{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:09:09Z","timestamp":1790748549413,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2857,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Amgen Inc. Mandy Suggitt of Amgen Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Hip fractures account for over one-half the morbidity, mortality, and cost associated with osteoporosis. Fragility of the proximal femur is the result of rapid and unbalanced bone remodeling events that excavate more bone than they deposit, producing a porous, thinned, and fragile cortex. We hypothesized that the slowing of remodeling during treatment with denosumab allows refilling of the many cavities excavated before treatment now opposed by excavation of fewer new resorption cavities. The resulting net effect is a reduction in cortical porosity and an increase in proximal femur strength. Images were acquired at baseline and 36 months using multidetector CT in 28 women receiving denosumab and 22 women receiving placebo in a substudy of FREEDOM, a randomized, double-blind, placebo-controlled trial involving women with postmenopausal osteoporosis. Porosity was quantified using StrAx1.0 software. Strength was estimated using finite element analysis. At baseline, the higher the serum resorption marker, CTx, the greater the porosity of the total cortex (r\u2009=\u20090.34, p\u2009=\u20090.02), and the higher the porosity, the lower the hip strength (r\u2009=\u2009\u20130.31, p\u2009=\u20090.03). By 36 months, denosumab treatment reduced porosity of the total cortex by 3.6% relative to baseline. Reductions in porosity relative to placebo at 36 months were 5.3% in total cortex, 7.9% in compact-appearing cortex, 5.6% in outer transitional zone, and 1.8% in inner transitional zone (all p\u2009&amp;lt;\u20090.01). The improvement in estimated hip integral strength of 7.9% from baseline (p\u2009&amp;lt;\u20090.0001) was associated with the reduction in total porosity (r\u2009=\u2009\u20130.41, p\u2009=\u20090.03). In summary, denosumab reduced cortical porosity of the proximal femoral shaft, resulting in increased mineralized matrix volume and improved strength, changes that may contribute to the reduction in hip and nonvertebral fractures reported with denosumab therapy. \u00a9 2016 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>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2855","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T21:46:56Z","timestamp":1460756816000},"page":"1827-1834","source":"Crossref","is-referenced-by-count":79,"title":["Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis"],"prefix":"10.1093","volume":"31","author":[{"given":"Roger","family":"Zebaze","sequence":"first","affiliation":[{"name":"Austin HealthUniversity of MelbourneMelbourneAustralia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Libanati","sequence":"additional","affiliation":[{"name":"Amgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"McClung","sequence":"additional","affiliation":[{"name":"Oregon Osteoporosis CenterPortlandORUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R","family":"Zanchetta","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Metab\u00f3licasBuenos AiresArgentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Kendler","sequence":"additional","affiliation":[{"name":"University of British ColumbiaVancouverBCCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"H\u00f8iseth","sequence":"additional","affiliation":[{"name":"Curato R\u00f8ntgenOsloNorway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wang","sequence":"additional","affiliation":[{"name":"Amgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ghasem-Zadeh","sequence":"additional","affiliation":[{"name":"Austin HealthUniversity of MelbourneMelbourneAustralia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ego","family":"Seeman","sequence":"additional","affiliation":[{"name":"Austin HealthUniversity of MelbourneMelbourneAustralia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"issue":"3","key":"2024021014184797700_jbmr2855-bib-0001","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1359\/jbmr.061113","article-title":"Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025","volume":"22","author":"Burge","year":"2007","journal-title":"J Bone Miner Res"},{"issue":"12","key":"2024021014184797700_jbmr2855-bib-0002","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1007\/s00198-006-0172-4","article-title":"An estimate of the worldwide prevalence and disability associated with osteoporotic fractures","volume":"17","author":"Johnell","year":"2006","journal-title":"Osteoporos Int"},{"key":"2024021014184797700_jbmr2855-bib-0003","year":"2004"},{"issue":"21","key":"2024021014184797700_jbmr2855-bib-0004","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1056\/NEJMra053077","article-title":"Bone quality\u2014the material and structural basis of bone strength and fragility","volume":"354","author":"Seeman","year":"2006","journal-title":"N Engl J Med"},{"issue":"6","key":"2024021014184797700_jbmr2855-bib-0005","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1177\/028418519003100619","article-title":"Femoral cortical\/cancellous bone related to age","volume":"31","author":"H\u00f8iseth","year":"1990","journal-title":"Acta Radiol"},{"issue":"2","key":"2024021014184797700_jbmr2855-bib-0006","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1172\/JCI110039","article-title":"Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis","volume":"67","author":"Riggs","year":"1981","journal-title":"J Clin Invest"},{"issue":"9727","key":"2024021014184797700_jbmr2855-bib-0007","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/S0140-6736(10)60320-0","article-title":"Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study","volume":"375","author":"Zebaze","year":"2010","journal-title":"Lancet"},{"issue":"1","key":"2024021014184797700_jbmr2855-bib-0008","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0021-9290(88)90186-8","article-title":"Stiffness of compact bone: effects of porosity and density","volume":"21","author":"Schaffler","year":"1988","journal-title":"J Biomech"},{"issue":"Suppl 4","key":"2024021014184797700_jbmr2855-bib-0009","first-page":"iv2","article-title":"Structural basis of growth-related gain and age-related loss of bone strength","volume":"47","author":"Seeman","year":"2008","journal-title":"Rheumatology (Oxford)"},{"issue":"8","key":"2024021014184797700_jbmr2855-bib-0010","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":"2","key":"2024021014184797700_jbmr2855-bib-0011","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1359\/jbmr.081112","article-title":"Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine\/human) RANKL","volume":"24","author":"Kostenuik","year":"2009","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024021014184797700_jbmr2855-bib-0012","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrd3705","article-title":"Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab","volume":"11","author":"Lacey","year":"2012","journal-title":"Nat