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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 83 - 83
2 Jan 2024
Halloum A Kold S Rölfing J Abood A Rahbek O
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The aim of this scoping review is to understand the extent and type of evidence in relation to the use of guided growth for correcting rotational deformities of long bones. Guided growth is routinely used to correct angular deformities in long bones in children. It has also been proven to be a viable method to correct rotational deformities, but the concept is not yet fully examined. Databases searched include Medline, Embase, Cochrane Library, Web of Science and Google Scholar. All identified citations were uploaded into Rayyan.ai and screened by at least two reviewers. The search resulted in 3569 hits. 14 studies were included: 1 review, 3 clinical trials and 10 pre-clinical trials. Clinical trials: a total of 21 children (32 femurs and 5 tibiae) were included. Surgical methods were 2 canulated screws connected by cable, PediPlates obliquely oriented, and separated Hinge Plates connected by FiberTape. Rotation was achieved in all but 1 child. Adverse effects reported include limb length discrepancy (LLD), knee stiffness and rebound of rotation after removal of tethers. 2 pre-clinical studies were ex-vivo studies, 1 using 8-plates on Sawbones and 1 using a novel z-shaped plates on human cadaver femurs. There were 5 lapine studies (2 using femoral plates, 2 using tibial plates and 1 using an external device on tibia), 1 ovine (external device on tibia), 1 bovine (screws and cable on metacarp) and a case-report on a dog that had an external device spanning from femur to tibia. Rotation was achieved in all studies. Adverse effects reported include implant extrusions, LLD, articular deformities, joint stiffness and rebound. All included studies conclude that guided growth is a viable treatment for rotational deformities of long bones, but there is great variation in models and surgical methods used, and in reported adverse effects


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 115 - 115
11 Apr 2023
Tay M Carter M Bolam S Zeng N Young S
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Unicompartmental knee arthroplasty (UKA) has a higher risk of revision than total knee arthroplasty, particularly for low volume surgeons. The recent introduction of robotic-arm assisted systems has allowed for increased accuracy, however new systems typically have learning curves. The objective of this study was to determine the learning curve of a robotic-arm assisted system for UKA. Methods A total of 152 consecutive robotic-arm assisted primary medial UKA were performed by five surgeons between 2017 and 2021. Operative times, implant positioning, reoperations and patient-reported outcome measures (PROMS; Oxford Knee Score, EuroQol-5D, and Forgotten Joint Score) were recorded. There was a learning curve of 11 cases with the system that was associated with increased operative time (13 minutes, p<0.01) and improved insert sizing over time (p=0.03). There was no difference in implant survival (98.2%) between learning and proficiency phases (p = 0.15), and no difference in survivorship between ‘high’ and ‘low’ usage surgeons (p = 0.23) at 36 months. There were no differences in PROMS related to the learning curve. This suggested that the learning curve did not lead to early adverse effects in this patient cohort. The introduction of a robotic-arm assisted UKA system led to learning curves for operative time and implant sizing, but there was no effect on patient outcomes at early follow- up. The short learning curve was independent of UKA usage and indicated that robotic-arm assisted UKA may be particularly useful for low-usage surgeons


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 89 - 89
2 Jan 2024
Gao Y Wu X Zhang Z Xu J
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Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced bone regeneration disorders. In summary, our findings confirm the endogenous inhibitory effect of Nr4a1 on TGF- β1 and uncover the effectiveness of Nr4a1 agonists as a therapeutic tool to improve bone regeneration, which provides a new solution strategy for the treatment of clinical bone defects and inflammatory skeletal diseases


