Aims

To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.

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Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients’ quality of life.

Aims. The aim of this study was to perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted medial unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA). Methods. Ten-year follow-up of patients who were randomized to rUKA (n = 64) or mUKA (n = 65) was performed. Patients completed the EuroQol five-dimension health questionnaire preoperatively, at three months, and one, two, five, and ten years postoperatively, which was used to calculate quality-adjusted life years (QALY) gained and the incremental cost-effectiveness ratio (ICER). Costs for the index and additional surgery and healthcare costs were calculated. Results. mUKA had a lower survival for reintervention (84.8% (95% CI 76.2 to 93.4); p = 0.001), all-cause revision (88.9% (95% CI 81.3 to 96.5); p = 0.007) and aseptic revision (91.9% (95% CI 85.1 to 98.7); p = 0.023) when compared to the rUKA group at ten years, which was 100%. The rUKA group had a greater QALY gain per patient (mean difference 0.186; p = 0.651). Overall rUKA was the dominant intervention, being cost-saving and more effective with a greater health-related quality of life gain. On removal of infected reinterventions (n = 2), the ICER was £757 (not discounted) and £481 (discounted). When including all reintervention costs, rUKA was cost-saving when more than 100 robotic cases were performed per year. When removing the infected cases, rUKA was cost-saving when undertaking more than 800 robotic cases per year. Conclusion. rUKA had lower reintervention and revision risks at ten years, which was cost-saving and associated with a greater QALY gain, and was the dominant procedure. When removing the cost of infection, which could be a random event, rUKA was a cost-effective intervention with an ICER (£757) which was lower than the willingness-to-pay threshold (£20,000). Cite this article: Bone Joint J 2025;107-B(1):72–80

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The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

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Functional alignment (FA) in total knee arthroplasty (TKA) aims to achieve balanced gaps by adjusting implant positioning while minimizing changes to constitutional joint line obliquity (JLO). Although FA uses kinematic alignment (KA) as a starting point, the final implant positions can vary significantly between these two approaches. This study used the Coronal Plane Alignment of the Knee (CPAK) classification to compare differences between KA and final FA positions.

The December 2024 Wrist & Hand Roundup³⁶⁰ looks at: Variability in thumb ulnar collateral ligament rupture management across the UK: survey insights; Identifying five distinct hand osteoarthritis pain phenotypes highlights the impact of biopsychosocial factors; Long-term outcomes of MAÏA TMC joint prosthesis for osteoarthritis: a possible alternative to trapeziectomy; Diagnostic and management strategies for malignant melanoma of the hand; Early versus delayed surgery for distal radius fractures: comparable outcomes but higher complications in delayed treatment; Perioperative anticoagulant and antiplatelet use does not increase complications in wide-awake hand surgery; Variability in treatment of metacarpal shaft fractures highlights need for standardized care; Low-intensity pulsed ultrasound ineffective in reducing time to union for scaphoid nonunion post-surgery.

The December 2024 Research Roundup³⁶⁰ looks at: Skeletal muscle composition, power, and mitochondrial energetics in older men and women with knee osteoarthritis; Machine-learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation; Aetiology of patient dissatisfaction following primary total knee arthroplasty in the era of robotic-assisted technology; Efficacy and safety of commonly used thromboprophylaxis agents following hip and knee arthroplasty; The COVID-19 effect continues; Nickel allergy in knee arthroplasty: does self-reported sensitivity affect outcomes?; Tranexamic acid use and joint infection risk in total hip and knee arthroplasty.

As advancements in total knee arthroplasty progress at an exciting pace, two areas are of special interest, as they directly impact implant design and surgical decision making. Knee morphometry considers the three-dimensional shape of the articulating surfaces within the knee joint, and knee phenotyping provides the ability to categorize alignment into practical groupings that can be used in both clinical and research settings. This annotation discusses the details of these concepts, and the ways in which they are helping us better understand the individual subtleties of each patient’s knee.

Cite this article: Bone Joint J 2024;106-B(12):1363–1368.

