{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:18:50Z","timestamp":1793013530726,"version":"4.5.0"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"17","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,4,26]]},"abstract":"<jats:p>We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six serum peptides, corresponding to six proteins, reached AUC 77% probability to distinguish those who developed OA from age-matched individuals who did not develop OA up to 8 years later. Prediction based on these blood biomarkers was superior to traditional prediction based on age and BMI (AUC 51%) or knee pain (AUC 57%). These results identify a prolonged molecular derangement of joint tissue before the onset of radiographic OA abnormalities consistent with an unresolved acute phase response. Among all 24 protein biomarkers predicting incident knee OA, the majority (58%) also predicted knee OA progression, revealing the existence of a pathophysiological \u201cOA continuum\u201d based on considerable similarity in the molecular pathophysiology of the progression to incident OA and the progression of established OA.<\/jats:p>","DOI":"10.1126\/sciadv.adj6814","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T17:58:41Z","timestamp":1714154321000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":37,"title":["An osteoarthritis pathophysiological continuum revealed by molecular biomarkers"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8173-8258","authenticated-orcid":true,"given":"Virginia Byers","family":"Kraus","sequence":"first","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."},{"name":"Department of Medicine, Duke University School of Medicine, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2182-5488","authenticated-orcid":true,"given":"Shuming","family":"Sun","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-0214","authenticated-orcid":true,"given":"Alexander","family":"Reed","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.","family":"Soderblom","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-738X","authenticated-orcid":true,"given":"M. Arthur","family":"Moseley","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-8589","authenticated-orcid":true,"given":"Kaile","family":"Zhou","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-9778","authenticated-orcid":true,"given":"Vaibhav","family":"Jain","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Arden","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4834","authenticated-orcid":true,"given":"Yi-Ju","family":"Li","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University, Durham, NC, USA."},{"name":"Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.10.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31678-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2020.11.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00673-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2017.08.006"},{"key":"e_1_3_2_7_2","unstructured":"V. Kraus \"Preclinical and Early Osteoarthritis\" in Rheumatology E-Book M. Hochberg A. Silman J. Smolen M. Weinblatt W. MH E. Gravallese Eds. (Elsevier ed. 7th 2019) chap. 187."},{"key":"e_1_3_2_8_2","unstructured":"V. Kraus T. Vincent \"Osteoarthritis\" in Goldman-Cecil Medicine L. Goldman A. Schafer Eds. (Elsevier ed. 26th 2020) vol. 2 chap. 246 pp. 1698-1703."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"M. Hochberg V. Kraus S. Lohmander A. Guermazi F. Roemer A. Mobasheri \"Osteoarthritis\" in Clinical Innovation in Rheumatology Past Present and Future J. Liebowitz P. Seo Eds. (CRC Press Taylor and Francis 2022) chap. 5 pp. 47-63.","DOI":"10.1201\/9781003207160-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.01.012"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.11.007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/1947603520941239"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0005-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1063-4584(10)60151-3"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.30412"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.04.009"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.02.007"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0976-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.03.023"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq5095"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23932"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67730-y"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2022.100200"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203620"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86064-x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.04.011"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4137\/BMI.S645"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199911)42:11<2356::AID-ANR14>3.0.CO;2-R"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2015.1105498"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-018-1932-y"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2002.0819"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.607186"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2023.100425"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530169"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2006.09.006"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac415"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.41793"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.3049"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12355"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15062"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13558-y"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01068"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/36.2.164"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-016-9113-1"},{"key":"e_1_3_2_45_2","first-page":"100114","article-title":"Complement system dysregulation in synovial fluid from patients with persistent inflammation following anterior cruciate ligament reconstruction surgery","volume":"3","author":"Keller L.","year":"2023","unstructured":"L. Keller, L. Fortier, C. Lattermann, E. Hunt, S. Zhang, Q. Fu, C. Jacobs, Complement system dysregulation in synovial fluid from patients with persistent inflammation following anterior cruciate ligament reconstruction surgery. J. Cartil. Jt. Preserv. 3, 100114 (2023).","journal-title":"J. Cartil. Jt. Preserv."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00270285"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0258855"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jos.2018.08.003"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2022.10.001"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.02.003"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2003.09.004"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.01.007"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina56090455"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18148-7"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.53.3.158"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199901)42:1<17::AID-ANR2>3.0.CO;2-E"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v077.i01"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-19120-0"},{"key":"e_1_3_2_60_2","doi-asserted-by":"crossref","unstructured":"D. Rubin Multiple Imputation for Nonresponse in Surveys (John Wiley & Sons 1987).","DOI":"10.1002\/9780470316696"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2005.00503.x"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwk052"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.143.1.7063747"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531595"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adj6814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T17:59:20Z","timestamp":1714154360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adj6814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":63,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2024,4,26]]}},"alternative-id":["10.1126\/sciadv.adj6814"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adj6814","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]},"assertion":[{"value":"2023-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadj6814"}}