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