Bone turnover in prolonged critical illness: effect of vitamin D

J Clin Endocrinol Metab. 2003 Oct;88(10):4623-32. doi: 10.1210/jc.2003-030358.


In prolonged critical illness, increased bone resorption and osteoblast dysfunction have been reported facing low 25 hydroxy vitamin D [25(OH)D] concentrations. The current study investigates the extent to which lack of nutritional vitamin D and time in intensive care contribute to bone loss in the critically ill. Prolonged critically ill patients (n = 22) were compared with matched controls and then randomized to daily vitamin D supplement of either +/- 200 IU (low dose) or +/- 500 IU (high dose). At intensive care admission, serum concentrations of 25(OH)D, 1,25 dihydroxyvitamin D(3), vitamin D-binding protein, ionized calcium, IL-1, and soluble IL-6-receptor were low, and PTH was normal. Circulating type-I collagen propeptides were high, alkaline phosphatase was normal, and osteocalcin was low. Bone resorption markers [(carboxy terminal cross-linked telopeptide of type I collagen (betaCTX), pyridinoline, deoxypyridinoline (DPD)] were 6-fold increased. Serum C-reactive protein (CRP) was 40-fold, IL-6 400-fold, TNFalpha levels 5-fold, and osteoprotegerin concentrations 3-fold higher than in controls. Soluble receptor activator of nuclear factor kappaB ligand was undetectable. High-dose vitamin D only slightly increased circulating 25 hydroxy vitamin D (P < 0.05), but 1,25 dihydroxyvitamin D(3) was unaltered. High-dose vitamin D slightly increased serum osteocalcin (P < 0.05) and decreased carboxy terminal propeptide type-I collagen (P < 0.05) but did not affect other bone turnover markers. Bone-specific alkaline phosphatase, urinary pyridinoline and DPD, and serum betaCTX markedly increased with time (P < 0.01). Circulating CRP and IL-6 decreased with time, whereas TNFalpha and IL-1 remained unaltered. The fall in CRP and IL-6 was more pronounced with the high- than low-dose vitamin D (P < 0.05). Except for a mirroring of betaCTX rise by a fall in osteoprotegerin, cytokines were unrelated to the progressively aggravating bone resorption. In conclusion, prolonged critically ill patients were vitamin D deficient. The currently recommended vitamin D dose did not normalize vitamin D status. Furthermore, severe bone hyperresorption further aggravated (up to 15-fold the normal values) with time in intensive care and was associated with impaired osteoblast function.

Publication types

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

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Bone Resorption / blood
  • Bone Resorption / drug therapy*
  • Bone Resorption / pathology*
  • C-Reactive Protein / metabolism
  • Calcitriol / blood
  • Calcium / blood
  • Creatinine / blood
  • Critical Care
  • Critical Illness*
  • Female
  • Humans
  • Hydroxylation
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Osteoblasts / physiology
  • Osteoclasts / physiology
  • Parathyroid Hormone / blood
  • Prospective Studies
  • Urea / blood
  • Vitamin D / administration & dosage*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / pathology*


  • Interleukin-6
  • Parathyroid Hormone
  • Vitamin D
  • Urea
  • C-Reactive Protein
  • Creatinine
  • Calcitriol
  • Calcium