Bone turnover in prolonged critical illness: effect of vitamin D.
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.
Van den Berghe
Greet
G
Department of Intensive Care Medicine, University of Leuven, B-3000 Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be
Van Roosbroeck
David
D
Vanhove
Philippe
P
Wouters
Pieter J
PJ
De Pourcq
Lutgart
L
Bouillon
Roger
R
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D003422:Critical Care; D016638:Critical Illness; D005260:Female; D006801:Humans; D006900:Hydroxylation; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D014508:Urea / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*
D015850:Interleukin-6; D010281:Parathyroid Hormone; D014807:Vitamin D; D014508:Urea; D002097:C-Reactive Protein; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium