Biomedical Engineering Reference
In-Depth Information
Parathyroid hormone causes an early and direct apposition of lamellar bone
within the first several weeks following the initiation of treatment [
90
,
91
]. At the
same time, it may increase the trabecular and endocortical bone surfaces activation
frequency for remodeling, causing a transient increase in porosity at sites com-
posed of cortical bone. This can lead to a temporary reduction in BMD at those
sites, which has been observed most notably at the hip [
92
]. Increased remodeling
also occurs in cancellous bone, but new sites of bone resorption on trabeculae
eventually overfill, with bone formation extending beyond the margins of the
erosion cavity [
6
-
8
], leading to a net gain in bone even at those remodeling sites.
These observations led to the concept of an anabolic window in which the early
increase in bone formation and volume, and presumably strength, was not offset by
the initiation of bone resorption as a consequence of increased activation fre-
quency [
93
,
94
]. The anabolic window occurs even with prior exposure to
alendronate or raloxifene [
95
].
Initially, there was concern that the early increase in bone remodeling would
weaken an already osteoporotic skeleton, and that even though this was temporary,
it could lead to an early increase in fracture risk within the first 6 months of
treatment. This, however, has not been observed clinically. No investigator has
reported an increased fracture incidence within the first 1 to 3 months of treatment
even though many women on teriparatide therapy have extremely low bone mass.
And longer-term studies clearly demonstrate anti-fracture efficacy at non-vertebral
sites in postmenopausal women with osteoporosis [
96
]. Moreover, although there
is an initial decline in BMD at the hip within the first 6 months of treatment, BMD
increases at the hip during the 2 year of treatment [
97
]. This suggests that the
increase in porosity is either a transient phenomenon, or that apposition of bone to
trabecular and endocortical surfaces more than compensates for the intracortical
loss after the first year.
Following 18-24 months of treatment with teriparatide, BMD in the spine is
increased by 10-15% [
3
,
9
]. The reduction in risk of fracture with teriparatide
treatment is comparable to that found with bisphosphonate administration. Nine-
teen months of treatment with teriparatide reduced the relative risk of spine
fracture by 65% (absolute risk: 9.3%), and nonvertebral fragility fractures by 53%
(absolute risk: 2.9%), but no significant reduction in hip fractures [
3
], similar to the
findings with PTH (1-84) [
88
].
6 The Effect of Teriparatide on Geometry and Architecture
6.1 Cortical Bone
Teriparatide increases cortical thickness, but whether apposition of bone to the
periosteal surface contributes to this is controversial. rhPTH (1-34) stimulates both
periosteal and endocortical bone formation in animals [
98
-
101
], but this was not
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