{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:55:04Z","timestamp":1792446904932,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the impact of exercise therapy on molecular biomarkers related to cartilage and inflammation in individuals at risk of, or with established, knee osteoarthritis by conducting a systematic review of randomized controlled trials (RCTs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a literature search up to September 2017 in 5 major databases with no restriction on publication year or language. Data were extracted from the first available follow\u2010up time point, and we performed a narrative synthesis for the effect of exercise therapy on molecular biomarkers related to cartilage and inflammation. A subset of studies reporting sufficient data was combined in a meta\u2010analysis, using an adjusted random\u2010effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve RCTs involving 57 study comparisons at 4 to 24 weeks following an exercise\u2010therapy intervention were included. Exercise therapy decreased molecular biomarkers in 17 study comparisons (30%), had no effect in 36 (63%), and increased molecular biomarkers in 4 study comparisons (7%). Meta\u2010analyses of 9 biomarkers showed that exercise therapy was associated with nonsignificant reductions of the C\u2010reactive protein level, C\u2010terminal crosslinking telopeptide of type II collagen, tumor necrosis factor (TNF), soluble TNF receptors 1 and 2, C2C neoepitope of type II collagen, and cartilage oligomeric matrix protein, compared to nonexercising control groups, and exercise therapy had no effect on interleukin\u20106 and soluble interleukin\u20106 receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exercise therapy is not harmful, because it does not increase the concentration of molecular biomarkers related to cartilage turnover and inflammation, implicated in osteoarthritis progression. The overall quality of evidence was downgraded to low because of the limited number of RCTs available.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.23786","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T11:37:45Z","timestamp":1539603465000},"page":"1504-1515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Impact of Exercise Therapy on Molecular Biomarkers Related to Cartilage and Inflammation in Individuals at Risk of, or With Established, Knee Osteoarthritis: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-918X","authenticated-orcid":false,"given":"Alessio","family":"Bricca","sequence":"first","affiliation":[{"name":"Herlev and Gentofte Hospitals University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Struglics","sequence":"additional","affiliation":[{"name":"Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Larsson","sequence":"additional","affiliation":[{"name":"Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Steultjens","sequence":"additional","affiliation":[{"name":"Glasgow Caledonian University  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten B.","family":"Juhl","sequence":"additional","affiliation":[{"name":"University of Southern Denmark, Odense, and Herlev and Gentofte Hospitals University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa M.","family":"Roos","sequence":"additional","affiliation":[{"name":"Herlev and Gentofte Hospitals University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703856114"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61729-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003677-200510000-00008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.02.048"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546517712945"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X16670613"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2017-097503"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.05.007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2010.02.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.01.003"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202745"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.05.002"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.11.002"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-126"},{"key":"e_1_2_6_16_1","first-page":"CD004376","article-title":"Exercise for osteoarthritis of the knee","volume":"1","author":"Fransen M","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38290"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cml022"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.03.009"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2013-203726rep"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.01.012"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.02.007"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.09.005"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.274"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2011.12.017"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2016-095999"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3064"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1999.0293"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.07.018"},{"key":"e_1_2_6_30_1","unstructured":"HigginsJP GreenS editors.Cochrane handbook for systematic reviews of interventions version 5.1.0. 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