The sense of embodiment (SoE), when an individual takes bodily ownership over an artificial body part as their own, has been shown to produce analgesic effects. SoE can be facilitated through virtual reality (VR) and spherical video-based virtual reality (SVVR), where users may experience embodiment of virtual limbs. In this study we used pre-recorded embodiment-inducing SVVR as a nonpharmacological analgesic intervention for individuals with hand osteoarthritis (HOA) who experienced chronic pain. The study used a pre/post within-subjects design (N = 10) to evaluate the immediate effects of SVVR and a 3-week single-subject design (N = 2) to evaluate potential prolonged effects. Results revealed that SVVR significantly reduced pain in the pre/post study during SVVR ( p = 0.02; r = 0.82) and immediately after ( p = 0.01; r = 0.90). The single-subjects study demonstrated significant analgesic effects during the week of the intervention for one participant ( p < 0.001), but not for the other participant ( p = 0.89). Embodiment-inducing SVVR shows potential as an nonpharmacological and cost-effective way to manage pain and support functioning in people with HOA.

To investigate the associations of maternal and personal smoking with the risk of knee, hip, hand, and overall osteoarthritis (OA) and the role of genetic predisposition to OA. A total of 321,075 UK Biobank participants (mean age 56 years, 55% female) without OA at baseline were included; 29.9% reported maternal smoking, 24.3% reported former smoking, and 9.5% reported current smoking. Maternal smoking around childbirth (yes/no) and personal smoking status (never/former/current) and dose (pack-years) were self-reported by the participants. Cox proportional hazards models were used to explore the associations of maternal and personal smoking status and personal smoking dose with the risk of OA. Genetic susceptibility of OA was assessed using polygenic risk scores (PRS). During follow-up, 18,470 (5.8%), 12,064 (3.8%), 6605 (2.1%) and 52,853 (16.5%) participants developed knee, hip, hand, and overall OA, respectively. Both maternal and personal smoking were positively associated with the risk of knee, hip, hand, and overall OA (maternal smoking hazard ratio [HR]=1.08 to 1.23; personal smoking HR=1.18-1.40) . There were significant dose-responsive associations between personal smoking dose and OA risk (p for trend<0.05). The association between maternal and personal smoking and OA risk was similar across different PRS strata. Both maternal and personal smoking are independently associated with an elevated risk of OA. These associations are universal across different genetic susceptibility of OA.

To characterise radiographic progression over 2 years and associated characteristics in patients with hand osteoarthritis. Baseline and year 2 data from the Hand OSTeoArthritis in Secondary (HOSTAS) care cohort were used, including patients from a rheumatology outpatient clinic.We collected demographics, disease and patient characteristics and MRI scans of the right hand. Erosive disease was classified using the Verbruggen-Veys system.Dorso-volar hand radiographs were scored blinded, paired, in chronological order, with the Osteoarthritis Research Society International system (osteophytes and joint space narrowing (JSN), scored 0-3/0-1, depending on the joint) per joint (sum score 0-88), with high to excellent reliability. We used the smallest detectable changes to classify progressors (all joints, thumb-base joints and IP joints).Associations between progression and characteristics were analysed with logistic regression. Among 417 patients (mean age 61 years, 86% female), 272 (65%) showed osteophyte progression (median sum score (IQR) change 1 (0-2)) and 135 (32%) JSN progression (median sum score (IQR) change 1 (0-2)). Both osteophyte and JSN progressors had more radiographic damage at baseline. Associations were found between baseline erosive disease or bone marrow lesions and osteophyte progression in IP joints, and between female sex and osteophyte progression in thumb-base joints. The association of baseline osteophytes with change in osteophytes was strongest in younger females. Over 2 years, a considerable proportion of patients demonstrated radiographic progression. Progressors were especially those with erosive disease, more radiographic damage (most pronounced in younger females) and bone marrow lesions at baseline.