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 136 - 136
11 Apr 2023
Glatt V Woloszyk A Agarwal A
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Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats. Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT. Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling. The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 10 - 10
2 Jan 2024
Martínez T Mariscal G Hevia E Barrios C
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The multimodal management of canal stenosis is increasing, and inhibitors of central sensitization are playing a crucial role in central sensitization processes. Pregabalin and gabapentin are antiepileptic drugs that reduce presynaptic excitability. The objective of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of canal stenosis. A literature search was conducted in four databases. The inclusion criteria were studies that compared pregabalin or gabapentin with a control group in lumbar canal stenosis. Randomized clinical trials and a comparative retrospective cohort study were included. The main clinical endpoints were VAS/NRS, ODI, and RDQ (Roland Morris Disability Questionnaire) at 2, 4, 8 weeks, and 3 months, adverse events, and walking distance were also collected. Data were combined using Review Manager 5.4 software. Six studies and 392 patients were included. The mean age was 60.25. No significant differences were observed in VAS at 2, 4, and 8 weeks: (MD: 0.23; 95% CI: −0.63-1.09), (MD: −0.04; 95% CI: −0.64 to −0.57), and (MD: −0.6; 95% CI: −1.22 to 0.02). Significant differences were observed in favor of pregabalin with respect to VAS at three months: (MD: −2.97; 95% CI: −3.43 to −2.51). No significant differences were observed in ODI (MD: −3.47; 95% CI: −7.15 to −0.21). Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95%CI 1.28-27.05). Walking distance and RDQ could not be compared, although the results were controversial. Gabapentinoids have not been shown to be superior to other drugs used in the treatment of LSS or to placebo. However, they have shown a higher incidence of adverse effects, improved results in VAS at 3 months, and a slight improvement in ambulation at 4 months in combination with NSAIDs compared to NSAIDs in monotherapy


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 126 - 126
2 Jan 2024
Schmidt S Klampfleuthner F Diederichs S
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The signaling molecule prostaglandin E2 (PGE2), synthesized by cyclooxygenase-2 (COX-2), is immunoregulatory and reported to be essential for skeletal stem cell function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in osteoarthritis (OA) analgesia, but cohort studies suggested that long-term use may accelerate pathology. Interestingly, OA chondrocytes secrete high amounts of PGE2. Mesenchymal stromal cell (MSC) chondrogenesis is an in vitro OA model that phenocopies PGE2 secretion along with a hypertrophic OA-like cell morphology. Our aim was to investigate cause and effects of PGE2 secretion in MSC-based cartilage neogenesis and hypertrophy and identify molecular mechanisms responsible for adverse effects in OA analgesia. Human bone marrow-derived MSCs were cultured in chondrogenic medium with TGFβ (10ng/mL) and treated with PGE2 (1µM), celecoxib (COX-2 inhibitor; 0.5µM), AH23848/AH6809 (PGE2 receptor antagonists; 10µM), or DMSO as a control (n=3–4). Assessment criteria were proteoglycan deposition (histology), chondrocyte/hypertrophy marker expression (qPCR), and ALP activity. PGE2 secretion was measured (ELISA) after TGFβ withdrawal (from day 21, n=2) or WNT inhibition (2µM IWP-2 from day 14; n=3). Strong decrease in PGE2 secretion upon TGFβ deprivation or WNT inhibition identified both pathways as PGE2 drivers. Homogeneous proteoglycan deposition and COL2A1 expression analysis showed that MSC chondrogenesis was not compromised by any treatment. Importantly, hypertrophy markers (COL10A1, ALPL, SPP1, IBSP) were significantly reduced by PGE2 treatment, but increased by all inhibitors. Additionally, PGE2 significantly decreased ALP activity (2.9-fold), whereas the inhibitors caused a significant increase (1.3-fold, 1.7-fold, 1.8-fold). This identified PGE2 as an important inhibitor of chondrocyte hypertrophy. Although TGFβ and WNT are known pro-arthritic signaling pathways, they appear to induce a PGE2-mediated antihypertrophic effect that can counteract pathological cell changes in chondrocytes. Hampering this rescue mechanism via COX inhibition using NSAIDs thus risks acceleration of OA progression, indicating the need of OA analgesia adjustment


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 97 - 97
17 Apr 2023
Gupta P Butt S Mahajan R Galhoum A Lakdawala A
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Prompt mobilisation after the Fracture neck of femur surgery is one of the important key performance index (‘KPI caterpillar charts’ 2021) affecting the overall functional outcome and mortality. Better control of peri-operative blood pressure and minimal alteration of renal profile as a result of surgery and anaesthesia may have an implication on early post-operative mobilisation. Aim was to evaluate perioperative blood pressure measurements (duration of fall of systolic BP below the critical level of 90mmHg) and effect on the post-operative renal profile with the newer short acting spinal anaesthetic agent (prilocaine and chlorprocaine) used alongside the commonly used regional nerve block. 20 patients were randomly selected who were given the newer short acting spinal anaesthetic agent along with a regional nerve block between May 2019 and February 2020. Anaesthetic charts were reviewed from all patients for data collection. The assessment criteria for perioperative hypotension: Duration of systolic blood pressure less than 90 mm of Hg and change of pre and post operative renal functions. Only one patient had a significant drop in systolic BP less than 90mmHg (25 minutes). 3 other patients had a momentary fall of systolic BP of less than 5 minutes. None of the above patients had mortality and had negligible change in pre and post op renal function. Only one patient in this cohort had elevation of post-operative creatinine levels but did not have any mortality. Only 1 patient died on day 3 post operatively who had multiple comorbidities and was under evaluation for GI cancer. Even in this patient the peri-operative blood pressure was well maintained (never below 90mmHg systolic) and post-operative renal function was also shown to have improved (309 pre-operatively to 150 post-operatively) in this patient. The use of short-acting spinal anaesthesia has shown to be associated with a better control of blood pressure and end organ perfusion, less adverse effects on renal function leading to early mobilisation and a more favourable patient outcome with reduced mortality, earlier mobilisation, shorter hospital stay and earlier discharge in this elderly patient cohort


