{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:35:00Z","timestamp":1786120500559,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Osteoarthritis Foundation International"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthroplasty"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Knee osteoarthritis is a highly prevalent condition that eventually ends up in arthroplasty at advanced stages. It is unknown whether the prolonged use of drugs for its symptomatic treatment, including non-steroidal anti-inflammatory drugs (NSAIDs), opioids, non-opioid analgesics, and symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), has an impact on the risk of arthroplasty. The purpose of this study was to assess whether long-term use of different medications prescribed for the symptomatic treatment of knee osteoarthritis is associated with the risk of undergoing surgical joint replacement compared with short-term use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A case-control study nested in a cohort of 264,014 patients with a recorded diagnosis of knee osteoarthritis was carried out in BIFAP, a Spanish primary healthcare database. From this cohort, we identified 15,892 cases of primary knee arthroplasty and matched them with up to 3 controls on age, sex, healthcare district, and index date using risk-set sampling. Through a conditional logistic regression, we computed the adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) associated with durations of treatment 1\u20133,\u2009&gt;\u20093\u20135, and\u2009&gt;\u20095\u00a0years in comparison with\u2009&lt;\u20091\u00a0year within the same pharmacological class. A test for trend was carried out.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A trend to an increased risk of arthroplasty was found as treatment duration of NSAIDs increases, while no such trend was observed with SYSADOAs or analgesics. Patients using NSAIDs for more than 5\u00a0years showed an AOR of 2.35 (2.10\u20132.63) as compared to\u2009&lt;\u20091\u00a0year. Both males and females, and subjects younger and older than 70\u00a0years old, shared this pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This observational study shows that the prolonged use of NSAIDs in patients with knee osteoarthritis is associated with an increased risk of arthroplasty, while residual confounding by OA severity cannot be excluded. Results from SYSADOAs, opioids, and non-opioid analgesics are consistent with no association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42836-026-00421-7","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T23:02:03Z","timestamp":1786057323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term use of drugs used for knee osteoarthritis and their association with primary arthroplasty: a nested case-control study"],"prefix":"10.1186","volume":"8","author":[{"given":"Sara","family":"Rodr\u00edguez-Mart\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarnaci\u00f3n","family":"Fern\u00e1ndez-Ant\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Alonso-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rodr\u00edguez-Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Verg\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"de Abajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"issue":"1","key":"421_CR1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1186\/s12891-019-2895-3","volume":"20","author":"M Vitaloni","year":"2019","unstructured":"Vitaloni M, Botto-van Bemden A, Sciortino Contreras RM, Scotton D, Bibas M, Quintero M, et al. Global management of patients with knee osteoarthritis begins with quality of life assessment: a systematic review. BMC Musculoskelet Disord. 