Alendronate with and without cholecalciferol for osteoporosis: Results of a 15-week randomized controlled trial

Robert R. Recker, Paul Lips, Dieter Felsenberg, Kurt Lippuner, Laurent Benhamou, Federico Hawkins, Pierre D. Delmas, Clifford Rosen, Ronald Emkey, Gretel Salzmann, Weili He, Arthur C. Santora

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Abstract

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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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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