{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:06:55Z","timestamp":1790089615326,"version":"4.0.1"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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. Surg."],"abstract":"<jats:p>Knee osteoarthritis (KOA) is a leading cause of chronic pain and physical disability in the aging global population, placing an immense burden on healthcare systems. Despite its rising incidence, clinical practice and research remain disproportionately focused on late-stage joint replacement, neglecting early-stage preventive and conservative care for high-risk individuals. To address this gap, this narrative review searched major databases including PubMed\/MEDLINE, Embase, Web of Science, and the Cochrane Library for clinical guidelines, high-quality systematic reviews, and randomized controlled trials focusing on non-surgical interventions for early KOA and high-risk populations. Search terms included \u201cearly knee osteoarthritis,\u201d \u201cnon-surgical treatment,\u201d \u201cexercise therapy,\u201d and \u201cweight management\u201d. Literature analysis demonstrates that a structured, \u201clifelong, stepped\u201d non-surgical paradigm yields significant clinical efficacy. Specifically, combining dietary weight loss with physical exercise optimally reduces mechanical joint loading and systemic inflammatory markers; targeted muscle strengthening, alongside mind-body exercises like Tai Chi or yoga, improves the joint microenvironment and neuromuscular control; biomechanical orthoses and physical therapies offer substantial short-term pain relief; and topical or systemic NSAIDs combined with intra-articular injections effectively manage refractory acute symptoms. Crucially, continuous clinical supervision and structured patient education are vital for enhancing long-term treatment adherence and delaying radiological disease progression. Ultimately, implementing early, proactive non-surgical interventions, grounded in patient education and integrating weight management, targeted exercise, and multimodal stepped therapies, effectively alleviates pain, restores physical function, and delays or entirely prevents the need for future joint replacement.<\/jats:p>","DOI":"10.3389\/fsurg.2026.1941764","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:47:10Z","timestamp":1790088430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-surgical management of knee osteoarthritis: a stepped conservative care paradigm for early-stage disease and high-risk populations"],"prefix":"10.3389","volume":"13","author":[{"given":"Yongwei","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Shijiazhuang People\u2019s Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenfeng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Shijiazhuang People\u2019s Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the global burden of disease study 2021","volume":"5","author":"Steinmetz","year":"2023","journal-title":"Lancet Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1056\/NEJMcp1903768","article-title":"Osteoarthritis of the knee","volume":"384","author":"Sharma","year":"2021","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","article-title":"Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association","volume":"29","author":"Altman","year":"1986","journal-title":"Arthritis Rheum"},{"key":"B4","first-page":"3","article-title":"Osteoarthritis is a serious disease","author":"Hawker","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1002\/art.42089","article-title":"Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the global burden of disease study 2019","volume":"74","author":"Long","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.joca.2017.12.007","article-title":"Health care resource use, health care expenditures and absenteeism costs associated with osteoarthritis in US healthcare system","volume":"26","author":"Menon","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"B7","doi-asserted-by":"publisher","first-page":"725","DOI":"10.7326\/0003-4819-155-11-201112060-00004","article-title":"Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey and cohort data","volume":"155","author":"Nguyen","year":"2011","journal-title":"Ann Intern Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0140-6736(11)60752-6","article-title":"Knee replacement","volume":"379","author":"Carr","year":"2012","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1016\/j.acra.2026.03.054","article-title":"Development of novel and interpretable automated models for predicting total knee replacement in knee osteoarthritis: an international multicenter study","volume":"33","author":"Zhao","year":"2026","journal-title":"Acad Radiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e72049","DOI":"10.1002\/hsr2.72049","article-title":"Comparative