injury.

Neurologic injury occurs significantly higher in Gartland type III and IV paediatric supracondylar fractures. AIN palsies remain the most common, with an expected 65% chance of full recovery by three month. 40% of all PIN palsies are expected to fully recover by three month. Ulnar motor nerve palsies were slowest to recover at 0% by the three month mark, and had an average recovery time of approximately 5.8 months. Our study findings provide further evidence for setting clinical and parental expectations following neurologic injury in paediatric supracondylar elbow fractures.


L. Shefelbine M. Bouchard V. Bompadre

C-reactive protein (CRP) level is used at our tertiary paediatric hospital in the diagnosis, management, and discharge evaluation of paediatric septic arthritis patients. The purpose of this study was to evaluate the efficacy of a discharge criterion of CRP less than 2 mg/dL for patients with septic arthritis in preventing reoperation and readmission. We also aimed to identify other risk factors of treatment failure.

Patients diagnosed with septic arthritis between January 1, 2007 and December 31, 2017 were reviewed retrospectively. The diagnosis of septic arthritis was made based on clinical presentation, laboratory results and the finding of purulent material on joint aspiration or the isolation of a bacterial pathogen from joint fluid or tissue. Bivariate tests of associations between patient or infection factors and readmission and reoperation were performed. Quantitative variables were analyzed using Mann-Whitney tests and categorical variables were analyzed using Chi-square tests.

One hundred eighty-three children were included in the study. Seven (3.8%) were readmitted after hospital discharge for further management, including additional advanced imaging, and IV antibiotics. Six (85.7%) of the readmitted patients underwent reoperation. Mean CRP values on presentation were similar between the two groups: 8.26 mg/dL (± 7.87) in the single-admission group and 7.94 mg/dL (± 11.26) in the readmission group (p = 0.430). Mean CRP on discharge for single-admission patients was 1.71 mg/dL (± 1.07), while it was 1.96 mg/dL (± 1.19) for the readmission group (p = 0.664), with a range of < 0 .8 to 6.5 mg/dL and a median of 1.5 mg/dL for the two groups combined. A total of 48 children (25.9%) had CRP values greater than the recommended 2 mg/dL at discharge, though only three of these patients (6.2%) were later readmitted. The only common variable in the readmitted children was either a negative culture result at time of discharge or atypical causative bacteria.

CRP values are useful in monitoring treatment efficacy but not as reliable as a discharge criterion to prevent readmission or reoperation in children with septic arthritis. We recommend determining discharge readiness on the basis of clinical improvement and downtrending CRP values. There was a higher risk of readmission in children with an atypical causative bacteria and when culture results were negative at discharge. Close monitoring of these patients after discharge is suggested to identify signs of persistent infection.


V. Teissier M. Hamadouche M. Bensidhoum H. Petite

Polyethylene wear-debris induced inflammatory osteolysis is known as the main cause of aseptic loosening and long term revision total hip arthroplasty. Although recent reports suggest that antioxidant impregnated ultra-high molecular weight polyethylene (UHMWPE) wear-debris have reduce the osteolytic potential in vivo when compared to virgin UHMWPE, little is known about if and/or how PE rate of oxidation affects osteolysis in vivo. We hypothesized that oxidized UHMWPE particles would cause more inflammatory osteolysis in a murine calvarial bone model when compared to virgin UHMWPE.

Male C57BL/6 eight weeks old received equal amount of particulate debris overlaying the calvarium of (n=12/group): sham treatment (no particles), 2mg (6,75×107 particles/mg) of endotoxin-free UHMWPE particles (PE) or of endotoxin-free highly oxidized-UHMWPE (OX) particles. In vivo osteolysis was assessed using high resolution micro-CT and inflammation with L-012 probe dependent luminescence. At day 10, calvarial bone was examined using high resolution micro-CT, histomorphometric, immunohistochemistry analyses and qRT-PCR to assess OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP genes expression using the protocol defined by individual TaqManTM Gene Expression Assays Protocol (Applied Biosystems).

In vivo inflammation was significantly higher in the OX (1.60E+06 ± 8.28E+05 photons/s/cm2) versus PE (8.48E+05 ± 3.67E+05) group (p=0.01). Although there was a statistically significant difference between sham (−0.27% ± 2.55%) and implanted (PE: −9.7% ± 1.97%, and OX: − 8.38% ± 1.98%) groups with regards to bone resorption (p=0.02), this difference was not significant between OX and PE (p = 0.14). There was no significant difference between groups regarding PCR analyses for OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP (p = 0.6, 0.7, 0.1, 0.6, 0.3, 0.4, 0.7 respectively). Bone volume density was significantly decreased in PE (13.3%±1.2%) and OX (12.2%±1.2%) groups when compared to sham (15%±0.9%) (p < 0 .05). Histomorphometric analyses showed a significantly decreased Bone Thickness/Tissue Thickness ratio in the implanted group (0.41±0.01 mm and 0.43±0.01 mm) compared to sham group (0.69± 0.01) (p < 0 .001). However, there were no significant difference between OX and PE (p = 0.2).

Our findings suggest that oxidized UHMWPE particles display increased inflammatory potential. Results were not significant regarding in vivo or ex vivo osteolysis. As antioxidant-diffused UHMWPE induce less inflammation activity in vivo, the mechanism by which they cause reduced osteolysis requires further investigation.


D. Petruccelli T. Wood M. J. Winemaker J. De Beer

Overall, hip and knee total joint replacement (TJR) patients experience marked benefit, with reported satisfaction rates of greater than 80% with regard to pain relief and improved function. However, many patients experience ‘nuisance’ symptoms, an annoyance which may cause discomfort, which can negatively impact postoperative satisfaction. The purpose of this study was to evaluate the prevalence of nuisance symptoms among TJR patients and impact on overall patient satisfaction.

A prospective survey study to assess type and prevalence of primary hip/knee TJR related nuisance symptoms, and impact on patient satisfaction at six-months to one-year post-TJR was conducted. The survey was administered over a one-year period at one academic arthroplasty centre. Survey questions tapped occurrence of commonly reported nuisance symptoms (e.g. localized pain, swelling, stability, incision appearance/numbness, stiffness, clicking/noise, ability to perform activities of daily living), and impact of the symptom on overall hip/knee satisfaction rated on a 10-point visual analogue scale (VAS), (0=no impact, 10=to a great extent). Overall VAS satisfaction with TJR was also assessed (0=not at all satisfied, 10=extremely satisfied). Survey responses were analysed using descriptive statistics.

