Biomedical Engineering Reference
In-Depth Information
blunt the full effect of PTH. Although bisphosphonates and PTH each have their
own specific profile, mechanisms of action, and effects on bone mass, archi-
tecture and tissue properties, both have been shown to effectively reduce ver-
tebral and non-vertebral fractures and improve the health of postmenopausal
women and older men.
1 Introduction
At the most basic level, there are only two ways to alter bone mass and thus reduce
the risk of fractures caused by osteoporosis (Fig.
1
). One way—the anti-catabolic
route—is to prevent the loss of bone that accompanies aging and the reduction in
sex hormones. The other—the anabolic route—is to increase bone mass through
net bone formation.
Bisphosphonates (BPs) are the most common anti-catabolic agents whether
taken daily, weekly, monthly, or yearly—orally or as an intravenous infusion-BPs
significantly decrease fracture incidence at vertebral and non-vertebral sites, as
documented in several clinical trials of postmenopausal osteoporotic women
which have been summarized elsewhere [
1
]. Similar efficacy exists for reducing
fractures in other conditions associated with increased fracture risk such as aged
men, glucocorticoid-induced osteoporosis, Paget's disease, osteogenesis imperfect
and cancer patients. The most widely studied condition where BPs have shown
fracture risk reduction is post-menopausal women where vertebral and non-ver-
tebral fracture risk is almost universally reduced over 1-3 years of treatment—the
duration of most clinical trials. In general BPs reduce fracture risk by *60% in
post-menopausal women at the vertebra, hip, and non-vertebral sites. The success
of the BPs in reducing fracture risk is generally attributed to their suppression of
bone remodeling, which maintains (or minimally increases) bone mass as well as
increasing its mineralization. Together these changes typically result in bone
mineral density (BMD) increasing by 3-12% [
1
,
2
].
The only current anabolic agent approved for the treatment of osteoporosis is
recombinant human parathyroid hormone, PTH(1-34), or teriparatide. Taken once
daily as a subcutaneous injection, teriparatide is generally used for women with
extremely low BMD who need a therapy that can significantly increase bone mass
rather than simply reducing loss. Teriparatide significantly reduces fracture risk at
both vertebral and non-vertebral sites in post-menopausal women [
3
], and is used
to treat other conditions such as hypophosphatasia [
4
]. The success of teriparatide
in reducing fracture risk is attributed to its ability to increase the amount of bone
by stimulating direct apposition of new bone to trabecular surfaces [
5
-
7
] and by
allowing overfilling of resorption spaces at each bone remodeling site [
8
]. This
typically results in BMD increases of 10-15% [
3
,
9
] over 18-24 months of
treatment.
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