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. 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 (Aims
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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. In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1.Aims
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Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing
Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments. Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed.Aims
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Aims. Adult spinal deformity (ASD) surgery can reduce pain and disability. However, the actual surgical efficacy of ASD in doing so is far from desirable, with frequent complications and limited improvement in quality of life. The accurate prediction of surgical outcome is crucial to the process of clinical decision-making. Consequently, the aim of this study was to develop and validate a model for predicting an ideal surgical outcome (ISO) two years after ASD surgery. Methods. We conducted a retrospective analysis of 458 consecutive patients who had undergone spinal fusion surgery for ASD between January 2016 and June 2022. The outcome of interest was achievement of the ISO, defined as an improvement in patient-reported outcomes exceeding the minimal clinically important difference, with no postoperative complications. Three machine-learning (ML) algorithms – LASSO, RFE, and Boruta – were used to identify key variables from the collected data. The dataset was randomly split into training (60%) and test (40%) sets. Five different ML models were trained, including logistic regression, random forest, XGBoost, LightGBM, and multilayer perceptron. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Results. The analysis included 208 patients (mean age 64.62 years (SD 8.21); 48 male (23.1%), 160 female (76.9%)). Overall, 42.8% of patients (89/208) achieved the ideal surgical outcome. Eight features were identified as key variables affecting prognosis: depression, osteoporosis, frailty, failure of pelvic compensation, relative functional cross-sectional area of the paraspinal
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. Patients who received core decompression for ONFH between 1 January 2009 and 31 December 2018 and were followed up until 31 December 2019 (mean 33 months (0.2 to 132)) were retrieved from Taiwan’s National Health Insurance claims database. A total of 2,918 patients were identified and included in the study. The mean age at the time of core decompression was 46 years (SD 12.5), with a male-to-female ratio of 7:3. The first total hip arthroplasty or hip hemiarthroplasty after the index core decompression was considered as the outcome of conversion to hip arthroplasty. For the analysis of conversion risk, patients’ demographic characteristics, economic status, comorbidities, and data on the type of hospital and surgeons’ experience were included.Aims
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Osseous invasion exhibited in soft-tissue sarcoma (STS) is recognized as a prognostic risk factor. Achieving a wide margin is the default surgical approach for local control. However, for STSs where the tumour is in contact with the adjacent cortex but without clear evidence of osseous invasion, such as medullary invasion, the question of whether bone resection can provide better local control or survival than more conservative sub-periosteal excision remains controversial. The aim of this study was to assess whether bone resection for thigh STS with cortical contact of the adjacent bone results in better local control and survival compared to sub-periosteal dissection, and to investigate the prognostic factors for clinical outcomes in STS. A retrospective cohort study was conducted on 142 patients with thigh STS exhibiting cortical contact but without medullary invasion, from May 2000 to May 2020. Patients underwent either composite bone resection or sub-periosteal excision. Demographics, clinical outcomes, and functional outcomes were compared between the two groups. Additionally, Cox regression analysis was used to analyze risk factors for local recurrence.Aims
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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. All CTHAs performed at our tertiary orthopaedic institution between January 2008 and January 2020 following previous ipsilateral hip fracture surgery were included. Patients were followed up clinically using Oxford Hip Scores (OHS), and radiologically until death or revision surgery. Postoperative complications, radiological implant failure, and indications for revision surgery were reviewed.Aims
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In our previous research, we have found that melatonin (MEL) affects the osteoporotic process. By balancing bone remoulding, autophagy is involved in age-related bone loss. However, as a regulator of autophagy, whether MEL influences senile osteoporosis via regulating autophagy remains unclear. Cellular, radiological, and histopathological evaluations were performed on 36 16-month-old male C57BL6/L mice or aged bone marrow-derived mesenchymal stem cells. A MEL-gelatin methacrylamide system was constructed to aid osteoporotic fracture healing.Aims
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The aim of the study was to apply 3D measurements for fracture displacement in minimally to moderately displaced acetabular fractures treated nonoperatively, and to evaluate whether this measurement can be used to estimate the likelihood of conversion to total hip arthroplasty (THA) at follow-up. A multicentre, cross-sectional study was performed on 144 patients who were treated nonoperatively for an acetabular fracture in four level 1 trauma centres between January 2000 and December 2020. For each patient, fracture displacement was measured on CT-based 3D models. The 3D gap area represents fracture displacement (mm2) between all fracture fragments. A receiver operating characteristic curve was generated to determine a 3D gap area threshold representing the optimal sensitivity and specificity to predict conversion to THA. Native hip survival was reported using Kaplan-Meier curves. Predictors of conversion to THA were determined using Cox regression analysis.Aims
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In this study, we aimed to evaluate incidence trends and potential risk factors associated with Perthes’ disease in Denmark, using publicly available data. Our population-based case-control study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,924,292 infants born between 1985 and 2016. We estimated age-specific incidence rates for four birth periods of equal duration (1985 to 1992, 1993 to 2000, 2001 to 2008, and 2009 to 2016) and investigated associations with perinatal conditions, congenital malformations, coagulation defects, autism spectrum disorders (ASD), and attention deficit hyperactivity disorders (ADHD).Aims
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The February 2025 Foot & Ankle Roundup360 looks at:Percutaneous Zadek osteotomy for insertional Achilles tendinopathy; Association of extraosseous arterial diameter with talar dome osteochondral lesions; Autologous chondrocyte implantation for osteochondral lesions of the talus; Symptomatic thromboembolism and mortality in foot and ankle surgery in the UK; Corticosteroid or hyaluronic acid in Morton’s neuroma?
