ALENDRONATE TREATMENT OF THE POSTMENOPAUSAL OSTEOPOROTIC WOMAN - EFFECT OF MULTIPLE DOSAGES ON BONE MASS AND BONE REMODELING

BACKGROUND: The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated. PATIENT S AND METHODS: In a multicenter, randomized, double-blind, placebo-con trolled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendr onate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year follo wed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate. RESULTS: At each dose, alendronate prod uced significant reductions in markers of bone resorption and formatio n, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spinel in subjects receiving placebo. In the 10-mg group, mean urinary deoxyp yridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months wi th 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27 % +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P <0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P <0.05). CONCLUSION: Alendronate, a potent inhibitor of bone resorpti on, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at th erapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.