Effect of Alendronate and Vitamin D3 on Fractional Calcium Absorption in a Double-Blind, Randomized, Placebo-Controlled Trial in Postmenopausal Osteoporotic Women

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D-3 (ALN+D) would increase fractional calcium absorption (FCA). In this randomized, double-blind, placebo-controlled multicenter clinical trial, 56 postmenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70mg plus vitamin D-3 2800 IU (ALN+D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual-tracer stable-calcium isotope method. FCA and 25(OH) D were similar between treatment groups at baseline (0.31 +/- 0.12 ng/mL and 19.8 +/- 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN+D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [-0.016 (-0.044, 0.012)]. After ALN+D treatment, patients had higher 25(OH) D levels (LS mean difference 7.3 ng/mL, p<.001). The rise in serum 1,25-dihydroxyvitamin D-3 (p<.02) and parathyroid hormone (p<.001) were greater in the ALN+D group than in placebo-treated patients. ALN+D was associated with an increase in FCA of 0.07. To our knowledge, there is no other trial showing such a marked rise in calcium absorption owing to treatment with a bisphosphonate or owing to a small rise in 25(OH) D. This unique response of ALN+D is important for the treatment of osteoporosis, but the exact mechanism requires further study. (C) 2011 American Society for Bone and Mineral Research.