The effect of vitamin D3 supplementation on fracture incidence in an aging population - The Finnish vitamin D trial.

BACKGROUND: The effectiveness of vitamin D supplementation for fracture prevention at the population level remains a matter of debate. In this study, we evaluated the impact of vitamin D₃ supplementation on fracture risk among an aging population in Finland. METHODS: The study included 2495 participants, men ≥60 years and women ≥65 years, who were randomized for 5 years into three groups: 1600 IU/day or 3200 IU/day of vitamin D₃, or placebo. Fracture diagnoses were retrieved from two national care notification registers. RESULTS: During the mean 4.1-year supplementation period, there were 49, 73 and 52 fractures in the placebo, 1600 IU/day (compared to placebo: HR = 1.52, 95% CI = 1.06-2.18) and 3200 IU/day (HR = 1.07, 95% CI = 0.72-1.58) arms, respectively. During the extended 7.3-year follow-up, 104, 139 and 111 fractures occurred in the placebo, 1600 IU/day (HR = 1.40, 95% CI = 1.08-1.80) and 3200 IU/day (HR = 1.08, 95% CI = 0.83-1.41) arms, respectively. No statistically significant differences were observed in fracture subtypes. Age, sex, BMI, history of fracture or fall, osteoporosis diagnosis, or calcium supplement use did not modify the effects. In the sub-cohort of 550 participants, the mean ± SD baseline serum 25-hydroxyvitamin D concentration was 74.8 ± 18.2 nmol/L. After 12 months, the concentrations were 73.0 ± 17.8, 99.7 ± 21.1 and 120.4 ± 21.8 nmol/L in the placebo, 1600 IU/day and 3200 IU/day arms, respectively (P < 0.001). CONCLUSIONS: The 5-year vitamin D3 supplementation of 1600 IU/day or 3200 IU/day did not reduce the risk of fractures among a largely vitamin D-sufficient aging population. The findings do not support use of high vitamin D doses for fracture prevention in such populations. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.