2019;20(1):493. https:\/\/doi.org\/10.1186\/s12891-019-2895-3.","journal-title":"BMC Musculoskelet Disord"},{"key":"421_CR2","doi-asserted-by":"publisher","unstructured":"GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(9):e508\u201322. https:\/\/doi.org\/10.1016\/S2665-9913(23)00163-7.","DOI":"10.1016\/S2665-9913(23)00163-7"},{"issue":"10182","key":"421_CR3","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","volume":"393","author":"DJ Hunter","year":"2019","unstructured":"Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745\u201359. https:\/\/doi.org\/10.1016\/S0140-6736(19)30417-9.","journal-title":"Lancet"},{"issue":"8","key":"421_CR4","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1002\/art.39707","volume":"68","author":"C Reyes","year":"2016","unstructured":"Reyes C, Leyland KM, Peat G, Cooper C, Arden NK, Prieto-Alhambra D. Association Between Overweight and Obesity and Risk of Clinically Diagnosed Knee, Hip, and Hand Osteoarthritis: A Population-Based Cohort Study. Arthritis Rheumatol. 2016;68(8):1869\u201375. https:\/\/doi.org\/10.1002\/art.39707.","journal-title":"Arthritis Rheumatol"},{"issue":"2","key":"421_CR5","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/rheumatology\/kep388","volume":"49","author":"AT Toivanen","year":"2010","unstructured":"Toivanen AT, Heli\u00f6vaara M, Impivaara O, Arokoski JP, Knekt P, Lauren H, et al. Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteoarthritis\u2013a population-based study with a follow-up of 22 years. Rheumatology (Oxford). 2010;49(2):308\u201314. https:\/\/doi.org\/10.1093\/rheumatology\/kep388.","journal-title":"Rheumatology (Oxford)"},{"issue":"7","key":"421_CR6","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1002\/1529-0131(200007)43:7<1443::AID-ANR5>3.0.CO;2-1","volume":"43","author":"D Coggon","year":"2000","unstructured":"Coggon D, Croft P, Kellingray S, Barrett D, McLaren M, Cooper C. Occupational physical activities and osteoarthritis of the knee. Arthritis Rheum. 2000;43(7):1443\u20139. https:\/\/doi.org\/10.1002\/1529-0131(200007)43:7%3c1443::AID-ANR5%3e3.0.CO;2-1.","journal-title":"Arthritis Rheum"},{"issue":"11","key":"421_CR7","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/j.joca.2019.06.004","volume":"27","author":"E Burn","year":"2019","unstructured":"Burn E, Murray DW, Hawker GA, Pinedo-Villanueva R, Prieto-Alhambra D. Lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis: a real-world cohort study. Osteoarthritis Cartilage. 2019;27(11):1627\u201335. https:\/\/doi.org\/10.1016\/j.joca.2019.06.004.","journal-title":"Osteoarthritis Cartilage"},{"issue":"10158","key":"421_CR8","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/S0140-6736(18)32344-4","volume":"392","author":"AJ Price","year":"2018","unstructured":"Price AJ, Alvand A, Troelsen A, Katz JN, Hooper G, Gray A, et al. Knee replacement. Lancet. 2018;392(10158):1672\u201382. https:\/\/doi.org\/10.1016\/S0140-6736(18)32344-4.","journal-title":"Lancet"},{"issue":"645","key":"421_CR9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3399\/bjgp16X684433","volume":"66","author":"A Davis","year":"2016","unstructured":"Davis A, Robson J. The dangers of NSAIDs: look both ways. Br J Gen Pract. 2016;66(645):172\u20133. https:\/\/doi.org\/10.3399\/bjgp16X684433.","journal-title":"Br J Gen Pract"},{"key":"421_CR10","doi-asserted-by":"publisher","first-page":"h1225","DOI":"10.1136\/bmj.h1225","volume":"350","author":"GC Machado","year":"2015","unstructured":"Machado GC, Maher CG, Ferreira PH, Pinheiro MB, Lin CW, Day RO, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225. https:\/\/doi.org\/10.1136\/bmj.h1225.","journal-title":"BMJ"},{"key":"421_CR11","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/ejp.1522","volume":"24","author":"P Welsch","year":"2020","unstructured":"Welsch P, Petzke F, Klose P, H\u00e4user W. Opioids for chronic osteoarthritis pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks double-blind duration. Eur J Pain. 2020;24:685\u2013703. https:\/\/doi.org\/10.1002\/ejp.1522.","journal-title":"Eur J Pain"},{"issue":"3","key":"421_CR12","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00296-009-0969-5","volume":"30","author":"YH Lee","year":"2010","unstructured":"Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis. Rheumatol Int. 2010;30(3):357\u201363. https:\/\/doi.org\/10.1007\/s00296-009-0969-5.","journal-title":"Rheumatol Int"},{"key":"421_CR13","doi-asserted-by":"publisher","first-page":"c4675","DOI":"10.1136\/bmj.c4675","volume":"341","author":"S Wandel","year":"2010","unstructured":"Wandel S, J\u00fcni P, Tendal