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Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-\u03baB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48\u2009weeks treatment with denosumab 60\u2009mg every 3\u2009months (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200951, 41 females) or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200949, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72);\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/trial\/2015-003223-53\/BE\" ext-link-type=\"uri\">2015-003223-53<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-024-02822-0","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T06:02:53Z","timestamp":1707976973000},"page":"829-836","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6367-9466","authenticated-orcid":false,"given":"Ruth","family":"Wittoek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gust","family":"Verbruggen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8058-5253","authenticated-orcid":false,"given":"Tine","family":"Vanhaverbeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roos","family":"Colman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-974X","authenticated-orcid":false,"given":"Dirk","family":"Elewaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"2822_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41584-021-00747-3","volume":"18","author":"M Favero","year":"2022","unstructured":"Favero, M. et al. 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The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}