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 27 - 27
2 Jan 2024
Smith RK
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Stem cells represent an exciting biological therapy for the management of many musculoskeletal tissues that suffer degenerative disease and/or where the reparative process results in non-functional tissue (‘failed healing’). The original hypothesis was that implanted cells would differentiate into the target tissue cell type and synthesise new matrix. However, this has been little evidence that this happens in live animals compared to the laboratory, and more recent theories have focussed on the immunomodulatory effects via the release of paracrine factors that can still improve the outcome, especially since inflammation is now considered one of the central processes that drive poor tendon healing. Because of the initial ‘soft’ regulatory environment for the use of stem cells in domestic mammals, bone and fat-derived stem cells quickly established themselves as a useful treatment for naturally occurring musculoskeletal diseases in the horse more than 20 years ago (Smith, Korda et al. 2003). Since the tendinopathy in the horse has many similarities to human tendinopathy, we propose that the following challenges and, the lessons learnt, in this journey are highly relevant to the development of stem cells therapies for human tendinopathy:. Source – while MSCs can be recovered from many tissues, the predominant sources for autologous MSCs have been bone and fat. Other sources, including blood, amnion, synovium, and dental pulp have also been commercialised for allogenic treatments. Preparation – ex vivo culture requires transport from a licensed laboratory while ‘minimally manipulated’ preparations can be prepared patient-side. Cells also need a vehicle for transport and implantation. Delivery – transport of cells from the laboratory to the clinic for autologous ex vivo culture techniques; implantation technique (usually by ultrasound-guided injection to minimise damage to the cells (or, more rarely, incorporated into a scaffold). They can also be delivered by regional perfusion via venous or arterial routes. Retention – relatively poor although small numbers of cells do survive for at least 5 months. Immediate loss to the lungs if the cells are administered via vascular routes. Synovially administered cells do not engraft into tendon. Adverse effects – very safe although needle tracts often visible (but do not seen to adversely affect the outcome). Allogenic cells require careful characterisation for MHC Class II antigens to avoid anaphylaxis or reduced efficacy. Appropriate injuries to treat – requires a contained lesion when administered via intra-lesional injection. Intrasynovial tendon lesions are more often associated with surface defects and are therefore less appropriate for treatment. Earlier treatment appears to be more effective than delayed, when implantation by injection is more challenging. Efficacy - beneficial effects shown at both tissue and whole animal (clinical outcome) level in naturally-occurring equine tendinopathy using bone marrow-derived autologous MSCs Recent (licenced) allogenic MSC treatment has shown equivalent efficacy while intra-synovial administration of MSCs is ineffective for open intra-synovial tendon lesions. Regulatory hurdles – these have been lighter for veterinary treatments which has facilitated their development. There has been greater regulation of commercial allogenic MSC preparations which have required EMA marketing authorisation


Bone & Joint Research
Vol. 6, Issue 6 | Pages 366 - 375
1 Jun 2017
Neves N Linhares D Costa G Ribeiro CC Barbosa MA

Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions. This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1


