EPIDEMIOLOGY OF AGE RELATED BONE LOSS AND FRACTURES

骨质疏松症在美国是一个巨大的公共健康问题， 据估计，有2600万欧洲裔美国女性经历了 每年有100多万人因骨质疏松而骨折 超过100亿美元。我们的具体目标是试图填补知识空白 这阻碍了有效控制程序的设计和实施 来治疗这种疾病。目标1)通过延长对我们最初年龄的跟踪- 分层抽样罗切斯特，MN女性长达20年，我们将 从基线测量评估骨折的长期可预测性 潜在危险因素，包括骨密度(BMD) 脊椎和臀部。这将允许从预期数据中验证 正在提出的长期裂缝风险的理论模型 协助临床决策。目标2)关于新发展的 罗切斯特的女性和男性，以及少数族裔居民的额外样本 罗切斯特，我们将进行全面的研究，以定义特定的性别 与年龄相关的骨密度和骨转换(横断面)和 骨丢失(纵向)并确定残留的影响 血清性和肾上腺类固醇水平、血清年龄相关性升高 甲状旁腺激素、脂肪量和血清胰岛素对 这些变化。我们还将确定骨质疏松症的风险是否被修改 通过维生素D受体(VDR)基因类型的差异以及这些基因是否可以 预测骨密度和骨丢失率。通过评估这些综合体 以人群为基础的平行男性研究中的同时关系 和女性，我们希望解决相互矛盾的数据并完善假设 骨质疏松病理生理学。目标3)通过抽取新的随机样本 奥姆斯特县农村男女与罗切斯特的比较 居民，我们将确定体育活动是否对 骨密度是由瘦体重以及运动和运动的差异 肌肉质量是农村居民骨密度较高的原因，因此较低的骨密度 在奥姆斯特县农村地区观察到的髋部骨折发生率 与罗切斯特相比。目标4)最后，在重新评估诊断后 标准与后续X线片，我们将使用定量 椎体形态计量学评价椎体病变患病率 罗切斯特男性的骨折与女性的比较。与的其他比较 来自南卡罗来纳州查尔斯顿的女性将帮助确定是否有 因种族或性别差异而导致的患病率差异 骨密度或维生素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 以人口为基础的流行病学研究。我们将采用最先进的技术 方法采用双能X线骨密度仪测量总吸光度和总吸光度。 局部骨密度和瘦体质量--新的骨生化标志物 营业额和评估基因的分子生物学技术 易患骨质疏松症。这项研究将使我们能够确定 并在总体上量化骨丢失和骨折的决定因素 以更好地识别那些有感染风险的人 骨质疏松症，然后可以作为预防性干预的目标。

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.