Establishing the Precursors of Osteoporosis in Children

描述(申请人提供)：阐明儿童时期骨质疏松的先兆可能导致在以后的生活中预防或减轻骨质疏松的干预措施。这一应用的中心焦点是研究DEXA测量的骨量，包括骨矿含量(BMC)、骨面积(BA)和骨密度(BMD)与一系列可能的骨质疏松前体的关系。我们将研究中国安庆市1998-2000年以前登记的6-21岁儿童和青少年的一个大的预期双胞胎队列(-2,000对双胞胎)。目前，NIH资助的一项研究正在跟踪这对双胞胎，以确定代谢综合征(MS)的先兆。具体目标是：(1)在基线和后续研究中测量1500对双胞胎中已知或怀疑影响骨健康的生物标记物，包括骨建模和重塑标记物：骨保护素(OPG)、NFKB配体的可溶性受体激活剂(SRANKL)、甲状旁腺激素(PTH)、骨钙素(OC)、抗酒石酸酸性磷酸酶5b(TRAP-5b)；营养标记物：镁、维生素K1和25(OH)维生素D；以及MS资助研究涵盖的其他相关生物标记物，包括类固醇激素：雄激素、雌激素、睾酮、黄体生成素和卵泡刺激素；代谢标志物：空腹和OGTT后2小时胰岛素、血糖、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；以及炎症标志物：C反应蛋白(CRP)、白介素6(IL-6)和肿瘤坏死因子(TNF)；(2)进行横断面和纵向双生分析，以检验以下假设：(A)BMC、BA和BMD水平分别与基线和随访时的生物标志物水平相关；(B)BMC、BA和BMD在基线调查和后续调查之间的变化与基线调查中的生物标志物水平相关；(C)BMC、BA和BMD的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、青春期阶段、体重和成分、营养摄入量和体力活动，以及生物标记物和协变量之间是否存在交互作用。识别儿童和青少年骨质疏松的潜在重要先兆将代表着我们对骨量生物学基础的理解向前迈出了一大步，并将对检测骨质疏松高危人群具有重要意义。

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.