Alendronate with and without cholecalciferol for osteoporosis: results of a 15‐week randomized controlled trial^*

ABSTRACT

Objective: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) 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 (2800 IU) (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 25OHD 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 25OHD ≥ 9 ng/mL were randomized to ALN + D ( n = 360) or ALN (n = 357).

Main outcome measures: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N‐telopeptide collagen cross-links (NTX).

Results: Serum 25OHD 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 25OHD was 26% higher ( p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 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 25OHD < 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 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.

Trial registration: ClinicalTrials.gov identifier: NCT00092066.

Key words: :

• Alendronate
• Cholecalciferol
• Osteoporosis
• Randomized controlled trial
• Serum 25‐hydroxyvitamin D
• Vitamin D

Notes

* This work was presented in part at the American Society for Bone and Mineral Research Annual Meeting, Nashville, TN, USA, September 23-27, 2005 [ClinicalTrials.gov registry number: 00092066]