{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:17:15Z","timestamp":1791303435333,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"FDA","doi-asserted-by":"publisher","award":["#1U01FD007772-01"],"award-info":[{"award-number":["#1U01FD007772-01"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Society for Bone Mineral Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Emerging anti-osteoporosis therapies might present varied mechanisms of action and demand active control groups or sequential therapies due to ethical or mechanistic reasons. We previously showed a strong association between treatment-induced changes in total hip BMD (THBMD) at 12 and 24\u00a0mo and reduced fracture risk in placebo-controlled trials. We determined the surrogate threshold effect: the minimum THBMD difference (active-placebo) in a trial that would predict a significant reduction in fracture risk in trials. In this analysis, we investigated whether these associations are influenced by drug mechanism of action or trial design, including treatment with an anabolic followed by an antiresorptive compared to active control or placebo. We analyzed individual patient data from 22 randomized, placebo-controlled trials (17 antiresorptive, 3 PTH analogs, 1 odanacatib, and 1 romosozumab placebo-controlled phase), and 3 trials of an anabolic followed by an antiresorptive (1 PTH analog and 2 romosozumab). We established treatment-related differences in THBMD changes, calculated fracture risk reductions for radiologic vertebral and all clinical fractures, and estimated study-level associations between these features via meta-regression. We found consistent associations between treatment-related THBMD changes and fracture risk reduction across different drug mechanisms and trial designs. Among placebo-controlled trials, the r2 values for vertebral fractures were 0.73 (p\u2009=\u2009.0001) and 0.78 (p\u2009=\u2009.0002) at 24 mo, and 0.59 (p\u2009=\u2009.0003) and 0.70 (p\u2009=\u2009.0007) at 12 mo for all drugs vs only antiresorptive drugs, respectively. Similarly, for all clinical fractures, the r2 were 0.71 (p\u2009&amp;lt;\u2009.0001) and 0.65 (p\u2009=\u2009.0009) at 24 mo and 0.46 (p\u2009=\u2009.0007) and 0.51 (p\u2009=\u2009.002) at 12 mo for all drugs vs only antiresorptive drugs. For trials of an anabolic followed by an antiresorptive, the association between THBMD change and fracture risk reduction was similar to that for the placebo-controlled monotherapy trials. Our analyses indicate robust associations between treatment-induced THBMD changes and fracture risk reduction across various anti-osteoporosis therapies and trial designs, suggesting that treatment-induced changes in THBMD predict anti-fracture efficacy regardless of drug mechanism or trial design.<\/jats:p>","DOI":"10.1093\/jbmr\/zjaf100","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T11:40:30Z","timestamp":1753530030000},"page":"1228-1237","source":"Crossref","is-referenced-by-count":10,"title":["Treatment-related changes in total hip bone mineral density are applicable to trials of varied study designs and to drugs with differing mechanisms of action: meta-regression results from the FNIH-ASBMR SABRE study"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-6076","authenticated-orcid":false,"given":"Tatiane","family":"Vilaca","sequence":"first","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield , Sheffield , S57AU,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yung","family":"Lui","sequence":"additional","affiliation":[{"name":"Research Institute, California Pacific Medical Center , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-2095","authenticated-orcid":false,"given":"Marian","family":"Schini","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield , Sheffield , S57AU,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K","family":"Ewing","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-6184","authenticated-orcid":false,"given":"Austin","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8535-0920","authenticated-orcid":false,"given":"Eric","family":"Vittinghoff","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]},{"name":"Department of Medicine, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco , San Francisco, CA 94158 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-7414","authenticated-orcid":false,"given":"Mary L","family":"Bouxsein","sequence":"additional","affiliation":[{"name":"Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, and Department of Orthopedic Surgery, Harvard Medical School , Boston, MA 02215 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-3366","authenticated-orcid":false,"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, University of Sheffield , Sheffield , S57AU,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"2025103115322093100_ref1","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/S2213-8587(20)30159-5","article-title":"Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials","volume":"8","author":"Black","year":"2020","journal-title":"Lancet Diabetes 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