Aims. To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO). Methods. Overall, 90 patients who underwent OWHTO without bone grafting were enrolled in this nonrandomized retrospective study, and 45 patients treated with LIPUS were compared with 45 patients without LIPUS treatment in terms of bone healing and functional recovery postoperatively. Clinical evaluations, including the pain visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score, were performed preoperatively as well as six weeks and three, six, and 12 months postoperatively. The progression rate of gap filling was evaluated using anteroposterior radiographs at six weeks and three, six, and 12 months postoperatively. Results. The pain VAS and JOA scores significantly improved after OWHTO in both groups. Although the LIPUS group had better pain scores at six weeks and three months postoperatively, there were no significant differences in JOA score between the groups. The lateral hinge united at six weeks postoperatively in 34 (75.6%) knees in the control group and in 33 (73.3%) knees in the LIPUS group. The progression rates of gap filling in the LIPUS group were 8.0%, 15.0%, 27.2%, and 46.0% at six weeks and three, six, and 12 months postoperatively, respectively, whereas in the control group at the same time points they were 7.7%, 15.2%, 26.3%, and 44.0%, respectively. There were no significant differences in the progression rate of gap filling between the groups. Conclusion. The present study demonstrated that LIPUS did not promote bone healing and functional recovery after OWHTO with a locking plate. The routine use of LIPUS after OWHTO was not recommended from the results of our study. Cite this article: Bone Jt Open 2022;3(11):885–893

Aims. Treatment of Weber B ankle fractures that are stable on weightbearing radiographs but unstable on concomitant stress tests (classified SER4a) is controversial. Recent studies indicate that these fractures should be treated nonoperatively, but no studies have compared alternative nonoperative options. This study aims to evaluate patient-reported outcomes and the safety of fracture treatment using functional orthosis versus cast immobilization. Methods. A total of 110 patients with Weber B/SER4a ankle fractures will be randomized (1:1 ratio) to receive six weeks of functional orthosis treatment or cast immobilization with a two-year follow-up. The primary outcome is patient-reported ankle function and symptoms measured by the Manchester-Oxford Foot and Ankle Questionnaire (MOxFQ); secondary outcomes include Olerud-Molander Ankle Score, radiological evaluation of ankle congruence in weightbearing and gravity stress tests, and rates of treatment-related adverse events. The Regional Committee for Medical and Health Research (approval number 277693) has granted ethical approval, and the study is funded by South-Eastern Norway Regional Health Authority (grant number 2023014). Discussion. Randomized controlled trials are needed to evaluate alternative nonoperative treatment options for Weber B/SER4a ankle fractures, as current clinical guidelines are based on biomechanical reasoning. The findings will be shared through publication in peer-reviewed journals and presentations at conferences. Cite this article: Bone Jt Open 2023;4(9):713–719

Aims. Pelvic tilt (PT) can significantly change the functional orientation of the acetabular component and may differ markedly between patients undergoing total hip arthroplasty (THA). Patients with stiff spines who have little change in PT are considered at high risk for instability following THA. Femoral component position also contributes to the limits of impingement-free range of motion (ROM), but has been less studied. Little is known about the impact of combined anteversion on risk of impingement with changing pelvic position. Methods. We used a virtual hip ROM (vROM) tool to investigate whether there is an ideal functional combined anteversion for reduced risk of hip impingement. We collected PT information from functional lateral radiographs (standing and sitting) and a supine CT scan, which was then input into the vROM tool. We developed a novel vROM scoring system, considering both seated flexion and standing extension manoeuvres, to quantify whether hips had limited ROM and then correlated the vROM score to component position. Results. The vast majority of THA planned with standing combined anteversion between 30° to 50° and sitting combined anteversion between 45° to 65° had a vROM score > 99%, while the majority of vROM scores less than 99% were outside of this zone. The range of PT in supine, standing, and sitting positions varied widely between patients. Patients who had little change in PT from standing to sitting positions had decreased hip vROM. Conclusion. It has been shown previously that an individual’s unique spinopelvic alignment influences functional cup anteversion. But functional combined anteversion, which also considers stem position, should be used to identify an ideal THA position for impingement-free ROM. We found a functional combined anteversion zone for THA that may be used moving forward to place total hip components. Cite this article: Bone Jt Open 2021;2(10):834–841

