Biomedical Engineering Reference
In-Depth Information
Using the mathematical model, an investigation is conducted into the
effects of intermittent PTH application on the site of bone remodeling at three
different stages: the beginning, middle, and end of remodeling. The results
show that, because of the negative effect on bone mass at the beginning of
PTH application, which occurs in all PTH therapies, it is optimum therapy
that PTH be administered at the beginning of the remodeling process in order
to decrease the negative effect and obtain more bone gain. The development
of this conclusion provides a reasonable basis for supporting the design of
optimal dosing strategies for PTH-based anti-osteoporosis treatments.
As indicated in references 2 and 3 and Chapter 1, bone is a highly
specialized support tissue that is characterized by its rigidity and hardness.
It is composed of support cells (osteoblasts and osteocytes), remodeling cells
(osteoclasts), a nonmineral matrix of collagen and noncollagenous proteins
(osteoid), and inorganic mineral salts deposited within the matrix. The
major functions of bone are (a) to provide structural support for the body
and protection of vital organs, (b) to provide an environment for marrow
(both blood forming and fat storage), and (c) to act as a mineral reservoir for
calcium homeostasis in the body.
It is well known that a bone is a living organ that undergoes remodeling
throughout life. Remodeling involves a coordinated action of a number
of cells that work in concert in BMUs. In the remodeling process, bone is
destroyed or resorbed by osteoclasts and then laid down by osteoblasts.
The life span of a single BMU is about 6-9 months, during which several
generations of osteoclasts (average life of about 2 weeks) and osteoblasts
(average life of about 3 months) are formed. Remodeling results from
the action of osteoblasts and osteoclasts, which are the two principal cell
types found in bones, and defects such as microfractures are repaired
by their coupling reaction. Osteoblasts produce the matrix that becomes
mineralized in a well-regulated manner. This mineralized matrix can be
removed by the activity of osteoclasts when activated. In a homeostatic
equilibrium, resorption and formation are balanced so that old bone tis-
sues are continuously replaced by new tissue regulated by a variety of
biochemical and mechanical factors. In 1963 Frost defined this phenom-
enon as bone remodeling [4].
In normal adults there is a balance between the amount of bone resorbed
by osteoclasts and the amount formed by osteoblasts [5]. In this complex pro-
cess, a bone is remodeled by groups of cells derived from different BMUs [6].
The remodeling cycle consists of three consecutive phases [7]: resorption,
reversal, and formation. Resorption begins with the migration of partially
differentiated mononuclear preosteoclasts to the bone surface, where
they form multinucleated osteoclasts. After the completion of osteoclastic
resorption, there is a reversal phase when mononuclear cells appear on the
bone surface. These cells prepare the surface for new osteoblasts to begin
bone formation and provide signals for osteoblast differentiation and
migration. The formation phase follows, with osteoblasts laying down bone
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