Although gut microbiome dysbiosis is associated with symptomatic hand osteoarthritis (SHOA), the role of bile acids (BAs), key metabolites in host-microbiota interactions, in SHOA pathogenesis remains unexplored. We investigated the association between plasma BA metabolism and SHOA. The associations between plasma BAs and SHOA were examined in the Xiangya Osteoarthritis (XO) Study and validated in an independent cohort through logistic regression models. Gut microbiome data from a previous study conducted within the XO Study were integrated to explore associations between SHOA-related gut microbes and key BAs. As an exploratory analysis, gene-based meta-analyses evaluated associations between genes encoding key BA receptors and hand OA. In the discovery cohort (n = 1,359, mean age ± SD 63.1 ± 9.0 years, 58.4% women, SHOA prevalence 5.2%, all participants being Asian), elevated levels of deoxycholic acid (DCA) species (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.96) and DCA (OR 2.14, 95% CI 1.24-3.70) were positively associated with SHOA presence and severity. These associations were replicated in an independent cohort (n = 142). Multiomics analyses revealed significant correlations of DCA species, DCA, and the DCA species-to-total BAs ratio with SHOA-related gut microbes. DCA interacted with SHOA-related gut microbes and was associated with SHOA. Gene-based meta-analyses identified significant associations between genes encoding the Farnesoid X receptor and the pregnane X receptor and hand OA. Dysregulated BA metabolism, particularly elevated DCA levels, is associated with SHOA. The observation that DCA interacts with SHOA-related gut microbes, together with genes encoding DCA receptors, may help guide future biologically and clinically relevant studies.

BackgroundThis study aimed to estimate the global, regional, and national Osteoarthritis (OA) burden and trends in older adults from 1990 to 2021, with a particular focus on the contribution of high body mass index (BMI) to the OA burden.MethodsUsing 2021 Global Burden of Disease Study data, we estimated the incidence, DALYs, and trends of OA in older adults across 204 countries and territories from 1990 to 2021. Spearman’s correlation analysis was applied to investigate relationships between age-standardized rates and the sociodemographic index (SDI). We quantified the BMI-attributable contribution to the OA burden. The Bayesian Age-Period-Cohort (BAPC) model was applied to project the global OA trend in older adults up to 2040.ResultsFrom 1990 to 2021, global OA cases in older adults increased by 148.65%. Age-standardized incidence and DALY rates increased annually by 0.08% and 0.31%, respectively. East and Southeast Asia exhibited the fastest increase in age-standardized DALY rates. The OA burden peaked in the 65–69-year age group, with women compared with men experiencing a higher burden. Knee OA imposed the heaviest burden, followed by hand OA, with regional variations across four anatomical sites. The OA burden, including specific sites, positively correlated with the SDI. The attributable proportion of OA burden due to high BMI increased by 21.39%, with the knee OA burden from high BMI exceeding the hip OA burden. The BAPC model predicted that OA burden will continue to rise in the future.ConclusionsOA in older adults is a major global challenge, with knee OA being the most burdensome. High BMI, a modifiable risk factor, contributes significantly to OA, particularly in the knees. To reduce the OA burden, public health strategies should prioritize obesity prevention through weight management and awareness campaigns for older adults.

