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Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology\u2010continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics\u2010based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short\u2010term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab\u2010related clinical studies. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cnm.2584","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T06:58:40Z","timestamp":1377845920000},"page":"1-27","source":"Crossref","is-referenced-by-count":51,"title":["Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti\u2010catabolic drug denosumab"],"prefix":"10.1002","volume":"30","author":[{"given":"S.","family":"Scheiner","sequence":"first","affiliation":[{"name":"Institute for Mechanics of Materials and Structures Vienna University of Technology  Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Pivonka","sequence":"additional","affiliation":[{"name":"Australian Institute for Musculoskeletal Science The University of Melbourne  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.\u2009W.","family":"Smith","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Computing and Mathematics The University of Western Australia  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.\u2009R.","family":"Dunstan","sequence":"additional","affiliation":[{"name":"School of Aerospace, Mechanical and Mechatronic Engineering The University of Sydney  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hellmich","sequence":"additional","affiliation":[{"name":"Institute for Mechanics of Materials and Structures Vienna University of Technology  Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2006.03.003"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08827-X"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200207000-00018"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031975"},{"key":"e_1_2_12_6_1","unstructured":"Amgen Inc. 2011. 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