{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:16:15Z","timestamp":1793682975001,"version":"4.5.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Accumulating evidence suggested the potential role of exercise in alleviating rheumatoid arthritis (RA). However, whether exercise improves physical function (walk test, grip strength, muscle strength, joint assessments) and inflammatory biomarkers in patients with RA is unclear. This umbrella meta-analysis aimed to examine the effect of exercise in patients with RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>PubMed, Scopus, Web of Science, Embase, and Cochrane Central Library databases were systematically searched for meta-analyses of randomized control trials (RCTs) to retrieve relevant studies. The effect sizes were pooled using a random-effects model, with standardized or weighted mean differences (SMDs or WMDs) and 95% confidence intervals (CIs) as summary statistics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventeen studies were included. The improving effects of exercise on fatigue levels (SMD = \u22120.28, 95% CI: \u22120.44, \u22120.13), pain intensity (ES = \u22120.50, 95% CI: \u22120.87, \u22120.14), disease activity score in joints (DAS) (WMD = \u22120.54, 95% CI: \u22120.99, \u22120.09; and SMD = \u22120.47, 95% CI: \u22120.64, \u22120.30), and ESR (ES = \u22120.85, 95% CI: \u22121.66, \u22120.03) were significant. No significant impact on the hand grip, muscle strength, walk test, joints and inflammatory biomarkers was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exercise significantly reduces fatigue, pain, DAS, and ESR in RA but shows no impact on grip strength, muscle strength, walk test, joints, or other inflammatory biomarkers. This highlights its role in symptom management rather than broad physiological changes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2025.1558214","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:22:06Z","timestamp":1744176126000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The effect of exercise therapy on pain, fatigue, bone function and inflammatory biomarkers individuals with rheumatoid arthritis and knee osteoarthritis: a meta-research review of randomized controlled trials"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoting","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuijuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e16816","DOI":"10.1097\/MD.0000000000016816","article-title":"Factors influencing erythrocyte sedimentation rate in adults: new evidence for an old test","volume":"98","author":"Alende-Castro","year":"2019","journal-title":"Med. Baltim."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.4314\/ahs.v21i3.30","article-title":"Aerobic versus resistance exercises on systemic inflammation and sleep parameters in obese subjects with chronic insomnia syndrome","volume":"21","author":"Al-Jiffri","year":"2021","journal-title":"Afr. Health Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"20f13681","DOI":"10.4088\/JCP.20f13681","article-title":"Mean difference, standardized mean difference (SMD), and their use in meta-analysis: as simple as it gets","volume":"81","author":"Andrade","year":"2020","journal-title":"J. Clin. Psychiatry"},{"key":"B50","doi-asserted-by":"crossref","first-page":"9098442","DOI":"10.1155\/2023\/9098442","article-title":"Effectiveness of Yoga and Acupuncture in Rheumatoid Arthritis: A Systematic Review and Meta\u2010Analysis","author":"Andrea Cort\u00e9s-Ladino","year":"2023","journal-title":"Evid Based Complement Alternat. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1093\/rheumatology\/ker330","article-title":"Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized controlled trials","volume":"51","author":"Baillet","year":"2012","journal-title":"Rheumatology,"},{"key":"B52","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/acr.20146","article-title":"Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: meta\u2010analysis of randomized controlled trials","volume":"62","author":"Baillet","year":"2010","journal-title":"Arthritis Care Res (Hoboken),"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1093\/ptj\/pzy030","article-title":"A mechanism-based approach to physical therapist management of pain","volume":"98","author":"Chimenti","year":"2018","journal-title":"Phys. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S0002-9440(10)64272-1","article-title":"A question of transformation: the synovial fibroblast in rheumatoid arthritis","volume":"162","author":"Davis","year":"2003","journal-title":"Am. J. Pathol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"bmj"},{"key":"B8","doi-asserted-by":"publisher","first-page":"857","DOI":"10.4314\/ahs.v13i4.1","article-title":"Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial","volume":"13","author":"El-Kader","year":"2013","journal-title":"Afr. Health Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"104106","DOI":"10.1016\/j.msard.2022.104106","article-title":"High-intensity resistance training in people with multiple sclerosis experiencing fatigue: a randomised controlled trial","volume":"68","author":"Englund","year":"2022","journal-title":"Multiple Scler. Relat. Disord."},{"key":"B10","doi-asserted-by":"publisher","first-page":"13","DOI":"10.61838\/kman.intjssh.7.2.2","article-title":"Enhancing cognitive abilities and delaying cognitive decline in the elderly through exercise-based health management systems","volume":"7","author":"Faraziani","year":"2024","journal-title":"Int. J. Sport Stud. Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.scispo.2022.08.004","article-title":"Acute effects of high-intensity functional training with or without whole-body electromyostimulation on serum irisin and brain-derived neurotrophic factor in overweight individuals","volume":"38","author":"Ghalamsiah","year":"2023","journal-title":"Sci. and Sports"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"Cd004849","DOI":"10.1002\/14651858.Cd004849","article-title":"Tai chi for treating rheumatoid arthritis","author":"Han","year":"2004","journal-title":"Cochrane Database Syst Rev."},{"key":"B13","first-page":"1","article-title":"Structured education and neuromuscular exercise program for hip and\/or knee osteoarthritis: a health Technology assessment","volume":"18","year":"2018","journal-title":"Ont. Health Technol. Assess. Ser."},{"key":"B54","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1016\/S2665-9913(23)00122-4","article-title":"Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis","volume":"5","author":"Holden","year":"2023","journal-title":"The Lancet Rheumatology,"},{"key":"B55","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD006853.pub2","article-title":"Dynamic exercise programs (aerobic capacity and\/or muscle strength training) in patients with rheumatoid arthritis","author":"Hurkmans","year":"2009","journal-title":"Cochrane Database Syst Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"284","DOI":"10.31138\/mjr.20230801.oo","article-title":"Overview of rheumatoid arthritis and scientific understanding of the disease","volume":"34","author":"Jahid","year":"2023","journal-title":"Mediterr. J. Rheumatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1152\/physrev.00035.2013","article-title":"Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs","volume":"95","author":"Joyner","year":"2015","journal-title":"Physiol. Rev."},{"key":"B56","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/acr.23570","article-title":"Aerobic exercise and fatigue in rheumatoid arthritis participants: a meta\u2010analysis using the minimal important difference approach","volume":"70","author":"Kelley","year":"2018","journal-title":"Arthritis Care Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.5435\/JAAOS-22-07-465","article-title":"Mechanical loading: potential preventive and therapeutic strategy for osteoarthritis","volume":"22","author":"Leong","year":"2014","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1089621","DOI":"10.3389\/fimmu.2022.1089621","article-title":"Clinical effect and biological mechanism of exercise for rheumatoid arthritis: a mini review","volume":"13","author":"Li","year":"2022","journal-title":"Front. Immunol."},{"key":"B57","doi-asserted-by":"crossref","first-page":"633","DOI":"10.4314\/tjpr.v22i3.22","article-title":"Effects of routine drug therapy in combination with health exercise training on pain and joint function in patients with rheumatoid arthritis: A meta analysis","volume":"22","author":"Liu","year":"2023","journal-title":"Trop. J. Pharm. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4141","DOI":"10.1113\/JP273355","article-title":"Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena","volume":"595","author":"Lima","year":"2017","journal-title":"J. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11156","DOI":"10.3390\/ijms241311156","article-title":"Cytokines as biomarkers for evaluating physical exercise in trained and non-trained individuals: a narrative review","volume":"24","author":"Ma\u0142kowska","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1007\/s40279-021-01615-6","article-title":"Acute effects of aerobic exercise on muscle strength and power in trained male individuals: a systematic review with meta-analysis","volume":"52","author":"Markov","year":"2022","journal-title":"Sports Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"Cd004849","DOI":"10.1002\/14651858.CD004849.pub2","article-title":"Tai Chi for rheumatoid arthritis","volume":"9","author":"Mudano","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"B22","doi-asserted-by":"crossref","first-page":"Es205","DOI":"10.36076\/ppj.2012\/15\/ES205","article-title":"Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise?","volume":"15","author":"Nijs","year":"2012","journal-title":"Pain Physician"},{"key":"B23","doi-asserted-by":"publisher","first-page":"134","DOI":"10.4330\/wjc.v9.i2.134","article-title":"Aerobic vs anaerobic exercise training effects on the cardiovascular system","volume":"9","author":"Patel","year":"2017","journal-title":"World J. Cardiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3390\/biomedicines10010126","article-title":"Impact of physical activity and exercise on the epigenome in skeletal muscle and effects on systemic metabolism","volume":"10","author":"Plaza-Diaz","year":"2022","journal-title":"Biomedicines"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1249\/MSS.0000000000000605","article-title":"Resistance exercise training alters mitochondrial function in human skeletal muscle","volume":"47","author":"Porter","year":"2015","journal-title":"Med. Sci. Sports Exerc"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.jpain.2019.03.005","article-title":"Exercise-induced hypoalgesia in pain-free and chronic pain populations: state of the art and future directions","volume":"20","author":"Rice","year":"2019","journal-title":"J. Pain"},{"key":"B60","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/acr.22561","article-title":"Effect of aerobic exercise training on fatigue in rheumatoid arthritis: a meta\u2010analysis","volume":"67","author":"Rongen\u2010van Dartel","year":"2015","journal-title":"Arthritis Care Res."},{"key":"B61","doi-asserted-by":"crossref","first-page":"101832","DOI":"10.1016\/j.smrv.2023.101832","article-title":"The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis\u2013A systematic review with meta-analysis","volume":"71","author":"Runge","year":"2023","journal-title":"Sleep Med. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0210292","DOI":"10.1371\/journal.pone.0210292","article-title":"Comparative effectiveness of aerobic, resistance, and combined training on cardiovascular disease risk factors: a randomized controlled trial","volume":"14","author":"Schroeder","year":"2019","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1371\/journal.pone.0210292","article-title":"The Effect of Coaching Programs on Physical Activity and Pain in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"24","author":"Sezgin","year":"2023","journal-title":"Pain Manag. Nurs."},{"key":"B28","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2165\/00007256-199213010-00003","article-title":"Changes in beta-endorphin levels in response to aerobic and anaerobic exercise","volume":"13","author":"Schwarz","year":"1992","journal-title":"Sports Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1136\/bmj.j4008","article-title":"AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both","author":"Shea","year":"2017","journal-title":"bmj"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/acr.22783","article-title":"2015 American College of rheumatology guideline for the treatment of rheumatoid arthritis","volume":"68","author":"Singh","year":"2015","journal-title":"Arthritis Care Res. Hob."},{"key":"B31","doi-asserted-by":"publisher","first-page":"9471","DOI":"10.3390\/ijms21249471","article-title":"Exercise as an adjuvant to cartilage regeneration therapy","volume":"21","author":"Smith","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1080\/14397595.2021.1886653","article-title":"Does exercise therapy improve patient-reported outcomes in rheumatoid arthritis? A systematic review and meta-analysis for the update of the 2020 JCR guidelines for the management of rheumatoid arthritis","volume":"32","author":"Sobue","year":"2022","journal-title":"Mod Rheumatol,"},{"key":"B32","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1093\/oxfordjournals.bmb.a072564","article-title":"Aerobic exercise, anaerobic exercise and the lactate threshold","volume":"48","author":"Spurway","year":"1992","journal-title":"Br. Med. Bull."},{"key":"B33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/j.1749-6632.2010.05808.x","article-title":"Mechanical loading, cartilage degradation, and arthritis","volume":"1211","author":"Sun","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"54","DOI":"10.61838\/kman.hn.1.4.7","article-title":"The association between physical activity and cancer prevention, recovery, and recurrence: a narrative review","volume":"1","author":"Tahira","year":"2023","journal-title":"Health Nexus"},{"key":"B35","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/ede.0b013e3181fe7999","article-title":"PRISMA statement","volume":"22","author":"Takkouche","year":"2011","journal-title":"Epidemiology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Vos","year":"2020","journal-title":"lancet"},{"key":"B37","first-page":"884","article-title":"Relative sensitivity to change of the erythrocyte sedimentation rate and serum C-reactive protein concentration in rheumatoid arthritis","volume":"31","author":"Ward","year":"2004","journal-title":"J. Rheumatol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1136\/annrheumdis-2013-205079","article-title":"Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials","volume":"74","author":"Ward","year":"2015","journal-title":"Ann. Rheumatic Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e25019","DOI":"10.1097\/MD.0000000000025019","article-title":"Effectiveness of resistance exercises in the treatment of rheumatoid arthritis: a meta-analysis","volume":"100","author":"Wen","year":"2021","journal-title":"A meta-analysis. Med. Baltim."},{"key":"B59","first-page":"CD003832","article-title":"Exercise for rheumatoid arthritis of the hand","volume":"2018","author":"Williams","year":"2018","journal-title":"Cochrane Database Syst Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1079841","DOI":"10.3389\/fphys.2023.1079841","article-title":"The effects of Tai Chi on physical function and safety in patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"14","author":"Wu","year":"2023","journal-title":"Front. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"7666","DOI":"10.3390\/ijms25147666","article-title":"Understanding autoimmunity: mechanisms, predisposing factors, and cytokine therapies","volume":"25","author":"Yasmeen","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13102-022-00408-2","article-title":"Effectiveness and safety of aerobic exercise for rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials","volume":"14","author":"Ye","year":"2022","journal-title":"BMC Sports Sci Med Rehabil."},{"key":"B64","doi-asserted-by":"crossref","first-page":"586665","DOI":"10.3389\/fmed.2020.586665","article-title":"Yoga for treating rheumatoid arthritis: a systematic review and meta-analysis","volume":"7","author":"Ye","year":"2020","journal-title":"Front. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1515\/hukin-2015-0118","article-title":"Central and peripheral fatigue during resistance exercise - a critical review","volume":"49","author":"Zaj\u0105c","year":"2015","journal-title":"J. Hum. Kinet."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1558214\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:22:13Z","timestamp":1744176133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1558214\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":57,"alternative-id":["10.3389\/fphys.2025.1558214"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2025.1558214","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]},"article-number":"1558214"}}