Computational model of the dual action of PTH — Application to a rat model of osteoporosis

Abstract

This paper presents a pharmacokinetic/pharmacodynamic (PK/PD)model of the action of PTH(1-34)on bone modelling and remodelling, developed for quantitatively investigating the dose- and administration pattern-dependency of the bone tissue response to this drug. Firstly, a PK model of PTH(1-34)was developed, accounting for administration via subcutaneous injections. Subsequently, the PK model was coupled to a (mechanistic)bone cell population model of bone modelling and remodelling, taking into account the effects of PTH(1-34)on the differentiation of lining cells into active osteoblasts, on the apoptosis of active osteoblasts, and on proliferation of osteoblast precursors, as well as on the k..