Biomedical Engineering Reference
In-Depth Information
Fig. 6 Hypothetical effect of
changing trabecular bone in
response to teriparatide
treatment. Based on
mathematical modeling of
Silva et al. [ 109 ] which
determined the mechanical
consequences of reducing
BV/TV by either decreasing
trabecular thickness or
number, the increase in
mechanical properties
achieved by teriparatide are
optimized by increasing the
trabecular number as opposed
to altering thickness
smaller improvements in bone volume fraction simply by altering the curvature of
the trabecular surfaces [ 110 ], a beneficial effect that would be most pronounced
when the bone volume fraction is low.
7 Effects of Teriparatide on Bone Matrix Properties
Teriparatide has a significant and rapid effect on increasing bone mass, but by
increasing remodeling rate, it also renews aging tissue. Treatment with teriparatide
results in the replacement of older, more highly mineralized bone with younger,
less mineralized tissue, resulting in greater tissue heterogeneity [ 111 - 113 ]. This
also results in a lower mineralization density, with less highly crystalline
hydroxyapatite. Moreover, it results in a higher ratio of divalent to trivalent cross-
links in collagen, the direct result of a higher turnover rate. In cynomolgus
monkeys treated with two different doses of rhPTH (1-34), the changes in tissue
properties were fully reversible at the lower dose, but were sustained for at least
two remodeling periods after withdrawal in the animals given the higher dose
[ 114 ]. This is consistent with the effects being closely tied to remodeling rate. The
stimulation of remodeling by PTH not only alters tissue properties, but also
removes excess microdamage [ 115 ], and would create additional interfaces that
arrest the growth of new microcracks. The mechanical effect of each of these
changes individually is not clear, but in combination the result is a toughening
effect, making the tissue more compliant and allowing the bone to absorb more
energy prior to fracture [ 102 , 116 ].
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