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A bone remodeling model governed by cellular micromechanics and physiologically based pharmacokinetics
M T Bahia1, M B Hecke2, E G F Mercuri3
1Departamento de Mecânica, Instituto Federal de Santa Catarina, Rua Pavão, 1377, Costa e Silva, CEP 89220-618, Joinville, Brazil; Grupo de Bioengenharia, Programa de Pós-Graduação em Métodos Numéricos em Engenharia, Universidade Federal do Paraná, Curitiba, Brazil.
Journal of the Mechanical Behavior of Biomedical Materials
|March 17, 2020
Summary
This study presents a mathematical model integrating bone cell activity, mechanical forces, and drug effects to simulate bone remodeling. The model accurately predicts bone adaptation to stimuli, aiding in the development of new bone disease therapies.
Area of Science:
- Biomedical Engineering
- Computational Biology
- Pharmacology
Background:
- Bone remodeling is a complex process influenced by cellular signaling, mechanical loads, and pharmacological agents.
- Understanding these interactions is crucial for developing effective treatments for bone diseases.
Purpose of the Study:
- To develop and validate an integrated mathematical model for bone remodeling.
- To incorporate bone cell dynamics, microscale mechanical stimuli, and drug pharmacokinetics.
- To simulate the effects of bone-seeking agents on bone remodeling.
Main Methods:
- Developed a physiologically based pharmacokinetic (PBPK) model for bone-seeking agents.
- Integrated PBPK model with a bone remodeling algorithm.
- Simulated drug effects by modifying RANKL expression, osteoclast apoptosis, and preosteoblast differentiation.
- Utilized a 3D finite element model of a proximal femur for simulations in Matlab.
Main Results:
- The integrated model successfully captured bone's adaptive response to mechanical and pharmacological stimuli.
- Simulations demonstrated the model's ability to predict bone remodeling under various conditions.
- The PBPK model provided accurate drug concentration data at bone sites.
Conclusions:
- The proposed integrated model offers a robust platform for investigating bone remodeling.
- This computational approach can aid in the preclinical study of novel drugs for bone diseases.
- The model has potential for optimizing therapeutic strategies and drug development.
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