The sample comprised of 974 primary TJR patients, including 590 knees (61%) and 384 hips 39%) who underwent surgery over a one-year period. Among knees, the most commonly reported nuisance symptoms and associated impact to satisfaction per mean VAS scores included: difficulty kneeling (78.2%, mean VAS 4.3, ±3.3), limited ability to run or jump (71.6%, VAS 3.3, ±3.3), numbness around incision (46.3%, VAS 3.8, ±3.3), clicking/noise from the knee (44.2%, VAS 2.7, ±2.7) and stiffness (43.3%, 3.3, ±2.7) following knee arthroplasty. Overall, 88.1% of knee patients surveyed experienced at least one self-reported nuisance symptom at one-year postoperative. Mean overall VAS satisfaction with knee TJR was reported as 9/10 (±1.7). Among hip TJR patients, the most commonly reported nuisance symptoms and associated impact to satisfaction per VAS scores were: limited ability to run or jump (68.6%, VAS 3.4, ±3.4), muscular pain in the thigh (44.8%, VAS 3 ±2.7), limp when walking (37.6%, VAS 4.1, ±3.2), hip stiffness (31%, VAS 3.1, ±2.4), and new or worsening low back pain (24.3%, VAS 2.9, ±2.5). Overall, 93.7% of patients experienced at least one self-reported nuisance symptom at one-year postoperative. Mean overall VAS satisfaction following total hip arthroplasty at one year was reported as 8.9/10 (±1.7).

Nuisance symptoms following primary total hip and knee arthroplasty are very common. Despite the high prevalence of such symptoms, impact of individual symptoms to overall TJR satisfaction is minimal and overall TJR patient satisfaction remains high. Careful preoperative counselling regarding the prevalence of such symptoms is prudent and will help establish realistic expectations following primary hip and knee TJR.


D. Petruccelli T. Wood C. Kabali M. J. Winemaker J. De Beer

The relationship between pain catastrophizing and emotional disorders including anxiety and depression in patients with hip or knee osteoarthritis undergoing total joint replacement (TJR) is an emerging area of study. The purpose of this study was to examine the association between catastrophizing, anxiety, depression and postoperative pain and functional outcomes following primary TJR.

A prospective cohort study of preoperative TJR patients at one academic arthroplasty centre over a one-year period was conducted. Pain catastrophizing was assessed using the Pain Catastrophizing Scale (PCS), and anxiety/depression using the Hospital Anxiety and Depression Scale (HADS-A, HADS-D) at preoperative assessment. Postoperative outcomes at one-year included patient perceived level of hip/knee pain using a visual analogue scale (VAS), subjective perception of function using the Oxford Hip/Knee Scores, and objective function using the Knee Society Score (KSS) and Harris Hip scores (HHS). Median regression was used to assess pattern of relationship between preoperative PCS clinically relevant catastrophizing (CRC), abnormal HADS-A, abnormal HADS-D and postoperative outcomes at one-year. Median difference and 95% confidence interval (CI) were reported. T-tests were performed to determine mean differences in postoperative outcomes among patients with PCS CRC, abnormal HADS-A, and abnormal HADS-D scores versus those with normal scores at preoperative assessment. P-values less than 0.05 were considered statistically significant.

The sample included 463 TJR patients (178 hips, 285 knees). Both the PCS-rumination CRC sub-domain (median difference 1, 95% CI 0.31–1.69, p=0.005) and abnormal HADS-A (median difference 1, 95% CI 0.36–1.64, p=0.002) were identified as significant predictors of one-year VAS pain. PCS-magnification CRC sub-domain was also identified as a significant predictor of KSS/HHS at one-year (median difference 1.3, 95% CI −5.23–0.11, p=0.041). Preoperative VAS pain, Oxford and HHS/KSS scores were significantly inferior in patients who had CRC PCS, abnormal HADS-A, and abnormal HADS-D scores compared to patients with normal scores. At one-year, PCS CRC patients also had significantly inferior VAS pain (p=0.001), Oxford (p < 0 .0001) and KSS/HHS (p=0.025). Abnormal HADS-A and HADS-D patients experienced significantly inferior postoperative VAS pain (HADS-A p=0.025, HADS-D p=0.030), Oxford (HADS-A p=0.001, HADS-D p=0.030), but no difference in KSS/HHS (HADS-A = 0.069, HADS-D = 0.071) compared to patients with normal PCS/HADS scores. However, patients with CRC PCS experienced significantly greater improvement in preoperative to postoperative VAS pain (p < 0 .0001), Oxford (p=0.003) and HHS/KSS (p < 0 .0001). Similarly, patients with abnormal HADS scores showed significant improvement in preoperative to one-year postoperative change scores, as compared to normal patients in VAS pain (HADS-A p=0.011, HADS-D p=0.024), KSS/HHS (HADS-A p=0.017, HADS-D p=0.031), but not Oxford (HADS-A p=0.299, HADS-D p=0.558).

Patients who are anxious, depressed or who pain catastrophize have worse preoperative function and pain. Postoperatively, pain and functional outcomes are also inferior in such patients, however they do experience a significantly greater improvement in outcomes. Furthermore, it appears that rumination and anxiety traits predict pain levels postoperatively. Although these patients report higher levels of pain postoperatively, as compared to preoperative, great improvement can be expected following hip and knee TJR.


J. Wolfstadt D. Pincus H. Kreder D. Wasserstein

Socially deprived patients face significant barriers that reduce their access to care, presenting unique challenges for orthopaedic surgeons. Few studies have investigated the outcomes of surgical fracture care among those socially deprived, despite the increased incidence of fractures, and the inequality of care received in this group. The purpose of this study was to evaluate whether social deprivation impacted the complications and subsequent management of marginalized/homeless patients following ankle fracture surgery.

In this retrospective, population-based cohort study involving 202 hospitals in Ontario, Canada, we evaluated 45,444 patients who underwent open reduction internal fixation for an ankle fracture performed by 710 different surgeons between January 1, 1994, and December 31, 2011. Socioeconomic deprivation was measured for each patient according to their residential location by using the “deprivation” component of the Ontario Marginalization Index (ON-MARG). Multivariable logistic regression models were used to assess the relationship between deprivation and shorter-term outcomes within 1 year (implant removal, repeat ORIF, irrigation and debridement due to infection, and amputation). Multivariable cox proportional hazards (CPH) models were used to assess longer-term outcomes up to 20 years (ankle fusion and ankle arthroplasty).

