In Reply: In response to Dr Mak, the increased rate of falls is evident across each of the first 3 months following dosing. The rate ratio for falls between the vitamin D and placebo groups for the first 5 months following dosing was 1.2, 1.3, 1.4, 1.0, and 1.1 for months 1, 2, 3, 4, and 5, respectively. In the biochemistry subset of participants, baseline 25-hydroxycholecalciferol and PTH levels were not statistically different between the treatment groups. We consider it highly improbable that the adverse results could be attributable to slight differences in baseline serum 25-hydroxycholecalciferol or PTH in a randomized group of more than 2000 participants. It seems more likely that the significant changes in both serum 25-hydroxycholecalciferol and PTH in the vitamin D group at 1 and 3 months after dose would contribute to the mechanism that resulted in increased falls and fracture risk.
Sanders KM, Stuart AL, Nicholson GC. High-Dose Oral Vitamin D Supplementation and Risk of Falls in Older Women—Reply. JAMA. 2010;304(8):854-857. doi:10.1001/jama.2010.1169