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Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_1 | Pages 90 - 90
1 Feb 2015
Della Valle C
Full Access

A “two-stage exchange” remains the gold standard for treatment of the infected TKA in North America. Although there is interest in “one-stage exchange” this technique is not as familiar to many US surgeons and it is unclear if the reported results of Europe can be translated to North American practice. Specific concerns include the “radicalness” of the debridement required (which oftentimes includes the collateral ligaments, hence the popularity of hinged implants where this approach is common) and the use of fully cemented stems, which are extremely difficulty to remove if infection recurs. Thus while the idea of a one stage exchange is attractive to many North American surgeons, careful study will be required to determine if success can be achieved with a more “conservative” debridement and the use of cementless stems which are preferred by some surgeons.

The basic principles of a two-stage exchange include: Thorough debridement of all infected appearing foreign material and all cement; Placement of an interval antibiotic loaded spacer (note that the addition of antibiotics to bone cement is NOT FDA approved) – 4–6g of antibiotics per pkg of cement; typically vancomycin + tobramycin; Higher viscosity cement may be associated with higher elution; The combination of antibiotics also leads to higher elution.

Antibiotic spacers can be “articulating” or “static”. Potential advantages of an articulating spacer include greater patient comfort and an easier approach at the second stage exchange as soft tissue tension and range of motion is maintained. However, these spacers are oftentimes more costly and can break or dislocate.

The first stage is followed by approximately 6 weeks of organism specific IV antibiotics. An interdisciplinary approach with an infectious disease specialist, internal medicine and a nutritionist optimises outcomes.

Our protocol then includes weekly ESR and CRP to monitor their trend. These labs are re-checked two weeks after cessation of antibiotics to ensure the trend has not changed. The knee is routinely aspirated at this time point and the fluid obtained sent for a synovial fluid WBC count with differential and cultures (although the value of such cultures is controversial). We have found that while the ESR and CRP are significantly lower than prior to removal of the infected implant, they often times DO NOT normalise and there is no specific cut-off value that predicts persistent infection.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_12 | Pages 51 - 51
1 Jul 2014
Jones R
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Infection after total knee arthroplasty poses formidable challenges to the surgeon. Once an infection is diagnosed, the identification of the organism and its sensitivity to antibiotics is essential. The host's healing capacity is vital. Optimisation of modifiable comorbidities, supplemental nutrition and cessation of smoking can improve wound healing. Surgical goals include debridement of necrotic tissue and elimination of the dead space. Intravenous antibiotics and a two-stage protocol are the standard of care. At our institution, the first stage is performed with an implant and antibiotic-cement composite. This articulating spacer maintains limb length and tissue compliance. The patient can maintain a functional status between stages. Definitive reconstruction is more readily accomplished with this method in contrast to the static spacer approach. The clinical efficacy of this protocol has been well documented in the literature.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_13 | Pages 60 - 60
1 Nov 2015
Pagnano M
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Deep periprosthetic infection after hip or knee arthroplasty is a disconcerting problem for patient and surgeon alike. The diagnosis of infection is sometimes obvious but frequently requires that the surgeon maintain a substantial index of suspicion for infection as the cause of pain or poor outcome after any joint arthroplasty. While surgical debridement with component retention is appropriate in a subgroup of patients with an acute periprosthetic infection most delayed and chronic infections are best treated with component resection. The pre-eminent role of two-stage exchange as the definitive treatment was established over 30 years ago. Two-stage exchange remains the gold-standard in treatment with an established track record from multiple centers and with multiple different types of infecting organisms. Some of the historical problems with two-stage exchange, such as limited mobility during the interval stage, have been mitigated with the development of effective articulating spacer techniques. Further, the emergence of drug resistant bacteria and the possibility of fungal infection make two-stage exchange the best choice for the majority of patients with deep periprosthetic joint infection in 2015.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_8 | Pages 67 - 67
1 May 2014
Haidukewych G
Full Access

Infection after TKA remains a common reason for reoperation, and represents a significant burden for the patient and health care system. Having effective treatment strategies, therefore, is important to ensure the highest possible rate of success, and the lowest possible rate of reoperation due to treatment failure. This lecture will focus on the chronically infected TKA, where treatment options include either one stage exchange or two stage exchange. Proponents of one stage exchange cite lower costs, less morbidity, and reasonable success rates when compared to two stage exchange protocols. One must realise that strict selection criteria are generally used by proponents of single stage exchange. Favorable pathogens, healthy hosts, good soft tissues, minimal bone loss, etc. are generally used as indications to consider one stage exchange. Such “ideal” clinical situations, however, are exceedingly rare. The overwhelming majority of infected TKA in my practice involve resistant bacteria, significant bone loss, hosts with medical comorbidity, and often, poor soft tissues. In these situations, two stage exchange remains the gold standard to which all other interventions should be compared. With few exceptions, the published success rates for two stage procedures have been better, albeit slightly, than those published for one stage exchanges. Both static and articulating cement spacers have been used with good results. Further research is needed to better define the most effective treatment protocols, however, until further information is available, two stage exchange, with success rates of 80–90%, remains the most successful intervention for chronically infected TKA.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_22 | Pages 66 - 66
1 May 2013
Della Valle C
Full Access

A “two-stage exchange” remains the gold standard for treatment of the infected THA in North America. Although there is interest in “one-stage exchange” this technique is predicated on the use of fixation of the revision implants with antibiotic loaded cement, which is not as popular in North America.

Diagnosis is critical and in general consists of a screening serum ESR and CRP followed by selective aspiration if the above are abnormal and/or if the clinical history is suspicious. The aspirated fluid is sent for a synovial fluid WBC (cut-off approximately 3,000 WBC/μL), differential (cut-off 80% PMN) and culture.

The basic tenets of treatment include:

Thorough debridement of all infected appearing cement and all foreign material

Placement of an interval antibiotic loaded spacer (note that the addition of antibiotics to bone cement is NOT FDA approved)

4–6 g of antibiotics per pkg of cement; typically vancomycin + tobramycin

Higher viscosity cement may be associated with higher elution

Higher elution with combination of antibiotics

Antibiotic spacers can be “articulating” or “static”. Potential advantages of an articulating spacer include greater patient comfort and an easier approach at the second stage exchange as leg length and soft tissue tension is maintained. However, these spacers are oftentimes more costly and can dislocate. May not be appropriate in cases where there is severe bone loss that cannot support partial weight bearing or if the abductors are compromised (higher risk of dislocation).

The first stage is followed by approximately 6 weeks of organism specific IV antibiotics. An interdisciplinary approach with an infectious disease specialist, internal medicine and a nutritionist optimises outcomes.

Our protocol then includes weekly ESR and CRP to monitor their trend. These labs are re-checked two weeks after cessation of antibiotics to ensure the trend has not changed. We have found that while the ESR and CRP are significantly lower than prior to the 1st stage, they often times DO NOT normalise and there is no specific cut-off value that predicts persistent infection. An intra-operative aspiration for synovial fluid WBC count and differential is obtained intra-operatively (cut-off values of approximately 3,000 WBC/μl and 80% PMN) and are the best tests to identify persistent infection.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 721 - 728
1 Sep 2024
Wetzel K Clauss M Joeris A Kates S Morgenstern M

Aims

It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs.

Methods

The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 22 - 22
1 Apr 2019
Massari L Bistolfi A Grillo PP Causero A
Full Access