effectiveness of combined orthotic and physiotherapy interventions versus monotherapy in the management of knee osteoarthritis on clinical parameters: a systematic review of randomized controlled trials","volume":"9","author":"Zangi","year":"2026","journal-title":"Health Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3892\/etm.2023.12180","article-title":"Knee osteoarthritis: current status and research progress in treatment (review)","volume":"26","author":"Geng","year":"2023","journal-title":"Exp Ther Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.joca.2026.01.003","article-title":"Osteoarthritis year in review 2025: biomechanics","volume":"34","author":"Qualter","year":"2026","journal-title":"Osteoarthritis Cartilage"},{"key":"B13","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s13287-025-04783-8","article-title":"Mesenchymal stem cells and extracellular vesicles for knee osteoarthritis: clinical application, mechanism exploration and prospect","volume":"16","author":"Li","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"B14","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3 K\/AKT\/mTOR signaling pathway in osteoarthritis: a narrative review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthritis Cartilage"},{"key":"B15","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/jor.24457","article-title":"Role of inflammation and the immune system in the progression of osteoarthritis","volume":"38","author":"Woodell-May","year":"2019","journal-title":"J Orthop Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1089\/ten.TEB.2018.0245","article-title":"Hybrid and composite scaffolds based on extracellular matrices for cartilage tissue engineering","volume":"25","author":"Setayeshmehr","year":"2019","journal-title":"Tissue Eng Part B Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"101093","DOI":"10.1016\/j.jot.2026.101093","article-title":"Mechanisms and precision interventions in sarcopenia and osteoarthritis comorbidity: a narrative review","volume":"58","author":"Ma","year":"2026","journal-title":"J Orthop Translat"},{"key":"B18","doi-asserted-by":"publisher","first-page":"119064","DOI":"10.1016\/j.biopha.2026.119064","article-title":"The dual role of extracellular vesicles in OA: pathological mediators, diagnostic biomarkers, and therapeutic targets","volume":"196","author":"Leng","year":"2026","journal-title":"Biomed Pharmacother"},{"key":"B19","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1002\/cbin.11137","article-title":"Cell death: a review of the major forms of apoptosis, necrosis and autophagy","volume":"43","author":"D'Arcy","year":"2019","journal-title":"Cell Biol Int"},{"key":"B20","doi-asserted-by":"publisher","first-page":"119583","DOI":"10.1016\/j.biopha.2026.119583","article-title":"Metabolic syndrome-osteoarthritis axis: beyond mechanical loading toward a cardiometabolic OA phenotype","volume":"200","author":"Zhong","year":"2026","journal-title":"Biomed Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1136\/annrheumdis-2013-204599","article-title":"Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis","volume":"74","author":"Zhang","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1038\/s41588-018-0247-0","article-title":"Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis","volume":"50","author":"Styrkarsdottir","year":"2018","journal-title":"Nat Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"194417","DOI":"10.1016\/j.bbagrm.2019.194417","article-title":"Non-coding RNA regulatory networks","volume":"1863","author":"Panni","year":"2019","journal-title":"Biochim Biophys Acta Gene Regul Mech"},{"key":"B24","doi-asserted-by":"publisher","first-page":"810","DOI":"10.3390\/antiox9090810","article-title":"Irisin mitigates oxidative stress, chondrocyte dysfunction and osteoarthritis development through regulating mitochondrial integrity and autophagy","volume":"9","author":"Wang","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1016\/j.joca.2025.03.003","article-title":"Risk factors for the development of knee osteoarthritis across the lifespan: a systematic review and meta-analysis","volume":"33","author":"Duong","year":"2025","journal-title":"Osteoarthritis Cartilage"},{"key":"B26","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.joca.2014.11.019","article-title":"Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis","volume":"23","author":"Silverwood","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"key":"B27","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","article-title":"Osteoarthritis","volume":"11","author":"Tang","year":"2025","journal-title":"Nat Rev Dis Primers"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1007\/s11999-016-4732-4","article-title":"Classifications in brief: Kellgren-Lawrence classification of