To analyze the current status and temporal trends of the disease burden of osteoarthritis (OA) in China from 1990 to 2023, stratified by anatomical sites (knee, hip, hand, and other), utilizing data from the 2023 Global Burden of Disease (GBD) study, and to explore the site-specific heterogeneity of disease burden attributed to high body mass index (BMI), providing a scientific basis for formulating precision prevention and control strategies. Based on the GBD 2023 database, data on the incidence, prevalence, and years lived with disability (YLDs), as well as their corresponding age-standardized rates of OA in China from 1990 to 2023, were collected and stratified by gender, age, and anatomical site (knee, hip, hand, and other). A log-linear regression model was employed to calculate the estimated annual percentage change (EAPC) to analyze temporal trends. Additionally, the population attributable fraction (PAF) was used to quantify the contribution of high BMI to OA across different sites and to analyze the heterogeneity of this attribution. In 2023, the disease burden of OA in China increased. In terms of anatomical distribution, knee OA constituted the heaviest burden, with 115.0032 million prevalent cases, accounting for approximately 65.78% of the total. Attribution analysis showed that knee OA was slightly more affected by high BMI than hip OA, and the PAF increased significantly over time. In 2023, the PAFs for knee and hip OA in females (29.49% and 28.57%, respectively) were substantially higher than those in 1990 (19.10% and 18.38%). A similar upward trend was observed in males (26.65% and 25.92% in 2023). Regarding attribution differences, female PAF levels were consistently higher than those of males across all years and sites. Hand OA exhibited the fastest growth rate, with the EAPC of its age-standardized YLDs rate reaching 1.64%, far exceeding that of knee OA (0.43%). Demographically, all burden indicators were higher in females than in males. Hand OA demonstrated an intergenerational cumulative effect. The difference in YLDs rates between 2023 and 1990 widened with age, reaching 123.29 per 100 000 in the >95 years old group, highlighting the severe challenges posed by population aging. From 1990 to 2023, the disease burden of OA in China continued to rise. Knee OA remains the heaviest burden category and is significantly driven by high BMI, whereas hand OA shows the fastest growth trend. Prevention and control strategies should focus on weight management for knee and hip OA, while prioritizing the prevention and care of hand OA in the elderly population.

Objective To evaluate the diagnostic performance of dual-energy computed tomography (DECT), ultrasound (US), cone-beam computed tomography (CBCT), and multi-energy spectral photon-counting computed tomography (SPCCT) for detecting calcium pyrophosphate (CPP) and hydroxyapatite crystal deposition. Method We prospectively enrolled patients scheduled for finger-joint surgery due to osteoarthritis. Preoperative cross-sectional assessment included visual analogue scale pain, and in vivo index tests with DECT, US, and CBCT; the postoperative ex vivo index test was SPCCT of excised joint material. Reference tests comprised compensated polarized light microscopy of synovial fluid and histology with Alizarin Red S staining of excised joint material. Tests for crystals were scored on a binary basis. We calculated sensitivity, specificity, and likelihood ratios (LRs); a test with positive LR > 10 or negative LR < 0.1 was considered ‘very good’. Results We included 12 participants, nine of whom had at least one positive reference test for calcium crystals. None of the index tests met our predefined cut-offs for a very good test. The best sensitivity and specificity were 0.29 [95% confidence interval (CI) 0.04–0.71] and 0.67 (0.09–0.99) for DECT, 0.89 (0.52–1.00) and 1.00 (0.16–1.00) for US, 0.33 (0.07–0.70) and 0.67 (0.09–0.99) for CBCT, and 1.00 (0.66–1.00) and 0.00 (0.00–0.98) for SPCCT. Wide CIs reflected the small sample size. Participants with CPP in the synovial fluid had more pain than those without. Conclusion SPCCT and US had high sensitivity for calcium crystal detection, although no test achieved the strict definition of a very good test. Trial registration ClinicalTrials.gov (NCT04585113)