Rev Drug Discov"},{"issue":"2","key":"2024021014184797700_jbmr2855-bib-0013","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bone.2011.03.769","article-title":"Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody","volume":"49","author":"Kostenuik","year":"2011","journal-title":"Bone"},{"key":"2024021014184797700_jbmr2855-bib-0014","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bone.2013.11.016","article-title":"Differing effects of denosumab and alendronate on cortical and trabecular bone","volume":"59","author":"Zebaze","year":"2014","journal-title":"Bone"},{"issue":"2","key":"2024021014184797700_jbmr2855-bib-0015","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bone.2013.07.011","article-title":"Improvements in hip trabecular, subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab","volume":"56","author":"Genant","year":"2013","journal-title":"Bone"},{"issue":"12","key":"2024021014184797700_jbmr2855-bib-0016","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1359\/jbmr.080805","article-title":"Femoral bone strength and its relation to cortical and trabecular changes after treatment with PTH, alendronate, and their combination as assessed by finite element analysis of quantitative CT scans","volume":"23","author":"Keaveny","year":"2008","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024021014184797700_jbmr2855-bib-0017","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1359\/jbmr.091033","article-title":"Age-dependence of femoral strength in white women and men","volume":"25","author":"Keaveny","year":"2010","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2024021014184797700_jbmr2855-bib-0018","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/jbmr.2325","article-title":"Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis","volume":"30","author":"Poole","year":"2015","journal-title":"J Bone Miner Res"},{"key":"2024021014184797700_jbmr2855-bib-0019","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/bonekey.2013.120","article-title":"Finite element analysis for prediction of bone strength","volume":"2","author":"Zysset","year":"2013","journal-title":"Bonekey Rep"},{"issue":"2","key":"2024021014184797700_jbmr2855-bib-0020","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jocd.2012.02.014","article-title":"Denosumab densitometric changes assessed by quantitative computed tomography at the spine and hip in postmenopausal women with osteoporosis","volume":"16","author":"McClung","year":"2013","journal-title":"J Clin Densitom"},{"issue":"1","key":"2024021014184797700_jbmr2855-bib-0021","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bone.2013.01.007","article-title":"A new method of segmentation of compact-appearing, transitional and trabecular compartments and quantification of cortical porosity from high resolution peripheral quantitative computed tomographic images","volume":"54","author":"Zebaze","year":"2013","journal-title":"Bone"},{"issue":"8","key":"2024021014184797700_jbmr2855-bib-0022","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00198-015-3118-x","article-title":"Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures","volume":"26","author":"Ahmed","year":"2015","journal-title":"Osteoporos Int"},{"key":"2024021014184797700_jbmr2855-bib-0023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2015.06.016","article-title":"Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures","volume":"81","author":"Shigdel","year":"2015","journal-title":"Bone"},{"issue":"1","key":"2024021014184797700_jbmr2855-bib-0024","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"},{"issue":"1","key":"2024021014184797700_jbmr2855-bib-0025","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.bone.2013.08.018","article-title":"Anti-resorptive agents reduce the size of resorption cavities: a three-dimensional dynamic bone histomorphometry study","volume":"57","author":"Matheny","year":"2013","journal-title":"Bone"},{"issue":"983","key":"2024021014184797700_jbmr2855-bib-0026","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/206489a0","article-title":"Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling","volume":"206","author":"Hattner","year":"1965","journal-title":"Nature"},{"key":"2024021014184797700_jbmr2855-bib-0027","first-page":"315\u2013","author":"Parfitt","year":"1996"},{"key":"2024021014184797700_jbmr2855-bib-0028","first-page":"179\u2013","author":"Baron","year":"1977"},{"key":"2024021014184797700_jbmr2855-bib-0029","first-page":"49\u2013","author":"Frost","year":"1985"},{"issue":"6","key":"2024021014184797700_jbmr2855-bib-0030","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1359\/jbmr.2003.18.6.1012","article-title":"Aging of microstructural compartments in human compact bone","volume":"18","author":"Akkus","year":"2003","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2024021014184797700_jbmr2855-bib-0031","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bone.2011.04.001","article-title":"Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys","volume":"49","author":"Ominsky","year":"2011","journal-title":"Bone"},{"issue":"12","key":"2024021014184797700_jbmr2855-bib-0032","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1002\/jbmr.157","article-title":"A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover","volume":"25","author":"Burghardt","year":"2010","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024021014184797700_jbmr2855-bib-0033","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.bone.2007.01.012","article-title":"The bone mineralization density distribution as a fingerprint of the mineralization process","volume":"40","author":"Ruffoni","year":"2007","journal-title":"Bone"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2855","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbmr.2855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbmr.2855","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/10\/1827\/56651851\/jbmr2855.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/10\/1827\/56651851\/jbmr2855.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:56:16Z","timestamp":1710341776000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/31\/10\/1827-1834\/7605504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,15]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,4,15]]},"published-print":{"date-parts":[[2016,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2855","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,10,1]]},"published":{"date-parts":[[2016,4,15]]}}}