A higher level of deprivation was associated with an increased risk of I&D (quintile 5 vs. quintile 1: odds ratio (OR) 2.14, 95% confidence interval (CI), 1.25–3.67, p = 0.0054) and amputation (quintile 4 vs. quintile 1: OR 3.56, 95% CI 1.01–12.4, p = 0.0466). It was more common for less deprived patients to have their hardware removed compared to more deprived patients (quintile 5 vs. quintile 1: OR 0.822, 95% CI 0.76–0.888, p < 0.0001). There was no correlation between marginalization and subsequent revision ORIF, ankle fusion, or ankle arthroplasty.

Marginalized patients are at a significantly increased risk of infection and amputation following operatively treated ankle fractures. However, these complications are still extremely rare among this group. Thus, socioeconomic deprivation should not prohibit marginalized patients from receiving operative management for unstable ankle fractures.


M. Camp A. W. Howard D. Westacott J. Kennedy

Distal femoral physeal fractures can cause of growth distrurbance which frequently requires further surgical intervention. The aim of this study was to determine if tibial tuberosity ossification at the time of injury can predict further surgery in patients who have sustained a physeal fracture of the distal femur.

We retrospectively investigated all patients who had operative treatment for a distal femoral physeal fracture at a paediatric level one trauma center over a 17 year period. Logistic regression analysis was performed investigating associations between the need for further surgery to treat growth disturbance and tibial tuberosity ossification, age, Salter Harris grade, mode of fixation or mechanism of injury.

74 patients met the inclusion criteria. There were 57 boys (77%) and 17 girls (23%). The average age at time of injury was 13.1 years (range 2.-17.1 years). Following fixation, 30 patients (41%) underwent further surgery to treat growth disturbance. Absence of tibial tuberosity fusion to the metaphysis was significantly associated with need for further surgery (p = < 0 .001). Odds of requiring secondary surgery after tibial tuberosity fusion to metaphysis posteriorly (compared with not fused) were 0.12, 95% CI (0.04, 0.34). The estimate of effect of tibial tuberosity ossification on reoperation rates did not vary when adjusted for gender, mechanism, fixation and Salter Harris grade. When accounting for age, the odds of further operation if the tibial tuberosity is fused to the metaphysis posteriorly (compared with not fused) were 0.28, 95% CI (0.08, 0.94).

Tibial tuberosity ossification stage at time of injury is a predictor of further surgery to treat growth disturbance in paediatric distal femoral fractures. Children with distal femoral physeal fractures whose tibial tuberosity was not fused to the metaphysis posteriorly were 8.3 times more likely to require further surgery.


C. Hardesty M. Janas

A growing number of children are being implanted with magnetically controlled growing rods. Some also have baclofen pumps, a device that delivers a neuromodulating medication using a magnet. There has been no previous testing to determine if the External Remote Controller (ERC) would stall the baclofen pump during magnetic rod lengthening, a potentially life-threatening event.

Two baclofen pumps, 20 mL and 40 mL, were placed in varying proximity to the ERC while the magnetic field was generated. The speed (dose) of the baclofen pump, the distance from the ERC, the length of time the ERC was run, the position of the pump in relationship to the magnetic field, and the presence or absence of a stall were recorded.

To stall a baclofen pump, the ERC needed to be running continuously for at least 30 mm of lengthening (about 3 minutes). The pump would not stall if it was more than 1 cm away from the ERC, even if the ERC generated a field for 3 minutes. The speed of the pump did not affect the instance of a motor stall. The pump was more likely to stall if it was positioned in front of or behind the magnetic field, as opposed to the center of the field.

Baclofen pumps are always more than 1 cm away from the magnetic rods when both are implanted in a child. The typical lengthening interval is under 10 mm, much less than what was required to stall a baclofen pump. The ERC is highly unlikely to stall a baclofen pump during a magnetic rod lengthening, making a life-threatening event almost impossible.


S. Bzovsky H. Johal D. Axelrod S. Sprague B. Petrisor K. Jeray D. Heels-Ansdell M. Bhandari

Despite long-standing dogma, a clear relationship between the timing of surgical irrigation and the development of subsequent deep infection has not been established in the literature. Traditionally, irrigation of an open fracture has been recommended within six-hours of injury based on animal studies from the 1970s, however the clinical basis for this remains unclear. Using data from a multi-centre randomized controlled trial of 2,447 open fracture patients, the primary objective of this secondary analysis is to determine if a relationship exists between timing of wound irrigation (within six hours of injury versus beyond six hours) and subsequent reoperation rate for infection or healing complications within one year for patients with open extremity fractures requiring surgical treatment.

To adjust for the influence of patient and injury characteristics on the timing of irrigation, a propensity score was developed from the data set. Propensity-adjusted regression allowed for a matched cohort analysis within the study population to determine if early irrigation put patients independently at risk for reoperation, while controlling for confounding factors. Results were reported as odds ratios (ORs), 95% Confidence Intervals (CIs), and p-values. All analyses were conducted using STATA 14 (StataCorp LP, College Station, TX, USA).

Two thousand, two hundred eighty-six of 2,447 patients randomized to the trial from 41 orthopaedic trauma centers across five countries had complete data regarding time to irrigation. Prior to matching, the patients managed with early irrigation had a higher proportion requiring reoperation for infection or healing complications (17% versus 12.8%, p=0.02), however this does not account for selection bias of more severe injuries preferentially being treated earlier. After the propensity score-matching algorithm was applied, there were 373 matched pairs of patients available for comparison. In the matched cohort, reoperation rates did not differ between early and late groups (16.1% vs 16.6%, p=0.84). When accounting for propensity matching in a logistic regression analysis, early irrigation was not associated with reoperation (OR 0.93, 95% CI 0.62 to 1.40, p=0.73).

When accounting for other variables, late irrigation does not independently increase risk of reoperation.


M. Xu M. G. Johnson M. Zarrabian

There is evidence that preoperative physical fitness impacts surgical outcomes, specifically preceding abdominal, cardiovascular and spine surgery. To our knowledge, there are no papers on self-reported exercise frequency as a predictor of cervical spine surgery outcomes. Our objectives were to quantify self-report of exercise frequency in cervical spine surgery patients, and to elucidate if self-reported exercise prior to surgery confers less pain, improved health state and/or less disability post-surgery.