Periprosthetic joint infection represents a devastating complication after total elbow arthroplasty. Several measures can be implemented before, during, and after surgery to decrease infection rates, which exceed 5%. Debridement with antibiotics and implant retention has been reported to be successful in less than one-third of acute infections, but still plays a role. For elbows with well-fixed implants, staged retention seems to be equally successful as the more commonly performed two-stage reimplantation, both with a success rate of 70% to 80%. Permanent resection or even amputation are occasionally considered. Not uncommonly, a second-stage reimplantation requires complex reconstruction of the skeleton with allografts, and the extensor mechanism may also be deficient. Further developments are needed to improve our management of infection after elbow arthroplasty.

Cite this article: Bone Joint J 2024;106-B(11):1321–1326.

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This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

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This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Aims. 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. Methods. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results. Mean callus volume was larger in the elastic fixation group (1,755 mm. 3. (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm. 3. (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion. Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN. Cite this article: Bone Joint Res 2024;13(10):559–572

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 early postoperative mortality and morbidity in older patients with a fracture of the femoral neck, between those who underwent total hip arthroplasty (THA) and those who underwent hemiarthroplasty. Methods. This nationwide, retrospective cohort study used data from the Japanese Diagnosis Procedure Combination database. We included older patients (aged ≥ 60 years) who underwent THA or hemiarthroplasty after a femoral neck fracture, between July 2010 and March 2022. A total of 165,123 patients were included. The THA group was younger (mean age 72.6 (SD 8.0) vs 80.7 years (SD 8.1)) and had fewer comorbidities than the hemiarthroplasty group. Patients with dementia or malignancy were excluded because they seldom undergo THA. The primary outcome measures were mortality and complications while in hospital, and secondary outcomes were readmission and reoperation within one and two years after discharge, and the costs of hospitalization. We conducted an instrumental variable analysis (IVA) using differential distance as a variable. Results. The IVA analysis showed that the THA group had a significantly higher rate of complications while in hospital (risk difference 6.3% (95% CI 2.0 to 10.6); p = 0.004) than the hemiarthroplasty group, but there was no significant difference in the rate of mortality while in hospital (risk difference 0.3% (95% CI -1.7 to 2.2); p = 0.774). There was no significant difference in the rate of readmission (within one year: risk difference 1.3% (95% CI -1.9 to 4.5); p = 0.443; within two years: risk difference 0.1% (95% CI -3.2 to 3.4); p = 0.950) and reoperation (within one year: risk difference 0.3% (95% CI -0.6 to 1.1); p = 0.557; within two years: risk difference 0.1% (95% CI -0.4 to 0.7); p = 0.632) after discharge. The costs of hospitalization were significantly higher in the THA group than in the hemiarthroplasty group (difference $2,634 (95% CI $2,496 to $2,772); p < 0.001). Conclusion. Among older patients undergoing surgery for a femoral neck fracture, the risk of early complications was higher after THA than after hemiarthroplasty. Our findings should aid in clinical decision-making in these patients. Cite this article: Bone Joint J 2024;106-B(9):986–993

Aims. 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. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

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The aims of this study were to describe the demographic, socioeconomic, and educational factors associated with core surgical trainees (CSTs) who apply to and receive offers for higher surgical training (ST3) posts in Trauma & Orthopaedics (T&O).