Introduction. Trabecular Titanium is a biomaterial characterized by a regular three-dimensional hexagonal cell structure imitating trabecular bone morphology. Components are built via Electron Beam Melting technology in aone- step additive manufacturing process. This biomaterial combines the proven mechanical properties of Titanium with the elastic modulus provided by its cellular solid structure (Regis 2015 MRS Bulletin). Several in vitro studies reported promising outcomes on its osteoinductive and osteoconductive properties: Trabecular Titanium showed to significantly affect osteoblast attachment and proliferation while inhibiting osteoclastogenesis (Gastaldi 2010 J Biomed Mater Res A, Sollazzo 2011 ISRN Mater Sci); human adipose stem cells were able to adhere, proliferate and differentiate into an osteoblast-like phenotype in absence of osteogenic factors (Benazzo 2014 J Biomed Mater Res A). Furthermore, in vivo histological and histomorphometric analysis in a sheep model indicated that it provided bone in-growth in cancellous (+68%) and cortical bone (+87%) (Devine 2012 JBJS). A multicentre prospective study was performed to assess mid-term outcomes of acetabular cups in Trabecular Titanium after Total Hip Arthroplasty (THA). Methods. 89 patients (91 hips) underwent primary cementless THA. There were 46 (52%) men and 43 (48%) women, with a median (IQR) age and BMI of 67 (57–70) years and 26 (24–29) kg/m2, respectively. Diagnosis was mostly primary osteoarthritis in 80 (88%) cases. Radiographic and clinical evaluations (Harris Hip Score [HHS], SF-36) were performed preoperatively and at 7 days, 3, 6, 12, 24 and 60 months. Bone Mineral Density (BMD) was determined by dual-emission X-ray absorptiometry (DEXA) according to DeLee &Charnley 3 Regions of Interest (ROI) postoperatively at the same time-points using as baseline the measureat 1 week. Statistical analysis was carried out using Wilcoxon test. Results. Median (IQR) HHS and SF-36 improved significantly from 48 (39–61) and 49 (37–62) preoperatively to 99 (96–100) and 76 (60–85) at 60 mo. (p≤0.0001). Radiographic analysis showed evident signs of bone remodelling and biological fixation, with presence of superolateral and inferomedial bone buttress, and radial trabeculae in ROI I/II. All cups resulted radiographically stable without any radiolucent lines. The macro-porous structure of this biomaterial generates a high coefficient of friction (Marin 2012 Hip Int), promoting a firm mechanical interlocking at the implant-bone interface which could be already observed in the operating room. BMD initially declined from baseline at 7 days to 6 months. Then, BMD slightly increased or stabilized in all ROIs up to 24 months, while showing evidence of partial decline over time with increasing patient' age at 60 months, although without any clinical significance in terms of patients health status or implant stability. Statistical significant correlations in terms of bone remodeling were observed between groups of patients on the basis of gender and age (p≤0.05). No revision or implant failure was reported. Conclusions. All patients reported significant improvements in quality of life, pain relief and functional recovery. Radiographic evaluation confirmed good implant stability at 60 months. These outcomes corroborate the evidence reported on these cups by orthopaedic registries and literature (Perticarini 2015 BMC Musculoskelet Disord; Bistolfi 2014 Min Ortop)


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 123 - 123
1 Jul 2020
J.Dixon S Beaucage K Nagao M Lajoie G Veras M Fournier D Holdsworth D Bailey C Hammond J Séguin C
Full Access

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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 1 - 1
1 Nov 2016
Outerleys J Dunbar M Richardson G Kozey C Wilson J
Full Access

Total knee arthroplasty (TKA) has been shown to improve knee joint function during gait post-operatively. However, there is considerable patient to patient variability, with most gait mechanics metrics not reaching asymptomatic levels. To understand how to target functional improvements with TKA, it is important to identify an optimal set of functional metrics that remain deficient post-TKA. The purpose of this study was to identify which combination of knee joint kinematics and kinetics during gait best discriminate pre-operative gait from postoperative gait, as well as post-operative from asymptomatic. Seventy-three patients scheduled to receive a TKA for severe knee osteoarthritis underwent 3D gait analysis 1 week before and 1 year after surgery. Sixty asymptomatic individuals also underwent analysis. Eleven discrete gait parameters were extracted from the gait kinematic and kinetic waveforms, as previously defined (Astephen et al., J Orthop Res., 2008). Stepwise linear discriminant analyses were used to determine the sets of parameters that optimally separated pre-operative from post-operative gait, and post-operative from asymptomatic gait. Cross-validation was used to quantify group classification error. Knee flexion angle range, knee adduction moment first peak, and gait velocity were included in the optimal discriminant function between the pre- and post-operative groups (P<0.05), with relatively equal standardised canonical coefficients (0.567, −0.501, 0.565 respectively), and a total classification rate of 74%. A number of metrics were included in the discriminant function to optimally separate post-operative and asymptomatic gait function, including the knee flexion angle range, peak stance knee flexion angle, minimum late stance knee extension moment, minimum mid-stance knee adduction moment, and peak knee internal rotation moment (P<0.05). The mid-stance knee adduction moment had the largest standardised canonical coefficients in the function, and 89.5% of cases were correctly classified. Separation of pre and post-operative gait patterns included only three parameters, suggesting that current standard of care TKA significantly improves only walking velocity, knee flexion angle range, and the peak value of the knee adduction moment. A number of gait metrics, which were included in the discriminant function between post-operative and asymptomatic gait, could benefit from further improvement either through rehabilitation or design. With almost 90% classification, separation of post-operative gait function from asymptomatic levels is significant. The consolidation of knee joint function during gait into single, discrete discriminant scores allows for an efficient summary representation of patient-specific (or implant-specific) improvement in gait function from TKA surgery


