Aims. Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific genetic mechanisms underlying OA remain only partially understood, hindering the development of targeted therapeutic strategies. Methods. A transcriptome-wide association study (TWAS) was conducted for site-specific OA phenotypes using functional summary-based imputation (FUSION). High-confidence candidate genes were identified through rigorous quality control measures, including joint/conditional analysis, permutation tests, best model evaluation, and colocalization analysis. Co-expression network analysis was performed to elucidate the functional biology of these candidate genes. Druggable gene targets and their structural models were retrieved from the DrugBank and SWISS-MODEL databases. Finally, the enrichment of mitogen-activated protein kinase 3 (MAPK3) and SMAD3 in OA was validated biochemically using in vitro and in vivo OA models, as well as human histological sections. Results. Utilizing the FUSION algorithm, TWAS identified 794 candidate genes for OA. After quality control, 14 genes were classified as high-confidence genes, with seven recognized as potential drug targets including GCAT, MAPK3, MST1R, PFKM, RAD9A, SMAD3, and USAP8. Co-expression analysis revealed a strong biological association between SMAD3 and MAPK3. Both in vitro and in vivo experiments demonstrated high activity and enriched expression of these two genes in OA. Conclusion. The present study identified tissue-specific candidate genes and validated high-confidence druggable targets for OA, providing new insights into the genetic landscape and biological processes involved in OA. Further functional studies are warranted to confirm these findings. Cite this article: Bone Joint Res 2025;14(3):224–235

Aims. The effectiveness of total hip arthroplasty (THA) for patients with no or minimal radiological signs of osteoarthritis (OA) is unclear. In this study, we aimed to: 1) assess the outcome of such patients; 2) identify patient comorbidities and CT or MRI findings which predicted outcome; and 3) compare their outcome to the expected outcome of THA for hip OA. Methods. Adult patients undergoing THA for hip pain, with no or minimal radiological features of OA (Tönnis grading scale ≤ 1), were identified from a consecutive series of 1,925 THAs. Exclusion criteria were: inflammatory arthritis; osteonecrosis of the femoral head; prior trauma or infection; and patients without minimum one-year follow-up and patient-reported outcome measures (PROMs). The primary outcome measure was the Oxford Hip Score (OHS). Secondary outcome measures were EuroQol-visual analogue scale (EQ-VAS), University of California and Los Angeles (UCLA) scale, and patient satisfaction on a validated three-point ‘better’, ‘same’, or ‘worse’ scale. Results. A total of 107 patients with a median age of 41 years (IQR 18 to 73) were included, with mean follow-up of 6.0 years (SD 3.1). All patients underwent a diagnostic hip injection as a decision aid. Median postoperative OHS was 34 (IQR 28 to 42), with 36 patients (33%) achieving a patient-acceptable symptom state (OHS ≥ 42), lower than THA patients in international registries (40 to 43 points). Secondary outcomes were UCLA of 6 (4 to 8) and EQ-VAS of 73 (51 to 80); 91/102 patients (89%) felt ‘better’ and would ‘undergo surgery again'. Patients with chronic pain syndrome or hypermobility had lower OHS than patients without comorbidities (-6 points, p < 0.006). Overall, 84 patients had a CT and 34 patients an MRI. Patients with subchondral cysts (OHS 42 (37 to 45) vs 35 (26 to 36); p = 0.014) or joint space narrowing on CT (OHS 42 (IQR 37 to 44) vs 35 (26 to 36); p = 0.022) had higher function. Conclusion. Despite high satisfaction levels, patients undergoing THA with minimal or no radiological OA had lower postoperative function than typical THA patients. We recommend obtaining low-dose CT imaging and a diagnostic hip injection to aid decision-making. Cite this article: Bone Jt Open 2025;6(3):328–335

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Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy.

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Assessment of bone health is a multifaceted clinical process, incorporating biochemical and diagnostic tests that should be accurate and reproducible. Dual-energy X-ray absorptiometry (DXA) is the reference standard for evaluation of bone mineral density, but has known limitations. Alternatives include quantitative CT (q-CT), MRI, and peripheral quantitative ultrasound (QUS). Radiofrequency echographic multispectrometry (REMS) is a new generation of ultrasound technology used for the assessment of bone mineral density (BMD) at axial sites that is as accurate as quality-assured DXA scans. It also provides an assessment of the quality of bone architecture. This will be of direct value and significance to orthopaedic surgeons when planning surgical procedures, including fracture fixation and surgery of the hip and spine, since BMD alone is a poor predictor of fracture risk.

Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article: Bone Joint Res 2025;14(3):199–207

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The primary objective of this study was to compare short-term implant survival between cemented and cementless fixation for the mobile-bearing Oxford medial unicompartmental knee arthroplasty (UKA) across various age groups. The secondary objectives were to compare modes of failure and to evaluate patient-reported outcomes.

The last five years have seen notable advancements in foot and ankle surgery as a result of technical innovations and more consistent reporting of results. Much progress has been made in improving patient-reported outcome measures, in the development of basic research in this area, and in the development of personalized approaches which optimize outcomes for specific groups of patients. This review focuses on five main areas of development within foot and ankle surgery: ankle arthroplasty, osteomyelitis and the diabetic foot, sports injuries, minimally invasive surgery, and orthobiologics. The aim of this annotation is to discuss the progress made in these fields during recent years and propose avenues for further development.

Cite this article: Bone Joint J 2025;107-B(3):283–290.

