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.
Can the authors comment on whether newborn screening for Cystic fibrosis is occurring in the United Kingdom, on if so, describe the screening process? Can the authors comment on timing of diagnosis and Vitamin K status? What about Vitamin K status and Cognitive development? Why do I ask? In the United states, some states screen newborns for Cystic fibrosis on the basis of a randomized, controlled trial showing nutitional and cognitive benefits for screened newborns (early diagnosis) compared to traditionally diagnosed children (average age 3 to 4 years of age).Good evidence for this includes the results of Koscik, RL et al. suugest that prevention of prolonged malnutrition by early diagnosis and nutritional therapy, particularly minimizing Vitamin e deficiency, is associated with better cognitive function.Vitamin E deficiency (alpha-tocopherol less than 300 micrograms/dl) at diagnosis has been implicated as one nutritional deficiency associated with subsequent lower cognitive stores. Vitamin K is present in the brain and has a role in the brain growth receptor system.The Body stores very little vitamin K. In fact, Vitamin k is rapidly depleted without regular dietary intake. Even the adult hepatic storage pool, measured by Shearer , is surprisingly small 1.7 to 38.3 micrograms (median 7.8 micrograms).In a child with cystic fibrosis, it is conceivable that Vitamin K deficiency not only would accompany other deficiencies of nutrition, but might be one of the first deficiencies to occur? In summary,I commend the authors for this important work. Vitamin K has been associated with bone health, and cystic fibrosis with stunted growth. I believe the Leeds group provides more data to support the screening of newborns for cystic fibrosis.
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Conflict of Interest:
None declared