{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:03:54Z","timestamp":1779818634421,"version":"3.53.1"},"reference-count":14,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002836","name":"Chang Gung University","doi-asserted-by":"publisher","award":["ECRPD1P0111"],"award-info":[{"award-number":["ECRPD1P0111"]}],"id":[{"id":"10.13039\/501100002836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002836","name":"Chang Gung University","doi-asserted-by":"publisher","award":["EZRPD1Q0191"],"award-info":[{"award-number":["EZRPD1Q0191"]}],"id":[{"id":"10.13039\/501100002836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a leading cause of global disability, yet the temporal relationship between disease burden and research and translational activity has not been systematically examined using an integrated, system-level framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective, system-level analysis of osteoarthritis (OA) research and disease burden from 1999 to 2023. Annual global OA burden estimates (prevalence, YLDs, and DALYs) were obtained from the Global Burden of Disease framework and harmonized with year-wise data on OA publications, experimental model use, interventional clinical trials, and funding acknowledgements derived from PubMed and ClinicalTrials.gov. Publication domains were classified using predefined, rule-based queries applied to metadata fields. Temporal trends, proportional composition, and burden\u2013research scaling relationships were evaluated using descriptive regression and proportion-based analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 1999 and 2023, global osteoarthritis (OA) disability-adjusted life years (DALYs) approximately doubled, while annual OA publication volume increased more than fourfold. Log\u2013log regression indicated elastic scaling of research output relative to DALYs (\u03b2\u2009&gt;\u20091), reflecting disproportionate growth in publication activity. In contrast, interventional clinical trial initiation peaked in the late 2000s and declined in recent years, with trial activity representing a consistently small fraction of total OA publications. Human-relevant experimental approaches constituted a modest and relatively stable proportion of OA research over time. Lag-association analyses demonstrated strong temporal co-trending between DALYs and total publications, moderate alignment for human-relevant research, and weaker associations for clinical trial activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Over 1999\u20132023, osteoarthritis research activity expanded substantially relative to disease burden, while downstream clinical translation and adoption of human-relevant approaches remained comparatively limited.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0349128","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:23:51Z","timestamp":1779816231000},"page":"e0349128","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Global burden-integrated analysis of osteoarthritis research-to-translation dynamics, 1999\u20132023"],"prefix":"10.1371","volume":"21","author":[{"given":"Riya","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-6905","authenticated-orcid":true,"given":"Chung-Ming","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"pone.0349128.ref001","unstructured":"Osteoarthritis. [cited 2026 Feb 11]. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/osteoarthritis"},{"issue":"9","key":"pone.0349128.ref002","doi-asserted-by":"crossref","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":"JD Steinmetz","year":"2023","journal-title":"Lancet Rheumatol"},{"issue":"2","key":"pone.0349128.ref003","doi-asserted-by":"crossref","first-page":"100059","DOI":"10.1016\/j.ocarto.2020.100059","article-title":"Disease modification in osteoarthritis; pathways to drug approval","volume":"2","author":"JN Katz","year":"2020","journal-title":"Osteoarthr Cartil Open"},{"issue":"1","key":"pone.0349128.ref004","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12961-018-0302-4","article-title":"A comparison between health research output and burden of disease in Arab countries: evidence from Palestine","volume":"16","author":"L Albarqouni","year":"2018","journal-title":"Health Res Policy Syst"},{"key":"pone.0349128.ref005","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jclinepi.2018.01.006","article-title":"A mapping of 115,000 randomized trials revealed a mismatch between research effort and health needs in non\u2013high-income regions","volume":"98","author":"I Atal","year":"2018","journal-title":"J Clin Epidemiol"},{"issue":"2","key":"pone.0349128.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0228542","article-title":"Limited alignment of publicly competitive disease funding with disease burden in Japan","volume":"15","author":"S Nomura","year":"2020","journal-title":"PLoS One"},{"issue":"10","key":"pone.0349128.ref007","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.050583","article-title":"Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis models","volume":"17","author":"SJ Gilbert","year":"2024","journal-title":"Dis Model Mech"},{"key":"pone.0349128.ref008","unstructured":"Leading causes of DALYs. [cited 2026 Feb 11]. https:\/\/www.who.int\/data\/gho\/data\/themes\/mortality-and-global-health-estimates\/global-health-estimates-leading-causes-of-dalys"},{"key":"pone.0349128.ref009","doi-asserted-by":"crossref","first-page":"1043117","DOI":"10.3389\/fcell.2022.1043117","article-title":"3D organ-on-a-chip: the convergence of microphysiological systems and organoids","volume":"10","author":"LS Baptista","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"pone.0349128.ref010","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-22749-0","article-title":"Interconnected microphysiological systems for quantitative biology and pharmacology studies","volume":"8","author":"CD Edington","year":"2018","journal-title":"Scientific Reports"},{"issue":"9","key":"pone.0349128.ref011","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1038\/s41591-025-03923-0","article-title":"Global distribution of research efforts, disease burden, and impact of US public funding withdrawal","volume":"31","author":"L Schmallenbach","year":"2025","journal-title":"Nat Med"},{"issue":"2","key":"pone.0349128.ref012","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jclinepi.2018.01.006","article-title":"A mapping of 115,000 randomized trials revealed a mismatch between research effort and health needs in non\u2013high-income regions","volume":"98","author":"I Atal","year":"2018","journal-title":"J Clin Epidemiol"},{"issue":"6","key":"pone.0349128.ref013","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.semarthrit.2021.07.005","article-title":"Patient perspective on remission in rheumatoid arthritis: validation of patient reported outcome instruments to measure absence of disease activity","volume":"51","author":"L Rasch","year":"2021","journal-title":"Semin Arthritis Rheum"},{"issue":"7","key":"pone.0349128.ref014","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.joca.2021.03.011","article-title":"Anterior cruciate ligament abnormalities are associated with accelerated progression of knee joint degeneration in knees with and without structural knee joint abnormalities: 96-month data from the Osteoarthritis Initiative","volume":"29","author":"AS Gersing","year":"2021","journal-title":"Osteoarthr Cartil"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:23:55Z","timestamp":1779816235000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349128"}},"subtitle":[],"editor":[{"given":"Xindie","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349128","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}