Establishing the Precursors of Osteoporosis in Children

描述（由申请人提供）：阐明骨质疏松症的儿童前兆可能导致预防或减轻晚年骨质疏松症的干预措施。本应用程序的中心焦点是调查骨量，由DEXA测量，包括骨矿物质含量（BMC），骨面积（BA）和骨矿物质密度（BMD）与骨质疏松症的假定前驱的广泛关系。我们将研究一个大型的前瞻性双胞胎队列（- 2000对双胞胎），这些儿童和青少年是1998-2000年在中国安庆登记的，年龄范围为6-21岁。这对双胞胎目前正在接受美国国立卫生研究院资助的一项研究，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已知或怀疑影响1500对双胞胎骨骼健康的生物标志物，包括骨骼建模和重塑标志物：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 (trap5b)；营养指标：镁、维生素K1和25（OH）维生素D；并检查资助的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，睾丸激素，LH和FSH；代谢指标：空腹及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）、肿瘤坏死因子（TNF）；(2)通过横断面和纵向双胎分析来验证以下假设：(a) BMC、BA和BMD水平分别与基线和随访调查时的生物标志物水平相关；(b)基线和随访调查期间BMC、BA和BMD的变化与基线调查时的生物标志物水平相关；(c) BMC、BA和BMD的变化与基线和随访调查之间的生物标志物变化相关。我们将进一步研究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、体重和组成、营养摄入和身体活动，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的潜在重要前体的鉴定将代表着我们对骨量的生物学基础的理解向前迈出了一大步，并对骨质疏松症高危个体的检测具有重要意义。

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.