A General Mechano-Pharmaco-Biological Model for Bone Remodeling Including Cortisol Variation

The process of bone remodeling requires a strict coordination of bone resorption and formation in time and space in order to maintain consistent bone quality and quantity. Bone-resorbing osteoclasts and bone-forming osteoblasts are the two major players in the remodeling process. Their coordination is achieved by generating the appropriate number of osteoblasts since osteoblastic-lineage cells govern the bone mass variation and regulate a corresponding number of osteoclasts. Furthermore, diverse hormones, cytokines and growth factors that strongly link osteoblasts to osteoclasts coordinated these two cell populations. The understanding of this complex remodeling process and predicting its evolution is crucial to manage bone strength under physiologic and pathologic conditions. Several mathematical models have been suggested to clarify this remodeling process, from the earliest purely phenomenological to the latest biomechanical and mechanobiological models. In this current article, a general mathematical model is proposed to fill the gaps identified in former bone remodeling models. The proposed model is the result of combining existing bone remodeling models to present an updated model, which also incorporates several important parameters affecting bone remodeling under various physiologic and pathologic conditions. Furthermore, the proposed model can be extended to include additional parameters in the future. These parameters are divided into four groups according to their origin, whether endogenous or exogenous, and the cell population they affect, whether osteoclasts or osteoblasts. The model also enables easy coupling of biological models to pharmacological and/or mechanical models in the future.