We performed a retrospective review of prospectively collected data from the Canadian Spine Outcomes and Research Network (CSORN) Database from the time of its inception. Inclusion criteria specified all elective cervical surgery patients over 18 years old with degenerative pathology who proceeded to surgery and completed the pre- and post-operative outcomes measures up to 24 months post surgery (n=460). Outcome measures were visual analog scales (VAS) for neck and arm pain, Neck Disability Index (NDI), and EuroQOL score at baseline and 3, 12 and 24 months post-op. Exercise frequency was self-reported as “none” (n=212) versus “some” (n=248). These groups were further categorized into “none due to physical limitations”, “none” (not due to physical limitations), those to exercised “once or less per week” and those that exercised “twice or more per week”. Student's t-tests were used to compare the mean scores of the outcome measures, and analysis of variance for subgroup comparisons, with results considered significant at p < 0 .05.

At baseline, 56% of total patients reported exercise prior to surgery, of which 73% reported doing so twice or more per week. Of the 44% reporting no exercise, 74% could not exercise due to physical limitations. Those who reported “some” exercise had more favorable VAS neck and arm pain scores pre-operatively (neck: 5.55 vs 6.11, p < 0 .001) (arm: 5.69 vs 6.04, p=0.011), but no difference at 3 and 24 months post-operatively. Significantly lower NDI scores and higher EuroQOL Index scores were seen in the exercise group compared to the no exercise group pre-operatively (NDI: 39 vs 48, p < 0 .001) (EuroQOL: 0.60 vs 0.50 p < 0 .001) as well as at 3, 12, and 24 months post-op (NDI: 24 vs 31, p=0.007) (EuroQOL: 0.75 vs 0.68, p=0.001). Further subgroup analysis demonstrated that compared to the “no exercise due to physical limitation” group, the “twice or more” exercise group showed favorable NDI and EuroQOL scores up to 24 months post-op (NDI: 24.32 vs 32.33, p=0.001) (EuroQOL: 0.76 vs 0.66, p=0.001), whereas the “once or less times per week” group no longer demonstrated any significant difference at 24 months (NDI: 28.79 vs 32.33, p=1) (EuroQOL: 0.73 vs 0.66, p=0.269).

Self-reported exercise prior to cervical spine surgery does not predict improved long-term neck and arm pain at 2 years post-op. However, self-reported exercise does demonstrate less disability and improved health state at baseline and up to 2 years post-op and this relationship is dose dependent.


D. Tushinski M. J. Winemaker J. De Beer D. Petruccelli D. Mertz C. Main E. Piccirillo

Prosthetic joint infections (PJI) are amongst the most feared postoperative complication of total joint replacement (TJR). PJIs are associated with significant morbidity ranging from functional impairment to amputation. Staphylococcus aureus (S. aureus) is one of the most common causative organisms involved in PJI. More than one quarter of the general population are S. aureus carriers, and carrier status has been shown to increase the risk of developing surgical site infections including PJIs. Decolonization of S. aureus carriers prior to surgery has demonstrated promising results in general surgery, however, solid evidence supporting decolonization in orthopaedic patients is lacking. We aimed to seek further evidence supporting pre-operative screening and S. aureus decolonization in patients undergoing primary or revision hip and knee TJR.

A quasi-experimental quality improvement study was conducted to compare the 5-year baseline rates of deep PJIs to a one-year screening and decolonization intervention period. All consecutive patients who underwent primary or revision TJR at one tertiary care hospital in Hamilton, ON, Canada were included in both study periods.

Nasal and throat screening for S. aureus carriage of all eligible TJR patients in the preoperative clinic was implemented as standard of care. Patients who tested positive were contacted and provided with details on the S. aureus decolonization protocol. Decolonization included a standardized treatment protocol of 2% intranasal mupirocin twice daily for five days prior to surgery date (excluding day of surgery), and chlorhexidine gluconate wipes (2%) to be used once daily for 4 days prior to surgery date and on the morning of surgery. Regardless of the colonization status at the visit in the preoperative clinic, all patients were re-swabbed on the day of surgery.

Primary outcome of interest was the rate of deep PJI as per CDC/NHSN at one-year postoperative follow-up. Secondary outcomes included rate of deep PJIs due to S. aureus, adherence to the decolonization protocol, proportion of S. aureus carriers successfully decolonized, and the proportion of patients deemed as non-carriers following preoperative swab subsequently identified as carriers on the day of surgery. A total of 8,505 patients were included in the 5-year control group, and 1,883 during the intervention period, of which 424 (22.5%) were identified as S. aureus carriers.

The deep PJI rate was similar in the two groups, 0.4% (7/1,883) in the intervention group and 0.5% (42/8,505) in the control group (OR 0.75, 95%CI 0.34–1.67, p=0.58). More importantly, we found a significant reduction in PJI due to S. aureus to only one case in the intervention period (0.05%) as compared to 29 cases (0.3%) in the historic control (OR 0.15, 95%CI 0.004–0.94, p=0.0376).

We found a significant reduction in PJIs due to S. aureus by decolonizing S. aureus carriers prior to surgery. However, no significant difference in overall infection rates was observed. In conclusion, routine implementation of active screening for S. aureus and decolonization of carriers before TJR is feasible and helps to reduce PJI due to S. aureus.


J. Tynedal S. M. Heard L. A. Hiemstra G. M.L. Buchko S. Kerslake

The purpose of this study was to compare intra-operative, clinical, functional, and patient-reported outcomes following revision anterior cruciate ligament reconstruction (ACL-R) with a matched cohort of primary isolated ACL-R. A secondary purpose was to compare patient-reported outcomes within revision ACL-R based on intra-operative cartilage pathology.

Between January 2010 and August 2017, 396 patients underwent revision ACL-R, and were matched to primary isolated ACL-R patients using sex, age, body mass index (BMI), and Beighton score. Intra-operative assessments including meniscal and chondral pathology, and graft diameter were recorded. Lachman and pivot shift tests were completed independently on each patient at two-years post-operative by a physiotherapist and orthopaedic surgeon. A battery of functional tests was assssed including single-leg Bosu balance, and four single-leg hop tests. The Anterior Cruciate Ligament-Quality of Life Questionnaire (ACL-QOL) was completed pre-operatively and two-years post-operatively.

Descriptive statistics including means (M) and standard deviations (SD), and as appropriate paired t-tests were used to compare between-groups demographics, the degree and frequency of meniscal and chondral pathology, graft diameter, rate of post-operative ACL graft laxity, the surgical failure rate, and ACL-QOL scores. Comparative assessment of operative to non-operative limb performance on the functional tests was used to assess limb symmetry indices (LSI).

Revision ACL-R patients were 52.3% male, mean age 30.7 years (SD=10.2), mean BMI 25.3 kg/m2 (SD=3.79), and mean Beighton score 3.52 (SD=2.51). In the revision group, meniscal (83%) and chondral pathology (57.5%) was significantly more frequent than in the primary group (68.2% and 32.1%) respectively, (p < 0 .05). Mean graft diameter (mm) in the revision ACL-R group for hamstring (M=7.89, SD=0.99), allograft (M=8.42, SD=0.82), and patellar or quadriceps tendon (M=9.56, SD=0.69) was larger than in the primary ACL-R group (M=7.54, SD=0.76, M=8.06, SD=0.55, M=9, SD=1) respectively. The presence of combined positive Lachman and pivot shift tests was significantly more frequent in the revision (21.5%) than primary group (4.89%), (p < 0 .05). Surgical failure rate was higher in the revision (10.3%) than primary group (5.9%).

Seventy-three percent of revision patients completed functional testing. No significant LSI differences were demonstrated between the revision and primary ACL-R groups on any of the functional tests. No statistically significant differences were demonstrated in mean preoperative ACL-QOL scores between the revision (M=28.5/100, SD=13.5) and primary groups (M=28.5/100, SD=14.4). Mean two-year scores demonstrated statistically significant and minimally clinically important differences between the revision (M=61.1/100, SD=20.4) and primary groups (M=76.0/100, SD=18.9), (p < 0 .05). Mean two-year scores for revision patients with repair of the medial (M=59.4/100, SD=21.7) or lateral meniscus (M=59.4/100, SD=23.6), partial medial meniscectomy (M=59.7/100, SD=20), grade three or four osteoarthritis (M=55.9/100, SD=19.5), and medial femoral condyle osteoarthritis (M=59.1/100, SD=18) were lower compared with partial lateral meniscectomy (M=67.1/100, SD=19.1), grade one or two osteoarthritis (M=63.8/100, SD=18.9), and lateral femoral condyle osteoarthritis (M=62, SD=21).

Revision ACL-R patients demonstrated a greater amount of meniscal and chondral pathology at the time of surgery. Two-years post-operative these patients demonstrated higher rates of graft laxity and lower ACL-QOL scores compared with the primary ACL-R group. Higher grade and medial sided osteoarthritis was associated with inferior ACL-QOL scores in revision ACL-R.


A. Bois P. Knight K. Alhojailan K. Bohsali M. Wirth

A reverse total shoulder arthroplasty (RSA) is frequently performed in the revision setting. The purpose of this study was to report the clinical outcomes and complication rates following revision RSA (RRSA) stratified according to the primary shoulder procedure undergoing revision, including failed hemiarthroplasty (HA), anatomic total shoulder arthroplasty (TSA), RSA, soft tissue repair (i.e., rotator cuff repair), and open reduction internal fixation (ORIF).

A systematic review of the literature was performed using four databases (EMBASE, Medline, SportDISCUS, and Cochrane Controlled Trials Register) between January 1985 and September 2017. The primary outcomes of interest included active range-of-motion (ROM), pain, and functional outcome measures including the American Shoulder and Elbow Surgeons Score (ASES), Simple Shoulder Test (SST), and Constant-Murley (CS) Score. Secondary outcomes included complication rates, such as infection, dislocation, perioperative fracture, base plate failure, neurovascular injury, soft tissue injury, and radiological evidence of scapular notching. Clinical outcome data was assessed for differences between preoperative and postoperative results and complication results were reported as pooled complication rates.

Forty-five studies met the inclusion criteria for analysis, which included 1,016 shoulder arthroplasties with a mean follow-up of 45.2 months (range, 31.1 to 57.2 months) (Fig. 1). The mean patient age at revision was 60.2 years (range, 36 to 65.2 years). Overall, RSA as a revision procedure for failed HA revealed favorable outcomes with respect to forward elevation (FE), CS pain, ASES, SST, and CS outcome assessment scores, with mean improvements of 52.5° ± 21.8° (P = < 0 .001), 6.41 ± 4.01 SD (P = 0.031), 20.1 ± 21.5 (P = 0.02), 5.2 ± 8.7 (P = 0.008), and 30.7 ± 9.4 (P = < 0 .001), respectively. RSA performed as a revision procedure for failed TSA demonstrated an improvement in the CS outcome score (33.8 ± 12.4, P = 0.016). RSA performed as a revision procedure for failed soft tissue repair demonstrated significant improvements in FE (60.2° ± 21.2°, P = 0.031) and external rotation (20.8° ± 18°, P = 0.016), respectively. Lastly, RSA performed as a revision procedure for failed ORIF revealed favorable outcomes in FE (61° ± 20.2°, P = 0.031). There were no significant differences noted in RSA performed as a revision procedure for failed RSA, or when performed for a failed TSA, soft tissue repair, and ORIF in any other outcome of interest. Pooled complication rates were found to be highest in failed RSA (10.9%), followed by soft tissue repair (7.1%), HA (6.8%), TSA (5.4%) and ORIF (4.7%).

When compared to other revision indications, RRSA for failed HA demonstrated the most favorable outcomes, with significant improvements in ROM, pain, and in several outcome assessments. Complication rates were determined and stratified as per the index procedure undergoing RRSA, patients undergoing revision of a failed RSA were found to have the highest complication rates. With this additional information, orthopaedic surgeons will be better equipped to provide preoperative education regarding the risks, benefits and complication rates to those patients undergoing a RRSA.

For any figures or tables, please contact authors directly.


L. Sims W. Aibinder K. J. Faber G. J.W. King

Essex-Lopresti injuries are often unrecognized acutely with resulting debilitating adverse effects. Persistent axial forearm instability may affect load transmission at both the elbow and wrist, resulting in significant pain. In the setting of both acute and chronic injuries metallic radial head arthroplasty has been advocated, however there is little information regarding their outcome. The purpose of this study was to assess the efficacy of a radial head arthroplasty to address both acute and chronic Essex-Lopresti type injuries.

A retrospective review from 2006 to 2016 identified 11 Essex-Lopresti type injuries at a mean follow-up of 18 months. Five were diagnosed and treated acutely at a mean of 11 days (range, 8 to 19 days) from injury, while 6 were treated in a delayed fashion at a mean of 1.9 years (range, 2.7 months to 6.2 years) from injury with a mean 1.5 (range, 0 to 4) prior procedures. The cohort included 10 males with a mean age was 44.5 years (range, 28 to 71 years). A smooth stem, modular radial head arthroplasty was used in all cases. Outcomes included range of motion and radiographic findings such as ulnar variance, capitellar erosion, implant positioning and implant lucency using a modification of the method described by Gruen. Reoperations, including the need for ulnar shortening osteotomy, were also recorded.

