Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study

Osteoporos Int. 2017 Dec;28(12):3347-3354. doi: 10.1007/s00198-017-4190-1. Epub 2017 Aug 25.

Abstract

In this post hoc analysis of the VITdAL-ICU study, an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml, vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin.

Introduction: Observational studies have shown accelerated bone loss in ICU survivors. A reversible contributor is vitamin D deficiency. In a post hoc analysis of the VITdAL-ICU study, we evaluated the effect of high-dose vitamin D3 on the bone turnover markers (BTM) β-Crosslaps (CTX) and osteocalcin (OC).

Methods: The VITdAL-ICU study was a randomized, double-blind, placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 (a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU). In this analysis on 289 survivors (209 telephone, 80 personal follow-up visits), BTM were analyzed on days 0, 3, 7, 28, and 180; self-reported falls and fractures were assessed. Bone mineral density (BMD) was measured after 6 months.

Results: At baseline, CTX was elevated; OC was low in both groups-after 6 months, both had returned to normal. There were no differences between groups concerning BTM, BMD, falls, or fractures. In linear mixed effects models, CTX and OC showed a significant change over time (p < 0.001, respectively), but there was no difference between the vitamin D and placebo group (p = 0.688 and p = 0.972, respectively).

Conclusions: Vitamin D supplementation did not have a significant effect on BTM. Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors.

Trial registration: ClinicalTrials.gov NCT01130181.

Keywords: Bone loss; Bone mineral density; Bone turnover markers; Critical illness; Fracture; Long-term outcomes; Osteoporosis; Vitamin D3.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Cholecalciferol / pharmacology*
  • Cholecalciferol / therapeutic use
  • Collagen / blood
  • Critical Illness / therapy*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Peptide Fragments / blood
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / physiopathology

Substances

  • Bone Density Conservation Agents
  • Peptide Fragments
  • glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine
  • Osteocalcin
  • Vitamin D
  • Cholecalciferol
  • Collagen
  • 25-hydroxyvitamin D

Associated data

  • ClinicalTrials.gov/NCT01130181