Effect of calcifediol and cholecalciferol on muscle function in postmenopausal women: a randomized controlled trial.

Brief rationale: Limited evidence exists on calcifediol's effect on lower extremity function in postmenopausal women with osteoporosis or osteopenia.

Main result: Calcifediol (20 µg/day) showed no greater benefit than vitamin D3 (3200 IU/day) or placebo. Significance of the paper: Findings do not support high-dose vitamin D3 or calcifediol for improving lower extremity function.

Purpose: To test the effect of 20 µg/day of calcifediol compared with 3200 IU/day of vitamin D3 and placebo on lower extremity function in postmenopausal women with osteopenia or osteoporosis.

Methods: This is a 3-arm double-blind RCT among postmenopausal women aged 50-70 years with serum 25(OH)D < 30 ng/mL, and a DXA-based diagnosis of osteopenia or osteoporosis. Participants were randomized to receive either daily 20 µg calcifediol, daily 3200 IU vitamin D3, or placebo. The primary endpoint was a composite measure of lower extremity function, assessed at baseline, 3, and 6 months, including four tests: gait speed, knee flexor and extensor strength, and repeated sit-to-stand test. The primary endpoint was the probability of success (improvement or maintenance from baseline) in any of the eight tests, four tests at 3 months and four tests at 6 months.

Results: The trial enrolled 152 women (mean age, 61.0 years; mean serum 25(OH)D level, 23.4 ng/mL), and all but one woman completed all follow-up visits. Baseline characteristics, including the four tests of lower extremity function, were balanced across the three groups. The adjusted probability of success in any of the eight tests was 53.6% (95% confidence interval 47%, 60%) with calcifediol, 55.5% (50%, 61%) with vitamin D3, and 61.4% (55%, 67%) with placebo, without significant differences between treatment groups.

Conclusions: Our findings do not support supplementation with daily calcifediol or equivalent high-dose daily vitamin D3 for improving or maintaining lower extremity function among younger postmenopausal women (age 50-70) with osteopenia or osteoporosis, who were pre-selected for vitamin D insufficiency or deficiency (25(OH)D < 30 ng/mL; baseline mean 25(OH)D 23.4 ng/mL).

Trial registration: Clinicaltrials.gov; NCT02527668; https://clinicaltrials.gov/ct2/show/NCT02527668.