Aims. The use of patient-reported outcome measures (PROMs) to assess the outcome after total knee (TKA) and total hip arthroplasty (THA) is increasing, with associated regulatory mandates. However, the robustness and clinical relevance of long-term data are often questionable. It is important to determine whether using long-term PROMs data justify the resources, costs, and difficulties associated with their collection. The aim of this study was to assess studies involving TKA and THA to determine which PROMs are most commonly reported, how complete PROMs data are at ≥ five years postoperatively, and the extent to which the scores change between early and long-term follow-up. Methods. We conducted a systematic review of the literature. Randomized controlled trials (RCTs) with sufficient reporting of PROMs were included. The mean difference in scores from the preoperative condition to early follow-up times (between one and two years), and from early to final follow-up, were calculated. The mean rates of change in the scores were calculated from representative studies. Meta-analyses were also performed on the most frequently reported PROMs. Results. A total of 24 studies were assessed. The most frequently reported PROMs were the Oxford Knee Score (OKS) for TKA and the University of California, Los Angeles activity scale for THA. The mean rate of follow-up based on the number of patients available at final follow-up was 70.5% (39.2% to 91.0%) for knees and 82.1% (63.2% to 92.3%) for hips. The actual rates of collection of PROM scores were lower. For TKA, the mean OKS, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and transformed WOMAC changes were -16.3 (95% CI -17.5 to -15.2), 23.2 (95% CI 17.2 to 29.2), and -29.7 (95% CI -32.4 to -27.0) points for short-term follow-up. These decreased to 1.3 (95% CI -0.8 to 3.3), -3.4 (95% CI -7.0 to 0.3), and 4.7 (95% CI -1.5 to 10.9) points for the remaining follow-up. A similar meta-analysis was not possible for studies involving THA. We commonly observed that the scores plateaued after between one and two years, and that there was little or no change beyond this time. Conclusion. The long-term PROMs for TKA and THA beyond one or two years are often incomplete and lose sensitivity at this time. Given the considerable resources, costs, and challenges associated with the collection of these scores, their clinical value is questionable. Therefore, consideration should be given to abandoning the requirement for the collection of long-term PROMs in favour of more robust and reliable measures of success that offer more clinical relevance and use. Cite this article: Bone Joint J 2025;107-B(3):296–307

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Unicompartmental knee arthroplasty (UKA) is one option in the treatment of isolated unicompartmental advanced osteoarthritis (OA). While long-term results exist for medial mobile-bearing (MB) UKA, evidence regarding lateral MB-UKA is still limited. The Oxford Domed Lateral (ODL) implant aims to reduce the bearing dislocation rate in lateral MB-UKA through enhanced bearing entrapment. However, the long-term performance of this implant remains unclear. This study evaluated the long-term survival and clinical outcomes of the ODL in a non-designer centre.

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Core decompression is a commonly performed procedure to treat osteonecrosis of the femoral head (ONFH) prior to femoral head collapse. The aim of the study was to identify the incidence of hip arthroplasty after core decompression and the potential risk factors for conversion through a nationwide population-based study.

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To assess whether chronic knee pain (CKP) influenced health-related quality of life (HRQoL), knee-specific health, wellbeing, and use of opioid analgesia, and identify variables associated with CKP in patients awaiting knee arthroplasty.

The use of arthroscopy of the hand and wrist has recently increased sharply in the elective setting and this, not surprisingly, has been followed by an increasing use in the trauma setting. Advocates for the use of arthroscopy in these patients cite the improved assessment of the displacement and reduction of fractures and the early diagnosis of associated injuries, while others temper this with concerns about increased operating time and possible complications. The data relating to patient-reported benefits and costs are limited. The aim of this review was to discuss the current available literature for the use of arthroscopy in the management of injuries of the hand and wrist.

Cite this article: Bone Joint J 2025;107-B(3):291–295.

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The aim of this study was to examine the indications for further surgery and the characteristics of the patients within one year of medial unicompartmental knee arthroplasty (mUKA), providing an assessment of everyday clinical practice and outcomes in a high-volume country.

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Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex.

Aims. To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Methods. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Results. After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway. Conclusion. Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment. Cite this article: Bone Joint Res 2025;14(2):124–135

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The conversion of previous hip fracture surgery to total hip arthroplasty (CTHA) can be surgically challenging with unpredictable outcomes; reported complication rates vary significantly. This study aimed to establish the medium-term survival and outcomes of CTHA performed following a previous hip fracture surgery.

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Unicompartmental knee arthroplasty (UKA) is associated with an accelerated recovery, improved functional outcomes, and retention of anatomical knee kinematics when compared to manual total knee arthroplasty (mTKA). UKA is not universally employed by all surgeons as there is a higher revision risk when compared to mTKA. Robotic arm-assisted (ra) UKA enables the surgeon to position the prosthesis more accurately when compared to manual UKA, and is associated with improved functional outcomes and a lower early revision risk. Non-randomized data suggests that, when compared to mTKA, raUKA has a clinically meaningful greater functional benefit. This protocol describes a randomized controlled trial that aims to evaluate the clinical and cost-effectiveness of raUKA compared to mTKA for individuals with isolated medial compartment osteoarthritis (OA).

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This study aimed to investigate whether the use of CT-based navigation enhances: 1) the accuracy of cup placement; and 2) the achievement rate of required range of motion (ROM). Additionally, we investigated the impact of using a large femoral head and dual-mobility liner on the achievement rates.

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Machine learning (ML) holds significant promise in optimizing various aspects of total shoulder arthroplasty (TSA), potentially improving patient outcomes and enhancing surgical decision-making. The aim of this systematic review was to identify ML algorithms and evaluate their effectiveness, including those for predicting clinical outcomes and those used in image analysis.