{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:51:09Z","timestamp":1790254269779,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T00:00:00Z","timestamp":1423785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Denosumab (DMAb) administration to postmenopausal women with osteoporosis is associated with continued bone mineral density (BMD) increases and low fracture incidence through 8 years, despite persistently reduced bone turnover markers and limited fluorochrome labeling in iliac crest bone biopsies. BMD increases were hypothesized to result from additional accrual of bone matrix via modeling-based bone formation\u2014a hypothesis that was tested by examining fluorochrome labeling patterns in sections from ovariectomized (OVX) cynomolgus monkeys (cynos) treated with DMAb for 16 months. Mature OVX or Sham cynos were treated monthly with vehicle for 16 months, whereas other OVX cynos received monthly 25 or 50\u2009mg\/kg DMAb. DMAb groups exhibited very low serum bone resorption and formation biomarkers and near-absent fluorochrome labeling in proximal femur cancellous bone. Despite these reductions, femoral neck dual-energy X-ray absorptiometry (DXA) BMD continued to rise in DMAb-treated cynos, from a 4.6% increase at month 6 to 9.8% above baseline at month 16. Further examination of cortical bone in the proximal femur demonstrated consistent and prominent labeling on the superior endocortex and the inferior periosteal surface, typically containing multiple superimposed labels from month 6 to 16 over smooth cement lines, consistent with continuous modeling-based bone formation. These findings were evident in all groups. Quantitative analysis at another modeling site, the ninth rib, demonstrated that DMAb did not alter the surface extent of modeling-based labels, or the cortical area bound by them, relative to OVX controls, while significantly reducing remodeling-based bone formation and eroded surface. This conservation of modeling-based formation occurred concomitantly with increased femoral neck strength and, when coupled with a reduction in remodeling-based bone loss, is likely to contribute to increases in bone mass with DMAb treatment. Thus, this study provides preclinical evidence for a potential mechanism that could contribute to the clinical observations of continued BMD increases and low fracture rates with long-term DMAb administration. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2480","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T13:38:20Z","timestamp":1423834700000},"page":"1280-1289","source":"Crossref","is-referenced-by-count":115,"title":["Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab"],"prefix":"10.1093","volume":"30","author":[{"given":"Michael S","family":"Ominsky","sequence":"first","affiliation":[{"name":"Metabolic DisordersAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Libanati","sequence":"additional","affiliation":[{"name":"Clinical DevelopmentAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Tian","family":"Niu","sequence":"additional","affiliation":[{"name":"Metabolic DisordersAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogely W","family":"Boyce","sequence":"additional","affiliation":[{"name":"Comparative Biology & Safety SciencesAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Kostenuik","sequence":"additional","affiliation":[{"name":"Metabolic DisordersAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel B","family":"Wagman","sequence":"additional","affiliation":[{"name":"Clinical DevelopmentAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Oral MedicineInfection and ImmunityHarvard School of Dental MedicineBostonMAUSA"},{"name":"Harvard Medical SchoolEndocrine UnitMassachusetts General HospitalBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Dempster","sequence":"additional","affiliation":[{"name":"Regional Bone CenterHelen Hayes HospitalNew York State Department of HealthWest HaverstrawNYUSA"},{"name":"Clinical Pathology and Cell BiologyCollege of Physicians and Surgeons of Columbia UniversityNew York, NYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,13]]},"reference":[{"key":"2024020319051340200_jbmr2480-bib-0001","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N Engl J Med."},{"issue":"Suppl 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