OPTIMIZATION OF CALCIUM ABSORPTION AND BONE FORMATION DURING EARLY PUBERTY

青春期早期钙吸收和骨形成的优化

• 批准号: 7374929
• 负责人: STEVEN A ABRAMS
• 金额: $ 1.21万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374929
• 关键词: OPTIMIZATION; CALCIUM; ABSORPTION; BONE; FORMATION

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rapid increases in bone mass occur during puberty. Optimizing calcium absorption (Ca-abs) and bone calcium deposition (Vo+) during puberty can enhance peak bone mass and ultimately decrease the lifetime risk of osteoporosis. In this study, we will determine the influence of hormonal, genetic and dietary factors that lead to maximal Ca-abs and Vo+ in pubertal boys and girls. Hypotheses: Our overall hypotheses are that dynamic changes in mineral metabolism in early adolescence are based on identifiable hormonal and genetic factors and that specific nutritional interventions can enhance bone mass accumulation. Specifically, in this proposal we will evaluate the following: 1) Early nighttime increases in pubertal hormones will be closely correlated to Ca-abs and Vo+ in both boys and girls. In contrast, serum leptin will be negatively correlated with Vo+; 2) Putative genetic markers of osteoporosis, including vitamin D receptor polymorphisms, will be significantly correlated to Ca-abs and Vo+; 3) The addition of NDO will increase Ca-abs and Vo+ in pubertal children receiving recommended dietary calcium intakes. We will enroll 50 girls and 50 boys who are healthy, 10th to 90th %ile body mass index for age, and Tanner Stage 2 or 3. They will participate in comprehensive dual-tracer calcium stable isotopic kinetic studies. Results will be compared with pubertal hormonal studies, biochemical bone turnover markers, and dual-energy X-ray absorptiometry (DXA) measures of whole body and regional bone mineral content. Genetic markers related to bone mass will be assessed and related to both hormonal and calcium kinetic measurements. After these baseline studies, subjects will be randomized to receive calcium fortified foods either with or without added NDO. Calcium absorption will be measured again after 2 months. After 12 months, the baseline calcium kinetic, hormonal and DXA studies will be repeated to assess the effects both of pubertal development and the dietary intervention. At the conclusion of that study, supplementation with NDO will be stopped and a final DXA study performed 12 months later to assess whether bone mass differences identified during supplementation were maintained post-intervention. Conclusions: By identifying the relationships among hormonal changes of puberty, genetics and calcium metabolism, the characteristics leading to maximal calcium absorption and utilization can be identified. These insights will enable interventional strategies to enhance bone mass to be specifically related to identifiable population characteristics, with the ultimate goal of decreasing the incidence and severity of bone loss and osteoporosis.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。骨质的快速增加发生在青春期。在青春期优化钙吸收（Ca-abs）和骨钙沉积（Vo+）可以提高峰值骨量，并最终降低骨质疏松症的终生风险。在这项研究中，我们将确定激素，遗传和饮食因素的影响，导致最大的钙abs和Vo+在青春期的男孩和女孩。假设条件：我们的总体假设是，青春期早期矿物质代谢的动态变化是基于可识别的激素和遗传因素，特定的营养干预可以增强骨量积累。具体来说，在本提案中，我们将评估以下内容：1）在男孩和女孩中，青春期激素的夜间早期增加与Ca-abs和Vo+密切相关。相反，血清瘦素将与Vo+呈负相关; 2）骨质疏松症的推定遗传标志物，包括维生素D受体多态性，将与Ca-abs和Vo+显著相关; 3）添加NDO将增加接受推荐膳食钙摄入量的青春期儿童的Ca-abs和Vo+。我们将入组50名健康的女孩和50名男孩，他们的体重指数为年龄的第10 - 90%，并且是坦纳2或3期。他们将参加全面的双示踪剂钙稳定同位素动力学研究。结果将与青春期激素研究，生化骨转换标志物，双能X线吸收法（DXA）测量全身和局部骨矿物质含量进行比较。将评估与骨量相关的遗传标志物，并将其与激素和钙动力学测量值相关。在这些基线研究之后，受试者将被随机分配接受添加或不添加NDO的钙强化食品。2个月后将再次测量钙吸收。12个月后，将重复进行基线钙动力学、激素和DXA研究，以评估青春期发育和饮食干预的影响。在该研究结束时，将停止补充NDO，并在12个月后进行最终DXA研究，以评估在补充期间确定的骨量差异是否在干预后得到维持。结论：通过确定青春期激素变化、遗传和钙代谢之间的关系，可以确定导致最大钙吸收和利用的特征。这些见解将使提高骨量的干预策略与可识别的人群特征具体相关，最终目标是降低骨丢失和骨质疏松症的发生率和严重程度。