The February 2025 Knee Roundup360 looks at: Once-weekly semaglutide in patients with obesity and knee osteoarthritis; How many patients should have a unicompartmental knee arthroplasty?; Staged revision of the infected knee arthroplasty and endoprosthesis; The metal allergy argument and knee arthroplasty; Is kinematic alignment all it’s cracked up to be?; Is bone-patella-bone the gold standard for revision?; Blood flow restriction and the dissatisfied knee arthroplasty.
To evaluate the concurrent use of vancomycin and ε-aminocaproic acid (EACA) in primary total hip arthroplasty (THA). In total, 120 patients undergoing unilateral primary THA were divided into three groups: Group VE received intra-articular vancomycin and EACA; Group V received only intra-articular vancomycin; and Group E received only intra-articular EACA. Blood and joint fluids were sampled postoperatively to measure the vancomycin levels using chromatography. Blood loss and kidney function were monitored.Aims
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Over time, the locking mechanism of Modular Universal Tumour and Revision System (MUTARS) knee arthroplasties changed from polyethylene (PE) to polyether-ether-ketone Optima (PEEK) and metal-on-metal (MoM) in an attempt to reduce the risk of mechanical failure. In this study, we aimed to assess the cumulative incidence of locking mechanism revision for symptomatic instability by type of material, and assess potential associated risk factors. The MUTARS Orthopaedic Registry Europe was used for a retrospective review of 316 patients (54% male (n = 170), median age 44 years (IQR 23 to 61)) who underwent a MUTARS knee arthroplasty for oncological indications between December 1995 and January 2023. The minimum follow-up was 12 months, and the median follow-up was 7.9 years (IQR 3.3 to 13.0). A competing risk model was used to estimate the cumulative incidence of first locking mechanism revision with death and revision for any other reason as competing events. Possible risk factors were assessed employing a univariate cause-specific hazards regression model.Aims
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Hip fractures commonly occur in older patients, with high levels of frailty and comorbidity. Many of these patients have limited mobility before their fracture, and even after surgery, their mobility may remain limited. It is therefore not surprising that they are at a high risk of developing pressure sores, particularly on their heels, and a variety of devices and interventions have been proposed to reduce this risk. Foam or air mattresses, designed to reduce contact pressure on the patient’s whole body, are now routinely used in many healthcare systems. However, there is wide variation in their design. We developed the WHiTE 14;PRESSURE 3 trial to address the lack of evidence in this area. This is a three-arm multicentre randomized trial including health economic evaluation and recruiting patients from NHS hospitals in the UK. The trial compares standard strategies for the prevention of pressure sores with standard care plus a constant low-pressure device and with standard care plus a heel off-loading device. This annotation describes the development of this trial. Cite this article:
The aim of this study was to assess the necessity of revising the acetabular component in revision total hip arthroplasty (THA) in patients with a Vancouver type B2 periprosthetic femoral fracture (PFF) who require revision of the femoral component. The hypothesis was that revision of both the acetabular and femoral components and using a dual-mobility acetabular component would provide a lower postoperative risk of dislocation, without increasing perioperative morbidity and mortality. Data were retrospectively analyzed from a continuously gathered database. We included 150 revisions, performed between January 2015 and December 2022, in 150 patients, with 81 revisions limited to only the femoral component and 69 involving revision of both components. This resulted, after surgery, in 60 patients having a simple-mobility acetabular component and 90 having a dual-mobility component. The mean age of the patients was 79.7 years (SD 10.1), and 98 were female (65.3%). The mean follow-up was 31 months (SD 2.3).Aims
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The aims of this study, using a porcine model of multiple trauma, were to investigate the expression of microRNAs at the fracture site, in the fracture haematoma (fxH) and in the fractured bone, compared with a remote unfractured long bone, to characterize the patterns of expression of circulating microRNAs in plasma, and identify and validate messenger RNA (mRNA) targets of the microRNAs. Two multiple trauma treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). For this study, fxH, fractured bone, unfractured control bone, plasma, lung, and liver samples were harvested. MicroRNAs were analyzed using quantitative real-time polymerase chain reaction arrays, and the identified mRNA targets were validated in vivo in the bone, fxH, lung, and liver tissue.Aims
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