Bone & Joint Research
Vol. 4, Issue 5 | Pages 84 - 92
1 May 2015
Hamamura K Nishimura A Iino T Takigawa S Sudo A Yokota H

Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92


Bone & Joint Research
Vol. 3, Issue 6 | Pages 193 - 202
1 Jun 2014
Hast MW Zuskov A Soslowsky LJ

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint Res 2014;3:193–202


Bone & Joint Research
Vol. 4, Issue 7 | Pages 105 - 116
1 Jul 2015
Shea CA Rolfe RA Murphy P

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116


Bone & Joint Research
Vol. 4, Issue 6 | Pages 99 - 104
1 Jun 2015
Savaridas T Wallace RJ Dawson S Simpson AHRW

Objectives. There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed. Methods. Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests. Results. Uninjured cortical bone in the iban group had a significantly greater mean (standard deviation (. sd. )), p < 0.001, stress at failure of 219.2 MPa (. sd. 45.99) compared with the control group (169.46 MPa (. sd. 43.32)) following only nine weeks of therapy. Despite this, the cortical bone toughness and work to failure was similar. There was no significant difference in radiological density or physical dimensions of the cortical bone. Conclusions. Iban therapy increases the stress at failure of uninjured cortical bone. This has relevance when normalising the strength of repair in a limb when comparing it with the unfractured limb. However, the 20% increase in stress at failure with iban therapy needs to be interpreted with caution as there was no corresponding increase in toughness or work to failure. Further research is required in this area, especially with the increasing clinical burden of low-energy diaphyseal femoral fractures following prolonged use of bisphosphonates. Cite this article: Bone Joint Res 2015;4:99–104


Bone & Joint Research
Vol. 3, Issue 5 | Pages 161 - 168
1 May 2014
Mundi R Chaudhry H Mundi S Godin K Bhandari M

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding. Cite this article: Bone Joint Res 2014;3:161–8


Bone & Joint Research
Vol. 3, Issue 5 | Pages 169 - 174
1 May 2014
Rangan A Jefferson L Baker P Cook L

The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs. Cite this article: Bone Joint Res 2014;3:169–74


Bone & Joint Research
Vol. 4, Issue 5 | Pages 70 - 77
1 May 2015
Gupta A Liberati TA Verhulst SJ Main BJ Roberts MH Potty AGR Pylawka TK El-Amin III SF

Objectives. The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. Results. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Conclusions. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70–7


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_4 | Pages 100 - 100
1 Jan 2016
Verstraete M Luyckx T De Roo K Bellemans J Victor J
Full Access

