Osteoarthritis and Cartilage最新文献

{"title":"T2 and T1ρ Mapping Reveals Time-Dependent Cartilage Response to In-Scanner Cyclic Compression After ACL Reconstruction.","authors":"Hongtian Zhu, Woowon Lee, Timothy W Lowe, Emily Y Miller, Nancy C Emery, Jonathan T Bravman, Eric C McCarty, Rachel M Frank, Corey P Neu","doi":"10.1016/j.joca.2026.04.016","DOIUrl":"https://doi.org/10.1016/j.joca.2026.04.016","url":null,"abstract":"<p><strong>Objective: </strong>Anterior cruciate ligament injury is a major risk factor for the development of post-traumatic osteoarthritis, with cartilage degeneration frequently occurring despite successful reconstruction surgery. There is a growing need for sensitive, non-invasive imaging techniques to detect early biochemical changes in cartilage before irreversible structural damage occurs. This study aimed to evaluate the response of tibiofemoral cartilage to controlled biomechanical loading in healthy individuals, and in patients six- and twelve-months post anterior cruciate ligament reconstruction using quantitative magnetic resonance imaging.</p><p><strong>Methods: </strong>We employed quantitative relaxometry (T2 and T1ρ mapping) in conjunction with a custom-built pneumatic loading device capable of applying functional, in-scanner mechanical loading (0.5Hz, 50% body weight) to the knee joint. The scans were conducted before and after loading in 12 healthy controls (6 males, 6 females, 27.3±5.7 years old) and 27 post-operative patients (12 males, 15 females, 25.4±5.8 years old). The surgical cohort was further stratified into symptomatic and asymptomatic subgroups based on clinical outcomes.</p><p><strong>Results: </strong>Biomechanical loading led to different quantitative relaxometry outputs between the six- and twelve-month post-operative time points. Across all patients, T2 values increased after biomechanical loading by 8% and 7% at six- and twelve-month time points, respectively. However, our current loading scheme did not lead to MR relaxometry differences between healthy and post-surgery cohorts. Meanwhile, for ligament reconstruction patients, we found increased relaxometry values due to biomechanical load at both time points post-surgery.</p><p><strong>Conclusion: </strong>Biomechanical loading alters the structure and relaxivity of the knee cartilage, and T1ρ may be a more meaningful quantitative metric for post-ligament reconstruction evaluation.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841081","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":"The association of CT-detected intra-articular calcification with MRI-detected effusion-synovitis and Hoffa-synovitis in knee OA: The Multicenter Osteoarthritis study.","authors":"Jean W Liew, Mohamed Jarraya, Ali Guermazi, Nene C Ukonu, Gabriela Rabasa, Robert Terkeltaub, David Felson, Michael Nevitt, Cora E Lewis, James Torner, Tuhina Neogi","doi":"10.1016/j.joca.2026.04.017","DOIUrl":"10.1016/j.joca.2026.04.017","url":null,"abstract":"<p><strong>Background: </strong>CT-detected intra-articular (IA) calcification from calcium crystal deposition is associated with worsening cartilage damage and knee pain in osteoarthritis (OA); whether there is associated joint inflammation is unclear. We studied the relation of CT-detected IA calcification to imaging evidence of inflammation (i.e., effusion-synovitis and/or Hoffa-synovitis) on knee MRI in middle-aged and older adults, focusing on tissue-specific relationships.</p><p><strong>Methods: </strong>Participants from the Multicenter Osteoarthritis study with knee CTs and MRIs were included. Presence of IA calcification on CT was defined as Boston University Calcium Knee Score >0 in hyaline cartilage, meniscus, and capsule anywhere in the knee. Effusion-synovitis and Hoffa-synovitis were scored on MRI using MOAKS at baseline and two years later. We evaluated the relation of IA calcification (overall and in specific tissues) to presence of effusion-synovitis and/or Hoffa-synovitis longitudinally, using Poisson regression with generalized estimating equations, adjusting for age, sex, race, and body mass index.