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ARE ANTIRESORPTIVE AGENTS THE ULTIMATE THERAPY FOR OSTEOPOROSIS?
P.D. Delmas INSERM Research Unit 403 and Claude Bernard University of Lyon,
France
Paper republished with permission of its
authors
Treatments that are commonly used
in postmenopausal osteoporosis, i.e. hormone replacement
therapy (HRT), bisphosphonates, calcitonin, and more recently
selective estrogen receptor modulators (SERMs) act primarily by decreasing
osteoclastic bone resorption through different mechanisms. These agents
decrease the overall rate of bone turnover and increase bone mineral density
(BMD) by 2% to 10% according to the skeletal site and the type of agent.
In addition, some of these agents have been shown either in retrospective
cohort studies or in prospective placebo controlled studies to decrease
the incidence of new vertebral and other osteoporotic fractures by 30% to
50%. With the exception of calcium and low doses of vitamin D that are commonly
used in addition to other agents in the treatment of osteoporosis, combined
therapy has not been extensively studied, in contrast to other common
chronic diseases such as hypertension. The combination of an antiresorptive
agent with a bone forming agent is an exciting prospect for the future
for different reasons. First, if increased bone resorption is a major component
of skeletal fragility in osteoporotic patients, this combination might be
a prerequisite for using bone forming agents as those drugs that induce a
marked increase of osteoblastic bone formation (such as
fluoride and parathyroid hormone) do not decrease bone
resorption. Second, the reduction in fracture incidence
induced by antiresorptive therapy might not be sufficient in
some patients with severe osteoporosis, i.e. with very low BMD. Third, recent
data to be presented in this symposium indicate that HRT and fluoride can
have synergistic effect on BMD by inducing a marked imbalance between resorption
and formation. Although ultimately the utility of combined therapy will
have to be validated in terms of fracture efficacy, it is already possible to
speculate on various sequential or combined regimens using
antiresorptive and bone forming agents in osteoporosis.
P.D. Delmas Osteoporosis International, Sept. 11-15 1998, vol. 8 ,# 3 p.149
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