It is nowadays widely recognized that patient satisfaction following knee arthroplasty strongly depends on ligament balancing. To obtain this balancing, the occurring ligament strain is assumed to play a crucial role. To measure this strain, a method is described in this paper that allows full field 3D evaluation of the strains. The latter is preferred over traditional measurement techniques, e.g. displacement transducers or strain gauges, as human soft tissue is not expected to deform uniformly due to its highly inhomogeneous and anisotropic properties. To facilitate full field strain measurements, the 3D digital image correlation (DIC) technique was adopted. This technique was previously validated by our research group on human tissue. First, a high contrast speckle pattern was applied on the sMCL. Therefore, the specimens are first coated with a small layer of methylene blue. Following, a random white speckle pattern is applied. During knee flexion, two cameras simultaneously take pictures of the deforming region at predefined flexion angles. Using dedicated software, the captured images are eventually combined and result in 3D full field strains and displacements. Using this method, the strain distribution was studied in six cadaveric knees during flexion extension movement. Therefore, the femur was rigidly fixed in a custom test rig. The tibia was left unconstrained, allowing the six degrees of freedom in the knee. A load was applied to all major muscles in physiological directions of each muscle by attaching a series of calibrated weights (Farahmand et al., J Orthop Res., 1998;16(1)). The direction of the pulling cables was controlled using a digital inclinometer for each specimen. As a result, a statically balanced muscle loading of the knee was obtained. From these cadaveric experiments, it is observed that on average the sMCL behaves isometrically between 0° and 90° of flexion. However, high regional differences in strain distribution are observed from the full field measurements. The proximal region of the sMCL experiences relatively high strains upon flexion. These strains are positive (tension) in the anterior part and negative (compression) in the posterior region. In contrast, the distal region remains approximately isometric upon knee flexion (see Figure 1). It is accordingly concluded that the sMCL behaves isometric, though large regional differences are observed. The proximal region experiences higher strains. Furthermore, the DIC technique provided valuable insights in the deformation of the sMCL. This technique will therefore be applied to study the impact of knee arthroplasty in the near future. Caption with figure 1: Full field strain distribution in the sMCL's longitudinal direction for specimen in 45° (a) and 90° (b) of knee flexion


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_2 | Pages 84 - 84
1 Jan 2016
Jonishi K Kaneyama R Higashi H Oinuma K Shiratsuchi H
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Introduction. Incorrect restoration of the joint line during total knee arthroplasty (TKA) can result in joint instability, anterior knee pain, limited range of motion, and joint stiffness. Although restoration of the correct joint line (i.e., creating an optimal gap in extension and flexion) should be considered in all TKA procedures, no surgical techniques have been established for restoring it. We performed the femoral posterior condylar precut technique (Kaneyama R. Bone Joint Res. 2014; 3) in 91 TKA cases and evaluated the joint line by measuring the thickness of the surgically removed femoral bone and femoral components. Methods. A total of 91 knees in 73 patients who underwent primary TKA between June and December 2013 were reviewed retrospectively. The posterior cruciate ligament was preserved in all patients. First, in the femoral posterior condylar precut technique, the extension gap was created by the measured resection technique. Then we created a temporary gap in flexion 4 mm smaller than that created by the measured resection technique and remove posterior osteophytes and soft tissue for good ligament balance. Once the component gap was determined, final femoral posterior condyle cutting was performed to create an optimal gap and rotation. We evaluated the joint line from the differences in thickness between the surgically removed femoral bone and femoral components, and revised the thickness of the bone saw accordingly. The value was positive when the joint line had been raised and negative when it had been lowered. Results. Subjects were 17 men (20 knees) and 56 women (71 knees) with a mean age of 72.6 years. The amount of distal femoral bone surgically removed was 8.5±1.8 mm (medial) and 8.3±2.0 mm (lateral) and that of posterior bone was 9.8±1.2 mm (medial) and 7.2±0.8 mm (lateral). The difference in the joint line was −0.4±2.2 mm (medial) and 0.5±3.9 mm (lateral) in extension and 1.1±2.7 mm (medial) and −0.6±1.9 mm (lateral) in flexion. Discussion. There are no established surgical techniques for restoring the joint line. Typically, surgical procedures are decided preoperatively by considering the amount of femoral bone to be surgically removed and rotation and cannot be changed during the operation if the gap is found to be incorrect. In our femoral posterior condylar precut technique, however, is possible to fine-tune it at the final step in surgery, making it possible to control the surgical removal of femoral bone, thereby reducing differences in the joint line


