Effect of alendronate and vitamin D 3 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 70 mg 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. © 2011 American Society for Bone and Mineral Research