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This study was undertaken to quantify the contribution of magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>)\u2013evidenced changes in pain\u2010sensitive structures, bone marrow lesions (<jats:styled-content style=\"fixed-case\">BML<\/jats:styled-content>s), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1\u2010year follow\u2010up for <jats:styled-content style=\"fixed-case\">BML<\/jats:styled-content>s and synovitis seen on <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>, the pressure pain threshold (<jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [<jats:styled-content style=\"fixed-case\">CES<\/jats:styled-content>\u2010D]), and Western Ontario and McMaster Universities Osteoarthritis Index (<jats:styled-content style=\"fixed-case\">WOMAC<\/jats:styled-content>) pain survey. Natural\u2010effects models were used to quantify the extent that achieving a minimum clinically important difference (<jats:styled-content style=\"fixed-case\">MCID<\/jats:styled-content>) of \u226518% on the <jats:styled-content style=\"fixed-case\">WOMAC<\/jats:styled-content> pain scale could be mediated by weight loss\u2013induced changes in <jats:styled-content style=\"fixed-case\">BML<\/jats:styled-content>s, synovitis, <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>, and depressive symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 75 participants, 53.3% lost \u226520% of weight by 1 year. Of these, 75% attained the <jats:styled-content style=\"fixed-case\">MCID<\/jats:styled-content> for pain improvement, compared with 34.3% in those who had &lt;20% weight loss. Mediation analyses suggested that, in those with at least 20% weight loss, the odds of pain improvement increased by 62%, 15%, and 22% through changes in patella <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>, wrist <jats:styled-content style=\"fixed-case\">PPT<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CES<\/jats:styled-content>\u2010D, respectively, but pain improvement was not mediated by <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> changes in <jats:styled-content style=\"fixed-case\">BML<\/jats:styled-content>s or synovitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Weight loss\u2013induced knee pain improvement is partially mediated by changes in pain sensitization and depressive symptoms but is independent of <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> changes in <jats:styled-content style=\"fixed-case\">BML<\/jats:styled-content>s and synovitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41125","type":"journal-article","created":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T03:28:43Z","timestamp":1569641323000},"page":"420-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mediating Role of Bone Marrow Lesions, Synovitis, Pain Sensitization, and Depressive Symptoms on Knee Pain Improvement Following Substantial Weight Loss"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-9175","authenticated-orcid":false,"given":"S. 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