A Novel HCA Framework for Simulating the Cellular Mechanisms of Bone Remodeling

Abstract

Each year, bone metabolic diseases affect millions of people of all ages, genders, and races. Common diseases such as osteopenia and osteoporosis result from the disruption of the bone remodeling process and can place an individual at a serious fracture risk. Bone remodeling is the complex process by which old bone is replaced with new tissue. This process occurs continuously in the body and is carried out by bone cells that are regulated by numerous metabolic and mechanical factors. The remodeling process provides for various functions such as adaptation to mechanical loading, damage repair, and mineral homeostasis. An improved understanding of this process is necessary to identify patients at risk of bone disease and to assess appropriate treatment protocols. High-fidelity computer models are needed to understand the complex interaction of all parameters involved in bone remodeling. The primary focus of this investigation is to present a new computational framework that utilizes mathematical rules to mechanistically model the cellular mechanisms involved in the bone remodeling process. The computational framework used in this research combines accepted biological principles, cellular-level rules in a cellular automaton framework, and finite-element analysis. This computational model is referred to as hybrid cellular automaton (HCA) model. The simulations obtained with the HCA model allow to predict time-dependent morphology variations at the tissue level as a result of biological changes at the cellular level.