{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:51:17Z","timestamp":1790254277796,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T00:00:00Z","timestamp":1407110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cambridge Bone Group"},{"DOI":"10.13039\/501100004282","name":"The Evelyn Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004282","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cambridge NIHR Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60\u2009mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2325","type":"journal-article","created":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T08:42:47Z","timestamp":1407141767000},"page":"46-54","source":"Crossref","is-referenced-by-count":72,"title":["Denosumab Rapidly Increases Cortical Bone in Key Locations of the Femur: A 3D Bone Mapping Study in Women With Osteoporosis"],"prefix":"10.1093","volume":"30","author":[{"given":"Kenneth ES","family":"Poole","sequence":"first","affiliation":[{"name":"Department of MedicineUniversity of CambridgeCambridgeUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham M","family":"Treece","sequence":"additional","affiliation":[{"name":"Department of EngineeringUniversity of CambridgeCambridgeUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H","family":"Gee","sequence":"additional","affiliation":[{"name":"Department of EngineeringUniversity of CambridgeCambridgeUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques P","family":"Brown","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research CentreLaval UniversityQuebec CityCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"McClung","sequence":"additional","affiliation":[{"name":"Oregon Osteoporosis CenterPortlandORUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wang","sequence":"additional","affiliation":[{"name":"Oregon Osteoporosis CenterPortlandORUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Libanati","sequence":"additional","affiliation":[{"name":"Amgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,4]]},"reference":[{"key":"2024020319205360100_jbmr2325-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."},{"key":"2024020319205360100_jbmr2325-bib-0002","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3109\/17453679708996170","article-title":"Spontaneous hip fractures, 44\/872 in a prospective study","volume":"68","author":"Parker","year":"1997","journal-title":"Acta Orthop Scand."},{"key":"2024020319205360100_jbmr2325-bib-0003","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/jbmr.2033","article-title":"Microstructural failure mechanisms in the human proximal femur for sideways fall loading","volume":"29","author":"Nawathe","year":"2014","journal-title":"J Bone Miner Res."},{"key":"2024020319205360100_jbmr2325-bib-0004","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/jbmr.2024","article-title":"Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab","volume":"29","author":"Keaveny","year":"2014","journal-title":"J Bone Miner Res."},{"key":"2024020319205360100_jbmr2325-bib-0005","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1016\/j.jbiomech.2007.03.015","article-title":"In vitro replication of spontaneous fractures of the proximal human femur","volume":"40","author":"Cristofolini","year":"2007","journal-title":"J Biomech."},{"key":"2024020319205360100_jbmr2325-bib-0006","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1243\/09544119JEIM497","article-title":"Strain distribution in the proximal human femoral metaphysis","volume":"223","author":"Cristofolini","year":"2009","journal-title":"Proc Inst Mech Eng H."},{"key":"2024020319205360100_jbmr2325-bib-0007","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jbiomech.2011.11.048","article-title":"Are spontaneous fractures possible? 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