Three patients in each group (55%) reported persistent wrist pain. The mean ulnar variance improved from +5 mm (range, 1.8 to 7 mm) to +3.7 mm (range, 1 to 6.3 mm) at the time of final follow-up or prior to reoperation. Three (50%) patients in the chronic group underwent a staged ulnar shortening osteotomy (USO) to correct residual ulnar positive variance and to manage residual wrist pain. There were no reoperations in the acute group. Following USO, the ulnar variance in those three cases improved further to +3.5, +2.1, and −1.1 mm. No radial head prostheses required removal. Capitellar erosion was noted in five (45%) elbows, and was rated severe in one, moderate in two, and mild in two. Lucency about the radial head prosthesis stem was noted in eight (73%) cases, and rated as severe in 2 (18%), based on Gruen zones.

Treatment of acute and chronic Essex-Lopresti lesions with radial head arthroplasty often results in persistent wrist pain. In the chronic setting, a planned USO was often necessary to restore axial forearm stability after radial head arthroplasty. Essex-Lopresti lesions represent a rare clinical entity that are difficult treat, particularly in the chronic setting. Early recognition and management with a smooth stem modular radial head arthroplasty may provide improved outcomes compared to chronic reconstruction.


P. Railton J. Powell A. Parkar M. Abouassaly G.N. Kiefer K. Johnston

Despite recent advances in the management of slipped capital femoral epiphysis (SCFE), controversy remains about the treatment of choice for unstable slips. Surgical dislocation and open reduction has the advantage of identifying and preserving the blood supply of femoral head thereby potentially reducing the risk of avascular necrosis, (AVN). There is large variation in the literature from several small series about reported AVN rates ranging from two to 66% for unstable SCFE treated with surgical dislocation. The aim of our study was to analyze our experience with acute open reduction and internal fixation of unstable acute and unstable acute on chronic slips using the technique of surgical dislocation described by Professor Reinhold Ganz.

A retrospective review of 11 patients (12 hips) treated by surgical dislocation, reduction and pinning as the primary procedure for unstable acute and unstable acute on chronic SCFE in a tertiary referral children's hospital was undertaken. This represents the entire series treated in this manner from September 2007 to January 2018. These procedures were performed by a team of Orthopaedic surgeons with significant experience performing surgical dislocation of the hip including patients with chronic SCFE, Perthes' disease, impingement and acetabular fractures. Demographic data, intraoperative records, postoperative notes and radiographs including details of subsequent surgery were reviewed.

There were seven boys and four girls with mean age of 13.4 years, range 11 to 15 years at the time of surgical dislocation. Out of 12 hips, two had acute unstable slip while the remaining 10 had acute on chronic unstable slip. Six patients had good or excellent results. The remaining six patients developed AVN of which three patients had total hip replacement at six months, 17 months and 18 months following primary procedure. Seven patients required more than one operation. Three patients lost their correction and required re fixation despite surgical dislocation, reduction and fixation being their primary procedure.

This series demonstrates a high percentage of AVN (50%) in severe unstable SCFE treated with surgical dislocation despite careful attention to retinacular flap development and intra operative doppler studies. This is in direct contrast to our experience with subcapital reorientation with surgical dislocation in stable slips where excellent results were achieved with a low rate of AVN. Pre-operative imaging with MRI and perfusion studies may identify where ischemia has occurred and might influence operative treatment. Based on our results, we do not recommend routine use of surgical dislocation in unstable SCFE. This technique requires further scrutiny to define the operative indications in unstable SCFE.


J. Delisle M. Benderdour B. Benoit M. Giroux G. Y. Laflamme H. Nguyen P. Ranger Q. Shi F. Vallières J. Fernandes

Total Knee Arthroplasty (TKA) patients may present with effusion, pain, stiffness and functional impairment. A positive metal hypersensitivity (positive LTT) may be an indication for a revision surgery with a custom-made implant devoid of any hypersensitivity-related metal or an implant with the least possible ion content of the metal hypersensitivity, if no custom-made is available. The purpose of the current study is to assess the prevalence of metal hypersensitivity in subjects requiring a primary TKA and assess their early functional outcomes.

We are recruiting 660 subjects admitted for TKA. Subjects are randomly assigned to 2 groups: oxidized zirconium implant group or cobalt-chrome implant group. Functional outcomes and quality of life (QoL) are measured pre operatively, 3, 6 and 12 months post operatively with WHOQOL-BREF (domain1-Physical Health, domain 2- Psychological, domain 3- Social relationships, domain 4-Environment), KSS, KOOS and pain Visual Analog Scale (VAS). LTT and metal ions are evaluated pre operatively and 12 months post-surgery.

One hundred-sixty patients, 98 women, were enrolled in the study. Mean age was 65.6±8.9. Mean follow up (FU) was 7.1±3.8 months. Eighty-one (50.6%) were randomised in the cobalt-chrome group. Infection rate was 1.9%, one patient required debridement. Three patients (1.9%) presented with contracture at three months FU. At 12 months, WHOQOL-BREF domain 1, 2 and 4 improved significantly (p0,05).

Overall, all 160 patients improved their functional outcomes and QoL. At 12 months, VAS scores decreased from 7±2.06 at baseline to 1.95±2.79. Furthermore, the high prevalence of positive LTT (27/65) do not seem to affect early functional outcomes and QoL on patients that may have received a potential implant with hypersensitivity (18/27).


J.A. Wilson J. Outerleys D. Wilson G. Richardson M. J. Dunbar

Up to 20 percent of patients remain dissatisfied after primary total knee arthroplasty (TKA) surgery. Understanding the reasons for dissatisfaction post TKA may allow for better patient selection and optimized treatment for those who remain dissatisfied. The association between function, mobility and satisfaction are not well understood. The purpose of this study was to investigate the association between post-TKA satisfaction and i) pre-operative, ii) post-operative, and iii) change in knee joint function during gait.