Aims. Sagittal plane imbalance (SPI), or asymmetry between extension and flexion gaps, is an important issue in total knee arthroplasty (TKA). The purpose of this study was to compare SPI between kinematic alignment (KA), mechanical alignment (MA), and functional alignment (FA) strategies. Methods. In 137 robotic-assisted TKAs, extension and flexion stressed gap laxities and bone resections were measured. The primary outcome was the proportion and magnitude of medial and lateral SPI (gap differential > 2.0 mm) for KA, MA, and FA. Secondary outcomes were the proportion of knees with severe (> 4.0 mm) SPI, and resection thicknesses for each technique, with KA as reference. Results. FA showed significantly lower rates of medial and lateral SPI (2.9% and 2.2%) compared to KA (45.3%; p < 0.001, and 25.5%; p < 0.001) and compared to MA (52.6%; p < 0.001 and 29.9%; p < 0.001). There was no difference in medial and lateral SPI between KA and MA (p = 0.228 and p = 0.417, respectively). FA showed significantly lower rates of severe medial and lateral SPI (0 and 0%) compared to KA (8.0%; p < 0.001 and 7.3%; p = 0.001) and compared to MA (10.2%; p < 0.001 and 4.4%; p = 0.013). There was no difference in severe medial and lateral SPI between KA and MA (p = 0.527 and p = 0.307, respectively). MA resulted in thinner resections than KA in medial extension (mean difference (MD) 1.4 mm, SD 1.9; p < 0.001), medial flexion (MD 1.5 mm, SD 1.8; p < 0.001), and lateral extension (MD 1.1 mm, SD 1.9; p < 0.001). FA resulted in thinner resections than KA in medial extension (MD 1.6 mm, SD 1.4; p < 0.001) and lateral extension (MD 2.0 mm, SD 1.6; p < 0.001), but in thicker medial flexion resections (MD 0.8 mm, SD 1.4; p < 0.001). Conclusion. Mechanical and kinematic alignment (measured resection techniques) result in high rates of SPI. Pre-resection angular and translational adjustments with functional alignment, with typically smaller distal than posterior femoral resection, address this issue. Cite this article: Bone Jt Open 2024;5(8):681–687

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The aims of this study were to describe the epidemiology of metacarpal shaft fractures (MSFs), assess variation in treatment and complications following standard care, document hospital resource use, and explore factors associated with treatment modality.

Aims. 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. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

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Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty – the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most.

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

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Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

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During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon’s decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing.

Aims. 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. Methods. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results. This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10. -11. ), RIC8A (FDR = 7.05 × 10. -4. ), and SOX12 (FDR = 1.43 × 10. -3. ). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion. Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246

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The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

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Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

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Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

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Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

The April 2024 Shoulder & Elbow Roundup³⁶⁰ looks at: Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomized controlled trial; Prevalence and predisposing factors of neuropathic pain in patients with rotator cuff tears; Are two plates better than one? The clavicle fracture reimagined; A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution; Complication rates and deprivation go hand in hand with total shoulder arthroplasty; Longitudinal instability injuries of the forearm; A better than “best-fit circle” method for glenoid bone loss assessment; 3D supraspinatus muscle volume and intramuscular fatty infiltration after arthroscopic rotator cuff repair.

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Patients with midcarpal instability are difficult to manage. It is a rare condition, and few studies have reported the outcomes of surgical treatment. No prospective or retrospective study has reported the results of arthroscopic palmar capsuloligamentous suturing. Our aim was to report the results of a prospective study of arthroscopic suture of this ligament complex in patients with midcarpal instability.

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Modular dual-mobility (DM) articulations are increasingly used during total hip arthroplasty (THA). However, concerns remain regarding the metal liner modularity. This study aims to correlate metal artifact reduction sequence (MARS)-MRI abnormalities with serum metal ion levels in patients with DM articulations.

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The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

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While internet search engines have been the primary information source for patients’ questions, artificial intelligence large language models like ChatGPT are trending towards becoming the new primary source. The purpose of this study was to determine if ChatGPT can answer patient questions about total hip (THA) and knee arthroplasty (TKA) with consistent accuracy, comprehensiveness, and easy readability.