Balneotherapy is used since ancient times, effects on hand osteoarthritis however are not well elucidated. To evaluate therapeutic effects of serial thermal brine hand baths (tbhb) in patients experiencing painful hand osteoarthritis (HOA). Randomized, double-blind, sham-controlled monocentric clinical trial. Outpatient clinic, monocentric. Patients with painful bilateral painful HOA meeting the 1990 American College of Rheumatology classification criteria with a baseline pain level >30 mm on the Visual Analog Scale (VAS) and radiographic evidence of hand osteoarthritis in posteroanterior X-ray projection, classified as Kellgren and Lawrence grade ≥2. Probands were randomized to the intervention group (IG) receiving tbhb or the control group (CG) receiving tap water hand baths (sham). Both hand baths (tbhb and sham) were performed 6 times in 3 weeks with 15 min/bath at a water temperature of 25 °C. The primary outcome was the change in pain intensity (VAS [mm]) following the intervention. Secondary outcomes were changes in the Australian Canadian Osteoarthritis Hand Index (AUSCAN), grip strength, functional parameters of microcirculation (by O2C method), vascular endothelial growth factor (VEGF) and safety. Outcomes were primarily analysed after the last intervention followed by secondary analysis of the follow-up visits 4 and 12 weeks after intervention and during intervention. A total of 38 patients successfully completed the trial. Pain intensity significantly decreased due to tbhb (P<0.001), with sustained benefits observed up to 3 months post-intervention. The AUSCAN pain subscore was significantly reduced (P<0.001). There was no significant change in other AUSCAN subscores, nor in grip strength or functional parameters of microcirculation including VEGF due to tbhb. No adverse events due to tbhb were observed. Thermal brine hand baths represent a simple, effective, and well-tolerated method to achieve pain relief in HOA with results lasting up to 12 weeks after intervention. Thermal brine hand baths can be used to reduce pain in HOA.

Hand osteoarthritis (OA) is a prevalent and debilitating joint disorder that impairs daily functioning and quality of life. Current treatments are often inadequate in managing the symptoms and progression of the disease. The cytokine interleukin (IL)-17 has been implicated in the inflammatory processes associated with OA, making it a potential target for therapeutic intervention. This trial aims to evaluate the efficacy of vunakizumab, an IL-17A inhibitor, in reducing pain and improving functional outcomes in patients with erosive hand OA. This multicentre, randomised, placebo-controlled, double-blind trial will enrol 150 participants aged 30-80 years with symptomatic erosive hand OA. Participants will be randomised in a 1:1 ratio to receive either vunakizumab 120 mg or placebo subcutaneously every 4 weeks for 24 weeks, with a loading dose injection period during the first 4 weeks. The primary outcome is the change in hand pain assessed by the Visual Analogue Scale at 28 weeks. Secondary outcomes include changes in physical function measured by the Functional Index for Hand Osteoarthritis, the Quick Disabilities of the Arm, Shoulder and Hand questionnaire and the Health Assessment Questionnaire, as well as changes in grip strength and radiographic and MRI evaluations of the hands. Written informed consent will be obtained from all participants. The study was approved by the Ethics Committee of Shanghai Sixth People's Hospital (2024-217) and will adhere to the Declaration of Helsinki. Research results will be published in peer-reviewed journals. ChiCTR2500101031; https://www.chictr.org.cn/showproj.html?proj=264789.

To establish French recommendations for the management of people living with hand osteoarthritis (OA) on behalf of the French Society of Rheumatology (SFR) and of the French Society of Physical and Rehabilitation Medicine (SOFMER). A systematic review of the literature, including systematic reviews, meta-analyses, and randomized controlled trials on pharmacological and non-pharmacological treatments, was conducted from inception until November 24, 2023. Based on this review and expert consensus, a multidisciplinary group of 25 healthcare professionals-including rheumatologists, physical and rehabilitation medicine physicians, hand surgeons, general practitioner, geriatrician, occupational therapists, physiotherapists, and patients-formulated the recommendations. Each statement was assigned a level of evidence, a grade of recommendation, and a level of agreement based on EULAR standardized procedures for recommendations. The group established four general principles and 11 specific recommendations. The general principles emphasize treatment objectives, individualized management, patient education, and a multimodal approach combining non-pharmacological and pharmacological therapies. Four specific recommendations address non-pharmacological strategies, including exercise, ergonomic advice, assistive devices, orthoses and heat applications. The group advises against the use of electromagnetic waves, laser therapy, acupuncture, or kinesiotaping. Seven specific recommendations cover pharmacological treatments, advocating for topical and oral NSAIDs, acetaminophen, chondroitin sulfate for symptom relief, low-dose oral corticosteroids for inflammatory flares, and intra-articular steroid injections for inflammatory painful interphalangeal OA. Given the current data, the group advises against the use of conventional synthetic or biological disease-modifying anti-rheumatic drugs (DMARDs). These recommendations provide a structured approach for the management of people living with hand OA in France, aligning with national healthcare practices and patient needs.