osteoarthritis","volume":"474","author":"Kohn","year":"2016","journal-title":"Clin Orthop Relat Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/obr.12334","article-title":"Predicting adult obesity from childhood obesity: a systematic review and meta-analysis","volume":"17","author":"Simmonds","year":"2015","journal-title":"Obes Rev"},{"key":"B30","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.cmet.2019.05.008","article-title":"Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake","volume":"30","author":"Hall","year":"2019","journal-title":"Cell Metab"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.14744\/TurkPediatriArs.2019.60430","article-title":"Exercise in the treatment of childhood obesity","volume":"55","author":"B\u00fclb\u00fcl","year":"2020","journal-title":"Turk Pediatri Ars"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1002\/acr.23608","article-title":"Intentional weight loss in overweight and obese patients with knee osteoarthritis: is more better?","volume":"70","author":"Messier","year":"2018","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"ITC129","DOI":"10.7326\/ANNALS-24-01249","article-title":"Knee osteoarthritis","volume":"177","author":"Gelber","year":"2024","journal-title":"Ann Intern Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1136\/ard-2023-225041","article-title":"EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update","volume":"83","author":"Moseng","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e721","DOI":"10.5435\/JAAOS-D-21-01233","article-title":"AAOS clinical practice guideline summary: management of osteoarthritis of the knee (nonarthroplasty), third edition","volume":"30","author":"Brophy","year":"2022","journal-title":"J Am Acad Orthop Surg"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1001\/jama.2022.21893","article-title":"Effect of diet and exercise on knee pain in patients with osteoarthritis and overweight or obesity: a randomized clinical trial","volume":"328","author":"Messier","year":"2022","journal-title":"JAMA"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1001\/jama.2013.277669","article-title":"Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial","volume":"310","author":"Messier","year":"2013","journal-title":"JAMA"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1056\/NEJMoa2403664","article-title":"Once-weekly semaglutide in persons with obesity and knee osteoarthritis","volume":"391","author":"Bliddal","year":"2024","journal-title":"N Engl J Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1001\/jama.2023.0746","article-title":"Both high- and low-dose exercise therapy help knee osteoarthritis","volume":"329","author":"Larkin","year":"2023","journal-title":"JAMA"},{"key":"B40","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3390\/life11040303","article-title":"Treadmill exercise after controlled abnormal joint movement inhibits cartilage degeneration and synovitis","volume":"11","author":"Oka","year":"2021","journal-title":"Life (Basel"},{"key":"B41","doi-asserted-by":"publisher","first-page":"16104","DOI":"10.1038\/s41598-021-95426-4","article-title":"Effects of resistance training on gait velocity and knee adduction moment in knee osteoarthritis patients: a systematic review and meta-analysis","volume":"11","author":"Li","year":"2021","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1001\/jama.2021.0411","article-title":"Effect of high-intensity strength training on knee pain and knee joint compressive forces among adults with knee osteoarthritis: the START randomized clinical trial","volume":"325","author":"Messier","year":"2021","journal-title":"JAMA"},{"key":"B43","doi-asserted-by":"publisher","first-page":"r2281","DOI":"10.1136\/bmj.r2281","article-title":"Exercise for people living with knee osteoarthritis","volume":"391","author":"Van Der Windt","year":"2025","journal-title":"Br Med J"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.ard.2026.03.006","article-title":"EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis: 2025 update","volume":"85","author":"Rausch Osthoff","year":"2026","journal-title":"Ann Rheum Dis"},{"key":"B45","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s13018-022-03069-6","article-title":"Overall treatment effects of aquatic physical therapy in knee osteoarthritis: a systematic review and meta-analysis","volume":"17","author":"Ma","year":"2022","journal-title":"J Orthop Surg Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1016\/j.apmr.2019.12.023","article-title":"Aquatic cycling improves knee pain and physical functioning in patients with knee osteoarthritis: a randomized controlled trial","volume":"101","author":"Rewald","year":"2020","journal-title":"Arch Phys Med Rehabil"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1111\/sms.13630","article-title":"Effects of progressive aquatic resistance