</p><p><strong>Results: </strong>We included 1669 participants with available knee CT and MRI (mean age 60.6±9 years, 56% female, mean BMI 28.5±5 kg/m²; 21.6% knees with radiographic OA). Overall, at baseline, 9.2% had any IA calcification, 30.0% had effusion-synovitis, 37.0% Hoffa-synovitis, and 50% either effusion-synovitis and/or Hoffa-synovitis. The presence of any IA calcification was associated with 30% higher risk of effusion-synovitis and/or Hoffa-synovitis longitudinally (risk ratio 1.30, 95% CI 1.16, 1.46). Results were similar for IA calcification in the cartilage, meniscus, and capsule.</p><p><strong>Conclusion: </strong>CT-detected IA calcification in various tissues was associated with the presence of joint inflammation on MRI over 2 years.</p>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841120","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":"Why is there no treatment for osteoarthritis – Opportunity for AI based big data analytics to advance the field","authors":"F. Saxer ,&nbsp;G. Jansen ,&nbsp;S.M.A. Bierma-Zeinstra ,&nbsp;B. Holzhauer ,&nbsp;D. Demanse ,&nbsp;J. Melnick ,&nbsp;D. Vukadinovic Greetham ,&nbsp;T. Rall ,&nbsp;P. Mesenbrink ,&nbsp;M. Schieker","doi":"10.1016/j.joca.2025.12.021","DOIUrl":"10.1016/j.joca.2025.12.021","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) has long been researched but insights have not translated into novel treatments for OA. One reason may be the heterogeneity of patients suffering from OA. Developments in machine-learning (ML) especially privacy-preserving, federated approaches could help to detect patterns of patient characteristics that allow better segmentation of patient populations, generate prognostic insights on disease progression, and define regulatory acceptable pathways towards patient-relevant surrogate endpoints.</div></div><div><h3>Opportunity</h3><div>The article describes the vision of a collaborative inter-professional, inter-institutional and public-private activity leveraging the wealth of rich yet fragmented datasets to achieve this goal. We summarize the underlying assumptions, challenges and potential applications of such an ML-based approach.</div></div><div><h3>Use cases</h3><div>Employing federated training algorithms locally has the advantage of preserving privacy. The application of novel ML techniques to divers sets of multidimensional health care data such as registries, real-world evidence, trial data etc. allows not only prognostic and predictive inferences but can also overcome issues with incompleteness of variables, heterogeneity in database structures and multidimensionality of variables. This exploration of data can form the foundation for the development of covariates, digital twins, synthetic control groups and form a potential basis for trial emulation. In addition, the approach will enable the development of novel (surrogate) endpoints and inform enrichment strategies.</div></div><div><h3>Conclusion</h3><div>Leveraging ML in a federated framework, the richness of data on OA and the expertise from various areas including patients, providers, ethicists and regulators has the potential to revolutionize trial designs in OA and finally meet the needs of patients suffering from OA.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 657-666"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844828","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":"Reframing early-stage symptomatic knee osteoarthritis (EsSKOA): A strategic lens for trial design","authors":"Armaghan Mahmoudian ,&nbsp;Lauren K King ,&nbsp;Jean W Liew ,&nbsp;Qiuke Wang ,&nbsp;Francis Berenbaum ,&nbsp;Siddharth Das ,&nbsp;Changhai Ding ,&nbsp;Carolyn A Emery ,&nbsp;Stephanie R Filbay ,&nbsp;Marc C Hochberg ,&nbsp;Muneaki Ishijima ,&nbsp;Margreet Kloppenburg ,&nbsp;Nancy E Lane ,&nbsp;Elena Losina ,&nbsp;Ali Mobasheri ,&nbsp;C Thomas Appleton ,&nbsp;Martin Englund ,&nbsp;L Stefan Lohmander ,&nbsp;Jos Runhaar ,&nbsp;Aleksandra Turkiewicz ,&nbsp;Ida K Haugen","doi":"10.1016/j.joca.2025.12.016","DOIUrl":"10.1016/j.joca.2025.12.016","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 647-651"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796092","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 — A call to action","authors":"David J. Hunter,&nbsp;Virginia B. Kraus","doi":"10.1016/j.joca.2026.02.003","DOIUrl":"10.1016/j.joca.2026.02.003","url":null,"abstract":"","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 652-653"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258943","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":"Do rates of femorotibial cartilage loss in Kellgren-Lawrence 2 and 3 knees differ between those with mild-moderate vs. severe patellofemoral structural damage? – Data from the FNIH and IMI-APPROACH cohorts","authors":"Frank W. Roemer ,&nbsp;Mylène Jansen ,&nbsp;Susanne Maschek ,&nbsp;Simon Mastbergen ,&nbsp;Anna Wisser ,&nbsp;Harrie H. Weinans ,&nbsp;Francisco J. Blanco ,&nbsp;Francis Berenbaum ,&nbsp;Margreet Kloppenburg ,&nbsp;Ida K. Haugen ,&nbsp;David J. Hunter ,&nbsp;Ali Guermazi ,&nbsp;Wolfgang Wirth","doi":"10.1016/j.joca.2025.10.003","DOIUrl":"10.1016/j.joca.2025.10.003","url":null,"abstract":"<div><h3>Background</h3><div>The aim was to assess whether rates of quantitative femorotibial (FT) cartilage loss are increased for knees with semiquantitatively (sq)-defined severe patellofemoral (PF) cartilage damage and/or large bone marrow lesions (BMLs) vs. those without over a period of 24 months.</div></div><div><h3>Methods</h3><div>626 knees with Kellgren-Lawrence 2 and 3 from the FNIH and IMI-APPROACH studies were included. MRI assessment was performed using the MRI Osteoarthritis Knee Score (MOAKS) instrument. Baseline FT cartilage damage severity was defined as mild, moderate, or severe. PF cartilage damage was defined as mild-moderate vs. severe. A 2nd definition was based on the presence or absence of large BMLs. Quantitative cartilage thickness loss (defined as the difference from baseline to follow-up in mean cartilage thickness in the medial and in the lateral femorotibial joint, which were computed by summing the cartilage thickness measures observed in the respective cartilage plates) was derived from baseline and 24-month manual segmentations. Between-group comparisons were performed using analysis of covariance (ANCOVA) adjusting for age, sex and body mass index.</div></div><div><h3>Results</h3><div>410 (65%) knees were categorized as mild, 92 (15%) as moderate, and 124 (20%) as severe medial FT cartilage damage. For almost all categories of FT cartilage damage, the difference in quantitative medial FT cartilage loss was not statistically significant. Only for the category of knees with moderate medial FT cartilage damage, statistically higher rates of FT cartilage loss were observed for those with large PF BMLs compared to those without (mean adjusted difference −0.128 mm, 95% confidence interval [-0.238, −0.018], p=0.023).</div></div><div><h3>Conclusions</h3><div>Screening for PF cartilage damage and BMLs does not appear to be required in a disease-modifying OA drug trial.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 672-678"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288264","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":"Why most responder analyses are misleading","authors":"Aleksandra Turkiewicz ,&nbsp;Marius Henriksen ,&nbsp;Jos Runhaar ,&nbsp;Martin Englund","doi":"10.1016/j.joca.2025.12.020","DOIUrl":"10.1016/j.joca.2025.12.020","url":null,"abstract":"<div><h3>Objective</h3><div>So-called responder analyses are commonly used in randomized controlled trials (RCT) for osteoarthritis and are typically based on observed change from baseline in self-reported pain. However, it is well known in the methodological literature that such responder analyses are misleading. We aimed to illustrate the size of the problem using simulation.</div></div><div><h3>Design</h3><div>We generated individual pain trajectories based on real-life assumptions: normal distribution, mean pain 45 on visual analogue scale (VAS, range 0–100), within person standard deviation 12, between person standard deviation 25. Further, we generated plausible data from RCTs with true treatment effect on pain varying from 0 to 15 points on VAS and true proportion of responders 0% or 100%. We applied typical responder analysis to these generated trials.