Mathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab

S. Scheiner, P. Pivonka, David Smith, C.R. Dunstan, C.H. Hellmich

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    36 Citations (Scopus)


    Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. 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-continuum 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-based 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-term 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-related clinical studies. © 2013 John Wiley & Sons, Ltd.
    Original languageEnglish
    Pages (from-to)1-27
    Number of pages27
    JournalInternational Journal for Numerical Methods in Biomedical Engineering
    Issue number1
    Early online date30 Aug 2013
    Publication statusPublished - Jan 2014


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