Effects of long-term treatment of denosumab on bone mineral density: insights from an in-silico model of bone mineralization

Abstract

Denosumab is one of the most commonly prescribed anti-resorptive drugs for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab is to inhibit osteoclast differentiation and consequently bone resorption. Gains in bone mineral density (BMD) are achieved based on the ability of the bone matrix to undergo secondary mineralization. Experimental data show that the increase of BMD after commencing denosumab treatment are bone site specific. In this paper, we developed a comprehensive mechanistic pharmacokinetic-pharmacodymamic (PK-PD) model of the effect of denosumab on bone remodeling in postmenopausal osteoporosis (PMO). The PD model is based on a bone cell population..