Computer simulation-based modeling of the pharmaceutical intervention of postmenopausal osteoporosis by denosumab

Postmenopausal osteoporosis (PMO), leading to a higher bone fracture risk, is characterized by a significantly increasing bone porosity. Recently, denosumab, which is able to efficiently interfere with bone resorption, has been approved for the treatment of PMO. In order to optimize the design of drug administration regimes, we propose a computational methodology, based on mechanistic mathematical modeling of bone remodeling, considering the governing biochemical and biomechanical regulation mechanisms, and the targeted action of denosumab. The time-dependent serum concentration of denosumab, obtained from a pharmacokinetics model, is fed into a bone cell population model, allowing for prediction of porosity evolution in PMO patients. In order to account for the mechanobiology of bone remodeling, we utilize the concept of continuum micromechanics, which accurately provides the actual (microscopic) strain state of the investigated bone. Finally, different drug administration regimes are simulated, and their effect on the bone microarchitecture is discussed.