Aims. To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity. Methods. Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation. Results. Overall, 17 studies (566 feet) were included: 13 studies used clinical grading criteria to report a postoperative ‘success’ of 87% (75% to 100%), 14 reported on orthotic use with 88% reduced postoperative use, and one study reported on ankle kinematics improvements. Ten studies reported post-surgical complications at a rate of 11/390 feet (2.8%), but 84 feet (14.8%) had recurrent varus (68 feet, 12%) or occurrence of valgus (16 feet, 2.8%). Only one study included a patient-reported outcome measure (pain). Conclusion. Split tendon transfers are an effective treatment for children and youth with CP and spastic equinovarus foot deformities. Clinical data presented can be used for future study designs; a more standardized functional and patient-focused approach to evaluating outcomes of surgical intervention of gait may be warranted. Cite this article: Bone Jt Open 2023;4(5):283–298

Aims. We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks. Patients and Methods. We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks. Our desired outcomes were functional testing and measures to assess the feasibility and acceptability of the study. Results. A total of 724 patients were screened, of whom 143 (20%) were eligible for recruitment. Of these, 123 were approached and 29 (4%) elected to take part. However, seven patients did not complete the study. Compliance with the injections was 11 out of 15 (73%) showing the intervention to be acceptable and feasible in this patient population. Take home message: Only 4% of patients who met the inclusion criteria were both eligible and willing to consent to a study involving injections of PTH, so delivering this study on a large scale would carry challenges in recruitment and retention. Methodological and sample size planning would have to take this into account. PTH administration to patients to enhance fracture healing should still be considered experimental. Cite this article: Bone Joint J 2016;98-B:840–5

Objectives. Our objective was to predict the knee extension strength and post-operative function in quadriceps resection for soft-tissue sarcoma of the thigh. Methods. A total of 18 patients (14 men, four women) underwent total or partial quadriceps resection for soft-tissue sarcoma of the thigh between 2002 and 2014. The number of resected quadriceps was surveyed, knee extension strength was measured with the Biodex isokinetic dynamometer system (affected side/unaffected side) and relationships between these were examined. The Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), European Quality of Life-5 Dimensions (EQ-5D) score and the Short Form 8 were used to evaluate post-operative function and examine correlations with extension strength. The cutoff value for extension strength to expect good post-operative function was also calculated using a receiver operating characteristic (ROC) curve and Fisher’s exact test. Results. Extension strength decreased when the number of resected quadriceps increased (p < 0.001), and was associated with lower MSTS score, TESS and EQ-5D (p = 0.004, p = 0.005, p = 0.006, respectively). Based on the functional evaluation scales, the cutoff value of extension strength was 56.2%, the equivalent to muscle strength with resection of up to two muscles. Conclusion. Good post-operative results can be expected if at least two quadriceps muscles are preserved. Cite this article: A. Tanaka, Y. Yoshimura, K. Aoki, M. Kito, M. Okamoto, S. Suzuki, T. Momose, H. Kato. Knee extension strength and post-operative functional prediction in quadriceps resection for soft-tissue sarcoma of the thigh. Bone Joint Res 2016;5:232–238. DOI: 10.1302/2046-3758.56.2000631

Aims. To compare time dependent functional improvement for patients with medial, respectively lateral knee osteoarthritis (OA) after treatment with opening wedge osteotomy relieving the pressure on the osteoarthritic part of the knee. Methods. In all, 49 patients (52 knees) with a mean age of 47 years (31 to 64) underwent high tibial osteotomies (HTO), and 24 patients with a mean age of 48 years (31 to 62) low femoral osteotomies (LFO) with opening wedge technique due to medial, respectively lateral knee OA with malalignment. All osteotomies were stabilized with a Puddu plate and bone grafting performed in the same time period (2000 to 2008). The patients were evaluated by the Knee Injury and Osteoarthritis Outcome Score (KOOS) pre-operatively and at six months, and at one, two, five, and ten years postoperatively. The knee OA was graded according to the Ahlbäck and Kellgren-Lawrence radiological scoring systems. Results. The mean angular corrections were 8.0° (4° to 12°) for the HTO and 9.6° (4° to 20°) for the LFO. Both the pre-operative KOOS and the osteoarthritic gradings were similar for the two patient groups. The five subscores of KOOS increased significantly during the postoperative period (p < 0.001 to 0.029) levelling out after one year in both groups. The KOOS subscore symptoms was significantly higher for patients with HTO than those with LFO at all follow-up times, for sport and recreation in the period one to five years, and for pain and quality of life at two to five years (p < 0.001 to 0.009). Eight HTOs (15%) and five LFOs (21%) were converted to total knee arthroplasty after mean 6.7 years (2.0 to 9.8) and 5.4 years (4.0 to 8.0) respectively. The ten-year osteotomy survival rates were 88% for the HTO and 79% for the LFO (p = 0.745). Conclusion. Patients with unicompartmental knee OA improved after a corrective opening wedge osteotomy, but four of the five subscores of KOOS were significantly higher for those with medial than those with lateral OA in most of the ten-year follow-up period. Cite this article: Bone Joint Open 2020;1-7:346–354

