To the Editor: In their randomized controlled trial, Dr Sanders and colleagues1 hypothesized that an annual high-dose oral cholecalciferol administration would reduce the risk of fractures based on previous results in randomized and observational studies but found an increased risk. Other studies, including a Cochrane review,2 had yielded negative results. The mechanisms underlying increased fracture risk from bolus vitamin D supplementation are uncertain. The effects of treatment on 25-hydroxycholecalciferol 24-hydroxylase and 1-alpha-hydroxylase, renal and extrarenal, could be better interpreted if levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were determined in the substudy participants who underwent 25-hydroxycholecalciferol serum level assessment. The relative grade of activity of the 2 enzymes could determine increased, unchanged, or diminished serum levels of 1,25(OH)2D.
Gallieni M. High-Dose Oral Vitamin D Supplementation and Risk of Falls in Older Women. JAMA. 2010;304(8):854-857. doi:10.1001/jama.2010.1167