Assessment of Strategies for Safe Drug Discontinuation and Transition of Denosumab Treatment in PMO-Insights From a Mechanistic PK/PD Model of Bone Turnover.

ABSTRACT: Denosumab (Dmab) treatment against postmenopausal osteoporosis (PMO) has proven very efficient in increasing bone mineral density (BMD) and reducing the risk of bone fractures. However, concerns have been recently raised regarding safety when drug treatment is discontinued. Mechanistic pharmacokinetic-pharmacodynamic (PK-PD) models are the most sophisticated tools to develop patient specific drug treatments of PMO to restore bone mass. However, only a few PK-PD models have addressed the effect of Dmab drug holidays on changes in BMD. We showed that using a standard bone cell population model (BCPM) of bone remodelling it is not possible to account for the spike in osteoclast numbers observed after Dmab discontinuation. We show that inclusion of a variable osteoclast precursor pool in BCPMs

SUBMITTER: Martinez-Reina J 

PROVIDER: S-EPMC9367195 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature