Vitamin D and fibroblast growth factor 23 physiology in adolescent girls

青春期女孩的维生素 D 和成纤维细胞生长因子 23 生理学

基本信息

项目摘要

DESCRIPTION (provided by applicant): Fibroblast growth factor 23 (FGF23) is a hormone with a central role in regulating circulating phosphate (Pi) levels and vitamin D metabolism. Several human diseases are characterized by FGF23 excess, including X-linked hypophosphatemia, autosomal dominant hypophosphatemic rickets, and tumor-induced osteomalacia. These diseases are characterized by growth failure, severe bone disease, and myopathy. FGF23 deficiency causes hyperphosphatemic familial tumoral calcinosis, characterized by calcium deposition in soft tissues and aberrant bone growth. While there is growing understanding of the role of FGF23 in disease, its role in maintaining Pi and vitamin D homeostasis in the healthy state is less well-understood. In particular, the role of FGF23 in regulating bone mineralization during childhood growth has not been well-explored. Additional gaps in knowledge include the age- and pubertal-stage variation in circulating FGF23 levels and the identification of the primary stimulus for FGF23 secretion in the healthy state. This proposal aims to address these gaps in order to further understand the function and regulation of this critical hormone. We will recruit 100 healthy girls, aged 9-18 years, for a cross-sectional study of circulating FGF23 levels and bone mineralization. We will obtain bone imaging by both dual-emission X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography. We will examine the association of FGF23 with measures of bone mineral density, bone microarchitecture, and bone strength. We will obtain bone age x- rays and assess pubertal stage on physical exam and, using regression analyses, determine what, if any, variation in FGF23 levels exists by chronological age and/or pubertal stage. We will also measure circulating levels of other key factors in bone mineral metabolism including calcium, Pi, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, parathyroid hormone, and bone turnover markers. 30 pre-pubertal and early-pubertal girls with vitamin D deficiency (25OHD level 20 ng/mL) will be co-enrolled in a prospective, randomized, placebo-controlled trial and treated with ergocalciferol 50,000 international units weekly or placebo for 16 weeks. We will examine the change in circulating FGF23 with area-under-the-curve analyses. These studies will provide key data regarding FGF23 physiology in pediatric populations which will help guide identification of mineral ion disorders and may suggest new treatment modalities. In addition, an improved understanding of the regulation of bone mineralization may translate into novel therapies for optimizing bone mineral density and thus fracture prevention throughout the lifespan. PUBLIC HEALTH RELEVANCE: Fibroblast growth factor 23 (FGF23) is a hormone which regulates phosphate and vitamin D metabolism; FGF23 may also be critical for normal bone development independent of its phosphate and vitamin D effects. While its role in several rare diseases is increasingly well-described, less is known about its function and regulation in healthy people, particularly in children. The research described in this proposal will help better define the function of FGF23 in healthy children to enhance our understanding of bone and mineral metabolism and bone mass accrual during childhood.
说明(申请人提供):成纤维细胞生长因子23(FGF23)是一种激素,在调节循环磷酸盐(PI)水平和维生素D代谢中起核心作用。一些人类疾病的特征是FGF23过多,包括X连锁低磷血症、常染色体显性低磷血症性软骨病和肿瘤引起的骨软化症。这些疾病的特征是生长障碍、严重的骨病和肌病。FGF23缺乏导致高磷血症性家族性肿瘤钙质沉着症,其特征是软组织中的钙沉积和异常的骨生长。虽然人们对FGF23在疾病中的作用有了越来越多的了解,但它在维持健康状态下PI和维生素D动态平衡方面的作用却知之甚少。特别是,FGF23在调节儿童生长过程中的骨矿化方面的作用还没有得到很好的研究。其他知识空白包括循环FGF23水平的年龄和青春期变化,以及健康状态下FGF23分泌的主要刺激因素的确定。这项建议旨在解决这些差距,以便进一步了解这种关键激素的功能和调节。我们将招募100名9-18岁的健康女孩,进行循环FGF23水平和骨矿化的横断面研究。我们将通过双发射X射线吸收法(DXA)和高分辨率外周定量计算机断层扫描获得骨成像。我们将研究FGF23与骨密度、骨微结构和骨强度的关系。我们将获得骨龄X光,并通过体检评估青春期阶段,并使用回归分析来确定FGF23水平在年龄和/或青春期阶段是否存在变化。我们还将测量骨矿物质代谢的其他关键因素的循环水平,包括钙、PI、25-羟基维生素D(25OHD)、1,25-二羟基维生素D、甲状旁腺激素和骨转换标志物。30名缺乏维生素D的青春期前和青春期早期女孩(维生素D缺乏水平为20 ng/毫升)将共同参加一项前瞻性、随机、安慰剂对照试验,每周服用50000国际单位麦角钙化醇或服用安慰剂,为期16周。我们将用曲线下面积分析来检验循环中FGF23的变化。这些研究将提供有关儿科人群中FGF23生理学的关键数据,这将有助于指导矿物离子障碍的识别,并可能建议新的治疗方式。此外,对骨矿化规律的更好理解可能转化为优化骨矿密度的新疗法,从而在整个生命周期内预防骨折。 与公众健康相关:成纤维细胞生长因子23(FGF23)是一种调节磷酸盐和维生素D代谢的激素;FGF23可能也是正常骨骼发育的关键,不依赖于其磷酸盐和维生素D的影响。虽然它在几种罕见疾病中的作用越来越得到充分的描述,但对它在健康人,特别是儿童中的功能和调节知之甚少。这项建议中描述的研究将有助于更好地确定FGF23在健康儿童中的功能,以增强我们对儿童时期骨和矿物质代谢和骨量积累的了解。

项目成果

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Deborah Michelle Mitchell其他文献

Deborah Michelle Mitchell的其他文献

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{{ truncateString('Deborah Michelle Mitchell', 18)}}的其他基金

The effects of type 1 diabetes on bone health in children and adolescents
1 型糖尿病对儿童和青少年骨骼健康的影响
  • 批准号:
    9897529
  • 财政年份:
    2016
  • 资助金额:
    $ 6.47万
  • 项目类别:

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Direct effects of 25-hydroxyvitamin D on renal fibrosis
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Amelioration of Vesicant-Induced Skin Injury by High Dose 25-Hydroxyvitamin D
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