Suboptimal effect of different vitamin D3 supplementations and doses adapted to baseline serum 25(OH) D on achieved 25(OH) D levels in patients with a recent fracture: a prospective observational study

Abstract

Objective: Guidelines on the need for dose adaptation of vitamin D3 supplementation according to baseline serum 25(OH) D are inconclusive. The effects of increasing doses of vitamin D3 at lower baseline serum 25(OH) D values on the serum 25(OH) D after 4.2 and 11 months were determined in an observational study. Design: A prospective observational study. Methods: Out of 1481 consecutive women and men with a recent clinical fracture, 707 had a baseline 25(OH) D level<50 nmol/l and were supplemented with increasing doses of vitamin D3 (400, 800, 1700, and >= 3500 IU/day) according to the lower baseline 25(OH) D. Final analysis was restricted to the 221 participants who had full follow- up data available for 11 months. Results: Serum 25(OH) D >= 50 nmol/ l was achieved in 57-76% of patients after 4.2 months and in 73-79% after 11 months. These percentages were similar for all doses (P=0.06 and P=0.91 respectively). The mean achieved 25(OH) D was similar for all dose groups (56.1-64.0 nmol/l after 4.2 months and 60.2-76.3 nmol/ l after 11 months). With multivariate analysis, the increase in 25(OH) D (17G32.0 after 4.2 months and 24.3G34.0 nmol/l after 11 months) was dependent on the baseline 25(OH) D (P=0.001), not on supplementation dose, season, age, BMI, or gender. Conclusions: The increase in serum 25(OH) D was significantly larger with higher vitamin D3 supplementation doses. However, this dose-effect response was mainly explained by the baseline 25(OH) D, not the supplementation dose, with a greater magnitude of response at lower baseline 25(OH) D concentrations. In 21-27% of patients, serum 25(OH) D3 levels did not reach 50 nmol/l after 11 months, at any dose. Further studies are needed to identify possible causes of suboptimal response such as non-compliance, undiagnosed malabsorption syndromes, or variability in cholecalciferol content of the vitamin D supplements.