The recently released Early Postmenopausal Intervention Cohort (EPIC) study, the largest randomized controlled trial examining the effects of nonestrogen therapy in the prevention of postmenopausal osteoporosis, has found that the bisphosphonate alendronate (Fosamax ÂR ) continues to be safe and effective in preserving bone mass, even after 6 years of treatment.
"Treatment of early postmenopausal women with daily 2.5 and 5 mg alendronate effectively normalized bone resorption and increased and maintained bone density at the lumbar spine, hip femoral neck, hip trochanter, and total hip" over the 6-year study period, the authors wrote in the November issue of the Journal of Clinical Endocrinology and Metabolism.
"Because hormone replacement therapy is no longer recommended long-term, it is helpful to know that alendronate's effectiveness does not diminish over time," study author Michael R. McClung, MD, Founding Director of the Oregon Osteoporosis Center and Assistant Director of the Department of Medical Education at the Providence Portland Medical Center, in Portland, Oregon, told CIAOMed.
Dr. McClung and colleagues undertook the EPIC study in light of emerging evidence that reducing, if not eliminating, the accelerated bone loss and microarchitectural deterioration observed in the first decade after menopause, may control the increasing incidence of osteoporosis in this population.
Moreover, bisphosphonates may also serve as an important alternative to the standard preventive treatment in this population, hormone replacement therapy (HRT), which has been associated with several safety issues and is no longer considered an appropriate long-term preventive agent, particularly in women who do not have postmenopausal vasomotor symptoms.
Therefore, the investigators recruited 1609 healthy women in early menopause who were randomly assigned to receive placebo, 2.5 mg, or 5 mg of alendronate daily for 6 years. They monitored participants' bone mineral density (BMD) at several anatomic locations "lumbar spine, hip, and forearm" and total body at baseline and annually thereafter, as well as bone turnover markers every 6 months from baseline to the 2-year point, and annually thereafter.
Of the 585 women for whom 6-year results were available, those in the placebo arm had "significant progressive decreases" in BMD in all of the measured sites (P < .001). Women who received the 2.5 mg or the 5 mg daily dose of alendronate had significant BMD gains over baseline at the lumbar spine, hip trochanter, and total hip (P < .001). The study also found a decline in forearm BMD in the first 4 years of treatment, but with a leveling off in years 5 and 6.
"This is an important paper," Margery Gass, MD, P rofessor of Obstetrics and Gynecology at the University of Cincinnati College of Medicine, Cincinnati, Ohio, said in an interview with CIAOMed. "We've had alendronate on the market as a preventive therapy, but it has not gotten extensive use in that setting."
The women receiving the higher dose also had increases in BMD at the femoral neck (P .01). The analysis of biochemical markers showed that treated women had statistically significantly lower rates of bone resorption than did women in the placebo group (P < .001). The rate of adverse events was similar among all groups, the authors reported.
The study also found that overall, 61 women sustained a fracture during the study, though none was considered drug-related. "The EPIC study was not designed to evaluate the effect of alendronate on fracture risk," the authors wrote. "However, the documented association between increased BMD and reduced bone turnover, with reduced susceptibility to fractures suggests that, because alendronate effectively maintained bone mass, it will likely confer protection against fractures, as well."
"This paper strengthens the case for the use of alendronate for prevention," said Dr. Gass, who is also D irector of the University Hospital Menopause and Osteoporosis Center in Cincinnati, and Past President of the North American Menopause Society. " For those postmenopausal women at higher risk of osteoporosis, alendronate provides an effective and well-tolerated therapy."
The study was funded by Merck, which manufactures Fosamax.
Reference:
McClung MR, Wasnich RD, Hosking, DJ, et al. Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study. J Clin Endocrinol Metab. 2004;89:4879-4885.