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Grant Abstract

Grant Number: 1R03HD050530-01A1
PI Name: MODLESKY, CHRISTOPHER M.
Project Title: Vitamin K and Bone in Children with Cerebral Palsy

Abstract: DESCRIPTION (provided by applicant): Cerebral palsy (CP) is a brain disorder that can seriously impair movement and posture. A major secondary complication of moderate to severe CP is a substantial compromise of bone development and a high incidence of fracture in the femur. One factor that is closely tied to fracture but has not been evaluated in children with CP is vitamin K status. Vitamin K is necessary for the carboxylation of osteocalcin. Undercarboxylation of osteocalcin is associated with poor mineralization of the skeleton. Interestingly, vitamin K intake is not consistently associated with areal bone mineral density (aBMD), the primary marker of skeletal fragility, but it is associated with fracture. This discordance suggests vitamin K is more closely tied to features of the skeleton not captured by aBMD. It has been inferred that the level of carboxylated osteocalcin is associated with the trabecular microarchitecture and geometric structure of bone. Our long- term goal is to develop strategies that maximize growth and development of bone and reduce the incidence of fracture in children with CP. The specific aims of this study are: 1) to determine if children with moderate to severe CP have a higher level of undercarboxylated osteocalcin in the serum than children without CP;2) to determine if undercarboxylated osteocalcin is inversely related to the status of trabecular microarchitecture, geometric structure and strength of the femur in children with and without CP; and 3) to determine if undercarboxylated osteocalcin is inversely related to aBMD and bone mineral content in the femur in children with and without CP. To address our aims, 7 to 11 year-old prepubertal children with moderate to severe CP and children without CP will be studied. If the level of undercarboxylated osteocalcin is elevated in children with CP and if it is inversely related to trabecular microarchitecture, geometric structure and strength of bone, it would suggest that vitamin K may play an important role in fracture prevention in children with CP or other physical disabilities.

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