The trapeziometacarpal (TMC) joint is commonly affected by osteoarthritis (OA), and its unique morphology creates localized loading patterns that cause regional bone adaption. Radiographic OA is more prevalent than symptomatic OA, highlighting the disconnect between structural features and clinical disease. Ex vivo studies have demonstrated regional changes in trapezial bone microarchitecture but are limited to cadaveric specimen with advanced disease. In vivo studies are needed to characterize regional bone microarchitecture in symptomatic TMC OA. We investigated regional bone microarchitecture in females with TMC OA using high-resolution peripheral quantitative computed tomography (HR-pQCT), and whether these changes differed from those associated with ageing. HR-pQCT scans of the TMC joint were acquired from 13 females with TMC OA, 12 controls matched groupwise by age and sex, and 15 sex-matched young controls. Total bone mineral density, bone volume fraction (Tt.BV/TV), thickness, and separation were quantified by quadrant in the first metacarpal and trapezium. A mixed ANOVA assessed group, quadrant, and group-by-quadrant effects. Significant interaction effects were observed for all parameters in the trapezium and separation in the first metacarpal (p < 0.001). In OA, trapezial separation was higher, and Tt.BV/TV was lower in the ulnar-volar quadrant, while separation was lower in the radial-volar quadrant compared to young controls (p < 0.05). In the first metacarpal, radial-volar separation was lower in OA than young controls (p < 0.05). These results suggest that OA may disrupt the normal variation in first metacarpal and trapezial bone microarchitecture, highlighting the utility of HR-pQCT in early detection of structural bone changes in hand OA.

Repurposing osteoporosis medications for other diseases: a narrative review by the European Calcified Tissue Society (ECTS).

Determine the cross-sectional associations of serum inflammation with body composition and physical capacity in Canadian adults with/without osteoarthritis (OA) and multimorbidities. 30,097 participants from the Canadian Longitudinal Study on Aging were categorized into eight subgroups (presence/absence of lower extremity OA, hand OA, multimorbidities), disaggregated by sex. Linear regression models (multiple covariates and log-transformed CRP) were completed with body composition and physical function measures as dependent variables. A priori, the research team defined that an increase in the adjusted R2 between models by 1% or more was considered a meaningful change in explanatory power. Higher CRP levels [standardized β(95%CI)] was associated with greater whole body fat percent [females 0.14 (0.13, 0.16), males 0.13 (0.12, 0.15)], trunk fat percent [females 0.16 (0.15, 0.18), males 0.13 (0.12, 0.15)] and lower appendicular lean mass index [males -0.12 (-0.13, -0.11)], independent of OA or multimorbidity. There were small but meaningful associations between CRP and each of percent adiposity and appendicular lean mass index. These associations were present regardless of OA and multimorbidity status. Percent adiposity, but not OA status, was consistently associated with systemic inflammation, suggesting that adiposity driven inflammation may contribute to OA related health outcomes.