B, N\u00fcesch E, Villiger PM, Welton NJ, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. https:\/\/doi.org\/10.1136\/bmj.c4675.","journal-title":"BMJ"},{"issue":"1","key":"421_CR14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1136\/annrheumdis-2014-206792","volume":"75","author":"MC Hochberg","year":"2016","unstructured":"Hochberg MC, Martel-Pelletier J, Monfort J, M\u00f6ller I, Castillo JR, Arden N, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016;75(1):37\u201344. https:\/\/doi.org\/10.1136\/annrheumdis-2014-206792.","journal-title":"Ann Rheum Dis"},{"issue":"Suppl 1","key":"421_CR15","doi-asserted-by":"publisher","first-page":"S28","DOI":"10.1016\/j.joca.2010.02.016","volume":"18","author":"MC Hochberg","year":"2010","unstructured":"Hochberg MC. Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration. Osteoarthritis Cartilage. 2010;18(Suppl 1):S28-31. https:\/\/doi.org\/10.1016\/j.joca.2010.02.016.","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"421_CR16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41584-020-00523-9","volume":"17","author":"NK Arden","year":"2021","unstructured":"Arden NK, Perry TA, Bannuru RR, Bruy\u00e8re O, Cooper C, Haugen IK, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59\u201366. https:\/\/doi.org\/10.1038\/s41584-020-00523-9.","journal-title":"Nat Rev Rheumatol"},{"key":"421_CR17","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","volume":"27","author":"RR Bannuru","year":"2019","unstructured":"Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27:1578\u201389. https:\/\/doi.org\/10.1016\/j.joca.2019.06.011.","journal-title":"Osteoarthritis Cartilage"},{"issue":"6","key":"421_CR18","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1136\/ard.2010.140848","volume":"70","author":"LM Wildi","year":"2011","unstructured":"Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, et al. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis. 2011;70(6):982\u20139. https:\/\/doi.org\/10.1136\/ard.2010.140848.","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"421_CR19","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1185\/03007990802434932","volume":"24","author":"MC Hochberg","year":"2008","unstructured":"Hochberg MC, Zhan M, Langenberg P. The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate. Curr Med Res Opin. 2008;24(11):3029\u201335. https:\/\/doi.org\/10.1185\/03007990802434932.","journal-title":"Curr Med Res Opin"},{"issue":"10","key":"421_CR20","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1093\/rheumatology\/keab059","volume":"60","author":"TA Perry","year":"2021","unstructured":"Perry TA, Wang X, Nevitt M, Abdelshaheed C, Arden N, Hunter DJ. Association between current medication use and progression of radiographic knee osteoarthritis: data from the osteoarthritis initiative. Rheumatology (Oxford). 2021;60(10):4624\u201332. https:\/\/doi.org\/10.1093\/rheumatology\/keab059.","journal-title":"Rheumatology (Oxford)"},{"issue":"10","key":"421_CR21","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/pds.5006","volume":"29","author":"M-A Maci\u00e1-Mart\u00ednez","year":"2020","unstructured":"Maci\u00e1-Mart\u00ednez M-A, Gil M, Huerta C, Mart\u00edn-Merino E, \u00c1lvarez A, Bryant V, et al. Base de Datos para la Investigaci\u00f3n Farmacoepidemiol\u00f3gica en Atenci\u00f3n Primaria (BIFAP): A data resource for pharmacoepidemiology in Spain. Pharmacoepidemiol Drug Saf. 2020;29(10):1236\u201345. https:\/\/doi.org\/10.1002\/pds.5006.","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"6","key":"421_CR22","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1007\/s00223-014-9850-y","volume":"94","author":"G Requena","year":"2014","unstructured":"Requena G, Abbing-Karahagopian V, Huerta C, De Bruin ML, Alvarez Y, Miret M, et al. Incidence rates and trends of hip\/femur fractures in five European countries: comparison using e-healthcare records databases. Calcif Tissue Int. 2014;94(6):580\u20139. https:\/\/doi.org\/10.1007\/s00223-014-9850-y.","journal-title":"Calcif Tissue Int"},{"key":"421_CR23","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1002\/pds.3617","volume":"23","author":"FJ de Abajo","year":"2014","unstructured":"de Abajo FJ, Gil MJ, Garcia Poza P, Bryant V, Oliva B, Timoner J, et al. Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study. Pharmacoepidemiol Drug Saf. 2014;23:1128\u201338. https:\/\/doi.org\/10.1002\/pds.3617.","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"7","key":"421_CR24","doi-asserted-by":"publisher","first-page":"e0253932","DOI":"10.1371\/journal.pone.0253932","volume":"16","author":"R Mazzucchelli","year":"2021","unstructured":"Mazzucchelli R, Rodr\u00edguez-Mart\u00edn S, Garc\u00eda-Vadillo A, Gil M, Rodr\u00edguez-Miguel A, Barreira-Hern\u00e1ndez D, et al. Risk of acute myocardial infarction among new users of chondroitin sulfate: A nested case-control study. PLoS ONE. 2021;16(7):e0253932. https:\/\/doi.org\/10.1371\/journal.pone.0253932.","journal-title":"PLoS ONE"},{"key":"421_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1197238","volume":"14","author":"S Rodr\u00edguez-Mart\u00edn","year":"2023","unstructured":"Rodr\u00edguez-Mart\u00edn S, Barreira-Hern\u00e1ndez D, Mazzucchelli R, Gil M, Garc\u00eda-Lled\u00f3 A, Izquierdo-Esteban L, et al. Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study. Front Pharmacol. 2023;14:1197238. https:\/\/doi.org\/10.3389\/fphar.2023.1197238.","journal-title":"Front Pharmacol"},{"key":"421_CR26","unstructured":"Ministerio de Sanidad. Sistema de Informaci\u00f3n de listas de espera. Available at: https:\/\/www.sanidad.gob.es\/estadEstudios\/estadisticas\/inforRecopilaciones\/listaEsperaInfAnt.htm. Cited 2026 Feb 26."},{"key":"421_CR27","first-page":"105","volume-title":"Modern epidemiology","author":"T Lash","year":"2021","unstructured":"Lash T, Rothman KJ. Case-control studies. In: Lash TL, VanderWeele TJ, Haneuse S, Rothman KJ, editors. Modern epidemiology. 4th ed. Philadelphia: Wolters Kluwer; 2021. p. 105\u201340.","edition":"4th ed"},{"key":"421_CR28","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b5087","volume":"340","author":"LE L\u00e9vesque","year":"2010","unstructured":"L\u00e9vesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ. 2010;340:b5087. https:\/\/doi.org\/10.1136\/bmj.b5087.","journal-title":"BMJ"},{"issue":"7382","key":"421_CR29","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1136\/bmj.326.7382.219","volume":"326","author":"DG Altman","year":"2003","unstructured":"Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326(7382):219. https:\/\/doi.org\/10.1136\/bmj.326.7382.219.","journal-title":"BMJ"},{"issue":"5","key":"421_CR30","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1002\/art.39564","volume":"68","author":"N Veronese","year":"2016","unstructured":"Veronese N, Trevisan C, De Rui M, Bolzetta F, Maggi S, Zambon S, et al. Association of osteoarthritis with increased risk of cardiovascular diseases in the elderly: findings from the Progettto Veneto Anziano Study Cohort. Arthritis Rheumatol. 2016;68(5):1136\u201344. https:\/\/doi.org\/10.1002\/art.39564.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"421_CR31","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1053\/joca.1998.0176","volume":"7","author":"JT Dingle","year":"1999","unstructured":"Dingle JT. The effect of nonsteroidal antiinflammatory drugs on human articular cartilage glycosaminoglycan synthesis. Osteoarthritis Cartilage. 1999;7(3):313\u20134. https:\/\/doi.org\/10.1053\/joca.1998.0176.","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"421_CR32","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1186\/ar1846","volume":"8","author":"SC Mastbergen","year":"2006","unstructured":"Mastbergen SC, Jansen NWD, Bijlsma JWJ, Lafeber FPJG. Differential direct effects of cyclo-oxygenase-1\/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitro study. Arthritis Res Ther. 2006;8(1):R2. https:\/\/doi.org\/10.1186\/ar1846.","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"421_CR33","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1136\/ard.35.6.487","volume":"35","author":"LS McKenzie","year":"1976","unstructured":"McKenzie LS, Horsburgh BA, Ghosh P, Taylor TK. Effect of anti-inflammatory drugs on sulphated glycosaminoglycan synthesis in aged human articular cartilage. Ann Rheum Dis. 1976;35(6):487\u201397. https:\/\/doi.org\/10.1136\/ard.35.6.487.