Bone Adaptation

Ph.D. student: Charles Penninger

Each year, bone metabolic diseases affect millions of people of all ages, genders, and races. The bone remodeling process is responsible for maintaining and adapting our bones from daily loading. Osteoclasts and osteoblasts are specialized cells that perform remodeling by resorbing old bone and forming new bone, respectively. These cells are regulated by metabolic factors and mechanical stimuli, such as strain and microdamage. Imbalances in the remodeling process can cause common bone metabolic diseases such as osteopenia and osteoporosis. Researchers have used computational models simulate remodeling activity in response to changes in the bone’s mechanical environment. Developing accurate models provides a valuable tool for predicting (ab)normal remodeling behavior. The objective of this investigation is to incorporate cellular mechanisms of bone remodeling into a computational framework known as the hybrid cellular automaton (HCA) algorithm. The goal of bone remodeling simulations is not to try to develop rules for which bone architecture might be the answer to, but to simulate the metabolic processes, which possess the key information. Currently, only a few mathematical models have been formulated to characterize the remolding process in terms of the cellular mechanisms that are present. These mechanistic models of bone remodeling are needed to contribute to the understanding of the underlying biological activities involved. To pursue such a model, for representing both the resorptive and formative behavior during remodeling, one must first incorporate the most pertinent local regulatory factors, which mediate the recruitment, differentiation, and activation of osteoclasts and osteoblasts, respectively. The mathematical model formulated in this work is based on histomorphometric data and cellular activity that have been observed to occur in the bone microenvironment as cited in the literature.