Establishing the Precursors of Osteoporosis in Children

确定儿童骨质疏松症的前兆

• 批准号: 7922595
• 负责人: XIPING XU
• 金额: $ 30.52万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922595
• 关键词: Adipocytes; Adolescent; Affect; Age; Androgens; Area; Baseline Surveys; Biological; Biological Markers; Blood Pressure; Body Weight; Bone Density; Bone Mineral Contents; C-reactive protein; Child; Childhood; China; Data; Data Collection; Detection; Dietary Questionnaires; Dual-Energy X-Ray Absorptiometry; Enrollment; Environmental Exposure; Epidemiology; Estrogens; Event; Fasting; Fatty acid glycerol esters; Follow-Up Studies; Funding; Gender; Genetic; Gestational Age; Glucose; Individual; Insulin; Insulin-Like Growth Factor I; Intake; Interleukin-6; Intervention; Lead; Leptin; Life; Ligands; Lipids; Magnesium; Measures; Menarche; Metabolic Marker; Metabolic syndrome; Modeling; NF-kappa B; Nutritional; OGTT; Osteocalcin; Osteoporosis; Parathyroid Hormones; Phenotype; Physical activity; Pregnancy; Prospective Studies; Protein C; Research Design; Research Personnel; Sample Size; Socioeconomic Status; Somatomedins; Somatotropin; Staging; Surveys; Testing; Testosterone; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Tumor necrosis factor receptor 11b; Twin Multiple Birth; United States National Institutes of Health; Vitamin D; Vitamin K 1; Vitamins; adiponectin; base; bone; bone health; bone mass; cohort; cost; critical period; design; follow-up; high risk; human PTH protein; inflammatory marker; mother nutrition; prevent; prospective; receptor; skeletal; steroid hormone; tartrate-resistant acid phosphatase

DESCRIPTION (provided by applicant): Elucidating childhood precursors of osteoporosis may lead to interventions that prevent or mitigate osteoporosis later in life. The central focus of this application is to investigate bone mass as measured by DEXA, including bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in relation to a wide range of putative precursors of osteoporosis. We will study a large prospective twin cohort (-2,000 twin pairs) of children and adolescents, enrolled previously in 1998-2000 in Anqing, China, with an age range of 6-21 years. The twins are currently followed by a NIH funded study to identify precursors of metabolic syndrome (MS). The specific aims are: (1) To measure biomarkers that are known or suspected to affect bone health in 1,500 twin pairs at baseline and follow-up study, including bone modeling and remodeling markers: osteoprotegerin (OPG), soluble receptor activator of NFKB ligand (sRANKL), parathyroid hormone (PTH), osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRAP-5b); nutritional markers: magnesium, vitamin K1, and 25(OH) vitamin D; and also examine other relevant biomarkers covered by the funded MS study, including steroid hormones: androgen, estrogen, testosterons, LH, and FSH; metabolic markers: fasting and 2-hr post OGTT insulin, glucose, HOMA-IR, fasting lipids; growth hormones: insulin-like growth factor (IGF-I); adipocyte markers: leptin, adiponectin; and inflammatory markers: C-reactive protein (CRP), lnterleukin-6 (IL-6), and tumor necrosis factor (TNF); (2) To conduct cross-sectional and longitudinal co-twin analyses to test the following hypotheses: (a) BMC, BA and BMD attained levels are associated with biomarker levels at the baseline and follow-up survey, respectively; (b) BMC, BA, and BMD changes between the baseline and follow-up survey are associated with biomarker levels at the baseline survey; (c) BMC, BA, and BMD changes are associated with biomarker changes between the baseline and follow-up surveys. We will further examine if the above relationships are independent of other important covariates, including age, gender, pubertal stage, body weight and composition, nutritional intake, and physical activity, and if there are interactions between the biomarkers and the covariates. The identification of potential important precursors of osteoporosis in children and adolescents would represent a huge step forward in our understanding of the biological basis of bone mass and should have important implications for the detection of individuals at high risk for osteoporosis.

描述（由申请人提供）：阐明儿童骨质疏松症的前兆可能导致干预措施，预防或减轻骨质疏松症在以后的生活。本申请的中心焦点是研究通过DEXA测量的骨量，包括骨矿物质含量（BMC）、骨面积（BA）和骨矿物质密度（BMD），其与广泛的骨质疏松症的推定前兆有关。我们将研究1998- 2,000年在中国安庆招募的儿童和青少年的大型前瞻性双胞胎队列（约2，000对双胞胎），年龄范围为6-21岁。这对双胞胎目前正在接受NIH资助的研究，以确定代谢综合征（MS）的前兆。具体目标是：（1）在基线和随访研究中，测量1,500对双胞胎中已知或疑似影响骨健康的生物标志物，包括骨建模和重塑标志物：骨保护素（OPG）、可溶性NF κ B受体激活剂配体（sRANKL）、甲状旁腺激素（PTH）、骨钙素（OC）、抗酒石酸酸性磷酸酶5 b（TRAP-5 b）;营养标志物：镁、维生素K1和25（OH）维生素D;还检查资助的MS研究涵盖的其他相关生物标志物，包括类固醇激素：雄激素、雌激素、睾丸酮、LH和FSH;代谢标志物：空腹和OGTT后2小时胰岛素、葡萄糖、HOMA-IR、空腹脂质;生长激素：胰岛素样生长因子（IGF-I）;脂肪细胞标志物：瘦素、脂联素;和炎症标志物：（2）采用横断面和纵向双胞胎分析方法，对以下假设进行检验：（a）BMC、BA和BMD分别与基线和随访时的生物标志物水平相关;（B）基线和随访调查之间的BMC、BA和BMD变化与基线调查时的生物标志物水平相关;（c）基线和随访调查之间的BMC、BA和BMD变化与生物标志物变化相关。我们将进一步检查上述关系是否独立于其他重要协变量，包括年龄，性别，青春期阶段，体重和成分，营养摄入量和体力活动，以及生物标志物和协变量之间是否存在相互作用。儿童和青少年骨质疏松症潜在的重要前兆的识别将代表着我们在了解骨量的生物学基础上向前迈出了一大步，并应具有重要意义的个体在骨质疏松症的高风险检测。

项目成果

Hypophosphatemia with elevations in serum fibroblast growth factor 23 in a child with Jansen's metaphyseal chondrodysplasia.

患有 Jansen 干骺端软骨发育不良的儿童出现低磷血症并伴有血清成纤维细胞生长因子 23 升高。

• DOI: 10.1210/jcem.94.2.9988
• 发表时间: 2009
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Brown,WhitneyW;Jüppner,Harald;Langman,CraigB;Price,Heather;Farrow,EmilyG;White,KennethE;McCormick,KennethL
• 通讯作者: McCormick,KennethL