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Bone turnover in prolonged critical illness: effect of vitamin D


In prolonged critical illness, substantially increased bone resorption and osteoblast dysfunction have been reported in the face of low 25-hydroxy vitamin D [25(OH)D] concentrations. The current prospective, randomized, controlled study investigates the impact of increased daily vitamin D supplement during intensive care on the time course of bone turnover and its major regulators such as cytokines and calciotropic hormones.


Critically ill patients, assumed to require > 10 days of intensive care, were compared with healthy matched controls and randomly allocated to a daily vitamin D supplement of either ± 200 IU (low dose) or ± 500 IU (high dose). Of the 33 patients included, 22 remained in ICU for > 10 days and were analyzed. Urine from 24 hour collections and blood was sampled daily for characterization of vitamin D status, bone turnover and inflammation.


The 12 patients who received the high dose vitamin D and 10 patients who received the low dose were comparable at baseline. At intensive care admission, serum concentrations of 25(OH)D, 1,25(OH)2D, DBP, ionized calcium, osteocalcin, IL-1 and sIL-6-R were lower than in controls; PTH and bone-specific alkaline phosphatase levels were normal; serum carboxy and amino terminal of propeptide type-I collagen, serum and urinary collagen cross-links (β CTX, PYD and DPD) as well as IL-6, TNF-α and OPG were several fold elevated. sRANKL was undetectable.

The high dose increased circulating 25(OH)D (P < 0.05) but normal levels were not reached and low 1,25(OH)2D levels not altered. High dose vitamin D slightly increased osteocalcin and decreased carboxy terminal propeptide type-I collagen (P < 0.05). Bone-specific alkaline phosphatase and collagen cross-links markedly increased with time in both groups (P < 0.01). Elevated CRP and IL-6 decreased significantly with time and more so in the high dose group (P < 0.05). TNF-α and IL-1 remained unaltered. Except for a mirroring of βCTX rise by a decrease in OPG, circulating cytokines were unrelated to the progressively aggravating bone resorption.


Prolonged critically ill patients were vitamin D deficient. Increasing vitamin D supplement to the currently recommended dose did not normalize circulating 25(OH)D or 1,25(OH)2D. Furthermore, severe bone hyperresorption was associated with osteoblast dysfunction and aggravated with time in intensive care, independent of vitamin D supplementation.

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Vanhove, P., Van Roosbroeck, D., Wouters, P. et al. Bone turnover in prolonged critical illness: effect of vitamin D. Crit Care 7 (Suppl 2), P008 (2003).

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  • Bone Resorption
  • Bone Turnover
  • Osteocalcin
  • Alkaline Phosphatase Level
  • Healthy Matched Control