Vitamin D supplementation and bone turnover in advanced heart failure: the EVITA trial

Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status.

Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D₃ dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L.

In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)₂D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values.

Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)₂D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05).

A daily vitamin D₃ dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure.