Published online May 2, 2005
PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1325-1331 (doi:10.1542/peds.2004-1242)
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Vitamin K Status Among Children With Cystic Fibrosis and Its Relationship to Bone Mineral Density and Bone Turnover

Steven P. Conway, MB, BS*, Susan P. Wolfe, BSc*, Keith G. Brownlee, MB, ChB*, Helen White, BSc*, Brian Oldroyd{ddagger}, John G. Truscott, PhD{ddagger}, Julia M. Harvey, BSc§ and Martin J. Shearer, PhD§

* Pediatric Cystic Fibrosis Unit, St James' University Hospital, Leeds, United Kingdom
{ddagger} Centre for Bone and Body Composition Research, University of Leeds, Leeds, United Kingdom
§ Haemophilia Reference Centre, St Thomas' Hospital, London, United Kingdom

Objective. The aim of this study was to assess vitamin K status in an unselected population of children with cystic fibrosis (CF) and to investigate any vitamin K effect on bone turnover and bone mineral status.

Methods. Children ≥5 years of age who were attending the CF unit were invited to enter the study. Fasting blood samples were analyzed for levels of vitamin K1 and prothrombin produced in vitamin K absence; total, undercarboxylated, and carboxylated osteocalcin (OC); and bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide (bone formation markers). Levels of N-telopeptide and free pyridinoline and deoxypyridinoline (bone breakdown products) were measured in urine samples. Bone mineral density and bone mineral content were measured at the lumbar spine and for the total body with a GE Lunar Prodigy densitometer. Statistical analyses were performed with Minitab version 9.1.

Results. One hundred six children entered the study. Sixty-five of 93 children (70%) from whom blood samples were obtained showed suboptimal vitamin K status, on the basis of low serum vitamin K1 levels, increased prothrombin produced in vitamin K absence levels, or both abnormalities. Vitamin K1 levels showed a significant negative correlation with undercarboxylated OC levels but showed no significant correlation with any marker of bone turnover or measurement of bone mineral status. Undercarboxylated OC levels were correlated significantly with bone turnover markers, which themselves showed a significant negative correlation with measurements of bone mineral density and content. There were no significant correlations between carboxylated or undercarboxylated OC levels and bone density measurements.

Conclusions. Vitamin K1 deficiency is common among children with CF, and routine supplements should be considered. Through its role in the carboxylation of OC, vitamin K deficiency may be associated with an uncoupling of the balance between bone resorption and bone formation. A cause-effect relationship between vitamin K deficiency and low bone mass has not been proved.

Key Words: vitamin K • bone density • bone turnover • cystic fibrosis

Abbreviations: BMD, bone mineral density • BMC, bone mineral content • BSAP, bone-specific alkaline phosphatase • CF, cystic fibrosis • Gla-OC, carboxylated osteocalcin • Glu-OC, undercarboxylated osteocalcin • PICP, procollagen I carboxy-terminal propeptide • PIVKA-II, prothrombin produced in vitamin K absence • MAb, monoclonal antibody • OC, osteocalcin • AU, arbitrary unit

Accepted Sep 14, 2004.


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