Objective: Many osteoporosis patients have low 25-hydroxyvitamin D (250HD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 μg (2800IU) (ALN + D) versus alendronate 70 mg alone (ALN). Methods: This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 250HD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 250HD ≥ 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357). Main outcome measures: Serum 250HD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-tetopeptide collagen cross-links (NTX). Results: Serum 250HD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 250HD was 26% higher (p <0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 250HD <15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p <0.001]), and the RR of 250HD <9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p <0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). Conclusion: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 250HD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.
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