training on symptoms and quality of life in women with knee osteoarthritis: a secondary analysis","volume":"30","author":"Munukka","year":"2020","journal-title":"Scand J Med Sci Sports"},{"key":"B48","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4082\/kjfm.23.0102","article-title":"Aquatic versus land-based exercise for knee osteoarthritis: a randomized controlled trial","volume":"46","author":"Slouma","year":"2024","journal-title":"Korean J Fam Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41584-020-00523-9","article-title":"Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines","volume":"17","author":"Arden","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B51","doi-asserted-by":"publisher","first-page":"103188","DOI":"10.1016\/j.ctim.2025.103188","article-title":"Effects of different mind-body exercises on pain in patients with knee osteoarthritis: a pairwise, network, and dose-response meta-analysis","volume":"92","author":"Wu","year":"2025","journal-title":"Complement Ther Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.3390\/ijerph14091000","article-title":"The effect of taichi practice on attenuating bone mineral density loss: a systematic review and meta-analysis of randomized controlled trials","volume":"14","author":"Zou","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"B53","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1080\/15438627.2019.1663520","article-title":"Effects of taichi exercise on knee and ankle proprioception among individuals with knee osteoarthritis","volume":"28","author":"Hu","year":"2019","journal-title":"Res Sports Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"18495","DOI":"10.1038\/s41598-025-03943-3","article-title":"The effects of tai chi on clinical outcomes and gait biomechanics in knee osteoarthritis patients: a pilot randomized controlled trial","volume":"15","author":"Pan","year":"2025","journal-title":"Sci Rep"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e253698","DOI":"10.1001\/jamanetworkopen.2025.3698","article-title":"Yoga or strengthening exercise for knee osteoarthritis: a randomized clinical trial","volume":"8","author":"Abafita","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B56","doi-asserted-by":"publisher","first-page":"100421","DOI":"10.1016\/j.ijchp.2023.100421","article-title":"The modulation effects of the mind-body and physical exercises on the basolateral amygdala-temporal pole pathway on individuals with knee osteoarthritis","volume":"24","author":"Liu","year":"2023","journal-title":"Int J Clin Health Psychol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3928\/00989134-20170405-01","article-title":"Feasibility and efficacy of a shared yoga intervention for sleep disturbance in older adults with osteoarthritis","volume":"43","author":"Buchanan","year":"2017","journal-title":"J Gerontol Nurs"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.7326\/M22-1761","article-title":"Effectiveness of an unsupervised online yoga program on pain and function in people with knee osteoarthritis: a randomized clinical trial","volume":"175","author":"Bennell","year":"2022","journal-title":"Ann Intern Med"},{"key":"B59","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/msc.1538","article-title":"Effects of exercise on knee osteoarthritis: a systematic review","volume":"19","author":"Raposo","year":"2021","journal-title":"Musculoskeletal Care"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1249\/MSS.0b013e318213fefb","article-title":"American college of sports medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise","volume":"43","author":"Garber","year":"2011","journal-title":"Med Sci Sports Exerc"},{"key":"B61","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/art.38290","article-title":"Impact of exercise type and dose on pain and disability in knee osteoarthritis: a systematic review and meta-regression analysis of randomized controlled trials","volume":"66","author":"Juhl","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.3390\/biology14111537","article-title":"Exercise as osteoarthritis treatment in Wistar Rats promotes frequency-dependent benefits","volume":"14","author":"Colares","year":"2025","journal-title":"Biology (Basel)"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e0179162","DOI":"10.1371\/journal.pone.0179162","article-title":"The effects of different frequency treadmill exercise on lipoxin A4 and articular cartilage degeneration in an experimental model of monosodium iodoacetate-induced osteoarthritis in rats","volume":"12","author":"Yang","year":"2017","journal-title":"PLoS One"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e48913","DOI":"10.1097\/MD.0000000000048913","article-title":"Effect of aerobic exercise of different intensity on articular cartilage metabolism in patients with knee