To explore whether biologic levels of specific per- and polyfluoroalkyl substances (PFAS) and a mixture of PFAS-reflecting the overall effect and accounting for correlations among PFAS-relate to incident hand osteoarthritis (HOA) and progression. Among a case-cohort sample from the Osteoarthritis Initiative (n=1,878), we examined associations of eight PFAS in serum with odds of developing over the subsequent 4 years (1) symptomatic HOA and (2) an increased number of joints with radiographic osteoarthritis (Kellgren-Lawrence ≥2; yes/no). We used weighted logistic regression to assess single PFAS (continuous and quartiles) and quantile g-computation to assess the PFAS mixture in relation to our primary outcomes. Participants were primarily female (58%) and on average aged 62 years and overweight (mean body mass index=28.6 kg/m2). Participants with higher perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA; continuous variables) had greater odds of incident symptomatic HOA (odds ratio [OR] [95% confidence interval (CI)] per interquartile range increment: PFDA 1.12 [1.05-1.20]; PFNA 1.07 [1.00-1.13]), but associations were not monotonic when these PFAS were represented in quartiles. Participants with higher perfluorohexane sulfonic acid had lower odds of incident HOA (eg, OR 0.94 [95% CI 0.88-1.00] per interquartile range increment). We observed no other consistent associations between PFAS and either outcome. We observed possible associations of PFDA and PFNA serum concentrations with symptomatic HOA incidence, but we otherwise found no consistent evidence that greater PFAS concentrations relate to a greater chance of developing HOA incidence or progression.

To evaluate the capacity of the RA MRI Score (RAMRIS) in distinguishing rheumatoid arthritis (RA) and hand osteoarthritis (HOA). Patients with RA and HOA were retrospectively matched in pairs. Inflammatory and degenerative changes in MRI scans of the hands were quantified and compared using RAMRIS, focusing on bone marrow edema (BME), erosion, synovitis, and tenosynovitis. CRP, ESR, and autoantibodies (RF and ACPA) and clinical scores (DAS-28, FFbH, and pain level), smoking status, and medication use were assessed additionally. Overall, 100 RA and 100 HOA patients with confirmed diagnosis were included. Age, pain severity, and functional impairment did not differ between groups. RAMRIS revealed significantly higher synovitis subscores in RA compared to HOA (p<0.001), while no significant differences were found for BME (p = 0.076), erosion (p = 0.366), or tenosynovitis (p = 0.129). Higher RAMRIS scores were observed at the level of individual joints in RA. The mean erosion-subscore was found to be higher in RA males than in RA females, though this was not observed in all joints. In HOA, men exhibited a mean erosion score that was higher than that of women. Smoking status had limited association with RAMRIS findings, but RA non-smokers exhibited greater inflammatory burden than HOA non-smokers in multiple joints. RA exhibited significantly higher synovitis subscores, indicative of active inflammation and leading to overall higher RAMRIS scores, compared to HOA. However, HOA demonstrated high RAMRIS scores for synovitis, tenosynovitis, erosions, and BME. MRI may assist in distinguishing RA from HOA; however, its interpretation must be integrated into the clinical context.

Erosive hand osteoarthritis (EHOA) is a severe and rapidly progressing form of osteoarthritis that has been linked to systemic comorbidities (i.e., metabolic bone and cardiovascular diseases). The object of this study is to retrospectively evaluate the impact of comorbidities (i.e., osteoporosis, diabetes and overweight) on the clinical course and radiographic findings in a cohort of EHOA patients. This is a retrospective cross-sectional study. Patients underwent clinical assessments and completed the VAS scale, the AUSCAN and DREISER questionnaires. Metabolic, cardiovascular, and bone health data were collected. Radiographic features-osteophytes, joint space narrowing, malalignment, erosions, sclerosis, and subchondral cysts-were evaluated using the Altman system. Comorbidities were assessed using the Charlson Comorbidity Index, whereas metabolic syndrome, diabetes, and osteoporosis were defined according to the ATP III and WHO criteria. Statistical analysis was conducted via Spearman's correlation, using GraphPad Prism 9.1.0, with significance set at p < 0.05. Eighty-seven patients (88.5% female, mean age 63.17 ± 8.85) were included. Among comorbidities, 76.8% had at least one risk factor; BMI correlated with joint space narrowing (r = 0.22, p = 0.04). Severity of femoral and lumbar osteoporosis correlated with AUSCAN and DREISER scores; FRAX scores significantly correlated with several radiographic features of EHOA; VAS correlated with swollen and painful joint count, with AUSCAN and DREISER scores and with osteophytosis. Disease duration correlated with overall radiographic damage. Cardiovascular and metabolic bone comorbidities, especially overweight and osteoporosis, appear to be associated with higher pain burden, functional impairment, and greater structural damage in EHOA patients.