Aim. Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results. We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion. We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1

Objectives. X-linked hypophosphataemic rickets (XLHR) is a disease of impaired bone mineralization characterized by hypophosphataemia caused by renal phosphate wasting. The main clinical manifestations of the disorder are O-shaped legs, X-shaped legs, delayed growth, and bone pain. XLHR is the most common inheritable form of rickets, with an incidence of 1/20 000 in humans. It accounts for approximately 80% of familial cases of hypophosphataemia and serves as the prototype of defective tubular phosphate (PO4. 3+. ) transport, due to extra renal defects resulting in unregulated FGF23 activity. XLHR is caused by loss-of-function mutations in the PHEX gene. The aim of this research was to identify the genetic defect responsible for familial hypophosphataemic rickets in a four-generation Chinese Han pedigree and to analyze the function of this mutation. Methods. The genome DNA samples of all members in the pedigree were extracted from whole blood. We sequenced all exons of the PHEX and FGF23 genes, as well as the adjacent splice site sequence with Sanger sequencing. Next, we analyzed the de novo mutation c.1692 del A of the PHEX gene with an online digital service and investigated the mutant PHEX with SWISS-MODEL, immunofluorescence, and protein stability detection. Results. Through Sanger sequencing, we found a de novo mutation, c.1692 del A, in exon 16 of the PHEX gene in this pedigree. This mutation can make the PHEX protein become unstable and decay rapidly, which results in familial XLHR. Conclusion. We have found a de novo loss-of-function mutation, c.1692 del A, in exon 16 of the PHEX gene that can cause XLHR. Cite this article: J. Huang, X. Bao, W. Xia, L. Zhu, J. Zhang, J. Ma, N. Jiang, J. Yang, Q. Chen, T. Jing, J. Liu, D. Ma, G. Xu. Functional analysis of a de novo mutation c.1692 del A of the PHEX gene in a Chinese family with X-linked hypophosphataemic rickets. Bone Joint Res 2019;8:405–413. DOI: 10.1302/2046-3758.88.BJR-2018-0276.R1

Aims. Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods. The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England – Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024. Cite this article: Bone Jt Open 2024;5(4):343–349

Aims. Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

Aims. The aims were to assess whether joint-specific outcome after total knee arthroplasty (TKA) was influenced by implant design over a 12-year follow-up period, and whether patient-related factors were associated with loss to follow-up and mortality risk. Methods. Long-term follow-up of a randomized controlled trial was undertaken. A total of 212 patients were allocated a Triathlon or a Kinemax TKA. Patients were assessed preoperatively, and one, three, eight, and 12 years postoperatively using the Oxford Knee Score (OKS). Reasons for patient lost to follow-up, mortality, and revision were recorded. Results. A total of 94 patients completed 12-year functional follow-up (62 females, mean age 66 years (43 to 82) at index surgery). There was a clinically significantly greater improvement in the OKS at one year (mean difference (MD) 3.0 (95% CI 0.4 to 5.7); p = 0.027) and three years (MD 4.7 (95% CI 1.9 to 7.5); p = 0.001) for the Triathlon group, but no differences were observed at eight (p = 0.331) or 12 years’ (p = 0.181) follow-up. When assessing the OKS in the patients surviving to 12 years, the Triathlon group had a clinically significantly greater improvement in the OKS (marginal mean 3.8 (95% CI 0.2 to 7.4); p = 0.040). Loss to functional follow-up (53%, n = 109/204) was independently associated with older age (p = 0.001). Patient mortality was the major reason (56.4%, n = 62/110) for loss to follow-up. Older age (p < 0.001) and worse preoperative OKS (p = 0.043) were independently associated with increased mortality risk. An age at time of surgery of ≥ 72 years was 75% sensitive and 74% specific for predicting mortality with an area under the curve of 78.1% (95% CI 70.9 to 85.3; p < 0.001). Conclusion. The Triathlon TKA was associated with clinically meaningful greater improvement in knee-specific outcome when compared to the Kinemax TKA. Loss to follow-up at 12 years was a limitation, and studies planning longer-term functional assessment could limit their cohort to patients aged under 72 years. Cite this article: Bone Jt Open 2024;5(10):911–919