osteoarthritis: a randomized controlled trial","volume":"105","author":"Song","year":"2026","journal-title":"Medicine (Baltimore)"},{"key":"B65","doi-asserted-by":"publisher","first-page":"451","DOI":"10.3390\/healthcare14040451","article-title":"How intense is effective? Exploring aerobic exercise intensity for knee osteoarthritis through a Bayesian NetworkMeta-analysis","volume":"14","author":"Cabrera-Dur\u00e1n","year":"2026","journal-title":"Healthcare (Basel)"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e0295666","DOI":"10.1371\/journal.pone.0295666","article-title":"Physiological and clinical effects of low-intensity blood-flow restricted resistance exercise compared to standard rehabilitation in adults with knee osteoarthritis-protocol for a randomized controlled trial","volume":"18","author":"S\u00f8rensen","year":"2023","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/s41420-021-00746-z","article-title":"Moderate-intensity exercise alleviates pyroptosis by promoting autophagy in osteoarthritis via the P2X7\/AMPK\/mTOR axis","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e2109","DOI":"10.52225\/narra.v5i2.2109","article-title":"Impact of walking exercise intensity on cartilage IL-1, TNF-\u03b1, IL-4, MMP-13 and pain threshold in osteoarthritis rat models","volume":"5","author":"Handono","year":"2025","journal-title":"Narra J"},{"key":"B69","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1002\/acr.23181","article-title":"Physical activity minimum threshold predicting improved function in adults with lower-extremity symptoms","volume":"69","author":"Dunlop","year":"2017","journal-title":"Arthritis Care Res (Hoboken"},{"key":"B70","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1093\/cercor\/bhn013","article-title":"The runner\u2019s high: opioidergic mechanisms in the human brain","volume":"18","author":"Boecker","year":"2008","journal-title":"Cereb Cortex"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e018471","DOI":"10.1136\/bmjopen-2017-018471","article-title":"How does exercise dose affect patients with long-term osteoarthritis of the knee? A study protocol of a randomised controlled trial in Sweden and Norway: the SWENOR study","volume":"8","author":"Torstensen","year":"2018","journal-title":"BMJ Open"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1458983","DOI":"10.3389\/fragi.2025.1458983","article-title":"Optimal exercise modalities and doses for therapeutic management of osteoarthritis of the knee","volume":"6","author":"Whitfield","year":"2025","journal-title":"Front Aging"},{"key":"B73","doi-asserted-by":"publisher","first-page":"152755","DOI":"10.1016\/j.semarthrit.2025.152755","article-title":"The effect of walking interventions on biomechanical knee osteoarthritis outcomes: a systematic review and meta-analysis","volume":"73","author":"Budarick","year":"2025","journal-title":"Semin Arthritis Rheum"},{"key":"B74","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.joca.2022.10.009","article-title":"Recommendations for the delivery of therapeutic exercise for people with knee and\/or hip osteoarthritis. An international consensus study from the OARSI rehabilitation discussion group","volume":"31","author":"Holden","year":"2022","journal-title":"Osteoarthritis Cartilage"},{"key":"B75","doi-asserted-by":"publisher","first-page":"e947224","DOI":"10.12659\/MSM.947224","article-title":"Impact of monthly community follow-ups in knee osteoarthritis management for elderly patients","volume":"31","author":"Hu","year":"2025","journal-title":"Med Sci Monit"},{"key":"B76","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.jelekin.2012.10.007","article-title":"Influence of a valgus knee brace on muscle activation and co-contraction in patients with medial knee osteoarthritis","volume":"23","author":"Pagani CH","year":"2012","journal-title":"J Electromyogr Kinesiol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1136\/bjsports-2016-097108","article-title":"The effects of shoe-worn insoles on gait biomechanics in people with knee osteoarthritis: a systematic review and meta-analysis","volume":"52","author":"Shaw","year":"2017","journal-title":"Br J Sports Med"},{"key":"B78","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1080\/10400435.2021.1880495","article-title":"Effect of knee braces and insoles on clinical outcomes of individuals with medial knee osteoarthritis: a systematic review and meta-analysis","volume":"34","author":"Khosravi","year":"2021","journal-title":"Assist Technol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.joca.2019.05.004","article-title":"Effect of cane use on bone marrow lesion volume in people with medial tibiofemoral knee osteoarthritis: randomized clinical trial","volume":"27","author":"Van Ginckel","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B80","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","article-title":"2019 