No Bone Benefits With High-Dose Vitamin D in Older Women – MedPage Today
SEATTLE — High-dose vitamin D supplementation did not improve bone mineral density (BMD) in postmenopausal women, a randomized study sponsored by the NIH found.
Among women who received high-dose vitamin D for a year, calcium absorption did increase but the effect was small, and there was no difference compared with those given low-dose vitamin D or placebo in BMD at the spine, total hip, femoral neck, or total body, according to Karen Hansen, MD, of the University of Wisconsin in Madison, and colleagues.
“There’s a big debate about the optimal vitamin D levels for musculoskeletal health. The Endocrine Society recommends 30 ng/mL and higher per day, the Institute of Medicine [IOM] says that virtually everyone is vitamin D replete at 20 ng/mL, and the U.S. Preventive Task Force recommends against vitamin D supplementation for ambulatory community-dwelling adults because it doesn’t reduce the risk of fracture,” Hansen said at the American Society for Bone and Mineral Research meeting.
“In a pilot study we saw that correction of vitamin D insufficiency in postmenopausal women from 20 to 60 ng/mL increased their calcium absorption by 3%, so we conducted a clinical trial to test the hypothesis that correction of vitamin D insufficiency with high-dose vitamin D might yield beneficial effects,” she said.
The study randomized 230 postmenopausal women whose mean 25 (OH)D levels were 14 to 27 ng/mL, and whose mean age was 61, to high-dose vitamin D supplementation, low-dose supplementation, or placebo. They were stratified according to the presence of hyperparathyroidism and calcium intake above 1,000 mg/day.
Women were excluded if they were older than 75 and had conditions such as nephrolithiasis, recent cancer, or malabsorption. Other exclusion criteria included a glomerular filtration rate below 45 mL/min, a history of fracture, or using bone-active medications such as bisphosphonates, anticonvulsants, or oral corticosteroids.
The high-dose group received a loading dose of 50,000 IU daily for 15 days with the goal of rapidly raising the level of 25 (OH)D above 30 ng/mL, and then were given 50,000 IU every 15 days for 12 months. At any study visit, if their level fell below 30 ng/mL, they were given another loading dose and a higher maintenance dose.
Participants in the low-dose group were given vitamin D, 800 IU per day plus placebo capsules every 15 days, and the placebo arm received matched placebos daily and every 15 days. Throughout the study, participants in the low-dose group had levels between 20 and 30 ng/mL, while the level was slightly below 20 ng/mL in the placebo group.
After controlling for baseline calcium absorption, the total fractional calcium absorption increased by 1% in the high-dose arm, but decreased by 2% in the low-dose group (P=0.005 versus high-dose) and by 1.3% in the placebo group (P=0.03 versus high-dose).
The investigators also measured timed-up-and-go and 5 times-sit-to-stand tests, as well as pain on a visual analog scale at baseline and days 30, 60, 120, 240, and 365.
No difference was seen in the timed-up-and-go test, but after controlling for pain, a greater improvement in the 5-sit-to-stand test was seen for the high-dose group (P=0.02). However, the 0.4-second absolute change was not clinically significant, Hansen reported.
There also were no differences between the groups in the number of patients who reported falls or the total number of falls.
Hypercalciuria was observed on seven occasions in four patients in the high-dose group, and once each in the low-dose and placebo groups.
These results do not support the recommendation that serum 25 (OH)D levels should be raised to 30 ng/mL or higher for bone health, but rather support the IOM’s conclusion that vitamin D repletion should be considered 20 ng/mL, Hansen stated.
The study was supported by the NIH.
Hansen disclosed no relevant relationships with industry.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco