Treatment of vitamin D insufficiency in postmenopausal women: a randomized clinical trial
Alan Gaby, MD
Hansen KE, et al
Treatment of vitamin D insufficiency in postmenopausal women: a randomized clinical trial. JAMA Intern Med 2015;175:1612-1621.
Randomized, double-blind, placebo-controlled trial.
Two hundred thirty postmenopausal women aged 75 years or younger (mean age, 61 years) with a serum 25-hydroxyvitamin D level of 14-27 ng/ml.
Study Medication and Dosage:
Low-dose vitamin D3 (800 IU per day), high-dose vitamin D3 (800 IU per day plus 50,000 IU twice a month; equivalent to a total of about 4,100 IU per day), or placebo for 1 year.
Primary Outcome Measures:
Change in bone mineral density (BMD) of the spine, hip, femoral neck and total body; and number of falls.
There was no significant difference between groups for mean changes in BMD at any site, and there was no clear trend favoring high-dose over low-dose vitamin D. There was also no significant difference between groups in the number of falls.
Numerous studies have shown that vitamin D supplementation slows bone loss and prevents falls in postmenopausal women, although in other studies vitamin D was ineffective. While it is not clear why the results differed in different studies, the present research suggests that it was not because of an insufficient dose. In a previous double-blind trial, postmenopausal women received 800 IU or 6,500 IU of vitamin D3 per day for 1 year. BMD increased in both groups, but there was a nonsignificant trend toward a greater increase in BMD with 800 IU per day than with 6,500 IU per day.1 In another double-blind trial, postmenopausal women received a single dose of 500,000 IU of vitamin D3 once a year for 3 to 5 years. The number of falls was significantly higher in the vitamin group than in the placebo group.2 The excess number of falls in the vitamin D group tended to cluster into the first 3 months after each dose, which suggests that vitamin D toxicity may have caused a transient impairment of balance or muscle strength.
Taken together, these studies suggest that moderate doses of vitamin D (such as 800 to 2,000 IU per day) are preferable in most cases to large doses. As I have pointed out previously in this column, serum 25-hydroxyvitamin D may not be a reliable indicator of vitamin D status or a reliable guide to vitamin D dosing.
1 Grimnes G, et al. The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass – a randomized controlled 1-year trial. Osteoporos Int 2012;23:201-211.
2 Sanders KM, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010;303:1815-1822.