Mechanobiological Behavior of a Pathological Bone

*Imane Ait Oumghar, Abdelwahed Barkaoui and Patrick Chabrand*

### **Abstract**

Bone density and bone microarchitecture are two principle parameters needed for the evaluation of mechanical bone performance and consequently the detection of bone diseases. The mechanobiological behavior of the skeletal tissue has been described through several mathematical models. Generally, these models fingerboard different length scale processes, such as the mechanical, the biological, and the chemical ones. By means of the mechanical stimulus and the biological factors involved in tissue regeneration, bone cells' behavior and bone volume changes are determined. The emergence of bone diseases leads to disrupt the bone remodeling process and thus, induces bone mechanical properties' alteration. In the present chapter, an overview of bone diseases and their relationship with bone density alteration will be presented. Besides, several studies treating bone diseases' effect on bone remodeling will be discussed. Finally, the mechanobiological models proposed to treat bone healing and drugs' effect on bone, are going to be reviewed. For this sake, the chapter is subdivided into three main sequences: (i) Bone remodeling, (ii) Bone deterioration causes, (iii) Mathematical models of a pathological bone, and (iv) Mechanobiological models treating bone healing and drugs effect.

**Keywords:** mechanobiological modeling, bone remodeling, mathematical models, bone diseases, bone healing, drugs

#### **1. Introduction**

An adult body skeleton is renewed once each 10 years as a median frequency. The renewing is the result of a biological process, persisting in the human body, known as bone remodeling. This biological phenomenon has been defined, for the first time, as a dynamic process [1]. It permits to maintain the mechanical bone strength by preserving the most important minerals' homeostasis. It consists of a spatial and temporal coupling of two main phases: (i) old bone resorption and (ii) new bone formation. This process is controlled by a variety of signaling mechanisms that orchestrate bone cells functioning. These cells are: (i) osteoblasts, (ii) osteoclasts, and (iii) osteocytes. Osteoblasts are mononucleated cells that derive from mesenchymal stem cells (MSCs), which originate in the bone marrow. These lasts are responsible of bone formation. Then, osteoclasts are multinucleated cells that derive from hematopoietic stem cells, which are notably produced in the bone marrow. These lasts are the only cells able to degrade bone [2, 3]. Eventually, osteocytes are the cells type that represent the highest amount of bone cells in the

body (90–95%) [4]. They are the result of the last differentiation of the osteogenic lineage and have a mechanosensing feature that allow them to feel the mechanical loading applied on the bone matrix and release various signaling factors that triggers the other bone cells to start their activity. During bone remodeling process, these cells are interacting with each other and various biochemical and mechanical factors are orchestrating their functioning [5]. Bone diseases emerge when the normal process of bone remodeling is interrupted. This result is generally occurring when the balance of the biochemical factors controlling the process is lost. Indeed, there are many types of bone diseases. Yet, some of them are more common than the others. The most prevalent types of bone problems are osteoporosis, Paget's disease of bone, and cancer-associated bone loss. Three cancer types are affecting a large slice of society and induce bone degradation and fracturs: Multiple myeloma, Breast cancer, and Prostate cancer. Several studies have been interested in analyzing these bone diseases' effect and also drugs' effect on bone remodeling process [5–8] to predict the bone behavior after getting affected by the disease and determine to which extent a treatment's type or specific dose are reducing the effect of the disease. In the present chapter we are going to provide a description of bone remodeling and some diseases feature, then to present the different mechanobiological models dealing with bone diseases and drugs' effect on bone remodeling. The chapter is subdivided into three main sequences: (ii) Bone deterioration causes, (ii) Mathematical models of a pathological bone, and (iii) Mechanobiological models treating bone healing and drugs effect.