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"421_CR34","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/s1063-4584(03)00118-3","volume":"11","author":"M Miyamoto","year":"2003","unstructured":"Miyamoto M, Ito H, Mukai S, Kobayashi T, Yamamoto H, Kobayashi M, et al. Simultaneous stimulation of EP2 and EP4 is essential to the effect of prostaglandin E2 in chondrocyte differentiation. Osteoarthritis Cartilage. 2003;11(9):644\u201352. https:\/\/doi.org\/10.1016\/s1063-4584(03)00118-3.","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"421_CR35","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3109\/17453677908989752","volume":"50","author":"H R\u00f8nningen","year":"1979","unstructured":"R\u00f8nningen H, Langeland N. Indomethacin treatment in osteoarthritis of the hip joint. Does the treatment interfere with the natural course of the disease? Acta Orthop Scand. 1979;50(2):169\u201374. https:\/\/doi.org\/10.3109\/17453677908989752.","journal-title":"Acta Orthop Scand"},{"issue":"10","key":"421_CR36","first-page":"1941","volume":"22","author":"EC Huskisson","year":"1995","unstructured":"Huskisson EC, Berry H, Gishen P, Jubb RW, Whitehead J. Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis. J Rheumatol. 1995;22(10):1941\u20136.","journal-title":"J Rheumatol"},{"issue":"7","key":"421_CR37","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1136\/ard.2004.029546","volume":"64","author":"L Gossec","year":"2005","unstructured":"Gossec L, Tubach F, Baron G, Ravaud P, Logeart I, Dougados M. Predictive factors of total hip replacement due to primary osteoarthritis: a prospective 2 year study of 505 patients. Ann Rheum Dis. 2005;64(7):1028\u201332. https:\/\/doi.org\/10.1136\/ard.2004.029546.","journal-title":"Ann Rheum Dis"},{"key":"421_CR38","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.joca.2015.11.003","volume":"24","author":"N Hafezi-Nejad","year":"2016","unstructured":"Hafezi-Nejad N, Guermazi A, Roemer FW, Eng J, Zikria B, Demehri S. Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016;24:597\u2013604. https:\/\/doi.org\/10.1016\/j.joca.2015.11.003.","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"421_CR39","doi-asserted-by":"publisher","first-page":"6593","DOI":"10.1038\/s41598-024-56665-3","volume":"14","author":"Z Salis","year":"2024","unstructured":"Salis Z, Sainsbury A. Association of long-term use of non-steroidal anti- inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years. Sci Rep. 2024;14(1):6593. https:\/\/doi.org\/10.1038\/s41598-024-56665-3.","journal-title":"Sci Rep"},{"issue":"4","key":"421_CR40","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/jor.1100180409","volume":"18","author":"DE Hurwitz","year":"2000","unstructured":"Hurwitz DE, Ryals AR, Block JA, Sharma L, Schnitzer TJ, Andriacchi TP. Knee pain and joint loading in subjects with osteoarthritis of the knee. J Orthop Res. 2000;18(4):572\u20139. https:\/\/doi.org\/10.1002\/jor.1100180409.","journal-title":"J Orthop Res"},{"issue":"6","key":"421_CR41","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1136\/ard.2006.068882","volume":"67","author":"J Monfort","year":"2008","unstructured":"Monfort J, Pelletier J-P, Garcia-Giralt N, Martel-Pelletier J. Biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues. Ann Rheum Dis. 2008;67(6):735\u201340. https:\/\/doi.org\/10.1136\/ard.2006.068882.","journal-title":"Ann Rheum Dis"},{"issue":"8A","key":"421_CR42","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1111\/j.1582-4934.2009.00826.x","volume":"13","author":"P du Souich","year":"2009","unstructured":"du Souich P, Garcia AG, Verges J, Montell E. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. J Cell Mol Med. 2009;13(8A):1451\u201363. https:\/\/doi.org\/10.1111\/j.1582-4934.2009.00826.x.","journal-title":"J Cell Mol Med"},{"issue":"2","key":"421_CR43","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/art.24255","volume":"60","author":"A Kahan","year":"2009","unstructured":"Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster JY. