Dose-Dependent Short-Term Effects of Single High Doses of Oral Vitamin D3 on Bone Turnover Markers

We investigated the short-term effects on bone turnover markers of high doses of vitamin D₃ in order to identify what initial therapeutic dose can be safely administered in vitamin D-deficient subjects. Thirty-seven elderly subjects [mean age 75?±?3 (SD)?years] were consecutively randomized to the administration of a single oral bolus of 600000, 300000, or 100000?IU vitamin D₃. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90?days after vitamin D₃ administration. Twenty-four subjects served as controls. No relevant changes in bone turnover markers [C-terminal telopeptides of type I collagen (sCTX) and bone-specific alkaline phosphatase (BAP)] were observed in the controls. In treated patients a dose-dependent effect on sCTX was observed. With the administration of 600,000?IU vitamin D₃ a significant increase of sCTX was observed already at day 1, and it was sustained for 2?months. The changes in sCTX with smaller doses were considerably lower and reached statistical significance only within the first 3?days with the 300,000?IU dose. BAP remained unchanged in patients given 300,000 and 600,000?IU vitamin D₃, while it significantly rose by 15–23?% throughout the observation period in patients given 100,000?IU. Our results indicate that the use of a vitamin D bolus exceeding 100,000?IU may be associated with acute increases of sCTX.