Aims. This study aims to enhance understanding of clinical and radiological consequences and involved mechanisms that led to corrosion of the Precice Stryde (Stryde) intramedullary lengthening nail in the post market surveillance era of the device. Between 2018 and 2021 more than 2,000 Stryde nails have been implanted worldwide. However, the outcome of treatment with the Stryde system is insufficiently reported. Methods. This is a retrospective single-centre study analyzing outcome of 57 consecutive lengthening procedures performed with the Stryde nail at the authors’ institution from February 2019 until November 2020. Macro- and microscopic metallographic analysis of four retrieved nails was conducted. To investigate observed corrosion at telescoping junction, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX) were performed. Results. Adjacent to the nail’s telescoping junction, osteolytic changes were observed in bi-planar radiographs of 20/57 segments (35%) after a mean of 9.5 months (95% confidence interval 7.2 to 11.9) after surgery. A total of 8/20 patients with osseous alterations (40%) reported rest and ambulation pain of the lengthened segment during consolidation. So far, 24 Stryde nails were retrieved and in 20 (83%) macroscopic corrosion was observed at the nail’s telescoping junction. Before implant removal 11/20 radiographs (55%) of lengthened segments with these 20 nails revealed osteolysis. Implant retrieval analysis by means of SEM showed pitting and crevice corrosion. EDX detected chromium as the main metallic element of corrosion. Conclusion. Patients are exposed to the risk of implant-related osteolysis of unclear short- and long-term clinical consequences. The authors advocate in favour of an early implant removal after osseous consolidation. Cite this article: Bone Joint Res 2021;10(7):425–436

Objectives. The Precice nail is the latest intramedullary lengthening nail with excellent early outcomes. Implant complications have led to modification of the nail design. The aim of this study was to perform a retrieval study of Precice nails following lower-limb lengthening and to assess macroscopical and microscopical changes to the implants and evaluate differences following design modification, with the aim of identifying potential surgical, implant, and patient risk factors. Methods. A total of 15 nails were retrieved from 13 patients following lower-limb lengthening. Macroscopical and microscopical surface damage to the nails were identified. Further analysis included radiology and micro-CT prior to sectioning. The internal mechanism was then analyzed with scanning electron microscopy and energy dispersive x-ray spectroscopy to identify corrosion. Results. Seven male and three female patients underwent 12 femoral lengthenings. Three female patients underwent tibial lengthening. All patients obtained the desired length with no implant failure. Surface degradation was noted on the telescopic part of every nail design, less on the latest implants. Microscopical analysis confirmed fretting and pitting corrosion. Following sectioning, black debris was noted in all implants. The early designs were found to have fractured actuator pins and the pin and bearings showed evidence of corrosive debris. The latest designs showed evidence of biological deposits suggestive of fluid ingress within the nail but no corrosion. Conclusion. This study confirms less internal corrosion following modification, but evidence of titanium debris remains. We recommend no change to current clinical practice. However, potential reuse of the Precice nail, for secondary limb lengthening in the same patient, should be undertaken with caution. Cite this article: V. C. Panagiotopoulou, K. Davda, H. S. Hothi, J. Henckel, A. Cerquiglini, W. D. Goodier, J. Skinner, A. Hart, P. R. Calder. A retrieval analysis of the Precice intramedullary limb lengthening system. Bone Joint Res 2018;7:476–484. DOI: 10.1302/2046-3758.77.BJR-2017-0359.R1

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Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666

Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results. Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion. We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39

Objectives. The paradoxical migration of the femoral neck element (FNE) superomedially against gravity, with respect to the intramedullary component of the cephalomedullary device, is a poorly understood phenomenon increasingly seen in the management of pertrochanteric hip fractures with the intramedullary nail. The aim of this study was to investigate the role of bidirectional loading on the medial migration phenomenon, based on unique wear patterns seen on scanning electron microscopy of retrieved implants suggestive of FNE toggling. Methods. A total of 18 synthetic femurs (Sawbones, Vashon Island, Washington) with comminuted pertrochanteric fractures were divided into three groups (n = 6 per group). Fracture fixation was performed using the Proximal Femoral Nail Antirotation (PFNA) implant (Synthes, Oberdorf, Switzerland; n = 6). Group 1 was subjected to unidirectional compression loading (600 N), with an elastomer (70A durometer) replacing loose fracture fragments to simulate surrounding soft-tissue tensioning. Group 2 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading), also with the elastomer replacing loose fracture fragments. Group 3 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading) without the elastomer. All constructs were tested at 2 Hz for 5000 cycles or until cut-out occurred. The medial migration distance (MMD) was recorded at the end of the testing cycles. Results. The MMDs for Groups 1, 2, and 3 were 1.02 mm, 6.27 mm, and 5.44 mm respectively, with reliable reproduction of medial migration seen in all groups. Bidirectional loading groups showed significantly higher MMDs compared with the unidirectional loading group (p < 0.01). Conclusion. Our results demonstrate significant contributions of bidirectional cyclic loading to the medial migration phenomenon in cephalomedullary nail fixation of pertrochanteric hip fractures. Cite this article: G. W. Law, Y. R. Wong, A. K-S. Yew, A. C. T. Choh, J. S. B. Koh, T. S. Howe. Medial migration in cephalomedullary nail fixation of pertrochanteric hip fractures: A biomechanical analysis using a novel bidirectional cyclic loading model. Bone Joint Res 2019;8:313–322. DOI: 10.1302/2046-3758.87.BJR-2018-0271.R1

