Establishing the Precursors of Osteoporosis in Children

确定儿童骨质疏松症的前兆

• 批准号: 7497892
• 负责人: XIPING XU
• 金额: $ 32万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497892
• 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; Estrogens; Event; Fasting; Fatty acid glycerol esters; Follicle Stimulating Hormone; Follow-Up Studies; Funding; Gender; Genetic; Gestational Age; Glucose; Individual; Inflammatory; 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; Numbers; Nutritional; OGTT; Osteocalcin; Osteoporosis; Parathyroid Hormones; Phenotype; Physical activity; Pregnancy; Prospective Studies; Protein C; Range; Research Design; Research Personnel; Risk; Sample Size; Skeletal system; 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; cohort; cost; critical developmental period; design; follow-up; human PTH protein; human TNF protein; mother nutrition; prevent; prospective; receptor; 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）：阐明儿童时期骨质疏松症的前兆可能会导致在以后的生活中预防或减轻骨质疏松症的干预措施。该应用的中心重点是研究通过 DEXA 测量的骨量，包括与各种假定的骨质疏松症前兆相关的骨矿物质含量 (BMC)、骨面积 (BA) 和骨矿物质密度 (BMD)。我们将研究 1998-2000 年在中国安庆登记的儿童和青少年的大型前瞻性双胞胎队列（-2,000 对双胞胎），年龄范围为 6-21 岁。目前，美国国立卫生研究院 (NIH) 资助的一项研究正在对这对双胞胎进行追踪，以确定代谢综合征 (MS) 的先兆。具体目标是：（1）在基线和随访研究中测量已知或怀疑影响1,500对双胞胎骨骼健康的生物标志物，包括骨建模和重塑标志物：骨保护素（OPG）、NFKB配体可溶性受体激活剂（sRANKL）、甲状旁腺激素（PTH）、骨钙素（OC）、 抗酒石酸酸性磷酸酶 5b (TRAP-5b)；营养指标：镁、维生素K1、25(OH)维生素D；并检查受资助的 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、空腹血脂；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；炎症标志物：C反应蛋白（CRP）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）； (2) 进行横断面和纵向双孪生分析，以检验以下假设： (a) BMC、BA 和 BMD 达到的水平分别与基线和随访调查时的生物标志物水平相关； (b) 基线和后续调查之间的 BMC、BA 和 BMD 变化与基线调查时的生物标志物水平相关； (c) BMC、BA 和 BMD 变化与基线和后续调查之间的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的协变量，包括年龄、性别、青春期、体重和成分、营养摄入和体力活动，以及生物标志物和协变量之间是否存在相互作用。识别儿童和青少年骨质疏松症的潜在重要前兆将代表我们在了解骨量的生物学基础方面向前迈出了一大步，并且对检测骨质疏松症高风险个体具有重要意义。