Osteoarthritis and Cartilage最新文献

{"title":"Overall and specific treatment effects of pharmacological interventions for hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials","authors":"Zeqin Wen,Ziqi Chen,Hongyi He,Weiya Zhang,Michael Doherty,Yuqing Zhang,Guanghua Lei,Jie Wei,Chao Zeng","doi":"10.1016/j.joca.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.joca.2026.09.012","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"31 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting knee osteoarthritis radiographic progression: A multimodal diffusion approach.","authors":"Dingyu Wang, Xueqing Yu, Xinwei Du, Jiaxin Liu, Jiajun Liu, Shan Zeng, Tingting Jiang, Dong Jiang","doi":"10.1016/j.joca.2026.08.013","DOIUrl":"10.1016/j.joca.2026.08.013","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to develop KOA-Diff, a multimodal diffusion model predicting future knee radiographs for accurate, visually interpretable forecasting of knee osteoarthritis (KOA) progression.</p><p><strong>Methods: </strong>KOA-Diff utilizes a latent diffusion backbone and a multimodal fusion network to integrate baseline X-rays, MRIs, and clinical characteristics. A feature-targeting attention mechanism guides image generation toward critical anatomical structures. The model was trained and internally validated on the Osteoarthritis Initiative (OAI) dataset and externally validated on a private cohort (PUTH-KOA, n=80). We evaluated the synthesized future radiographs using joint space width error (JSWE, error relative to the actual width) and binary Kellgren-Lawrence (KL) grade accuracy (early [KL ≤2] vs. advanced [KL ≥3]). Additionally, blinded experts graded structural features. Finally, clinical utility was tested by using model outputs to assist clinicians in identifying high-risk patients exhibiting a longitudinal KL grade increase ≥2 levels over 8 years.</p><p><strong>Results: </strong>In the OAI dataset, KOA-Diff achieved a JSWE of 0.71%-1.21% and binary KL-grade accuracy of 84.0%-91.8% over 96 months. External validation demonstrated promising performance with 90.0% binary KL-grade accuracy and 2.06% JSWE. In the blinded evaluation, experts rated the accuracy of synthesized features on a 5-point scale. For the OAI cohort, the model scored 4.162 (joint space narrowing), 3.895 (osteophyte formation), and 3.943 (subchondral bone sclerosis). PUTH-KOA scores were consistently high (4.050, 3.925, 3.775, respectively). With model assistance, clinicians' accuracy in identifying high-risk patients improved from 58.3% to 77.5%.</p><p><strong>Conclusions: </strong>KOA-Diff synthesizes future radiographs reflecting accurate structural progression, providing an interpretable tool for KOA prediction.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formation of articular cartilage-like tissue in vitro with a calcifying zone requires elevated levels of phosphate.","authors":"Alena A Zelinka, Adele Changoor, Marc D Grynpas, Rita A Kandel","doi":"10.1016/j.joca.2026.08.010","DOIUrl":"10.1016/j.joca.2026.08.010","url":null,"abstract":"<p><strong>Objective: </strong>Articular cartilage (AC) deep zone (DZ) merges with a zone of calcified cartilage (ZCC) which is responsible for anchoring AC to bone. However, regulators of ZCC formation are poorly understood. As inorganic phosphate (P_i) modulates growth plate chondrocyte differentiation and is a component of hydroxyapatite, we hypothesize that increased P_i is required for formation of a localized ZCC by DZ chondrocytes (DZC).</p><p><strong>Design: </strong>Calf metacarpophalangeal joint DZC were grown in 3D culture for up to 7 weeks with or without P_i-containing compounds. In vitro-formed tissues and native AC were evaluated histologically, immunohistochemically, biochemically, and by electron microscopy and diffraction.</p><p><strong>Results: </strong>P_i levels and tissue non-specific alkaline phosphatase (TNAP) activities showed depth-dependent distribution in native DZ. With β-glycerophosphate (βGP) treatment, both TNAP_low and TNAP_high DZC formed tissue with a lower mineralized zone, however, TNAP_low DZC revealed delayed mineralization and P_i accumulation when compared to TNAP_high DZC. In the absence of βGP, no mineral accumulated. Both control and βGP-treated TNAP_low and TNAP_high tissues contained differentially distributed TNAP activity, ColX, and MMP13. Separation of upper and lower aspects of βGP-treated in vitro-formed tissues revealed greater P_i content in the lower, mineralizing region than in the upper, non-mineralized region. Chemical inhibition of P_i generation and transport prevented mineralization. P_i-treated DZC resulted in biphasic tissues with a lower, mineralized, high-P_i region, and an upper, non-mineralized, low-P_i region.</p><p><strong>Conclusions: </strong>This work establishes P_i as an important regulator of DZC mineralization and ZCC formation and suggests that P_i may regulate the phenotype of a DZC subpopulation.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin from the infrapatellar fat pad contributes to knee pain in MIA-induced osteoarthritis model rats by regulating nerve growth factor expression in the synovium.","authors":"Keisuke Atsumi, Naoya Hoshikawa, Daiki Saito, Ryosuke Arakawa, Tokifumi Majima, Makoto Hirao, Atsushi Sakai","doi":"10.1016/j.joca.2026.08.009","DOIUrl":"10.1016/j.joca.2026.08.009","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is characterized by progressive cartilage loss and is a major cause of chronic pain and disability. The infrapatellar fat pad (IFP) is an adipose tissue that contacts the synovium and is implicated in knee OA pain. However, the molecular mechanisms linking the IFP to pain remain poorly understood. In this study, we explored a potential IFP-derived mediator of knee OA pain.</p><p><strong>Design: </strong>Knee OA was induced in male and female Sprague Dawley rats by the intra-articular monoiodoacetic acid injection, and saline was injected as a control. Pain-related behaviors of MIA model rats were assessed using the Pressure Application Measurement (n = 7) and von Frey tests (n = 6-7). RNA sequencing was performed on IFP tissue from MIA model and control rats (n = 4). Expression levels of apelin and its receptor APJ were examined using quantitative polymerase chain reaction, and APJ distribution was examined with immunofluorescence. The involvement of apelin and nerve growth factor (NGF) in knee pain was investigated by intra-articular injection of [Pyr1]-apelin-13, the APJ antagonist ML221 and an anti-NGF antibody.</p><p><strong>Results: </strong>Apelin signaling was identified as the most significant pathway relating to differentially expressed genes in the IFP from rats with knee OA. Apelin expression was upregulated in the IFP, and the intra-articular injection of [Pyr1]-apelin-13 caused knee pain (estimated mean difference of -294.8 g and 95% CI of -487.3 to -102.3 g in the PAM test on day 1). APJ expression was markedly increased in synoviocytes of knee OA. The APJ antagonist ML221 alleviated knee OA pain (estimated mean difference of 239.9 g and 95% CI of 125.3-354.6 g in the PAM test on day 1), in association with reduced NGF expression in the synovium. [Pyr1]-apelin-13-induced knee pain was suppressed by anti-NGF antibody (estimated mean difference of 234.9 g and 95% CI of 124.9-344.9 g in the PAM test on day 1).</p><p><strong>Conclusions: </strong>Our findings indicate that apelin causes knee OA pain by regulating NGF expression in the synovium of MIA model rats. Targeting apelin signaling may therefore provide a novel analgesic therapy for knee OA pain.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEF2D as a key regulator of osteoarthritis with exploratory therapeutic potential.","authors":"Jingjin Dai, Xiaoshan Gong, Hao Tang, Zhaoyang Hu, Sha Yang, Yuwei He, Jiezhong Deng, Lanyi Liu, Wenhui Hu, Qijie Dai, Junyu Xiang, Shiwu Dong","doi":"10.1016/j.joca.2026.08.011","DOIUrl":"10.1016/j.joca.2026.08.011","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis is the most common degenerative joint disease worldwide, characterized by degeneration of articular cartilage caused by chondrocyte dysfunction and invasion of vessels from subchondral bone. However, the molecular mechanisms governing the dyshomeostasis of cartilage and subchondral bone during osteoarthritis remain unclear. Emerging evidence indicates that myocyte enhancer factor 2D (MEF2D) promotes chondrocyte hypertrophy and vascularization, whereas its role in osteoarthritis has not yet been reported.