</div></div><div><h3>Results</h3><div>With natural fluctuations of pain, the observed change in pain from baseline does not equal response to treatment. Even if a treatment is highly effective in reducing pain in all patients (100%) by 15 mm VAS, and no patient (0%) is responder to placebo, a typical responder analysis would suggest that 80% in the active treatment arm compared to 50% of persons in a placebo arm are responders, underestimating both the absolute and relative efficacy/effectiveness of the treatment and falsely implying heterogeneity in treatment effects.</div></div><div><h3>Conclusions</h3><div>Responder analysis based on change from baseline in VAS pain should be abandoned in analysis of parallel-group RCTs. Responder criteria based on change from baseline in other fluctuating outcomes, e.g. patients’ self-reported symptoms, function and global assessment, should be scrutinized, as they likely share similar limitations.”</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 716-720"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796091","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":"More than a prescription: The need for behavioral theory to guide exercise interventions for osteoarthritis - A narrative review","authors":"Christine A. Pellegrini ,&nbsp;Lisa C. Carlesso ,&nbsp;Daniel K. White","doi":"10.1016/j.joca.2026.02.012","DOIUrl":"10.1016/j.joca.2026.02.012","url":null,"abstract":"<div><h3>Objective</h3><div>Many clinical exercise trials show that participation in exercise, such as strength training and aerobic walking, reduce osteoarthritis (OA)-related pain and functional limitation. This has led to exercise being one of the most commonly prescribed treatments for OA. However, little attention is given to the complex <em>behavior</em> elements of exercise, that is exercise is an activity that adults need to choose to engage in regularly, which is necessary to ensure exercise can have long-term efficacy to address pain. The purpose of this review is to highlight the behavioral aspects of exercise.</div></div><div><h3>Design</h3><div>Narrative review</div></div><div><h3>Results</h3><div>Limitations of previous clinical exercise trials in OA and why and how behavioral theories should be used to guide exercise interventions are highlighted. Three behavioral theories commonly used for exercise and physical activity interventions in other populations are reviewed. An overview of choosing a behavioral theory, building a conceptual model, and linking behavior change techniques to theoretical constructs is provided. Finally, in order to make the results more generalizable and comparable across studies, a standardized approach to quantify exercise behaviors is recommended.</div></div><div><h3>Conclusion</h3><div>In conclusion, a shift to view exercise more as a behavior than a treatment is recommended. The use of behavioral theories is encouraged to guide interventions for clinical and research use to more effectively change exercise behaviors and reduce OA-related pain and functional limitations for the long-term.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 761-766"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326708","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":"Sex differences in preoperative pain intensity among patients undergoing total knee arthroplasty: A propensity score–matched cross-sectional study","authors":"So Tanaka ,&nbsp;Yuta Tomooka ,&nbsp;Akira Mibu ,&nbsp;Ryota Imai ,&nbsp;Hirofumi Yamashita ,&nbsp;Masahiro Manfuku ,&nbsp;Keiko Yamada ,&nbsp;Masami Tokunaga ,&nbsp;Takaaki Yoshimoto ,&nbsp;Takahiro Ushida ,&nbsp;Tomohiko Nishigami","doi":"10.1016/j.joca.2025.12.009","DOIUrl":"10.1016/j.joca.2025.12.009","url":null,"abstract":"<div><h3>Background</h3><div>Although sex differences in knee osteoarthritis (OA) pain are well documented, previous studies have not adequately adjusted for structural and inflammatory confounders. Clarifying whether preoperative sex differences in pain persist after such adjustment is clinically important in advanced OA because it may influence surgical decision-making, preoperative counselling, and strategies to prevent persistent postoperative pain.