A bone remodeling model governed by cellular micromechanics and physiologically based pharmacokinetics

Bahia, M. T.; Hecke, M. B.; Mercuri, E. G. F.; Pinheiro, M. M.

Affiliations

¹Departamento de Mecânica, Instituto Federal de Santa Catarina, Rua Pavão, 1377, Costa e Silva, CEP 89220-618, Joinville, Brazil

²Grupo de Bioengenharia, Programa de Pós-Graduação em Métodos Numéricos em Engenharia, Universidade Federal do Paraná, Curitiba, Brazil

³Departamento de Engenharia Ambiental, Universidade Federal do Paraná, Curitiba, Brazil

⁴Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

Abstract and keywords

This study describes a mathematical model for bone remodeling that integrates the bone cells activities with the pharmacological dynamics for bone-seeking agents. The evolution of bone cells population involves the osteoblast-osteoclast signaling mediated by biochemical factors and receives both mechanical stimulus evaluated at the microscale and pharmacological regulation. A physiologically based pharmacokinetic model (PBPK) for bone-seeking agents was developed to provide the drug concentration on bone sites and feed the remodeling algorithm. The drug effect on bone was reproduced coupling three different strategies: modification of the RANKL expression, increase the osteoclast apoptosis and change in the rate of differentiation of preosteoblasts. Computational simulations were performed in the PBPK model considering different dosing regimens. A 3D finite element model of a proximal femur was generated and the simulation of the bone remodeling algorithm were implemented in Matlab. The results indicate that the proposed integrated model is able to capture adequately the expected adaptive behavior of bone subjected to mechanical and pharmacological stimulus. The model demonstrated to have potential for use as a platform to investigate therapies and may help in the study of new drugs for bone diseases.

Keywords: Bone cell dynamics; Physiologically based pharmacokinetics (PBPK); Continuum michomechanics; Osteoporosis; Mathematical modeling

Links

DOI: 10.1016/j.jmbbm.2020.103657

PubMed: 32174414

WoS: 000525737000003

History

Received: 2019-01-23

Revised: 2020-01-11

Accepted: 2020-01-23

Online: 2020-01-31

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