</p><p><strong>Methods: </strong>To explore the role of MEF2D, we generated and identified MEF2D conditional knockout mice and established osteoarthritis models via DMM or ACLT surgery. Samples were evaluated using micro-CT, histological, and immunofluorescence analyses, whereas molecular mechanisms were elucidated by RNA-Seq, CUT&Tag, ChIP, and dual-luciferase reporter assays.</p><p><strong>Results: </strong>MEF2D was aberrantly overexpressed in murine osteoarthritis cartilage, whereas osteoarthritis progression was delayed in MEF2D knockout mice (p = 0.0359, OARSI grade, -1.048 [95% CI: -2.034, -0.06209]). Functionally, MEF2D bound to the promoter of lactate dehydrogenase A (LDHA) to activate its transcription, and induced the expression of inflammatory cytokines via LDHA/IκB-ζ signaling, which subsequently promoted the expression of catabolic genes. Moreover, MEF2D increased VEGF secretion by chondrocytes through upregulating brain-derived neurotrophic factor (BDNF) (p < 0.0001, MD = 9.486 [95% CI: 7.185, 9.622]). Additionally, BDNF secreted by chondrocytes binds to its receptor TrkB to form a BDNF/TrkB autocrine loop that positively regulates MEF2D expression (p = 0.0002, MD = 0.9250 [95% CI: 0.5709, 1.279]). Injection of a TrkB antagonist into the articular cavities of osteoarthritis model mice provided preliminary evidence of delayed cartilage degeneration, subchondral osteosclerosis, and osteophyte formation.</p><p><strong>Conclusion: </strong>Our study revealed a critical transcriptional regulatory role of MEF2D in osteoarthritis, and further suggested that targeting MEF2D may represent a potential therapeutic strategy.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular clustering in osteoarthritis primary tissues identifies shared inflammatory and tissue-specific pathway profiles.","authors":"Odysseas Sotirios Stergiou, Norbert Bittner, Georgia Katsoula, Diane Swift, Jeremy Mark Wilkinson, Eleftheria Zeggini","doi":"10.1016/j.joca.2026.08.008","DOIUrl":"10.1016/j.joca.2026.08.008","url":null,"abstract":"<p><strong>Objectives: </strong>To disentangle the molecular heterogeneity of knee osteoarthritis (OA) through the classification and characterization of transcriptomic clusters in multiple joint tissues, and to uncover distinct biological pathways that will facilitate improved patient stratification.</p><p><strong>Methods: </strong>We analyzed RNA sequencing data from 330 knee OA patients across low- and high-grade OA knee cartilage, synovium and infrapatellar fat pad tissues. We used unsupervised machine learning to identify distinct transcriptomic clusters and subsequently performed cluster-specific differential expression and pathway enrichment analyses. We applied multi-omics factor analysis in low-grade cartilage to construct a gene expression-based classifier for subtype prediction, which we validated in an independent knee OA RNA sequencing dataset.</p><p><strong>Results: </strong>We identified robust clusters across all four joint tissues. In low-grade cartilage, we identified two patient groups separated by differences in inflammation and transcriptional regulation. A gene classifier distinguished these groups with a cross-validated accuracy of 94.5% (95% CI 91.1-96.6%). We also reproduced these subtypes in an external cohort in which the same axis similarly separated the subgroups. In high-grade cartilage there were three distinct clusters, characterized by inflammatory, neuroactive receptor-signaling, and housekeeping-transcriptional programs. Both synovium and infrapatellar fat pad showed two distinct subgroups. Despite the histological differences between these two tissues, subgrouping was based on shared biological functions related to immune activation, alongside disease tissue-specific ones.