Aims. Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (. 99m. Tc-UBI. 29-41. -Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. Methods. 99m. Tc-UBI. 29-41. -Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. Results. Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. Conclusion. The hybrid tracer . 99m. Tc-UBI. 29-41. -Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79

Aims. Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods. The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results. Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion. Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article:Bone Joint Res. 2020;9(3):120–129

Objectives. As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration. Methods. All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation. Results. The 13 surgeons who participated in the discussion represented orthopaedic oncology practices from seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and Canada). Four categories and associated themes emerged from the discussion: the need for collaboration in the field of orthopaedic oncology due to the rarity of the tumours and the need for high level evidence to guide treatment; motivational factors for participating in collaborative research including establishing proof of principle, learning opportunity, answering a relevant research question and being part of a collaborative research community; barriers to participation including funding, personal barriers, institutional barriers, trial barriers, and administrative barriers and facilitators for participation including institutional facilitators, leadership, authorship, trial set-up, and the support of centralised study coordination. Conclusions. Orthopaedic surgeons involved in an ongoing international randomised controlled trial (RCT) were motivated by many factors to participate. There were a number of barriers to and facilitators for their participation. There was a collective sense of fatigue experienced in overcoming these barriers, which was mirrored by a strong collective sense of the importance of, and need for, collaborative research in this field. The experiences were described as essential educational first steps to advance collaborative studies in this area. Knowledge gained from this study will inform the development of future large-scale collaborative research projects in orthopaedic oncology. Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M. Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P. McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Vélez, K. Weiss, J. P. Zumárraga, M. Ghert. Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study. Bone Joint Res 2017;6:–314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1

Objectives. A patient-centred approach, usually achieved through shared decision making, has the potential to help improve decision making around knee arthroplasty surgery. However, such an approach requires an understanding of the factors involved in patient decision making. This review’s objective is to systematically examine the qualitative literature surrounding patients’ decision making in knee arthroplasty. Methods. A systematic literature review using Medline and Embase was conducted to identify qualitative studies that examined patients’ decision making around knee arthroplasty. An aggregated account of what is known about patients’ decision making in knee arthroplasties is provided. Results. Seven studies with 234 participants in interviews or focus groups are included. Ten themes are replicated across studies, namely: expectations of surgery; coping mechanisms; relationship with clinician; fear; pain; function; psychological implications; social network; previous experience of surgery; and conflict in opinions. Conclusions. This review is helpful in not only directing future research to areas that are not understood, or require confirmation, but also in highlighting areas that future interventions could address. These include those aimed at delivering information, which are likely to affect the satisfaction rate, demand, and use of knee arthroplasties. Cite this article: Bone Joint Res 2015;4;163–169

Objectives. Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that . 99m. Tc-methylene diphosphonate (. 99m. Tc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA). Methods. Within the present study, we evaluated whether this promising new method, using . 99m. Tc-hydroxydiphosphonate (. 99m. Tc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with . 99m. Tc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured. Results. We saw a higher uptake (up to 15-fold) of the tracer in the OSM group A compared with the CNTRL group B. Statistical analysis of the results (Student`s t-test) revealed a significantly higher amount of emitted gamma counts in the OSM group (p = 0.048). Qualitative and semi-quantitative analysis by Alizarin Red staining confirmed the presence of extracellular HA deposition in the OSM group. Conclusion. Our data indicate that . 99m. Tc-HDP labelling is a promising tool to track and quantify non-destructive local HA deposition in 3D stem cell cultures. Cite this article: T. L. Grossner, U. Haberkorn, T. Gotterbarm. . 99m. Tc-Hydroxydiphosphonate quantification of extracellular matrix mineralization in 3D human mesenchymal stem cell cultures. Bone Joint Res 2019;8:333–341. doi: 10.1302/2046-3758.87.BJR-2017-0248.R1

Introduction. The objective of this study was to determine if a synthetic bone substitute would provide results similar to bone from osteoporotic femoral heads during in vitro testing with orthopaedic implants. If the synthetic material could produce results similar to those of the osteoporotic bone, it could reduce or eliminate the need for testing of implants on bone. Methods. Pushout studies were performed with the dynamic hip screw (DHS) and the DHS Blade in both cadaveric femoral heads and artificial bone substitutes in the form of polyurethane foam blocks of different density. The pushout studies were performed as a means of comparing the force displacement curves produced by each implant within each material. Results. The results demonstrated that test material with a density of 0.16 g/cm. 3. (block A) produced qualitatively similar force displacement curves for the DHS and qualitatively and quantitatively similar force displacement curves for the DHS Blade, whereas the test material with a density of 0.08 g/cm. 3. (block B) did not produce results that were predictive of those recorded within the osteoporotic cadaveric femoral heads. Conclusion. This study demonstrates that synthetic material with a density of 0.16 g/cm. 3. can provide a good substitute for cadaveric osteoporotic femoral heads in the testing of implants. However we do recognise that no synthetic material can be considered as a definitive substitute for bone, therefore studies performed with artificial bone substrates may need to be validated by further testing with a small bone sample in order to produce conclusive results

Aims. To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements. Methods. A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization). Results. The pSFT remodelled into a ligament-like structure and no adverse inflammatory reaction was seen. The ground reaction force in the operated leg of the Endobutton group was higher at 11 weeks (p < 0.05). An indirect insertion was seen at the graft-bone interface characterized by Sharpey-like fibres. Qualitative differences in tendon remodelling were seen between the two groups, with greater crimp-like organization and more aligned collagen fibres seen with Endobutton fixation. One graft rupture occurred in the cross-pin group, which histologically showed low collagen organization. Conclusion. Decellularized pSFT xenograft remodels into a ligament-like structure after 12 weeks and regenerates an indirect-type insertion with Sharpey-like fibres. No adverse inflammatory reaction was observed. Cortical suspensory femoral fixation was associated with more enhanced graft remodelling and earlier functional recovery when compared with the stiffer cross-pin fixation

Objectives. To explore whether orthopaedic surgeons have adopted the Proximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial results routinely into clinical practice. Methods. A questionnaire was piloted with six orthopaedic surgeons using a ‘think aloud’ process. The final questionnaire contained 29 items and was distributed online to surgeon members of the British Orthopaedic Association and British Elbow and Shoulder Society. Descriptive statistics summarised the sample characteristics and fracture treatment of respondents overall, and grouped them by whether they changed practice based on PROFHER trial findings. Free-text responses were analysed qualitatively for emerging themes using Framework Analysis principles. Results. There were complete responses from 265 orthopaedic and trauma surgeons who treat patients with proximal humeral fractures. Around half (137) had changed practice to various extents because of PROFHER, by operating on fewer PROFHER-eligible fractures. A third (43) of the 128 respondents who had not changed practice were already managing patients non-operatively. Those who changed practice were more likely to be younger, work in a trauma unit rather than a major trauma centre, be specialist shoulder surgeons and treat fewer PROFHER-eligible fractures surgically. This group gave higher scores when assessing validity and applicability of PROFHER. In contrast, a quarter of the non-changers were critical, sometimes emphatically, of PROFHER. The strongest theme that emerged overall was the endorsement of evidence-based practice. Conclusion. PROFHER has had an impact on surgeons’ clinical practice, both through changing it, and through underpinning existing non-operative practice. Although some respondents expressed reservations about the trial, evidence from such trials was found to be the most important influence on surgeons’ decisions to change practice. Cite this article: L. Jefferson, S. Brealey, H. Handoll, A. Keding, L. Kottam, I. Sbizzera, A. Rangan. Impact of the PROFHER trial findings on surgeons’ clinical practice: An online questionnaire survey. Bone Joint Res 2017;6:590–599. DOI: 10.1302/2046-3758.610.BJR-2017-0170

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Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture.

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Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Cite this article: Bone Joint Res 2023;12(6):372–374.

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A core outcome set for adult, open lower limb fracture has been established consisting of ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. This study aims to identify which outcome measurement instruments (OMIs) should be recommended to measure each core outcome.

Objectives. This study aimed to characterise and qualitatively grade the severity of the corrosion particles released into the hip joint following taper corrosion. Methods. The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n = 13). Blood serum metal ion levels were collected before and after revision surgery. The haematoxylin and eosin tissue sections were graded on the presence of fibrin exudates, necrosis, inflammatory cells and corrosion products. The corrosion products were identified based on visible observation and graded on abundance. Two independent observers blinded to the clinical patient findings scored all cases. Elemental analysis was performed on corrosion products within tissue sections. X-Ray diffraction was used to identify crystalline structures present in taper debris. Results. The CoC/ABG Modular patients had a mean age of 64.6 years (49.4 to 76.5) and ASR/SROM patients had a mean age of 58.2 years (33.3 to 85.6). The mean time in situ for CoC/ABG was 4.9 years (2 to 6.4) and ASR/SROM was 6.1 years (2.5 to 8.1). The blood serum metal ion concentrations reduced following revision surgery with the exception of Cr levels within CoC/ABG. The grading of tissue sections showed that the macrophage response and metal debris were significantly higher for the ASR/SROM patients (p < 0.001). The brown/red particles were significantly higher for ASR/SROM (p < 0.001). The taper debris contained traces of titanium oxide, chromium oxide and aluminium nitride. Conclusion. This study characterised and qualitatively graded the severity of the corrosion particles released into the hip joint from tapers that had corrosion damage. Cite this article: S. Munir, R. A. Oliver, B. Zicat, W. L. Walter, W. K. Walter, W. R. Walsh. The histological and elemental characterisation of corrosion particles from taper junctions. Bone Joint Res 2016;5:370–378. DOI: 10.1302/2046-3758.59.2000507

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Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

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As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

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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.

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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.

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The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

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Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years.

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The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy.