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Comment & Response
January 7, 2020

High-Dose Vitamin D Supplementation and Bone Health—Reply

Author Affiliations
  • 1McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
JAMA. 2020;323(1):93-94. doi:10.1001/jama.2019.18153

In Reply Drs Lippi and Targher, as well as Dr Li and colleagues, comment that the findings of our trial are applicable to a specific study population. Although Lippi and Targher’s thresholds for 25(OH)D deficiency and insufficiency are above those of Health Canada and the Institute of Medicine (IOM),1 we share their concern that our results might be inappropriately interpreted as applicable to a population that is vitamin D–deficient. By most standards, the participants in our study were vitamin D–sufficient on study entry. Recent evidence suggests that 30 nmol/L is a useful threshold for vitamin D deficiency in bone (ie, osteomalacia or vitamin D–responsive low bone density).1,2 Although mild mineralization defects may be seen at levels greater than 30 nmol/L, the IOM report determined that a level of 50 nmol/L reflects adequate vitamin D exposure for 97.5% of the population. In our study, the mean baseline 25(OH)D level was 78.7 nmol/L. There were not enough participants with levels below 50 nmol/L (n = 24) for meaningful subgroup analysis. However, examining total volumetric BMD at the radius for the 138 participants with 25(OH)D levels of 75 nmol/L or less, a dose-dependent pattern of bone loss was seen similar to what was seen in the full cohort: greatest loss in the 10 000-IU group (Figure).