</p><p><strong>Conclusions: </strong>Our findings identify gene expression-based patient clusters in different primary joint tissues and point to shared and disease tissue-specific molecular programs in OA, thus setting the foundation for transcription signature-based patient stratification.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between canonical Wnt signaling and α5β1 integrins modulates mechanoresponse in human articular cartilage.","authors":"N Viudes-Sarrión, R Castro-Viñuelas, N Vaes, E J Blain, R J Lories, I Jonkers","doi":"10.1016/j.joca.2026.08.007","DOIUrl":"10.1016/j.joca.2026.08.007","url":null,"abstract":"<p><strong>Objectives: </strong>Mechanical cues are essential for cartilage homeostasis, yet their interaction with molecular pathways dysregulated in osteoarthritis (OA) remains poorly understood. Canonical Wnt signalling regulates cartilage biology and cell-matrix interactions, but its role in integrin-dependent mechanoregulation is unclear. This study investigated how Wnt activation affects chondrocyte responses to physiological mechanical loading, focusing on α5β1 integrin and cytoskeletal organisation.</p><p><strong>Methods: </strong>Human cartilage explants from non-OA and OA donors were subjected to short-term physiological cyclic compression. Canonical Wnt signalling was activated with CHIR99021, and α5β1 integrins were blocked with ATN-161 during loading. Chondrocyte responses were assessed by mechanoresponsive and matrix-related gene expression, α5β1 complex formation using proximity ligation assay, and F-actin organisation by confocal microscopy.</p><p><strong>Results: </strong>OA chondrocytes exhibited increased ITGA5 and ITGB1 but reduced ITGA10 expression. In non-OA cartilage, Wnt activation increased ITGB1 expression and α5β1 complex formation, while loading further enhanced ITGA5 and ITGB1 transcription under Wnt-activated conditions. Under control conditions, loading induced mechanoresponsive and anabolic gene expression, whereas these responses were attenuated by Wnt activation and partially restored by α5β1 blockade. Mechanical loading promoted cortical F-actin reorganisation across cartilage zones irrespective of disease status or treatment. Wnt activation did not induce distinct cytoskeletal phenotypes under loading, and load-induced actin remodelling remained comparable between groups.</p><p><strong>Conclusions: </strong>These findings identify α5β1 integrin as a key mediator of Wnt-driven chondrocyte mechanoresponsiveness. Although loading consistently promoted cortical F-actin reorganisation, Wnt-associated changes in load responsiveness were primarily mediated through integrin-dependent mechanisms rather than major alterations in actin organisation, highlighting integrin signalling as a potential therapeutic target in OA.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoarthritis pain extends beyond the nociceptive phenotype.","authors":"Mary-Ann Fitzcharles, Rodrigo Deamo Assis, David W Polly, Steven P Cohen","doi":"10.1016/j.joca.2026.08.005","DOIUrl":"10.1016/j.joca.2026.08.005","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TL1A(TNFSF15)-ENO1 axis promotes osteoarthritis by disrupting redox homeostasis via the PI3K/AKT pathway.","authors":"Xiang Gao, Juntan Li, Changyu Yin, Kai Li, Yuyang Gao, Zihao Zhang, Xu Li, Xun Sun","doi":"10.1016/j.joca.2026.08.002","DOIUrl":"10.1016/j.joca.2026.08.002","url":null,"abstract":"<p><strong>Objective: </strong>Osteoarthritis (OA) is characterized by cartilage degeneration, oxidative stress, and chondrocyte senescence. This study investigated whether TL1A promotes OA through ENO1-associated redox, senescence and PI3K-AKT signaling mechanisms.