Aims. Leg length discrepancy (LLD) is a common pre- and postoperative issue in total hip arthroplasty (THA) patients. The conventional technique for measuring LLD has historically been on a non-weightbearing anteroposterior pelvic radiograph; however, this does not capture many potential sources of LLD. The aim of this study was to determine if long-limb EOS radiology can provide a more reproducible and holistic measurement of LLD. Methods. In all, 93 patients who underwent a THA received a standardized preoperative EOS scan, anteroposterior (AP) radiograph, and clinical LLD assessment. Overall, 13 measurements were taken along both anatomical and functional axes and measured twice by an orthopaedic fellow and surgical planning engineer to calculate intraoperator reproducibility and correlations between measurements. Results. Strong correlations were observed for all EOS measurements (r. s. > 0.9). The strongest correlation with AP radiograph (inter-teardrop line) was observed for functional-ASIS-to-floor (functional) (r. s. = 0.57), much weaker than the correlations between EOS measurements. ASIS-to-ankle measurements exhibited a high correlation to other linear measurements and the highest ICC (r. s. = 0.97). Using anterior superior iliac spine (ASIS)-to-ankle, 33% of patients had an absolute LLD of greater than 10 mm, which was statistically different from the inter-teardrop LLD measurement (p < 0.005). Discussion. We found that the conventional measurement of LLD on AP pelvic radiograph does not correlate well with long leg measurements and may not provide a true appreciation of LLD. ASIS-to-ankle demonstrated improved detection of potential LLD than other EOS and radiograph measurements. Full length, functional imaging methods may become the new gold standard to measure LLD. Cite this article: Bone Jt Open 2022;3(12):960–968

Aims. To systematically review the predominant complication rates and changes to patient-reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation for shoulder instability. Methods. This systematic review, following PRISMA guidelines and registered in PROSPERO, involved a comprehensive literature search using PubMed, Embase, Web of Science, and Scopus. Key search terms included “allograft”, “shoulder”, “humerus”, and “glenoid”. The review encompassed 37 studies with 456 patients, focusing on primary outcomes like failure rates and secondary outcomes such as PROMs and functional test results. Results. A meta-analysis of primary outcomes across 17 studies revealed a dislocation rate of 5.1% and an increase in reoperation rates from 9.3% to 13.7% post-publication bias adjustment. There was also a noted rise in conversion to total shoulder arthroplasty and incidence of osteoarthritis/osteonecrosis over longer follow-up periods. Patient-reported outcomes and functional tests generally showed improvement, albeit with notable variability across studies. A concerning observation was the consistent presence of allograft resorption, with rates ranging from 33% to 80%. Comparative studies highlighted similar efficacy between distal tibial allografts and Latarjet procedures in most respects, with some differences in specific tests. Conclusion. OCA transplantation presents a promising treatment option for shoulder instability, effectively addressing both glenoid and humeral head defects with favourable patient-reported outcomes. These findings advocate for the inclusion of OCA transplantation in treatment protocols for shoulder instability, while also emphasizing the need for further high-quality, long-term research to better understand the procedure’s efficacy profile. Cite this article: Bone Jt Open 2024;5(7):570–580

Aims. 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. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484