Thirty-one patients scheduled to receive primary TKA for knee osteoarthritis (OA) diagnosis were recruited and visited the Dynamics of Human Motion laboratory for instrumented walking gait analysis (using a synchronized NDI Optotrak motion capture system and AMTI force platforms in the walkway) at two time points, first within the week prior to their surgery, and second at approximately one year after surgery. At their post-operative visit, patients were asked to indicate their satisfaction with their knee prosthesis on a scale from zero to 100, with zero being totally unsatisfied and 100 being completely satisfied. Knee joint mechanics during gait at both time points were characterized by discriminant scores, the projection of their three-dimensional knee angles and moments during gait onto an existing discriminant model that was created to optimize separation of severe knee OA and healthy asymptomatic gait patterns. This discriminant model was created using data from 73 healthy participants and 73 with severe knee OA, and includes the magnitude and pattern features (captured with principal component analysis) of the knee adduction and flexion moment, and the magnitude of the knee flexion angle during gait. Larger discriminant scores indicate improved function toward healthy patterns, and smaller scores indicate more severe function. Associations between post-operative satisfaction and pre, post and change in discriminant scores were examined using Pearson correlation analyses. We also examined associations between satisfaction and pre-operative BMI, EQ5D and Oxford 12 scores, as well as changes in these scores from pre to post-TKA.

Discriminant scores representing knee joint function during gait significantly improved on average after surgery (P =0.05).

While overall knee joint function improved after primary TKA surgery, the amount of improvement in function was not reflected in post-operative patient satisfaction. However, the pre-operative function of the patient was negatively associated with satisfaction, indicating that patients with higher pre-operative function are overall less satisfied with their TKA surgery, regardless of any functional improvement due to the surgery. Interestingly, the only significant association with post-operative satisfaction was knee joint function, and the relationship between function and patient satisfaction following TKA appears to relate only to the baseline functional state of the patient, and not with functional improvement. This suggests that dissatisfaction post-surgery is more likely reflecting the unmet expectations of a higher functioning patient, and has implications for the need for improved understanding of pre-operative patient functional variability in TKA triage and expectation management.


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F. Al-Shakfa Z. Wang V.T. Truong

Evaluate the complications and outcomes of off-hours spinal metastasis surgery.

Retrospective analysis of a prospective collected data.

Preoperative, operative and post-operative data were collected as well as the complications and Frankel score at all time checkpoints. Off-hours surgery was defined as surgery starting between 17:00 and 8:00 the following day or surgery during the weekend. p < 0 .05 was defined as statistical significance threshold.

376 patients were included with an incidence of off-hours surgery of 32%. There was an increase of neurologic complication in the off hours group. This was associated with a higher ASA score and older population group. Oddly, there was decreased operative time with off-hours surgery with no difference in bleeding and number of fusion levels. Nonetheless, there was a higher percentage of neurologic improvement with off hours surgery compared to in-hours surgery. Finally, there were no effect on patients' survival in this patient population.

To our knowledge, this is the first report of the effect of off-hours surgery on complications and outcomes of spinal metastasis. Greater neurological compromise and higher age and ASA scores were associated with higher incidence of off-hours surgery. It is associated with decreased surgical time with higher percentage of neurological improvement. Finally, there is no effect of surgical timing on survival rates.


A. Sepehri G.P. Slobogean N. O'Hara R. V. O'Toole

In the polytrauma patient, intraoperative patient positioning is one factor thought to influence pulmonary complications associated with intramedullary (IM) nailing of the femur. With regards to lateral femoral nailing, it is currently unknown as to whether the position of the injured lung contributes to changes in pulmonary function. It has been proposed that, similar to prone positioning in the ICU for acute respiratory distress syndrome management, having the injured lung in a dependent position during lateral femoral nailing would prevent barotrauma from hyperinflation and promote gas exchange in the non-dependent healthy lung. This study aims to assess the association between the position of the injured lung during lateral femoral nailing and pulmonary complications as determined by ICU LOS.

This retrospective cohort study was conducted at a single level 1 trauma centre. All patients treated with IM nailing for femur fracture between 2006 and 2014 were screened for inclusion. Only patients who 1) underwent lateral femoral nailing and 2) had a significant chest injury, defined by chest Abbreviated Injury Scale (AIS) of three or greater, were included. Patients with bilateral femur fractures or symmetric bilateral thoracic injuries were excluded. Intraoperative position of the lung injury was described depending on whether the injured lung was down, or in the dependent position, during lateral femoral nailing, versus the healthy lung down. The primary outcome was ICU LOS in all study patients. Secondary analysis was performed on the subgroup of patients who were admitted to ICU prior to femoral nailing. Data analysis assessing for differences in ICU LOS between groups was performed through Wilcoxan testing.

One hundred and thirteen femur fractures were included in the study. During lateral femoral nailing, 53 patients had the injured lung down and 60 patients had the healthy lung down. No differences between age, ICU admission rate, injury severity score, chest AIS or head AIS were detected between the groups. There were no detectable differences in the rate of ICU admission between patients with the injured lung down (47.2%) and patients with the healthy lung down (46.7%) (P=0.96).

We were unable to detect a difference in average ICU LOS between patients who had the injured lung down (4.9 days, 95% CI 2.8 – 7) compared to patients with the healthy lung down (6 days, 95% CI 3.7 – 8.4) during lateral femoral nailing (P=0.73). When looking only at patients who were admitted to ICU prior to femoral nailing, the LOS was 10.3 days (95% CI 7 – 13.7) in injured lung down patients compared to 12.9 days (9.2 – 16.6) in healthy lung down patients (P= 0.25).

In patients with chest AIS greater than three, the position of the injured lung during lateral femoral IM nailing does not appear to affect ICU LOS.


S. Sprague K. Okike G.P. Slobogean Swiontkowski M. Bhandari U. N. Udogwu M. Isaac

Internal fixation is currently the standard of care for Garden I and II femoral neck fractures in the elderly. However, there may be a degree of posterior tilt on the preoperative lateral radiograph above which failure is likely, and primary arthroplasty would be preferred. The purpose of this study was to determine the association between posterior tilt and the risk of subsequent arthroplasty following internal fixation of Garden I and II femoral neck fractures in the elderly.

This study represents a secondary analysis of data collected in the FAITH trial, an international multicenter randomized controlled trial comparing the sliding hip screw to cannulated screws in the management of femoral neck fractures in patients aged 50 years or older. For each patient who sustained a Garden I or II femoral neck fracture and had an adequate preoperative lateral radiograph, the amount of posterior tilt was categorized as < 2 0 degrees or ≥20 degrees. Multivariable Cox proportional hazards analysis was used to assess the association between posterior tilt and subsequent arthroplasty during the two-year follow-up period, while controlling for potential confounders.

