Alendronate and risedronate are bisphosphonate drugs that are widely used to lower the risk of bone fractures in postmenopausal women who have osteoporosis. Both these agents—but particularly alendronate—significantly increased bone mineral density (BMD) and lowered markers of bone turnover in the FACT (Fosamax Actonel Comparison Trial), a randomized, double-blind, multicenter study enrolling 1053 women, postmenopausal for at least 6 months, who initially had low values of BMD and were followed up after 12 months of treatment. Once-weekly doses of alendronate and risedronate were 70 and 35 mg, respectively. A one-year extension of the FACT now has been completed in 833 of the original participants. Changes in BMD were assessed at the trochanter, total hip, femoral neck, and lumbar spine.
Similar proportions of women in the two treatment groups took part in the extended study, and their demographic characteristics were similar. BMD increased significantly more at all sites in alendronate-treated women, and the differences increased over time. In addition, significantly more women treated with alendronate maintained or gained BMD at each measurement site, and fewer of them had lower BMD values after 2 years. Both drugs significantly reduced bone resorption as reflected by decreases in urinary N-telopeptide of type 1 human collagen (corrected for creatinine) and serum C-telopeptide. Both drugs lowered serum levels of two markers of bone formation, bone-specific alkaline phosphatase and N-terminal propeptide of type 1 procollagen.
There were no significant group differences in rates of total clinical adverse events, serious events, or withdrawal because of side effects after 2 years of treatment. Levels of upper gastrointestinal side effects such as dyspepsia, nausea, and reflux that prompted withdrawal from the study were similarly frequent in the two treatment groups. One risedronate-treated patient developed a bleeding duodenal ulcer during the extension period and died. Patients in the two groups were at similar risk of clinical fractures.
Clinical Research Center of North Texas, Denton, Texas; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Oregon Osteoporosis Center, Portland, Oregon; University of Maryland School of Medicine, Baltimore, Maryland; Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts; Arthritis Associates, Palm Harbor, Florida; Foundation for Osteoporosis Research and Education, Oakland, California; and Merck & Co., Inc., West Point, Pennsylvania
J Clin Endocrinol Metab 2006;91:2631–2637