</div></div><div><h3>Objective</h3><div>To compare preoperative pain intensity, pain sensitivity, psychosocial characteristics, and physical function between women and men with advanced knee OA using propensity score–matched analysis.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, 120 patients (60 women and 60 men) with advanced knee OA were propensity score–matched 1:1 on age, body mass index, Kellgren–Lawrence grade, C-reactive protein, synovitis, and bone marrow lesions. Primary outcomes were pain intensity at rest and during movement. Secondary outcomes were central sensitization-related symptoms (CSI-9), pressure pain thresholds (PPTs), psychosocial measures, and physical function.</div></div><div><h3>Results</h3><div>After matching, women reported significantly greater resting pain (23.3 ± 22.3 vs. 11.0 ± 15.2; mean difference = 12.3 mm, 95% CI: 5.1–19.5) but similar movement pain (47.2 ± 25.0 vs. 45.3 ± 24.6; mean difference = 1.9 mm, 95% CI: −7.4 to 11.2). They also showed higher CSI-9 scores, lower PPTs at the knee and forearm, and poorer physical function, with no significant differences in psychosocial measures.</div></div><div><h3>Conclusion</h3><div>Women with advanced knee OA awaiting surgery showed greater pain sensitivity and human-assumed central sensitization than men, independent of structural and inflammatory factors. This supports sex-specific mechanisms and underscores individualized pain assessment and rehabilitation.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 707-715"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784546","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":"Feasibility and predictive value of proposed early endpoints for randomized controlled trials in knee osteoarthritis","authors":"Jamie E. Collins ,&nbsp;Peter Mesenbrink ,&nbsp;Robin Dunn ,&nbsp;Leticia A. Deveza ,&nbsp;Zhaohua Zhu ,&nbsp;Amber Zimmerman ,&nbsp;C. Kent Kwoh ,&nbsp;Virginia B. Kraus ,&nbsp;David J. Hunter","doi":"10.1016/j.joca.2026.02.001","DOIUrl":"10.1016/j.joca.2026.02.001","url":null,"abstract":"<div><h3>Objective</h3><div>The designation of osteoarthritis (OA) as a serious disease allows for accelerated approval of a treatment based on an intermediate clinical endpoint. We evaluated proposed endpoints and assessed their feasibility for use in a randomized controlled trial (RCT). We examined associations between endpoints and subsequent total knee replacement (TKR), a proxy for long-term clinical benefit.</div></div><div><h3>Design</h3><div>We selected knees from the Osteoarthritis Initiative meeting typical RCT inclusion criteria, including pain and radiographic OA. Endpoints included TKR, end-stage knee OA (esKOA), Composite Knee Osteoarthritis Symptom Outcome (CKOASO), the FNIH OA Biomarkers Consortium endpoint, and several combinations of pain and/or functional limitations. We determined the cumulative incidence (CI) over four years and the associated sample size required for an RCT to detect a hazard ratio (HR) of 0.67 with 80% power (to assess feasibility). We assessed the association between reaching each endpoint and TKR over the subsequent 5 years.</div></div><div><h3>Results</h3><div>1350 knees (one per participant) were included. 4-year CI of TKR was 4.3%. CIs were highest for FNIH (13.8%), esKOA (34.4%), and CKOASO (63.6%). The required sample size per arm ranged from 229 (CKOASO) to 3028 (TKR). The relative risk (RR) of subsequent TKR was highest for the esKOA endpoint (RR 5.7), followed by CKOASO (4.3) and FNIH (2.6).</div></div><div><h3>Conclusions</h3><div>Based on feasibility (sample size) and clinical relevance (association with subsequent TKR), we propose that the esKOA, CKOASO, and FNIH endpoints be prioritized for further consideration. Given feasibility limitations, we would not recommend TKR alone as a DMOAD trial endpoint.</div></div>","PeriodicalId":19654,"journal":{"name":"Osteoarthritis and Cartilage","volume":"34 5","pages":"Pages 732-739"},"PeriodicalIF":9.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146777357","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}