Objectives. The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. Methods. A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. Results. A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). Conclusions. Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively. Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178–184. DOI: 10.1302/2046-3758.55.2000596

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This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture.

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Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells.

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This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Objectives. Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years. Methods. A total of 571 patients were included in this study, which analysed the incidence of cut-out in relation to several clinical variables: age; gender; the AO Foundation and Orthopaedic Trauma Association classification system (AO/OTA); type of nail; cervical-diaphyseal angle; surgical wait times; anti-osteoporotic medication; complete post-operative weight bearing; and radiological parameters (namely the lag-screw position with respect to the femoral head, the Cleveland system, the tip-apex distance (TAD), and the calcar-referenced tip-apex distance (CalTAD)). Results. The incidence of cut-out across the sample was 5.6%, with a higher incidence in female patients. A significantly higher risk of this complication was correlated with lag-screw tip positioning in the upper part of the femoral head in the anteroposterior radiological view, posterior in the latero-lateral radiological view, and in the Cleveland peripheral zones. The tip-apex distance and the calcar-referenced tip-apex distance were found to be highly significant predictors of the risk of cut-out at cut-offs of 30.7 mm and 37.3 mm, respectively, but the former appeared more reliable than the latter in predicting the occurrence of this complication. Conclusion. The tip-apex distance remains the most accurate predictor of cut-out, which is significantly greater above a cut-off of 30.7 mm. Cite this article: G. Caruso, M. Bonomo, G. Valpiani, G. Salvatori, A. Gildone, V. Lorusso, L. Massari. A six-year retrospective analysis of cut-out risk predictors in cephalomedullary nailing for pertrochanteric fractures: Can the tip-apex distance (TAD) still be considered the best parameter?. Bone Joint Res 2017;6:481–488. DOI: 10.1302/2046-3758.68.BJR-2016-0299.R1

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Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.

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Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

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Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

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This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Objectives. Osteosynthesis of anterior pubic ramus fractures using one large-diameter screw can be challenging in terms of both surgical procedure and fixation stability. Small-fragment screws have the advantage of following the pelvic cortex and being more flexible. The aim of the present study was to biomechanically compare retrograde intramedullary fixation of the superior pubic ramus using either one large- or two small-diameter screws. Materials and Methods. A total of 12 human cadaveric hemipelvises were analysed in a matched pair study design. Bone mineral density of the specimens was 68 mgHA/cm. 3. (standard deviation (. sd). 52). The anterior pelvic ring fracture was fixed with either one 7.3 mm cannulated screw (Group 1) or two 3.5 mm pelvic cortex screws (Group 2). Progressively increasing cyclic axial loading was applied through the acetabulum. Relative movements in terms of interfragmentary displacement and gap angle at the fracture site were evaluated by means of optical movement tracking. The Wilcoxon signed-rank test was applied to identify significant differences between the groups. Results. Initial axial construct stiffness was not significantly different between the groups (p = 0.463). Interfragmentary displacement and gap angle at the fracture site were also not statistically significantly different between the groups throughout the evaluated cycles (p ⩾ 0.249). Similarly, cycles to failure were not statistically different between Group 1 (8438, . sd. 6968) and Group 2 (10 213, . sd. 10 334), p = 0.379. Failure mode in both groups was characterised by screw cutting through the cancellous bone. Conclusion. From a biomechanical point of view, pubic ramus stabilisation with either one large or two small fragment screw osteosynthesis is comparable in osteoporotic bone. However, the two-screw fixation technique is less demanding as the smaller screws deflect at the cortical margins. Cite this article: Y. P. Acklin, I. Zderic, S. Grechenig, R. G. Richards, P. Schmitz, B. Gueorguiev. Are two retrograde 3.5 mm screws superior to one 7.3 mm screw for anterior pelvic ring fixation in bones with low bone mineral density? Bone Joint Res 2017;6:8–13. DOI: 10.1302/2046-3758.61.BJR-2016-0261

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A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Objectives. We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results. When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion. This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2