Biomedical Engineering Reference
In-Depth Information
6
Effect of Parathyroid Hormone
on Bone Me
tabolism
6.1 Introduction
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 RANK-
RANKL 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 descrip-
tion of bone remodeling using the latest experimental findings and can
explain the mechanism of the bone anabolic action by PTH that is admin-
istered intermittently as well as the catabolic effect when it is applied
continuously.
149