Objective: We aimed to comprehensively assess the impact of metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) on the incidence of clinically diagnosed knee, hip, and hand osteoarthritis (OA). Methods: This prospective study analyzed data from 350 273 participants in the United Kingdom Biobank, with outcomes including all-cause OA, knee, hip, and hand OA, and polyarthrosis. Multivariable Cox proportional hazards regression models were used to estimate the association. Results: A total of 131 821 (37.6%) participants had MAFLD, and 102 110 (29.2%) had MASLD. MAFLD was associated with a higher risk of total OA (HR=1.72, 95%CI: 1.68-1.75). There are different OA risks among MAFLD subtypes: overweight and metabolic dysfunction subtypes increase the risk of total OA (HR=1.75, 95%CI: 1.71-1.79), whereas lean metabolism disorder subtypes are not associated with OA in any body part. MASLD (HR=1.57, 95%CI: 1.54-1.60) was associated with a higher risk of total OA, and the association became more prominent with increasing alcohol intakes. The effect of MAFLD on OA was consistent regardless of the presence of MASLD. Conclusions: MAFLD and MASLD are associated with an increased risk of OA, especially for knee OA. Obesity and alcohol intake play a key driving role in the association of steatotic liver disease with OA.

Introducing an In Vivo Protocol to Evaluate Skin Penetration of Topical Drugs: Proof-of-Concept with Naproxen in Humans.

Transcutaneous auricular vagus nerve stimulation versus sham stimulation in patients with erosive hand osteoarthritis (ESTIVAL): a randomised, multicentre, double-blind, sham-controlled trial.

To provide an overview of the effects of exercise for osteoarthritis. Overview. Medline, Embase, Epistemonikos, PEDro, Cochrane and registries from inception to 8 November 2025. Reviews comparing exercise with placebo, no intervention or other interventions on pain and function for osteoarthritis. Supplementary trials were included to update inconclusive areas. Two independent reviewers extracted data and assessed bias. Data were standardised to a 0-100 scale and reanalysed using random-effects meta-analysis. Certainty was rated using Grading of Recommendations Assessment, Development and Evaluation. Five reviews (κ=100; n=8631) and 28 supplementary trials (knee/hip κ=23, hand κ=3, ankle κ=2; n=4360) were included. Evidence indicated small, short-term effects of exercise versus placebo (mean difference -10.8, 95% CI -19.1 to -2.6) and no-treatment (-12.4, 95% CI -15.6 to -9.2) for knee osteoarthritis pain, but certainty was very low and effects in larger or longer-term trials were smaller. Moderate evidence suggested negligible effects in hip (-6.7 95% CI -9.3 to -4.0) and small effects in hand (-10.0 95% CI -15.5 to -4.5) osteoarthritis. Varying certainty evidence indicated comparable outcomes to education, manual therapy, analgesics, injections and arthroscopy. Single trials in selected populations showed exercise was less effective than knee osteotomy (12.4 95% CI 4.7 to 20.2) and joint replacement (knee 17.1 95% CI 10.4 to 23.8; hip 24.2 95% CI 18.2 to 30.2) at longer term. Evidence on exercise for osteoarthritis remains largely inconclusive, suggesting negligible or short-lasting small effects comparable to, or less effective than, other treatments. These findings question its universal promotion and highlight the need to revisit research priorities and clinical discussions around its worthwhileness. CRD42023446888.