  Until recently many studies of bone remodeling at the cellular level have
focused on the behavior of mature osteoblasts and osteoclasts, and their
respective precursor cells, with the role of osteocytes and bone lining cells
left largely unexplored. This is particularly true with respect to the
mathematical modeling of bone remodeling. However, there is increasing evidence
that osteocytes play important roles in the cycle of targeted bone remodeling,
in serving as a significant source of RANKL to support osteoclastogenesis, and
in secreting the bone formation inhibitor sclerostin. Moreover, there is also
increasing interest in sclerostin, an osteocyte-secreted bone formation
inhibitor, and its role in regulating local response to changes in the bone
microenvironment. Here we develop a cell population model of bone remodeling
that includes the role of osteocytes, sclerostin, and allows for the
possibility of RANKL expression by osteocyte cell populations. This model
extends and complements many of the existing mathematical models for bone
remodeling but can be used to explore aspects of the process of bone remodeling
that were previously beyond the scope of prior modeling work. Through numerical
simulations we demonstrate that our model can be used to theoretically explore
many of the most recent experimental results for bone remodeling, and can be
utilized to assess the effects of novel bone-targeting agents on the bone
remodeling process.

Tissues and Organs;Cell Behavior