American college of rheumatology\/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1749-799X-9-1","article-title":"Patients with knee osteoarthritis demonstrate improved gait pattern and reduced pain following a non-invasive biomechanical therapy: a prospective multi-centre study on Singaporean population","volume":"9","author":"Elbaz","year":"2014","journal-title":"J Orthop Surg Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.joca.2025.10.008","article-title":"Osteoarthritis year in review 2025: rehabilitation and outcomes including sex and gender reporting","volume":"34","author":"Bruder","year":"2025","journal-title":"Osteoarthritis Cartilage"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.3390\/ijms21041217","article-title":"Shockwave therapy combined with autologous adipose-derived mesenchymal stem cells is better than with human umbilical cord Wharton\u2019s jelly-derived mesenchymal stem cells on knee osteoarthritis","volume":"21","author":"Hsu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s40520-025-03015-6","article-title":"Physical modalities for the treatment of knee osteoarthritis: a network meta-analysis","volume":"37","author":"Lan","year":"2025","journal-title":"Aging Clin Exp Res"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1016\/j.joca.2013.06.014","article-title":"Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: economic evaluation alongside a randomized controlled trial","volume":"21","author":"Pinto","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"key":"B86","doi-asserted-by":"publisher","first-page":"675","DOI":"10.2519\/jospt.2022.11062","article-title":"The benefits of adding manual therapy to exercise therapy for improving pain and function in patients with knee or hip osteoarthritis: a systematic review with meta-analysis","volume":"52","author":"Runge","year":"2022","journal-title":"J Orthop Sports Phys Ther"},{"key":"B87","doi-asserted-by":"publisher","first-page":"7459","DOI":"10.2147\/JIR.S518829","article-title":"Therapeutic effects of fire needling acupuncture on pain relief and cartilage protection in MIA-induced knee osteoarthritis rats: the role of macrophage polarization in synovium and angiogenesis in subchondral bone","volume":"18","author":"Wei","year":"2025","journal-title":"J Inflamm Res"},{"key":"B88","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1136\/bmjebm-2023-112626","article-title":"Clinical effect and contributing factors of acupuncture for knee osteoarthritis: a systematic review and pairwise and exploratory network meta-analysis","volume":"29","author":"Liu","year":"2024","journal-title":"BMJ Evid Based Med"},{"key":"B89","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13643-025-02762-x","article-title":"Efficacy and safety of acupuncture with moxibustion for knee osteoarthritis: a meta-analysis of randomized controlled trials","volume":"14","author":"Zhu","year":"2025","journal-title":"Syst Rev"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1016\/j.joca.2023.05.015","article-title":"Recommendations for the management of hip and knee osteoarthritis: a systematic review of clinical practice guidelines","volume":"31","author":"Gibbs","year":"2023","journal-title":"Osteoarthritis Cartilage"},{"key":"B91","doi-asserted-by":"publisher","first-page":"n2321","DOI":"10.1136\/bmj.n2321","article-title":"Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis","volume":"375","author":"da Costa","year":"2021","journal-title":"Br Med J"},{"key":"B92","doi-asserted-by":"publisher","first-page":"CD008609","DOI":"10.1002\/14651858.CD008609.pub2","article-title":"Topical analgesics for acute and chronic pain in adults\u2014an overview of cochrane reviews","volume":"5","author":"Derry","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B93","doi-asserted-by":"publisher","first-page":"46","DOI":"10.7326\/M14-1231","article-title":"Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis","volume":"162","author":"Bannuru","year":"2015","journal-title":"Ann Intern Med"},{"key":"B94","doi-asserted-by":"publisher","first-page":"CD005328","DOI":"10.1002\/14651858.CD005328.pub3","article-title":"Intra-articular corticosteroid for knee osteoarthritis","volume":"2015","author":"J\u00fcni","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"B95","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1186\/s13018-020-01919-9","article-title":"Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis","volume":"15","author":"Tang","year":"2020","journal-title":"J Orthop Surg Res"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e24503","DOI":"10.7759\/cureus.24503","article-title":"Role and effectiveness of intra-articular injection of hyaluronic acid in the treatment of knee osteoarthritis: a systematic