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

Total hip and knee arthroplasty (THA, TKA) are largely successful procedures; however, both have variable outcomes, resulting in some patients being dissatisfied with the outcome. Surgeons are turning to technologies such as robotic-assisted surgery in an attempt to improve outcomes. Robust studies are needed to find out if these innovations are really benefitting patients. The Robotic Arthroplasty Clinical and Cost Effectiveness Randomised Controlled Trials (RACER) trials are multicentre, patient-blinded randomized controlled trials. The patients have primary osteoarthritis of the hip or knee. The operation is Mako-assisted THA or TKA and the control groups have operations using conventional instruments. The primary clinical outcome is the Forgotten Joint Score at 12 months, and there is a built-in analysis of cost-effectiveness. Secondary outcomes include early pain, the alignment of the components, and medium- to long-term outcomes. This annotation outlines the need to assess these technologies and discusses the design and challenges when conducting such trials, including surgical workflows, isolating the effect of the operation, blinding, and assessing the learning curve. Finally, the future of robotic surgery is discussed, including the need to contemporaneously introduce and evaluate such technologies.

Cite this article: Bone Joint J 2024;106-B(2):114–120.

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65

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A novel enhanced cement fixation (EF) tibial implant with deeper cement pockets and a more roughened bonding surface was released to market for an existing total knee arthroplasty (TKA) system.This randomized controlled trial assessed fixation of the both the EF (ATTUNE S+) and standard (Std; ATTUNE S) using radiostereometric analysis.

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The aim of this study was to reassess the rate of neurological, psoas-related, and abdominal complications associated with L4-L5 lateral lumbar interbody fusion (LLIF) undertaken using a standardized preoperative assessment and surgical technique.

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Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

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Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

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Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

The December 2023 Knee Roundup³⁶⁰ looks at: Obesity is associated with greater improvement in patient-reported outcomes following primary total knee arthroplasty; Does mild flexion of the femoral prosthesis in total knee arthroplasty result in better early postoperative outcomes?; Robotic or manual total knee arthroplasty: a randomized controlled trial; Patient-relevant outcomes following first revision total knee arthroplasty, by diagnosis: an analysis of implant survivorship, mortality, serious medical complications, and patient-reported outcome measures using the National Joint Registry data set; Sagittal alignment in total knee arthroplasty: are there any discrepancies between robotic-assisted and manual axis orientation?; Tourniquet use does not impact recovery trajectory in total knee arthroplasty; Impact of proximal tibial varus anatomy on survivorship after medial unicondylar knee arthroplasty; Bone cement directly to the implant in primary total knee arthroplasty?; Maintaining joint line obliquity optimizes outcomes in patients with constitutionally varus knees.

Aims

Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Aims. To perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA). Methods. This was a five-year follow-up study of patients who were randomized to rUKA (n = 64) or mUKA (n = 65). Patients completed the EuroQol five-dimension questionnaire (EQ-5D) preoperatively, and at three months and one, two, and five years postoperatively, which was used to calculate quality-adjusted life years (QALYs) gained. Costs for the primary and additional surgery and healthcare costs were calculated. Results. rUKA was associated with a relative 0.012 QALY gain at five years, which was associated with an incremental cost per QALY of £13,078 for a unit undertaking 400 cases per year. A cost per QALY of less than £20,000 was achieved when ≥ 300 cases were performed per year. However, on removal of the cost for a revision for presumed infection (mUKA group, n = 1) the cost per QALY was greater than £38,000, which was in part due to the increased intraoperative consumable costs associated with rUKA (£626 per patient). When the absolute cost difference (operative and revision costs) was less than £240, a cost per QALY of less than £20,000 was achieved. On removing the cost of the revision for infection, rUKA was cost-neutral when more than 900 cases per year were undertaken and when the consumable costs were zero. Conclusion. rUKA was a cost-effective intervention with an incremental cost per QALY of £13,078 at five years, however when removing the revision for presumed infection, which was arguably a random event, this was no longer the case. The absolute cost difference had to be less than £240 to be cost-effective, which could be achieved by reducing the perioperative costs of rUKA or if there were increased revision costs associated with mUKA with longer follow-up. Cite this article: Bone Jt Open 2023;4(11):889–898

Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

Aims. 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. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666

Aims

Psychological status may be an important predictor of outcome after periacetabular osteotomy (PAO). The aim of this study was to investigate the influence of psychological distress on postoperative health-related quality of life, joint function, self-assessed pain, and sports ability in patients undergoing PAO.

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Aims

To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.