Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

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This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Aims. The Ponseti method is the benchmark treatment for the correction of clubfoot. The primary rate of correction is very high, but outcome further down the treatment pathway is less predictable. Several methods of assessing severity at presentation have been reported. Classification later in the course of treatment is more challenging. This systematic review considers the outcome of the Ponseti method in terms of relapse and determines how clubfoot is assessed at presentation, correction, and relapse. Patients and Methods. A prospectively registered systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that reported idiopathic clubfoot treated by the Ponseti method between 1 January 2012 and 31 May 2017 were included. The data extracted included demographics, Ponseti methodology, assessment methods, and rates of relapse and surgery. Results. A total of 84 studies were included (7335 patients, 10 535 clubfeet). The relapse rate varied between 1.9% and 45%. The rates of relapse and major surgery (1.4% to 53.3%) and minor surgery (0.6% to 48.8%) both increased with follow-up time. There was high variability in the assessment methods used across timepoints; only 57% of the studies defined relapse. Pirani scoring was the method most often used. Conclusion. Recurrence and further surgical intervention in idiopathic clubfoot increases with the duration of follow-up. The corrected and the relapsed foot are poorly defined, which contributes to variability in outcome. The results suggest that a consensus for a definition of relapse is needed. Cite this article: Bone Joint J 2019;101-B:639–645

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The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

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This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Aim. Restarting elective services presents a challenge to restore and improve many of the planned patient care pathways which have been suspended during the response to the COVID-19 pandemic. A significant backlog of planned elective work has built up representing a considerable volume of patient need. We aimed to investigate the health status, quality of life, and the impact of delay for patients whose referrals and treatment for symptomatic joint arthritis had been delayed as a result of the response to COVID-19. Methods. We interviewed 111 patients referred to our elective outpatient service and whose first appointments had been cancelled as a result of the response to the COVID-19 pandemic. Results. Patients reported significant impacts on their health status and quality of life. Overall, 79 (71.2%) patients reported a further deterioration in their condition while waiting, with seven (6.3%) evaluating their health status as ‘worse than death’. Conclusions. Waiting lists are clearly not benign and how to prioritize patients, their level of need, and access to assessment and treatment must be more sophisticated than simply relying on the length of time a patient has been waiting. This paper supports the contention that patients awaiting elective joint arthroplasty report significant impacts on their quality of life and health status. This should be given appropriate weight when patients are prioritized for surgery as part of the recovery of services following the COVID-19 pandemic. Elective surgery should not be seen as optional surgery—patients do not see it in this way

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Cite this article: Bone Joint Res 2024;13(9):462–473.

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To review the evidence and reach consensus on recommendations for follow-up after total hip and knee arthroplasty.

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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.

Aims. The Bundled Payments for Care Improvement (BPCI) initiative has identified pathways for improving the value of care. However, patient-specific modifiable and non-modifiable risk factors may increase costs beyond the target payment. We sought to identify risk factors for exceeding our institution’s target payment, the so-called ‘bundle busters’. Patients and Methods. Using our data warehouse and Centers for Medicare and Medicaid Services (CMS) data we identified all 412 patients who underwent total joint arthroplasty and qualified for our institution’s BPCI model, between July 2015 and May 2017. Episodes where CMS payments exceeded the target payment were considered ‘busters’ (n = 123). Risk ratios (RRs) were calculated using a modified Poisson regression analysis. Results. An increased risk of exceeding the target payment was significantly associated with increasing age (adjusted RR 1.04, 95% confidence interval (CI) 1.01 to 1.06) and body mass index (adjusted RR 1.03, 95% CI 1.003 to 1.06). Eight comorbid risk factors were also identified (all p < 0.05), only two of which were considered to be potentially modifiable (diabetes with complications and preoperative anaemia). An American Society of Anesthesiologist physical status classification system (ASA) score ≥ 3 (adjusted RR 2.3, 95% CI 1.67 to 3.18) and Charlson Comorbidity Index (CCI) ≥ 3 (adjusted RR 1.94, 95% CI 1.45 to 2.60) were risk factors for bundle busting. Conclusion. Non-modifiable preoperative risk factors can increase costs and exceed the target payment. Future bundled payment models should incorporate the stratification of risk. Cite this article: Bone Joint J 2019;101-B(7 Supple C):64–69

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There is a lack of published evidence relating to the rate of nonunion seen in occult scaphoid fractures, diagnosed only after MRI. This study reports the rate of delayed union and nonunion in a cohort of patients with MRI-detected acute scaphoid fractures.

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

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Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

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To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

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This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Aims. The aim of this study was to review the value of accepting referrals for children with ‘clicky hips’ in a selective screening programme for hip dysplasia. Patients and Methods. A single-centre prospective database of all referrals to the hip clinic was examined to identify indication for referrals, diagnosis, and treatment. All patients referred received a standardized ultrasound scan and clinical examination by an orthopaedic consultant. Results. There were 5716 children referred to the orthopaedic hip clinic between 1 June 2014 and 26 September 2018. In all, 1754 children (30.1%) were referred due to ‘clicky hip’ with no additional risk factors or indications for ultrasound scan. A total of 123 children (7.1%) referred with ‘clicky hip’ and no additional risk factors or examination findings had an abnormal initial hip ultrasound, including 16 children (0.9%) with dysplastic hips. Of the 141 children who required treatment in a Pavlik harness during the study period, 23 (16%) had been referred with a ‘clicky hip’ and no additional risk factors or examination findings, including six children with Graf 3 or 4 hips. Conclusion. There is significant value in reviewing children with an isolated ‘clicky hip’. Many children who require treatment are referred to the orthopaedic service as ‘clicky hip’ with no additional risk factors. In a pragmatic pathway with a diverse population of clinicians performing baby checks, ‘clicky hip’ is an important indication for referral and should not be discarded. Cite this article: Bone Joint J 2019;101-B:635–638

The August 2023 Knee Roundup³⁶⁰ looks at: Curettage and cementation of giant cell tumour of bone: is arthritis a given?; Anterior knee pain following total knee arthroplasty: does the patellar cement-bone interface affect postoperative anterior knee pain?; Nickel allergy and total knee arthroplasty; The use of artificial intelligence for the prediction of periprosthetic joint infection following aseptic revision total knee arthroplasty; Ambulatory unicompartmental knee arthroplasty: development of a patient selection tool using machine learning; Femoral asymmetry: a missing piece in knee alignment; Needle arthroscopy – a benefit to patients in the outpatient setting; Can lateral unicompartmental knees be done in a day-case setting?

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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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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.