{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:36:59Z","timestamp":1793399819403,"version":"4.5.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Denosumab is a potent antiresorptive agent that reduces fractures in postmenopausal women with osteoporosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Determine effects of up to 10 years of denosumab on bone histology, remodeling, and matrix mineralization characteristics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Setting<\/jats:title>\n                  <jats:p>International, multicenter, randomized, double-blind trial [Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM)] with a long-term open-label extension.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Postmenopausal women with osteoporosis (92 women in FREEDOM, 46 in extension) who provided iliac bone biopsies, including 11 who provided biopsies at multiple time points.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>FREEDOM subjects were randomized 1:1 to subcutaneous denosumab 60 mg or placebo every 6 months for 3 years. Long-term extension subjects continued receiving denosumab, open-label, for 7 additional years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>Bone histology, histomorphometry, matrix mineralization.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ten-year denosumab biopsies showed normal histology. Bone histomorphometry indicated normal bone structure and reduced bone remodeling after 10 years of denosumab, similar to levels after 2 and\/or 3 and 5 years of denosumab. The degree of mineralization of bone was increased and mineralization heterogeneity was reduced in the denosumab years 2\/3 group vs placebo. Changes in these mineralization variables progressed from years 2\/3 to year 5 of denosumab, but not thereafter.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Denosumab for 2\/3, 5, and 10 years was associated with normal histology, low bone remodeling rate, increased matrix mineralization, and lower mineralization heterogeneity compared with placebo. These variables were unchanged from year 5 to year 10. These data, in combination with the maintenance of low fracture rates for up to 10 years as previously reported with denosumab therapy, suggest that strong, prolonged remodeling inhibition does not impair bone strength.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2017-02669","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T18:04:10Z","timestamp":1523901850000},"page":"2498-2509","source":"Crossref","is-referenced-by-count":92,"title":["Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis"],"prefix":"10.1210","volume":"103","author":[{"given":"David W","family":"Dempster","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, New York"},{"name":"Helen Hayes Hospital, West Haverstraw, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques 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