EPIDEMIOLOGY OF AGE RELATED BONE LOSS AND FRACTURES

骨质疏松症在美国是一个巨大的公共卫生问题， 估计有2600万欧美女性 每年有超过100万例与糖尿病相关的骨折， 超过100亿美元我们的具体目标是试图填补知识空白 阻碍有效控制计划的设计和实施 治疗这种疾病目的1）通过延长对我们原始年龄的随访- 罗切斯特，明尼苏达州妇女的分层样本长达20年，我们将 从基线测量评估骨折的长期可预测性 潜在的风险因素，包括骨矿物质密度（BMD）的 脊椎和臀部这将允许从前瞻性数据中验证 长期骨折风险的理论模型， 帮助临床决策。目的2）在新开发的队列中， 罗切斯特的女性和男性，以及少数民族居民的额外样本 罗切斯特的性别差异，我们将进行全面的研究，以确定性别特异性 与年龄相关的骨密度和骨转换的差异（横截面）和 骨丢失（纵向），并确定残留的 血清性别和肾上腺类固醇水平，血清中与年龄相关的增加 甲状旁腺激素、脂肪量和血清胰岛素对调节 这些变化。我们还将确定骨质疏松症的风险是否会改变 维生素D受体（VDR）基因型的差异，以及这些基因型是否可以 预测BMD和骨丢失率。通过评估这些复杂的 在基于人群的平行研究中， 和妇女，我们希望解决相互矛盾的数据和完善的假设， 骨质疏松症病理生理学。目的3）通过抽取一个新的随机样本， 奥姆斯特德县农村的男性和女性与罗切斯特进行比较 居民，我们将确定是否对身体活动的影响 BMD是由瘦体重介导的，活动和 肌肉质量占较高的BMD在农村居民，因此，较低的 在奥姆斯特德县农村观察到的髋部骨折发病率 与罗切斯特相比。目的4）最后，在重新评估诊断后， 标准与后续的X线片，我们将使用定量 影像学椎体形态测量，以估计椎体 罗切斯特男性与女性的骨折比例。其他比较 来自南卡罗来纳州查尔斯顿的妇女将帮助确定是否有 由于种族或性别差异， BMD或维生素D代谢。在所有这些研究中，我们将继续 严重依赖罗切斯特流行病学项目，这是一个独特的资源， 基于人群的流行病学研究。我们将采用最先进的技术 使用双能X线吸收测定法评估总的和 区域BMD和瘦体重，新的骨生化标志物 以及用于评估遗传转化的分子生物学技术 易患骨质疏松症。这项研究将使我们能够识别 量化骨质流失和骨折的决定因素， 以更好地识别那些有风险的人， 骨质疏松症，然后可以有针对性地进行预防干预。

Osteoporosis is an enormous public health problem in the United States, affecting an estimated 26 million European-American women who experience over a million osteoporosis-related fractures each year at a cost exceeding $10 billion. Our specific aims attempt to fill gaps in knowledge that impede the design and implementation of an effective control program for this disorder. AIM 1) By extending follow-up on our original age- stratified sample of Rochester, MN women for up to 20 years, we will assess the long-term predictability of fractures from baseline measurement of potential risk factors, including bone mineral density (BMD) of the spine and hip. This will permit validation, from prospective data, of theoretical models of long-term fracture risk which are being proposed to aid in clinical decision making. AIM 2) On newly developed cohorts of Rochester women and men, and on an additional sample of minority residents of Rochester, we will make comprehensive studies to define gender-specific differences in age-related BMD and bone turnover (cross-sectionally) and bone loss (longitudinally) and to establish the effects that residual levels of serum sex and adrenal steroids, age-related increases in serum parathyroid hormone, and fat mass and serum insulin have on modulating these changes. We will also determine if risk for osteoporosis is modified by differences in vitamin D receptor (VDR) genotypes and whether these can predict BMD and rates of bone loss. By evaluating these complex relationships simultaneously in population-based, parallel studies of men and women, we hope to resolve conflicting data and refine hypotheses of osteoporosis pathophysiology. AIM 3) By drawing a new random sample of rural Olmsted County men and women for comparison with Rochester residents, we will determine whether the effects of physical activity on BMD are mediated by lean body mass and whether differences in activity and muscle mass account for higher BMD in rural residents and, thus, the lower incidence of hip fractures that has been observed in rural Olmsted County compared with Rochester. AIM 4) Finally, after reassessing diagnostic criteria with follow-up roentgenograms, we will use quantitative radiographic vertebral morphometry to estimate the prevalence of vertebral fractures in Rochester men compared to women. Additional comparisons with women from Charleston, SC will help determine whether there are differences in prevalence due to race- or gender-specific differences in BMD or vitamin D metabolism. In all of these studies, we will continue to rely heavily on the Rochester Epidemiology Project, a unique resource for population-based epidemiologic studies. We will employ state-of-the-art methods using dual energy x-ray absorptiometry to assess total and regional BMD and lean body mass, new biochemical markers for bone turnover, and molecular biology techniques for assessing genetic predisposition to osteoporosis. This research will allow us to identify and quantify the determinants of bone loss and fractures in the general population so as to recognize better those individuals at risk for osteoporosis, who could then be targeted for preventive intervention.