SHORT-TERM EFFECT OF ALENDRONATE ON BONE MASS AND BONE REMODELING IN POSTMENOPAUSAL WOMEN

The short-term dose-response relationship between treatment with the bisphosphonate alendronate, biochemical markers of bone turnover, and changes in lumbar spine bone mineral density (BMD) over 9 months was assessed using a double-masked controlled study design in 65 postmenopausal women (mean age 51.6 years, mean 1.5 years since last menses) receiving 5, 20, 40 mg of alendronate or placebo for 6 weeks. After 6 weeks of alendronate, serum calcium phosphate and osteocalcin decreased, and intact parathyroid hormone increased significantly in dose-dependent fashions in the alendronate-treated groups (T) compared with placebo (P). Generally similar changes (decreases) were noted in 24-h urinary calcium and pyridinoline (deoxy- and hydroxylysl pyridoline); by 30 weeks post-treatment no significant changes from baseline or between T and P were noted. Lumbar BMD by dual-energy X-ray absorptiometry demonstrated a dose-dependent response over 9 months (median % change +/- SD: -1.2 +/- 0.9 for 5 mg T, +0.7 +/- 0.8 for 20 mg T*, +1.2 +/- 1.1 for 40 mg T*; *p < 0.01 vs P). Alendronate was generally well tolerated over all dosages. These data demonstrate that short-term (6 weeks) oral alendronate treatment (5-40 mg daily) is well tolerated and effective in (reversibly) decreasing biochemical markers of bone turnover in early postmenopausal women, and in stabilizing spinal BMD over 9 months. Longer-term treatment with larger clinical populations is indicated to define more fully the potential efficacy and safety of chronic alendronate therapy.