</p><p><strong>Method: </strong>Human paired OA cartilage, primary chondrocytes, and mouse age-associated and destabilization of the medial meniscus (DMM)-induced OA models were used. TL1A and ENO1 were manipulated using genetic deletion, intra-articular adenoviral delivery, and siRNA-mediated silencing. Oxidative stress, cellular senescence, cartilage degeneration, ENO1-related regulatory mechanisms, and PI3K-AKT activation were assessed using histology, immunostaining, Western blotting, qPCR, RNA-seq, co-immunoprecipitation, ubiquitination assays, and pharmacological rescue experiments.</p><p><strong>Results: </strong>TL1A-positive chondrocytes were increased in damaged versus paired undamaged human cartilage (n = 8 paired patients) [mean paired difference, +64.24 percentage points; 95% CI, 57.80-70.68]. In DMM mice, Tl1a deletion reduced cartilage damage [OARSI Hodges-Lehmann (HL) difference, -2.50; 95% CI, -4 to 0], whereas intra-articular Tl1a overexpression induced mild OA-like cartilage changes [OARSI HL difference, +0.75; 95% CI, 0-1.50]. TL1A silencing reduced ROS fluorescence in IL-1β-treated human chondrocytes [mean change, -53.50%; 95% CI, -61.59 to -45.41]. TL1A interacted with ENO1 and was associated with altered ENO1 ubiquitination and protein abundance; Eno1 overexpression restored OA severity in DMM-operated Tl1a^-/- mice [OARSI HL difference, +3.75; 95% CI, 3-5.50]. PI3K-AKT activation contributed to this phenotype, as 740 Y-P increased OARSI scores in DMM-operated Tl1a^-/- mice [HL difference, +1.25; 95% CI, 0-2.50].</p><p><strong>Conclusion: </strong>TL1A contributes to OA progression by promoting ENO1-associated redox imbalance, chondrocyte senescence, and PI3K-AKT signaling, supporting the TL1A-ENO1 axis as a potential therapeutic target.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive descriptive analysis of hip and knee radiographic osteoarthritis in the UK Biobank in relation to joint pain, joint site interrelationships, obesity, race and deprivation: Findings from 59,475 individuals.","authors":"Asad Hashmi, Sophie Scott, Mijin Jung, Fiona R Saunders, Raja Ebsim, Jennifer S Gregory, Liubov Arbeeva, Amanda E Nelson, Nicholas C Harvey, Claudia Lindner, Richard M Aspden, Timothy Cootes, Jonathan H Tobias, Benjamin G Faber","doi":"10.1016/j.joca.2026.07.013","DOIUrl":"10.1016/j.joca.2026.07.013","url":null,"abstract":"<p><strong>Objective: </strong>Patients with osteoarthritis (OA) affecting multiple joints experience greater pain than those with single-joint disease, yet most research examines isolated joints, leaving a gap in multi-joint disease. This study aimed to describe radiographic hip (rHOA) and knee OA (rKOA) within UK Biobank (UKB), exploring interrelationships across joints and associations with joint pain, body size, race and deprivation.</p><p><strong>Design: </strong>This cross-sectional study applied machine learning to hip and knee dual-energy X-ray absorptiometry scans. Radiographic OA (rOA) was defined as custom grades ≥2. Joint pain was assessed through self-reported questionnaires. Logistic regression models examined bilateral and cross-joint associations, as well as associations with joint pain. Adjustments were made for age, sex, race, height, weight and deprivation.</p><p><strong>Results: </strong>Among 59,475 individuals (mean age 65 years; range 45-85; SD 7.7; 52.8% female), rHOA prevalence was 4098 (6.9%, right-side) and 4841 (8.1%, left-side). The corresponding estimates for rKOA were 3750 (6.3%) and 4220 (7.1%). Overall, increasing grades of rOA and number of joints affected were more strongly associated with concurrent joint pain (four-joints: OR 4.3 [95%CI 2.6-7.2]). Regarding joint-interrelationships, bilateral associations were stronger at the knee (26.1 [24.1-28.2]) than the hip (5.6 [5.2-6.1]). Cross-joint associations (hip-knee) were weaker. BMI was more strongly associated with rKOA (1.57 [1.52-1.61]) than rHOA (1.05 [1.02-1.09]). Greater height was positively associated with rHOA but appeared protective for rKOA.</p><p><strong>Conclusions: </strong>Radiographic hip and knee OA exhibit distinct patterns of interrelationship, associations with symptoms and risk factors, suggesting heterogeneity in disease processes and the need for joint-specific treatment.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}