Biomedical Engineering Reference
In-Depth Information
a bone can be used to treat not only long bone fractures [6] but also osteoar-
thritic joints [17] and osteoporotic bones [18,19], as well as to reverse femoral
head necrosis and augment spinal fusion [20].
The biological process involved in the osteogenesis of a bone engendered
by PEMF devices is known as cellular bone remodeling. At the cellular level,
bone remodeling is an organized process where osteoclasts remove the old
bone and osteoblasts replace it with newly formed bone. The osteoclasts and
osteoblasts work in a coupled manner within a BMU, which is a mediator
mechanism bridging individual cellular activity to whole bone morphol-
ogy [21] that follows an activation-resorption-formation sequence [22]. As
explained in Section 6.2, the RANK-RANKL-OPG pathway [23] provides a
clearer picture regarding the control of osteoclastogenesis and bone remod-
eling in general. The main switch for osteoclastic bone resorption is the
RANKL [24], a cytokine that is released by preosteoblasts [25].
Bone cell differentiation and proliferation are important factors during
bone remodeling, and clinical PEMF devices have been shown to affect dif-
ferentiation and proliferation of bone cells in vitro [19,26]. Although it has
been proposed that gap junctions, which are specialized intercellular junc-
tions, be considered as mediators of the PEMF-related cellular responses
[26-29], the underlying mechanism at cellular level that regulates bone
remodeling under PEMF remains poorly understood because of the incon-
sistent or even contradictory results from experiments. For example, cell
proliferation, as assayed by cell number and H-thymidine incorporation,
has been reported to increase [30], decrease [14], and remain unaffected [31]
by PEMF exposure. Similarly, the production of alkaline phosphatization
has been reported either to increase [32] or decrease [28] following PEMF
exposure.
In order to remove the limitations to generalization with respect to causes
and effects of bone remodeling under PEMF, mathematical models can
be used to provide a dynamic, quantitative, and systematic description of
the relationships among interacting components of the biological system.
Mathematical modeling has been recognized as a powerful tool for testing
and analyzing various hypotheses in complex systems that are very difficult
(such as time- or money consuming) or just impossible to apply in vivo or in
vitro. However, relatively few mathematical models have yet been proposed
regarding bone remodeling.
As mentioned in Chapter 6, Kroll [33] and Rattanakul et al. [34] each
proposed a mathematical model accounting for the differential activity
of PTH administration on bone accumulation. Komarova et al. [35] pre-
sented a theoretical model of autocrine and paracrine interactions among
osteoblasts and osteoclasts. Komarova [36] also developed a mathematical
model that describes the actions of PTH at a single site of bone remod-
eling, where osteoblasts and osteoclasts are regulated by local autocrine
and paracrine factors. Potter et al. [37] proposed a mathematical model
for PTH receptor (PTH1R) kinetics, focusing on the receptor's response
