{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:42:24Z","timestamp":1792665744081,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502296"],"award-info":[{"award-number":["82502296"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoporosis and sarcopenia frequently coexist in older adults, yet whether denosumab provides muscle\u2010related benefits beyond bone remains uncertain. We compared denosumab and zoledronic acid across functional, imaging, biologic and study\u2010defined sarcopenia outcomes based on an Asian Working Group for Sarcopenia (AWGS) 2025\u2010informed framework and examined whether early osteoprotegerin (OPG)\/soluble receptor activator of nuclear factor\u2010kappa B ligand (sRANKL) responses tracked with later benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective observational cohort study included 186 postmenopausal women with osteoporosis and prescreened sarcopenia risk (82 denosumab, 104 zoledronic acid). Assessments at baseline and 12, 24 and 36\u2009months included grip strength, gait speed, 5\u2010times chair stand, lumbar spine and femoral neck bone mineral density (BMD), dual\u2010energy X\u2010ray absorptiometry (DXA)\u2010derived appendicular skeletal muscle mass index (ASMI), computed tomography (CT)\u2010derived T12\u2010L4 skeletal muscle volume index (SMVI), skeletal muscle density (SMD), intermuscular fat volume index (IMFI), visceral fat volume index (VFI) and OPG\/sRANKL\u2010centred biologic markers. Continuous outcomes were analysed using linear mixed\u2010effects models, categorical outcomes with Fisher exact tests and responder and mediation analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Denosumab showed greater functional improvement than zoledronic acid. At 12\u2009months, grip strength increased by 1.45\u2009\u00b1\u20090.51 versus 0.66\u2009\u00b1\u20090.34\u2009kg, gait speed by 0.041\u2009\u00b1\u20090.013 versus 0.017\u2009\u00b1\u20090.011\u2009m\/s and 5\u2010times chair stand time by \u22120.82\u2009\u00b1\u20090.27 versus \u22120.32\u2009\u00b1\u20090.18\u2009s (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). At 36\u2009months, changes were 2.52\u2009\u00b1\u20090.63 versus 0.99\u2009\u00b1\u20090.45\u2009kg, 0.070\u2009\u00b1\u20090.017 versus 0.027\u2009\u00b1\u20090.012\u2009m\/s and \u22121.47\u2009s (\u22121.63, \u22121.34) versus \u22120.63\u2009s (\u22120.82, \u22120.50) (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). ASMI did not differ at 12\u2009months (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.119) but favoured denosumab at 24 and 36\u2009months (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; 36\u2010month change, 0.192\u2009\u00b1\u20090.059 vs. 0.089\u2009\u00b1\u20090.050\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). Sarcopenia prevalence was lower with denosumab at 12, 24 and 36\u2009months (52.1% vs. 69.8%, 30.2% vs. 50.7% and 20.0% vs. 46.0%), and remission was higher (36.7% vs. 15.5%, 63.5% vs. 37.3% and 75.0% vs. 37.0%). Denosumab also produced greater increases in SMVI and SMD and greater reductions in IMFI and VFI. The OPG\/sRANKL ratio increased more strongly at 12\u2009months (2.503 [2.053, 3.429] vs. 0.807 [0.549, 0.994],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). High responders had larger 36\u2010month gains in grip strength (2.80\u2009\u00b1\u20090.65 vs. 2.21\u2009\u00b1\u20090.44\u2009kg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and CT\u2010defined SMVI (2.816\u2009\u00b1\u20090.861 vs. 2.199\u2009\u00b1\u20090.524,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Twelve\u2010month OPG\/sRANKL change showed a pattern statistically consistent with partial mediation of the association between treatment group and 36\u2010month grip strength (37.0%) and CT\u2010defined SMVI (39.9%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with zoledronic acid, denosumab was associated with stronger early OPG\/sRANKL activation, earlier functional improvement, more favourable CT\u2010defined remodelling, later DXA\u2010derived muscle\u2010mass gain and lower study\u2010defined sarcopenia burden based on an AWGS 2025\u2010informed framework over 3\u2009years. These findings support validation of RANKL inhibition in osteosarcopenic phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70406","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:44:32Z","timestamp":1792586672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Denosumab Versus Zoledronic Acid for Muscle Strength and Physical Performance in Postmenopausal Osteoporosis: A 3\u2010Year Prospective Study"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-9401","authenticated-orcid":false,"given":"Xiangwen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiology Huashan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zineng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Clinical Medical College Fudan University  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