Vitamin K and Bone in Children with Cerebral Palsy

描述(申请人提供)：脑性瘫痪(CP)是一种脑部疾病，可严重损害运动和姿势。中到重度CP的一个主要继发并发症是骨骼发育的实质性损害和股骨骨折的高发生率。与骨折密切相关的一个因素是维生素K状况，但尚未在患有CP的儿童中进行评估。维生素K是骨钙素羧化所必需的。骨钙素的低羧化与骨骼的矿化不良有关。有趣的是，维生素K摄入量与骨骼脆性的主要标志--面骨密度(ABMD)并不一致，但它与骨折有关。这种不一致表明，维生素K与骨骼的特征更紧密地联系在一起，而骨密度不能捕捉到这些特征。已有研究推测，羧化骨钙素水平与骨小梁的微结构和几何结构有关。我们的长期目标是制定策略，最大限度地促进骨骼的生长和发育，减少脑瘫儿童骨折的发生率。本研究的具体目的是：1)确定中重度CP儿童血清中的低羧化骨钙素水平是否高于非CP儿童；2)确定CP儿童和非CP儿童的骨小梁微结构、几何结构和强度是否与骨钙素水平呈负相关；以及3)确定CP儿童和非CP儿童的骨钙素水平是否与BMD和股骨中的骨矿含量呈负相关。为了达到我们的目标，我们将研究患有中到重度脑性瘫痪的7-11岁青春期前儿童和没有脑性瘫痪的儿童。如果脑性瘫痪儿童骨钙素水平升高，并与骨小梁的微结构、几何结构和强度呈负相关，则提示维生素K可能在预防脑性瘫痪或其他肢体残疾儿童的骨折中发挥重要作用。

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.