Background. Adequate pain management is mandatory for patients' early rehabilitation and improvement of outcome after total knee arthroplasty (TKA). Conventional pain management, consisted of mainly opioids, has some adverse effects such as dizziness and nausea. Motor blockade occasionally resulted from epidural analgesics. A novel multimodal analgesic strategy with peripheral nerve block, peri-articular injection (PAI) and intravenous patient controlled analgesia (IVPCA) were utilized for our patients receiving TKA. In this study, we compared the clinical efficacy and adverse effects in the group of multimodal analgesia (MA) or epidural analgesia alone. Methods. One hundred and eighteen patients undergoing TKA with spinal anesthesia were enrolled. Patients of TKA received either our protocol of multimodal analgesia or patient controlled epidural analgesia (PCEA) alone. MA included ultrasound guided nerve block in femoral and obturator nerves before spinal anesthesia, and PAI mixed with NSAID, morphine, ropivacaine and epinephrine, as well as IVPCA after surgeries. The analgesic effect with numeric rating scale (NRS) and occurrence of adverse effects, including motor blockade, numbness, postoperative nausea/vomiting (PONV), and dizziness were recorded for all patients. Results. Thirty-one patients received MA, and eighty-seven patients received PCEA. No significant difference of NRS in MA and PCEA group within 24 hours after surgery either in rest (0.2 ± 1 compared with 0.22 ± 0.98; p = 0.930) or motion (0.40 ± 1.56 compared with 0.31± 1.23; p = 0.764). MA group sustained lesser motor blockade than PCEA (6.45% compared with 22.98%; p = 0.028) beyond 24 hours after surgery. The occurrence of numbness is lower in MA group (18.52%) compared with PCEA group(43.33%) (p=0.031). No statistic difference of PONV and dizziness is noted between two groups. However, there is a trend that lesser PONV and dizziness occurred in MA group than PCEA group. Conclusion. TKA patients receiving either MA or PCEA have adequate analgesic efficacy after surgeries. MA group has a lower incidence of motor blockade and PONV than PCEA. This multimodal analgesia proposed here has shown patients' safety and improved pain control after TKA, decreased narcotics use and their associated side effects. Besides, lesser motor blockade and adequate pain relief may encourage patient's early rehabilitation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 130 - 130
1 Nov 2021
Giorgino R Luca A Ruberto E Besozzi G Banfi G Peretti G
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Introduction and Objective. Over the past few years, a reorganization of the educational pathways has been promoted with the purpose of optimizing the acquisition of competences and their assessment, so as to reduce the risks to both health care professionals and end users. Virtual reality (VR) has been repeatedly tested, initially as a positive reinforcement for more traditional educational pathways and, more recently, as their potential substitute. The aim of this study was to demonstrate the potentiality of VR simulation training in spine surgery. Materials and Methods. The VR simulator reproduced the lateral lumbar access to the spine. The simulation included a tutorial, the preoperative settings, and the surgical session with different levels of procedural complexity. A total of 10 users were recruited for this study: 3 senior surgeons (group A) and 7 orthopedic residents or junior orthopedic surgeons (group B). Each user completed the simulation twice. Results. The user's age or previous experience with VR technology did not show any relevance. On average, the entire simulation was completed in 24 minutes and 36 seconds. Group B showed an improvement between the 2 attempts in both sessions, the preoperative settings and the surgical simulation. The number of major errors dropped from an average of 5.2 to 1.8 and from an average of 4 (1–6) to 1.4, respectively. The simulation was never interrupted because of technical bugs or adverse effects related to the technology. Conclusions. VR-based training pathways might promote a high standard of care. Our preliminary experience suggests an effective implementation of the traditional coaching process


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 44 - 44
1 Nov 2021
Salhab M Sonalwalkar S Anand S
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Introduction and Objective. Objectives: To determine the effectiveness of LIA compared to ACB in providing pain relief and reducing opiates usage in hamstring graft ACL reconstructions. Materials and Methods. In a consecutive series of hamstring graft ACL reconstructions, patients received three different regional and/or anaesthetic techniques for pain relief. Three groups were studied: group 1: general anaesthetic (GA)+ ACB (n=38); group 2: GA + ACB + LIA (n=31) and group 3: GA+LIA (n=36). ACB was given under ultrasound guidance. LIA involved infiltration at skin incision site, capsule, periosteum and in the hamstring harvest tunnel. Analgesic medications were similar between the three groups as per standard multimodal analgesia (MMA). Patients were similar in demographics distribution and surgical technique. The postoperative pain and total morphine requirements were evaluated and recorded. The postoperative pain was assessed using the visual analogue scores (VAS) at 0hrs, 2hrs, 4hrs, weight bearing (WB) and discharge (DC). Results. There was no statistically significant difference in opiates intake amongst the three groups. When comparing VAS scores; there were no statistical difference between the groups at any of the time intervals that VAS was measured. However, the GA+LIA group hospital's LOS (m=2.31hrs, SD=0.75) was almost half that of GA+ACB group (m=4.24hrs, SD=1.08); (conditions t(72)=8.88; p=0.000). There was no statistical significance in the incidence of adverse effects amongst the groups. Conclusions. The LIA technique provided equally good pain relief following hamstring graft ACL reconstructions when compared to ACB, while allowing for earlier rehabilitation, mobilisation and discharge