review","volume":"14","author":"Chavda","year":"2022","journal-title":"Cureus"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1016\/j.arthro.2023.03.001","article-title":"Patients with knee osteoarthritis who receive platelet-rich plasma or bone marrow aspirate concentrate injections have better outcomes than patients who receive hyaluronic acid: systematic review and meta-analysis","volume":"39","author":"Belk","year":"2023","journal-title":"Arthroscopy"},{"key":"B98","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s43019-025-00266-5","article-title":"Intraarticular leukocyte-poor platelet-rich plasma injection is more effective than intraarticular hyaluronic acid injection in the treatment of knee osteoarthritis: a systematic review and meta-analysis of 12 randomized controlled trials","volume":"37","author":"Peng","year":"2025","journal-title":"Knee Surg Relat Res"},{"key":"B99","doi-asserted-by":"publisher","first-page":"105947","DOI":"10.1016\/j.jbspin.2025.105947","article-title":"Efficacy of intra-articular platelet-rich plasma compared with placebo in knee osteoarthritis: a systematic review and meta-analysis","volume":"92","author":"Auroux","year":"2025","journal-title":"Joint Bone Spine"},{"key":"B100","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s11916-024-01320-9","article-title":"Efficacy of intra-articular platelet-rich plasma injections in treatment of knee osteoarthritis: a systematic review and meta-analysis","volume":"29","author":"Kaye","year":"2025","journal-title":"Curr Pain Headache Rep"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.3390\/jcm13102859","article-title":"Efficacy of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials from the years 2000 to 2023","volume":"13","author":"Knapik","year":"2024","journal-title":"J Clin Med"},{"key":"B102","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41434-025-00515-y","article-title":"Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and promotes cartilage repair in surgically induced osteoarthritis animal models","volume":"32","author":"Zhou","year":"2025","journal-title":"Gene Ther"},{"key":"B103","doi-asserted-by":"publisher","first-page":"7967","DOI":"10.1038\/s41598-023-34824-2","article-title":"The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia","volume":"13","author":"Budhiparama","year":"2023","journal-title":"Sci Rep"},{"key":"B104","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13018-023-03590-2","article-title":"Efficacy and safety of anti-interleukin-1 therapeutics in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials","volume":"18","author":"Yu","year":"2023","journal-title":"J Orthop Surg Res"},{"key":"B105","doi-asserted-by":"publisher","first-page":"10216","DOI":"10.1021\/acs.jmedchem.5c00394","article-title":"Identification of a RANKL\/TNF-\u03b1 dual-inhibitor as a potential disease-modifying agent for the treatment of knee osteoarthritis","volume":"68","author":"Shao","year":"2025","journal-title":"J Med Chem"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1016\/j.joca.2015.05.035","article-title":"Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy","volume":"23","author":"Larsson","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"B107","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.joca.2024.11.007","article-title":"Early-stage vs. established knee osteoarthritis: a comparative observational study on prevalence and changes in pain, function and quality of life after supervised exercise and education among 10,365 patients","volume":"33","author":"Drummen","year":"2024","journal-title":"Osteoarthritis Cartilage"},{"key":"B108","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.joca.2022.02.001","article-title":"Knee and hip osteoarthritis are more alike than different in baseline characteristics and outcomes: a longitudinal study of 32,599 patients participating in supervised education and exercise therapy","volume":"30","author":"Roos","year":"2022","journal-title":"Osteoarthritis Cartilage"},{"key":"B109","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1097\/CORR.0000000000002993","article-title":"Does the combination of platelet-rich plasma and supervised exercise yield better pain relief and enhanced function in knee osteoarthritis? A randomized controlled trial","volume":"482","author":"Argut S","year":"2024","journal-title":"Clin Orthop Relat Res"}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1941764\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:47:12Z","timestamp":1790088432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1941764\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":109,"alternative-id":["10.3389\/fsurg.2026.1941764"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2026.1941764","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1941764"}}