{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:58:19Z","timestamp":1792022299370,"version":"4.4.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":1692,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012317","name":"Astellas Pharma Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sclerostin, a protein produced by osteocytes, inhibits bone formation. Administration of sclerostin antibody results in increased bone formation in multiple animal models. Romosozumab, a humanized sclerostin antibody, has a dual effect on bone, transiently increasing serum biochemical markers of bone formation and decreasing serum markers of bone resorption, leading to increased BMD and reduction in fracture risk in humans. We aimed to evaluate the effects of romosozumab on bone tissue. In a subset of 107 postmenopausal women with osteoporosis in the multicenter, international, randomized, double-blind, placebo-controlled Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), transiliac bone biopsies were performed either after 2 (n\u2009=\u200934) or 12 (n\u2009=\u200973) months of treatment with 210 mg once monthly of romosozumab or placebo to evaluate histomorphometry and microcomputed tomography-based microarchitectural endpoints. After 2 months, compared with either baseline values assessed after a quadruple fluorochrome labeling or placebo, significant increases (P &amp;lt;\u20090.05 to P &amp;lt;\u20090.001) in dynamic parameters of formation (median MS\/BS: romosozumab 1.51% and 5.64%; placebo 1.60% and 2.31% at baseline and month 2, respectively) were associated with a significant decrease compared with placebo in parameters of resorption in cancellous (median ES\/BS: placebo 3.4%, romosozumab 1.8%; P =\u20090.022) and endocortical (median ES\/BS: placebo 6.3%, romosozumab 1.6%; P =\u20090.003) bone. At 12 months, cancellous bone formation was significantly lower (P &amp;lt;\u20090.05 to P &amp;lt;\u20090.001) in romosozumab versus placebo and the lower values for resorption endpoints seen at month 2 persisted (P &amp;lt;\u20090.001), signaling a decrease in bone turnover (P =\u20090.006). No significant change was observed in periosteal and endocortical bone. This resulted in an increase in bone mass and trabecular thickness with improved trabecular connectivity, without significant modification of cortical porosity at month 12. In conclusion, romosozumab produced an early and transient increase in bone formation, but a persistent decrease in bone resorption. Antiresorptive action eventually resulted in decreased bone turnover. This effect resulted in significant increases in bone mass and improved microarchitecture.\u00a9 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.3735","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T11:43:43Z","timestamp":1561463023000},"page":"1597-1608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":174,"title":["Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women With Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-7361","authenticated-orcid":false,"given":"Pascale","family":"Chavassieux","sequence":"first","affiliation":[{"name":"INSERM UMR 1033 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8214-6385","authenticated-orcid":false,"given":"Roland","family":"Chapurlat","sequence":"additional","affiliation":[{"name":"INSERM UMR 1033 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Portero-Muzy","sequence":"additional","affiliation":[{"name":"INSERM UMR 1033 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Roux","sequence":"additional","affiliation":[{"name":"INSERM UMR 1033 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Garcia","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Osteoporosis Center University Hospital of Monterrey Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques P","family":"Brown","sequence":"additional","affiliation":[{"name":"CHU de Quebec Research Centre and Department of Medicine Laval University Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-7839","authenticated-orcid":false,"given":"Cesar","family":"Libanati","sequence":"additional","affiliation":[{"name":"UCB Pharma Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogely W","family":"Boyce","sequence":"additional","affiliation":[{"name":"Amgen Inc Thousand Oaks CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wang","sequence":"additional","affiliation":[{"name":"Amgen Inc Thousand Oaks CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Grauer","sequence":"additional","affiliation":[{"name":"Amgen Inc Thousand Oaks CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"2024021014434131700_jbmr3735-bib-0001","first-page":"785","article-title":"NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy. 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