Bone turnover in prolonged critical illness: effect of vitamin D

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.