Of the 555 patients in the study sample, posterior tilt was classified as ≥20 degrees for 67 (12.1%) and < 2 0 degrees for 488 (87.9%). Overall, 13.2% (73/555) of patients underwent subsequent arthroplasty in the 24-month follow-up period. In the multivariable analysis, patients with posterior tilt ≥20 degrees had a significantly increased risk of subsequent arthroplasty compared to those with posterior tilt < 2 0 degrees (22.4% (15/67) vs 11.9% (58/488), Hazard Ratio (HR) 2.22, 95% confidence interval (CI) 1.24–4, p=0.008). The other factor associated with subsequent arthroplasty was age ≥80 (p=0.03).

In this study of patients with Garden I and II femoral neck fractures, posterior tilt ≥20 degrees was associated with a significantly increased risk of subsequent arthroplasty. Primary arthroplasty should be considered for Garden I and II femoral neck fractures with posterior tilt ≥20 degrees, especially among older patients.


F. Al-Shakfa Z. Wang V.T. Truong

Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center.

We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment.

The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases.

Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk.


C. Godbout A. Nauth E. H. Schemitsch B. Fung H. Lad E. Watts S. Desjardins K. Lam Tin Cheung

The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing.

The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small animal model, this study aimed to determine the impact on the induced membrane of impregnating spacers with antibiotics frequently used in the IMT.

We surgically created a five-mm segmental defect in the right femur of 25 adult male Sprague Dawley rats. The bone was stabilized with a plate and screws before filling the defect with a PMMA spacer. Animals were divided into five equal groups according to the type and dose of antibiotics impregnated in the spacer: A) no antibiotic (control), B) low-dose tobramycin (1.2 g/40 g of PMMA), C) low-dose vancomycin (1 g/40 g of PMMA), D) high-dose tobramycin (3.6 g/40 g of PMMA), E) high-dose vancomycin (3 g/40 g of PMMA). The animals were euthanized three weeks after surgery and the induced membranes were collected and divided for analysis. We assessed the expression of selected genes (Alpl, Ctgf, Runx2, Tgfb1, Vegfa) within the membrane by quantitative real-time PCR. Moreover, frozen sections of the specimens were used to quantify vascularity by immunohistochemistry (CD31 antigen), proliferative cells by immunofluorescence (Ki-67 antigen), and membrane thickness. Microscopic images of the entire tissue sections were taken and analyzed using FIJI software. Finally, we measured the concentration of vascular endothelial growth factor (VEGF) in the membranes by ELISA.

No significant difference was found among the groups regarding the expression of genes related to osteogenesis (Alpl, Runx2), angiogenesis (Vegfa), or synthesis of extracellular matrix (Ctgf, Tgfb1) (n = four or five). Similarly, the density of proliferative cells and blood vessels within the membrane, as well as the membrane thickness, did not vary substantially between the control, low-dose, or high-dose antibiotic groups (n = four or five). The concentration of VEGF was also not significantly influenced by the treatment received (n = four or five).

The addition of tobramycin or vancomycin to the spacer, at the defined low and high doses, does not significantly alter the bioactive characteristics of the membrane. These results suggest that orthopaedic surgeons could use antibiotic-impregnated spacers for the IMT without compromising the induced membrane and potentially bone healing.


A. Couture J. Davies J. Chapleau G.Yves Laflamme E. Sandman D. Rouleau

Radial head fractures are relatively common, representing approximately one-third of all elbow fractures. Outcomes are generally inversely proportional to the amount of force involved in the mechanism of injury, with simple fractures doing better than more comminuted ones. However, the prognosis for these fractures may also be influenced by associated injuries and patient-related factors (age, body index mass, gender, tobacco habit, etc.) The purpose of this study is to evaluate which factors will affect range of motion and function in partial radial head fractures. The hypothesis is that conservative treatment yields better outcomes.

This retrospective comparative cohort study included 43 adult volunteers with partial radial head fracture, a minimum one-year follow up, separated into a surgical and non-surgical group. Risk factors were: associated injury, heterotopic ossification, worker's compensation, and proximal radio-ulnar joint implication. Outcomes included radiographic range of motion measurement, demographic data, and quality of life questionnaires (PREE, Q-DASH, MEPS).

Mean follow up was 3.5 years (1–7 years). Thirty patients (70%) had associated injuries with decreased elbow extension (−11°, p=0.004) and total range of motion (−14°, p=0.002) compared to the other group. Heterotopic ossification was associated with decreased elbow flexion (−9°, p=0.001) and fractures involved the proximal radio-ulnar joint in 88% of patients. Only worker's compensation was associated with worse scores. There was no difference in terms of function and outcome between patients treated nonsurgically or surgically.

We found that associated injuries, worker's compensation and the presence of heterotopic ossification were the only factors correlated with a worse prognosis in this cohort of patients. Given these results, the authors reiterate the importance of being vigilant to associated injuries.


T. Burkhart A. Getgood M. Abbott A. Dentremont

Previous studies have identified the anterolateral complex (ALC) as having an important role in controlling anterolateral rotatory laxity following anterior cruciate ligament injury and subsequent reconstruction. In particular, injury to the iliotibial band (ITB) and its component deep (dITB) and capsulo-osseous (coITB) layers, have been shown to significantly correlate with different grades of the pivot-shift test in patients with acute ACL injuries. However, the kinematic properties of the capsulo-osseous layer of the ITB, throughout knee range of motion, are not fully understood.

The purpose of this study was to quantify the kinematic behaviour of the capsulo-osseous layer of the ITB through various degrees of knee flexion. Ten fresh-frozen cadaveric knee specimens were dissected to expose the capsulo-osseous layer of the iliotibial band. Radiopaque beads were embedded, at standardized increments (12.5%, 25%, 50% and 75% of total length from proximal to distal), into the tissue and fluoroscopic images were taken from 0o to 105o of knee flexion in 15° increments. The positions of the beads were identified in each image and the length, width, and area changes of the capsulo-osseous layer were calculated. Comparisons of the total length of the anterior and posterior borders of the coITB through knee ROM were conducted using a two-way (8 knee angles by 2 borders) repeated measures analysis of variance (rm-ANOVA), whereas the effect of knee angle on isometry and total area changes was assessed using one-way rm-ANOVAs (α=0.05)

There was a significant increase in the length of the anterior capsulo-osseous layer at flexion angles greater than 15o and on the posterior border at angles greater than 75 o with changes occurring primarily at 12.5 % of the total length. In addition, at all flexion angles the length changes were significantly larger in the anterior border compared to the post