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 34 - 34
1 Mar 2021
Cheong VS Roberts B Kadirkamanathan V Dall’Ara E
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Abstract. Objectives. Prediction of bone adaptation in response to mechanical loading is useful in the clinical management of osteoporosis. However, few studies have investigated the effect of repeated mechanical loading in the mouse tibia. Therefore, this study uses a combined experimental and computational approach to evaluate the effect of mechanical loading on bone adaptation in a mouse model of osteoporosis. Methods. Six female C57BL/6 mice were ovariectomised (OVX) at week 14 and scanned using in vivo micro computed tomography (10.4µm/voxel) at week 14, 16, 18, 20 and 22. The right tibiae were mechanically loaded in vivo at week 19 and 21 with a 12N peak load, 40 cycles/day, 3 days/week. Linear isotropic homogeneous finite element (microFE) models were created from the tissue mineral density calibrated microCT images. Changes in bone adaptation, densitometric and spatial analyses were measured by comparing the longitudinal images after image registration. Results. Mechanical loading increased periosteal apposition between weeks 18–20, which reduced slightly between weeks 20–22. Periosteal resorption reduced between weeks 18–20. At weeks 20–22, it remained lower than before treatment, but was up to 70% higher than after the first week of loading. Average SED increased due to OVX before decreasing due to mechanical loading. The highest increase in SED was at the proximal tibia between weeks 14 to 16 (102%), whereas the highest reduction (40%) occurred after the second week of loading in the proximal tibia. Conclusions. The decrease/increase in bone apposition/resorption between weeks 20–22, despite the similar strain distributions between weeks 18–20 and 20–22, suggests that the first application of mechanical loading had a greater effect on reversing the adverse effects of the disease than the second. This imply that a systematic increase in peak load or loading rate may be required to achieve a similar bone adaptation rate with time. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 10 - 10
1 Dec 2020
Lim JA Thahir A Korde VA Krkovic M
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Object. The aim of this study was to investigate the impact of the COVID-19 pandemic on the management and outcome of patients with neck of femur fractures. Methods. Data was collected for 96 patients with neck of femur fractures who presented to the emergency department between March 1, 2020 and May 15, 2020. This data set included information about their COVID-19 status. Parameters including inpatient complications, hospital quality measures, mortality rates, and training opportunities were compared between the COVID-19 positive and COVID-19 negative groups. Furthermore, our current cohort of patients were compared against a historical control group of 95 patients who presented with neck of femur fractures before the COVID-19 pandemic. Results. Seven (7.3%) patients were confirmed COVID positive by RT-PCR testing. The COVID positive cohort, when compared to the COVID negative cohort, had higher rates of postoperative complications (71.4% vs 25.9%), increased length of stay (30.3 days vs 12 days) and quicker time to surgery (0.7 days vs 1.3 days). The 2020 cohort compared to the 2019 cohort, had an increased 30-day mortality rate (13.5% vs 4.2%), increased number of delayed cases (25% vs 11.8%) as well as reduced training opportunities for Orthopaedic trainees to perform the surgery (51.6% vs 22.8%). Conclusions. COVID-19 has had a profound impact on the care and outcome of neck of femur fracture patients during the pandemic with an increase in 30-day mortality rate. There were profound adverse effects on patient management pathways and outcomes while also affecting training opportunities