Aims. The aim of this study was to compare the preinjury functional scores with the postinjury preoperative score and postoperative outcome scores following anterior cruciate ligament (ACL) reconstruction surgery (ACLR). Methods. We performed a prospective study on patients who underwent primary ACLR by a single surgeon at a single centre between October 2010 and January 2018. Preoperative preinjury scores were collected at time of first assessment after the index injury. Preoperative (pre- and post-injury), one-year, and two-year postoperative functional outcomes were assessed by using the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score, and Tegner Activity Scale. Results. We enrolled 308 males and 263 females of mean age 27 years (19 to 46). The mean preinjury and preoperative post-injury Lysholm Knee Scores were 94 (73 to 100) and 63 (25 to 85), respectively, while the respective mean scores at one and two years postoperatively were 84 (71 to 100) and 89 (71 to 100; p < 0.001). The mean Tegner preinjury and preoperative post-injury scores were 7 (3 to 9) and 3 (0 to 6), respectively, while the respective mean scores at one and two years postoperatively were 6 (1 to 8) and 6 (1 to 9) (p < 0.001). The mean KOOS scores at preinjury versus two years postoperatively were: symptoms (96 vs 84); pain (94 vs 87); activities of daily living (97 vs 91), sports and recreation function (84 vs 71), and quality of life (82 vs 69), respectively (p < 0.001). Conclusion. Functional scores improved following ACLR surgery at two years in comparison to preoperative post-injury scores. However, at two-year follow-up, the majority of patients failed to achieve their preinjury scores. The evaluation of ACLR outcomes needs to consider the preinjury scores rather than the immediate preoperative score that is usually collected. Cite this article: Bone Jt Open 2023;4(1):46–52

Aims. To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration. Methods. We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map. Results. After screening of 5,660 articles, we included 166 studies reporting prognostic factors for outcomes after rTKA, with a median sample size of 319 patients (30 to 303,867). Overall, 50% of the studies reported prospectively collected data, and 61% of the studies were performed in a single centre. In some studies, multiple associations were reported; 180 different prognostic factors were reported in these studies. The three most frequently studied prognostic factors were reason for revision (213 times), sex (125 times), and BMI (117 times). Studies focusing on functional scores and patient-reported outcome measures as prognostic factor for the outcome after surgery were limited (n = 42). The studies reported 154 different outcomes. The most commonly reported outcomes after rTKA were: re-revision (155 times), readmission (88 times), and reinfection (85 times). Only five studies included costs as outcome. Conclusion. Outcomes and prognostic factors that are routinely registered as part of clinical practice (e.g. BMI, sex, complications) or in (inter)national registries are studied frequently. Studies on prognostic factors, such as functional and sociodemographic status, and outcomes as healthcare costs, cognitive and mental function, and psychosocial impact are scarce, while they have been shown to be important for patients with osteoarthritis. Cite this article: Bone Jt Open 2023;4(5):338–356

Aims. 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. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Aims. Obesity is associated with an increased risk of hip osteoarthritis, resulting in an increased number of total hip arthroplasties (THAs) performed annually. This study examines the peri- and postoperative outcomes of morbidly obese (MO) patients (BMI ≥ 40 kg/m. 2. ) compared to healthy weight (HW) patients (BMI 18.5 to < 25 kg/m. 2. ) who underwent a THA using the anterior-based muscle-sparing (ABMS) approach. Methods. This retrospective cohort study observes peri- and postoperative outcomes of MO and HW patients who underwent a primary, unilateral THA with the ABMS approach. Data from surgeries performed by three surgeons at a single institution was collected from January 2013 to August 2020 and analyzed using Microsoft Excel and Stata 17.0. Results. This study compares 341 MO to 1,140 HW patients. Anaesthesia, surgery duration, and length of hospital stay was significantly lower in HW patients compared to MO. There was no difference in incidence of pulmonary embolism, periprosthetic fracture, or dislocation between the two groups. The rate of infection in MO patients (1.47%) was significantly higher than HW patients (0.14%). Preoperative patient-reported outcome measures (PROMs) show a significantly higher pain level in MO patients and a significantly lower score in functional abilities. Overall, six-week and one-year postoperative data show higher levels of pain, lower levels of functional improvement, and lower satisfaction scores in the MO group. Conclusion. The comorbidities of obesity are well studied; however, the implications of THA using the ABMS approach have not been studied. Our peri- and postoperative results demonstrate significant improvements in PROMs in MO patients undergoing THA. However, the incidence of deep infection was significantly higher in this group compared with HW patients. Cite this article: Bone Jt Open 2023;4(5):299–305