Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial.

Randomized, double-blind, placebo-controlled trial in postmenopausal women up to 75 years old with vitamin D insufficiency and no osteoporosis. Participants were recruited at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013.

Oral cholecalciferol was tested in two active regimens: a low-dose group received 800 IU/day, and a high-dose group received a 50,000 IU/day loading dose for 15 days followed by 50,000 IU every 15th day for 11.5 months. Both active regimens were compared with placebo capsules.

High-dose cholecalciferol modestly increased total fractional calcium absorption, but it did not produce meaningful improvements in bone mineral density, muscle function or mass, or falls. One-year TFCA change was +0.6% with high-dose versus -4.5% with low-dose and +0.9% with placebo (P = .009 vs low-dose; P = .46 vs placebo); adjusted TFCA change was +1% versus -2% and +1.3% (P = .005 vs low-dose; P = .03 vs placebo). Lumbar spine BMD, total-body BMD, femoral neck BMD, Timed Up and Go, Five Sit-to-Stand, health status, physical activity, and falls were not meaningfully different across groups. The findings do not support maintaining serum 25(OH)D at 30 ng/mL or greater in this population and are consistent with using 20 ng/mL or greater as adequate for repletion.

The trial was conducted at a single center in a relatively specific population of postmenopausal women with vitamin D insufficiency and no osteoporosis, which limits generalizability. The follow-up was 1 year and the study was likely underpowered to detect smaller differences in clinical outcomes such as falls. Participants were predominantly White, further limiting applicability to more diverse populations.