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 123 - 123
1 Dec 2020
Fong ELS Prabha EL Carney TJ
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Osteoporosis is a mineral bone disease arising from the predominance of osteoclastic bone resorption. Bisphosphonates which inhibit osteoclasts are commonly used in osteoporosis treatment, but are not without severe adverse effects like osteonecrosis of the jaw. The mechanisms behind the development of such phenomena is not well understood. Bone homeostasis is achieved through an intimate cross-talk between osteoclasts and osteoblasts. Thus, it is important to visualise activities of these cells simultaneously in situ. Currently, there are means to visualise osteoclast shape and numbers with tartrate-resistant alkaline phosphatase (TRAP) staining but no practical and accurate methods to quantify osteoclast activity in situ. This investigation aims to establish the use of ELF97, a substrate of TRAP, to visualise and quantify osteoclast activity. This provides vital clues to mechanisms of various bone disorders. TRAP dephosphorylation of ELF97 results in a detectable fluorescent product at areas of osteoclast activity. Osteoclastic activity was initiated in zebrafish by inducing crush injuries in tail fin rays. Colocalisation of ELF97 fluorescence with osteoclast-specific DsRed in transgenic zebrafish, visualised under confocal microscopy, is used to further establish the specificity of ELF97 to sites of osteoclastic activity. Quantification is established by comparing fluorescence between wild type, osteoclast-deficient mutants and bisphosphonate-treated zebrafish. The utility of ELF97 will also be investigated in terms of the stability of the florescent product. The investigation revealed that ELF97 and DsRed fluorescence were found commonly at crush sites with osteoclastic activity. Wild type zebrafish had greater fluorescence compared to osteoclast-deficient (p<0.0001) and bisphosphonate-treated zebrafish (p<0.0001) after 7 and 14 days post-crush, revealing that fluorescence from ELF97 corresponds to expected osteoclastic activity. Fluorescence of tail fins treated with ELF97 did not diminish over a period of 21 days of storage, demonstrating its stability. ELF97 is thus a useful means to visualise osteoclast activity, potentially crucial in more advanced investigations to understand bone disorders. It could be used in combination with other cellular markers in whole biological samples to study and experimentally manipulate bone remodelling


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 124 - 124
1 Mar 2021
Jelsma J Schotanus M Kleinveld H Grimm B Heyligers I
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An increase in metal ion levels is seen after implantation of all MoM hip prosthesis due to release from the surface directly, more so during articulation and corrosion of the bearing surfaces. The bearing surfaces in MoM prosthesis consist of cobalt, chromium and molybdenum. Several case-reports of cobalt toxicity due to a MoM prosthesis have been published in the last decade. Cobalt intoxication may lead to a variety of symptoms: neuro-ocular toxicity (tinnitus, vertigo, deafness, blindness, convulsions, headaches and peripheral neuropathy), cardiotoxicity and thyroid toxicity. Nausea, anorexia and unexplained weight loss have been described. Systemic effects from metal ions even with well functioning implants or with ion concentrations lower than those associated with known adverse effects may exist and warrant investigation. The aim of this study is to investigate self-reported systemic complaints in association with cobalt ion concentrations in patients with any type of MoM hip prosthesis. A cohort study was conducted. Patients with both unilateral and bilateral, resurfacing and large head metal on metal total hip arthroplasties were included for the current study. Blood metal ion concentrations (cobalt and chromium) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Based on the known cobalt toxicity symptoms of case-reports and toxicology reports a new non-validated questionnaire was developed. questions were subdivided in general questions/symptoms, vestibular symptoms, neurological symptoms, emotional health and cardio- and thyroid toxicity symptoms. Independent samples T test, Fishers Exact Test and Pearsons (R) correlation were used. Analysis was performed on two groups; a low cobalt ion concentration group and a high cobalt ion concentration group A total of 62 patients, 36 (58%) men and 26 (42%) women, were included with a mean age at surgery of 60.8 ± 9.3 years (41.6 – 78.1) and a mean follow up of 6.3 ± 1.4years (3.7 – 9.6). In these patients a total of 71 prosthesis were implanted: 53 unilateral and 9 bilateral. Of these, 44 were resurfacing and 27 large head metal on metal (LHMoM) total hip arthroplasties. Mean cobalt and chromium ion concentrations were 104 ± 141 nmol/L (9 – 833) and 95 ± 130nmol/L (6 – 592), respectively. Based on the different thresholds (120 – 170 or 220 nmol/L) the low cobalt ion concentration group consisted of 44 (71%), 51 (82%) or 55 (89%) subjects respectively. No differences were found in general characteristics, independently of the threshold. The composite score of vestibular symptoms (vision, hearing, tinnitus, dizziness) was significantly higher (p < .050) in all high cobalt ion concentrations groups, independent of the threshold value This study aimed to detect a trend in self-reported systemic complaints in patients with metal-on-metal hip arthroplasty due to raised cobalt ion concentrations. Vestibular symptoms were more common in high cobalt ion concentration groups independent of the three threshold levels tested. The upper limit of acceptable cobalt ion concentrations remains uncertain. With regards to proactively inquired, self-reported symptoms the threshold where effects may be present could be lower than values currently applied in clinical follow-up. It is unknown what exposure to elevated metal ion concentrations for a longer period of time causes with aging subjects. Further research with a larger cohort and a more standardized questionnaire is necessary to detect previously undiscovered or under-reported effects


