NOVEL TECHNIQUES FOR ANALYSIS OF BONE MINERAL BALANCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：探讨钙、锶稳定同位素技术在骨矿平衡评价中的应用价值。 骨质疏松症是老年人最常见的疾病之一，以骨量减少和骨小梁结构紊乱为特征，伴有骨骼脆性。在世界范围内，50岁以上的女性每3人中就有1人患有骨质疏松症，男性每4人中就有1人患有骨质疏松症。此外，随着人口规模和预期寿命的增加，与骨质疏松症相关的髋部骨折的发病率预计将在未来20年翻一番。营养不足、遗传易感性、体力活动减少、“年龄相关”因素和雌激素缺乏都可能导致绝经后和年龄相关性骨质疏松症的病理生理学。随着更年期或卵巢切除引起的循环雌激素水平的降低，骨骼周转和骨丢失迅速增加，突显出雌激素在女性骨质疏松发生中的关键作用。骨转换生化标记物的临床价值微乎其微，不适合检测骨矿物质动力学(骨骼对内分泌变化反应的关键成分)的快速变化，也不能用来测量骨矿物质的净平衡。为了克服这些问题，我们建议使用钙(Ca)和锶(Sr)稳定同位素技术，这些技术在地球化学中得到了很好的验证，但在生物医学中很少应用。这些技术承诺提供前所未有的细节和精确度的骨矿物质平衡数据，将被验证并应用于一种独特的低雌激素骨量维持的动物模型。这些新的非侵入性技术将被证明对骨质疏松症的研究具有无价的价值，并为未来的研究和临床应用提供了很好的前景。这项研究使用了动物服务和研究服务。

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. Objective: To explore the possible utility of calcium and strontium stable isotope techniques in the assessment of bone mineral balance. Osteoporosis, characterized by low bone mass and disordered trabecular architecture with attendant skeletal fragility, is among the most common diseases of older people. Worldwide, osteoporosis affects 1 in 3 women and 1 in 4 men over 50 years of age. Additionally, the incidence of osteoporosis-related hip fracture is expected to double in the next 20yrs with increasing population size and life expectancy. Nutritional insufficiencies, genetic predisposition, decreased physical activity, "age-related" factors, and estrogen deficiency all likely contribute to the pathophysiology of postmenopausal and age-related osteoporosis. Skeletal turnover and bone loss rapidly increase following reduction of circulating estrogen levels resulting from menopause or ovariectomy, highlighting the critical role of estrogen in the genesis of osteoporosis in women. Biochemical markers of bone turnover are of marginal clinical value, are poorly suited to detect rapid alterations in bone mineral kinetics (critical components of skeletal response to endocrine change), and cannot be used to measure net bone mineral balance. To overcome these problems, we propose employing calcium (Ca) and strontium (Sr) stable isotope techniques that are well validated in geochemistry, but rarely applied in biomedicine. These techniques, which promise to provide data on bone mineral balance of unprecedented detail and precision, will be validated and applied to a unique animal model of hypoestrogenic bone mass maintenance. These novel, noninvasive techniques will prove invaluable to osteoporosis research and afford high promise for future research and clinical applications. This research used Animal Services and Research Services.