ABSTRACT
In Chapters 3 and 4 we discussed internal and surface bone remodeling affected by temperature change and mechanical and electrical loading based on the concept of bone density. Bone remodeling processes induced by PTH, mechanical loading, and PEMF at the cellular level-based on the concept of the RANK-RANKL-OPG pathway-are described in this and the subsequent two chapters. The RANK-RANKL-OPG pathway involves three major components [1]:
1. The receptor activator of nuclear factor kappa B (NF-κB) (RANK) expressed on the surface of hemopoietic precursor cells (also referred to as osteoclast precursor cells)
2. RANKL, a polypeptide found on the surface of osteoblastic cells and proteolytically released in soluble form
3. OPG, a “decoy receptor” molecule released by osteoblastic cells
Differentiation and activation of osteoclast precursor cells into mature (active) osteoclasts requires binding of RANKL to RANK. The RANKRANKL interaction is inhibited by OPG, which binds to RANKL. We begin in this chapter with the introduction of a mathematical model for simulating the anabolic behavior of bone affected by PTH. The model incorporates a new understanding of the interaction of PTH and other factors with the RANK-RANKL-OPG pathway into bone remodeling, which is able to simulate anabolic actions of bone induced by PTH at the cellular level. The mathematical model described here provides a detailed biological description of bone remodeling using the latest experimental findings and can explain the mechanism of the bone anabolic action by PTH that is administered intermittently as well as the catabolic effect when it is applied continuously.
