Objective: Oral alendronate sodium is a potent, specific inhibitor of osteoclast-mediated bone resorption. To assess its efficacy and safety, a 3-year, randomized, double-blind, multicenter study of 478 postmenopausal women with osteoporosis was conducted.
Patients and methods: Subjects received either placebo, alendronate 5 or 10 mg/day for 3 years, or 20 mg/day for 2 years followed by 5 mg/day for 1 year (20/5 mg). All subjects received 500 mg/day of supplemental calcium. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA).
Results: After 3 years, alendronate 10 mg induced marked increases in BMD of the lumbar spine (9.6 +/- 0.4%), femoral neck (4.7 +/- 0.7%) and trochanter (7.4 +/- 0.6%) (mean +/- SE; each P < or = 0.001) versus decreases of 0.8 to 1.6% with placebo. Progressive increases at these sites in the alendoronate 10 mg group were significant during both the second and third years. Alendronate 10 mg increased total body BMD (1.6 +/- 0.3%, P < or = 0.001), and prevented loss but did not increase BMD at the 1/3 forearm site. Alendronate 20/5 mg was no more effective, whereas alendronate 5 mg was significantly less effective than 10 mg at all sites. Bone turnover decreased to a stable nadir over 3 months for resorption markers (urine deoxypyridinoline) and over 6 months for formation markers (alkaline phosphatase and osteocalcin). Mean loss of stature was reduced by 41% in alendronate treated subjects (P = 0.01).
Conclusion: The safety profile of alendronate was similar to that of placebo. At 10 mg, there were no trends toward increased frequency of any adverse experience except for abdominal pain, which was usually mild, transient, and resolved with continued treatment. Thus, alendronate appears to be an important advance in the treatment of osteoporosis in postmenopausal women.