Physiology of Bone Metabolism in an Aging Population

骨质疏松症是一个巨大的公共卫生问题。最近的估计表明，大约有4400万50岁及以上的美国女性和男性患有骨质疏松症或骨量不足，每年导致150万人骨折，其中包括30万髋部骨折，70万脊柱骨折，25万前臂骨折，以及25万其他部位的骨折。虽然传统上被认为是女性的疾病，但男性也会患上骨质疏松症。因此，在50岁时，女性患骨质疏松性骨折的终生风险为40%，而男性的可比数字为13%。鉴于这一问题的范围，以及随着人口老龄化，这种疾病的流行率预计会增加，合理的预防和治疗方法关键取决于更好地了解这种疾病的发病机制，以及评估其对社区的影响。上一个资金周期的工作现已确定，雌激素(E)缺乏不仅是女性，而且也是男性与年龄相关的骨丢失的一个关键因素；因此，所有项目的一个共同主题是E调节骨代谢。与过去一样，我们团队的主要优势是将不同的学科整合到协同互动中，目前的应用涵盖了基于人群的流行病学研究、临床研究中心的密集研究、使用新型小鼠基因敲除模型的动物研究，以及使用最先进的蛋白质组学技术的基础分子研究。这是通过五个项目和一个行政和生物统计学核心完成的：“老年男性骨质疏松症的病理生理学”和“老年女性骨质疏松症的病理生理学”分别利用临床研究中心对男性和女性进行的密集研究；“老年人髋部骨折的风险因素”利用基于人群的流行病学研究中的罗切斯特流行病学项目的资源；“雌激素受体辅活化子和骨代谢”侧重于E动作缺陷的新型小鼠敲除模型；以及“成骨细胞中雌激素受体辅调节因子的作用”建议在分子水平上剖析骨细胞中的E动作。总而言之，这些研究致力于全面评估这种重要疾病的发病机制和临床影响。

Osteoporosis is an enormous public health problem. Recent estimates indicate that about 44 million US women and men aged 50 years and older have osteoporosis or low bone mass, resulting in 1.5 million fractures per year, including 300,000 hip fractures, 700,000 spine fractures, 250,000 forearm fractures, and 250,000 fractures at other sites. While traditionally considered a disease of women, men also develop osteoporosis. Thus, at age 50, the lifetime risk of an osteoporotic fracture in women is 40%, and the comparable figure for men is 13%. Given the scope of this problem and the projected increase in the prevalence of this disease as the population ages, rational approaches to prevention and treatment depend critically on gaining a better understanding the pathogenesis of this disorder, as well as assessing its impact in the community. Work over the previous funding cycle has now identified estrogen (E) deficiency as a key factor in the development of age-related bone loss not only in women, but also in men; hence, a theme common to all projects is E regulation of bone metabolism. As in the past, the major strength of our group is to bring together diverse disciplines into synergistic interactions, and the present application spans the spectrum from population-based epidemiology studies, intensive studies in the clinical research center, animal studies using novel mouse knock out models, and basic molecular studies using state-of-the-art proteomics technology. This is accomplished through five Projects and an Administrative and Biostatistics Core: "Pathophysiology of Osteoporosis in Aging Men" and "Pathophysiology of Osteoporosis in Aging Women" utilize intensive studies in the clinical research center in men and women, respectively; "Risk Factors for Hip Fractures Among the Elderly" utilizes the resources of the Rochester Epidemiology Project in population-based epidemiology studies; "Estrogen Receptor Coactivators and Bone Metabolism" focuses on novel mouse knock out models with defects in E action; and "Actions of Estrogen Receptor Coregulators in Osteoblasts" proposes to dissect E action in bone cells at a molecular level. Collectively, these studies strive to provide a comprehensive assessment of the pathogenesis and clinical impact of this important disorder.