Bone & Joint Research
Vol. 3, Issue 7 | Pages 223 - 229
1 Jul 2014
Fleiter N Walter G Bösebeck H Vogt S Büchner H Hirschberger W Hoffmann R

Objective . A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation. Method . A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months. . Results . Systemic exposure to gentamicin after implantation was very low as local gentamicin concentrations were measured in wound exudate after six to ten hours. There were no signs of infectious complication throughout the clinical phase. Four patients had recurrent infections several weeks to months after implantation. The outcome was deemed successful by remission of infection in 16 (80%) of these problematic long-term treated patients. Safety laboratory measurements did not indicate nephrotoxic or hepatotoxic effects. . Conclusions . Local application of calcium sulphate/carbonate bone void filler comprising gentamicin revealed sufficient active local levels of the antibiotic by simultaneous significant low systemic exposure in patients with mostly chronic osteomyelitis/osteitis. The material was safe and well tolerated. Cite this article: Bone Joint Res 2014;3:223–9


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_1 | Pages 35 - 35
1 Jan 2016
Banks S Imam M Eifert A Field RE
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Introduction. Total knee arthroplasty (TKA) designs evolve as evidence accumulates on natural and prosthetic knee function. TKA designs based upon a medially conforming tibiofemoral articulation seek to reproduce essential aspects of normal knee stability and have enjoyed good clinical success and high patient satisfaction for over two decades. Fluoroscopic kinematic studies on several medially conforming knee designs show extremely stable knee function, but very small ranges of tibial axial rotation compared to healthy knees. The GMK Sphere TKA is a recent evolution in medially-conforming TKA designs that adopts a sagittally unconstrained lateral tibiofemoral articulation to allow more natural tibial rotation. This study was conducted to quantify motions in knees with this prosthesis to address two questions:. Does the medially conforming GMK Sphere design provide an AP-stable articulation that provides for tibiofemoral translations that are comparable to, but not larger than, translations measured in natural knees?. Does the medially conforming GMK Sphere design provide sufficient rotatory laxity to allow tibiofemoral rotations comparable to, but not larger than, rotations measured in natural knees?. Materials and Methods. Fifteen patients (9 females), mean age 65 years and mean BMI of 30 ±3, consented to participate. Sixteen knees received the GMK Sphere TKA. Mean Oxford Knee Score (OKS) improved significantly from 19±7 to 40±3 six months post surgery (P< 0.0001). On the day of the study, the mean OKS, Knee Society Score, EQ5D and Heath status scores were 40, 87, 0.83 and 85 respectively. Mean ROM from active maximum extension till maximum supine flexion was 108°±8°. Motions in 16 knees were observed using pulsed-fluoroscopy during a range of activities. Subjects were observed in maximum flexion kneeling and lunging positions, and in stepping up/down on a 22cm step. Model-image registration methods were used to quantify three-dimensional knee motions from digitized fluoroscopic images. Results. Tibial internal rotation averaged 8° during lunge and kneeling activities. During lunging, the medial and lateral condyles were an average of 2mm and 8mm posterior to the tibial sulcus, respectively, and 2mm and 9mm posterior to the tibial sulcus during kneeling. During the stair-stepping activity, the medial condyle did not translate significantly, while the lateral condyle moved 5mm posteriorly with flexion, accompanying 5° tibial internal rotation. Discussion. The GMK Sphere TKA was designed to provide intrinsic stability through a medially conforming articulation, and provide for more natural tibial rotation with an unconstrained lateral articulation. Fluoroscopic observation of these knees during lunge, kneel and stair-stepping activities showed a stable medial articulation with little translation, and a lateral articulation translating in direct relation to tibial rotation. Tibial rotation during kneeling (8° average) was approximately twice that observed in knees with an earlier medially conforming TKA design (Moonot et al., Knee Surg Sports Traumatol Arthrosc, 2009) and similar to that observed in natural knees with medial osteoarthritis (Hamai et al., J Orthop Res, 2009). At only six months follow-up, knees with the GMK Sphere arthroplasty show functional kinematics that are AP stable and have more natural tibial rotation, consistent with the implant design intent