Biomedical Engineering Reference
In-Depth Information
• Komarova et al. [18] presented a theoretical model of autocrine and
paracrine interactions among osteoblasts and osteoclasts.
• Komarova [19] also developed a mathematical model describing the
actions of PTH at a single site of bone remodeling, where osteoblasts
and osteoclasts are regulated by local autocrine and paracrine
factors.
• Potter et al. [20] proposed a mathematical model for PTH receptor
(PTH1R) kinetics, focusing on the receptor's response to PTH dosing
to discern bone formation responses from bone resorption.
• Lemaire et al. [21] incorporated detailed biological information and
a RANK-RANKL-OPG pathway into the remodeling cycle; how-
ever, only the catabolic effect of PTH on a bone is included in that
model.
• Pivonka et al. [22] developed an extended bone-cell population
model based on the work of Lemaire et al. [21] to explore the
model structure of cell-cell interactions theoretically and then
investigated the role of the RANK-RANKL-OPG system in bone
remodeling [1].
• Incorporating the latest experimental findings and mathematical
advances, Wang, Qin, and Kalyanasundaram [2] developed a
mathematical model of bone cell population dynamics that could
simulate the anabolic behavior of bone affected by intermittent
administration of PTH, and that model was further detailed in [2].
It is expected that the model concerning systemic and local regulation of
bone remodeling will lead to new approaches in the diagnosis and treatment
of skeletal disorders. In particular, this model will help to develop new thera-
peutic approaches at the molecular and cellular level based on the definition
of abnormalities of the osteoblastic and osteoclastic lineage that lead to bone
diseases such as osteoporosis. Emphasis in this chapter, however, is given to
the developments in references 2 and 21.
6.2 Structure of the Model and Assumption
The overall integrity of bone appears to be controlled by hormones and
many other proteins secreted by both hemopoietic bone marrow cells
and bone cells. There is both systemic and local regulation of bone cell
function. As stated in Chapter 1, PTH is the most important regulator of
calcium homeostasis, which can stimulate bone formation when given
intermittently and bone resorption when delivered continuously [23].
Moreover, PTH is currently involved in numerous clinical trials as an