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 23 - 23
1 Jan 2019
Prokopovich P
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The efficient delivery of therapeutic molecules to the cartilage of joints is major obstacle in developing useful therapeutic interventions; hence, a targeted drug delivery system for this tissue is critical. We have overcome the challenge by developing a system that employs electrostatic attraction between the negatively charged constituents of cartilage and a positively charged polymer, poly-beta amino esters (PBAEs). We have demonstrated cartilage uptake of dexamethasone (DEX) covalently bound to the PBAE was doubled and retention in tissues prolonged compared to the equivalent dose of the commercial drug formulation. Moreover, no adverse effects on chondrocytes were found. Our data also show [1, 2] that PBAEs can bind not only healthy cartilage tissues but also enzymatically treated cartilage mimicking early stages of OA. Our PBAEs-prodrug technology's advantages are fourfold; the specificity and efficacy of its targeting mechanism for cartilage, the ease of its production and the low-cost nature of the delivery system


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 77 - 77
1 Nov 2018
Molino G Dalpozzi A Ciapetti G Fiorillia S Vitale-Brovarone C
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Osteoporosis is a worldwide disease with a high prevalence in elderly population; it results in bone loss and decreased bone strength that lead to low-energy fractures. Since antiresorptive treatments could lead to long-term adverse effects, the ERC BOOST project aims to propose a biomimetic 3D-printed scaffold reproducing the architecture and chemistry of healthy bone. In this study, the structural parameters of healthy bone were studied in order to reproduce them through 3D printing; furthermore, structural and mechanical differences between healthy and osteoporotic (OP) bones were assessed. Healthy and OP humeral heads discarded during surgical interventions (following ethical approval by Istituto Ortopedico Rizzoli-Italy) were tomographically analysed to obtain bone structural parameters. Successively, 8 mm diameter biopsies were harvested from the heads and underwent compression and nanoindentation tests to investigate macroscopic and microscopic mechanical properties, respectively. XRD measurements were performed on bone fragments. OP bone samples exhibited inferior mechanical properties to their less interconnected and more anisotropic structure, with thinner trabeculae and larger pores. On the other hand, nanoindentations performed on OP trabeculae showed increased Young Modulus compared to healthy samples probably due to their increased hydroxyapatite crystal size, as revealed by XRD. Osteoporosis causes the weakening of the trabecular structure that leads to a decrease of bone mechanical properties. However, OP trabeculae are stiffer due to increased dimensions of hydroxyapatite crystals


Bone & Joint Research
Vol. 3, Issue 3 | Pages 76 - 81
1 Mar 2014
Okabe YT Kondo T Mishima K Hayase Y Kato K Mizuno M Ishiguro N Kitoh H

Objectives. In order to ensure safety of the cell-based therapy for bone regeneration, we examined in vivo biodistribution of locally or systemically transplanted osteoblast-like cells generated from bone marrow (BM) derived mononuclear cells. Methods. BM cells obtained from a total of 13 Sprague-Dawley (SD) green fluorescent protein transgenic (GFP-Tg) rats were culture-expanded in an osteogenic differentiation medium for three weeks. Osteoblast-like cells were then locally transplanted with collagen scaffolds to the rat model of segmental bone defect. Donor cells were also intravenously infused to the normal Sprague-Dawley (SD) rats for systemic biodistribution. The flow cytometric and histological analyses were performed for cellular tracking after transplantation. Results. Locally transplanted donor cells remained within the vicinity of the transplantation site without migrating to other organs. Systemically administered large amounts of osteoblast-like cells were cleared from various organ tissues within three days of transplantation and did not show any adverse effects in the transplanted rats. Conclusions. We demonstrated a precise assessment of donor cell biodistribution that further augments prospective utility of regenerative cell therapy. Cite this article: Bone Joint Res 2014;3:76–81


Bone & Joint Research
Vol. 5, Issue 3 | Pages 95 - 100
1 Mar 2016
Pilge H Fröbel J Prodinger PM Mrotzek SJ Fischer JC Zilkens C Bittersohl B Krauspe R

Objectives. Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results. We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions. Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595