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(2):524\u201333. https:\/\/doi.org\/10.1002\/art.24255.","journal-title":"Arthritis Rheum"},{"issue":"9","key":"421_CR44","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1007\/s10067-012-2022-4","volume":"31","author":"JJ Railhac","year":"2012","unstructured":"Railhac JJ, Zaim M, Saurel AS, Vial J, Fournie B. Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin Rheumatol. 2012;31(9):1347\u201357. https:\/\/doi.org\/10.1007\/s10067-012-2022-4. Erratum. In:ClinRheumatol.2014;33(10):1527.","journal-title":"Clin Rheumatol"},{"issue":"1","key":"421_CR45","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s13075-016-1149-0","volume":"18","author":"JP Pelletier","year":"2016","unstructured":"Pelletier JP, Raynauld JP, Beaulieu AD, Bessette L, Morin F, de Brum-Fernandes AJ, et al. Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study. Arthritis Res Ther. 2016;18(1):256. https:\/\/doi.org\/10.1186\/s13075-016-1149-0.","journal-title":"Arthritis Res Ther"},{"issue":"Suppl 1","key":"421_CR46","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s40266-019-00662-z","volume":"36","author":"G Honvo","year":"2019","unstructured":"Honvo G, Reginster JY, Rabenda V, et al. Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(Suppl 1):65\u201399. https:\/\/doi.org\/10.1007\/s40266-019-00662-z.","journal-title":"Drugs Aging"},{"key":"421_CR47","doi-asserted-by":"publisher","first-page":"1759720X2211139","DOI":"10.1177\/1759720X221113937","volume":"14","author":"R Mazzucchelli","year":"2022","unstructured":"Mazzucchelli R, Rodr\u00edguez-Mart\u00edn S, Cresp\u00ed-Villar\u00edas N, Garc\u00eda-Vadillo A, Gil M, Izquierdo-Esteban L, et al. Risk of ischaemic stroke among new users of glucosamine and chondroitin sulphate: a nested case-control study. Ther Adv Musculoskelet Dis. 2022;14:1759720X221113937. https:\/\/doi.org\/10.1177\/1759720X221113937.","journal-title":"Ther Adv Musculoskelet Dis"},{"issue":"3","key":"421_CR48","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.semarthrit.2019.04.008","volume":"49","author":"O Bruy\u00e8re","year":"2019","unstructured":"Bruy\u00e8re O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337\u201350. https:\/\/doi.org\/10.1016\/j.semarthrit.2019.04.008.","journal-title":"Semin Arthritis Rheum"},{"issue":"12","key":"421_CR49","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1136\/ard.2003.011742","volume":"62","author":"KM Jordan","year":"2003","unstructured":"Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145\u201355. https:\/\/doi.org\/10.1136\/ard.2003.011742.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"421_CR50","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1093\/aje\/kwg231","volume":"158","author":"WA Ray","year":"2003","unstructured":"Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158(9):915\u201320. https:\/\/doi.org\/10.1093\/aje\/kwg231.","journal-title":"Am J Epidemiol"}],"container-title":["Arthroplasty"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42836-026-00421-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42836-026-00421-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42836-026-00421-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T23:02:05Z","timestamp":1786057325000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s42836-026-00421-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["421"],"URL":"https:\/\/doi.org\/10.1186\/s42836-026-00421-7","relation":{},"ISSN":["2524-7948"],"issn-type":[{"value":"2524-7948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"10 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The BIFAP Scientific Committee approved the study (project #03\/2022_V2) on April 28th, 2022, and the Research Ethics Committee of the University Hospital Pr\u00edncipe de Asturias (EOm 17\/2023) on December 19th, 2023. The requirement for informed consent to participate was waived by the ethics committee referred to above, as patients cannot be identified, risks are minimal, and the number of patients would make the research unfeasible if such waiver were not granted.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"59"}}