PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION

这是P-01 AG 04875“老龄人群骨代谢生理学”第16-20年资助的竞争性更新申请。“骨质疏松症是与衰老有关的最重要的疾病之一，也是影响妇女健康的最重要问题之一。 骨质疏松症导致的骨折在残疾和费用方面造成了惊人的损失。 对于白色女性，一生中发生一次或多次与骨质疏松症相关的骨折的风险为40%-50%，对于黑人女性或白色男性，这一风险为三分之一。 我们的总体目标是更好地了解年龄相关性骨丢失和骨质疏松症的原因，以便制定更有效的治疗和预防策略。 该计划赠款申请包括采用不同的调查学科和行政/统计核心的项目，它们相互作用，两个允许比单独实现更快的进展。 “骨质疏松症的病理生理学”是临床研究的组成部分。 在新的假设，将被测试的是新发现的抗再吸收和促再吸收的细胞因子骨保护素及其同源配体是否是雌激素（E）对骨的作用和异常分泌的旁分泌介质有助于绝经后骨质疏松症，以及是否E缺乏症在老年男性骨丢失中起主要的因果作用。 “髋关节骨折的危险因素”，流行病学部分，包括一系列独特的，基于人群的回顾性（非当前，历史）队列研究，旨在评估某些疾病，药物和生活方式差异对骨折发生率的影响。 “性类固醇，生长因子和骨细胞功能”，基础科学部分，侧重于性类固醇调节骨细胞功能。 它将解决骨细胞生物学中两个最重要的当前问题-雌激素受体的α和β种类的浓度变化对骨细胞功能的影响，以及确定骨细胞上的主要旁分泌介质E。

This is a competitive renewal application for funding of years 16-20 of P-01 AG 04875 "Physiology of Bone Metabolism in an Aging Population." Osteoporosis is one of the most important diseases associated with aging and one of the most important issues affecting women's health. Fractures due to osteoporosis exact a staggering toll in disability and expense. The lifetime risk of having one or more fractures associated with osteoporosis is 40%-50% for a White women and is one third of this for a Black woman or a White man. Each year osteoporosis causes at least 1.5 million fractures and costs the health care system $14 billion in the United States. Our overall goal is to understand the causes of age-related bone loss and osteoporosis better so as to develop more effective strategies for their treatment and prevention. This program grant application comprises projects employing different investigative disciplines and an administrative/statistical core that interact synergistically two permit more rapid progress than could be achieved by each alone. "Pathophysiology of Osteoporosis," is the clinical investigative component. Among the novel hypotheses that will be tested are whether the newly discovered anti-resorptive and pro-resorptive cytokines-osteoprotegrin and its cognate ligand-are the paracrine mediators of estrogen (E) action on bone and abnormalities in their secretion contribute to postmenopausal osteoporosis and whether E deficiency plays a major causal role in bone loss in aging men. "Risk Factors for Hip Fractures," the epidemiology component, features a series of unique, population-based retrospective (non-current, historical) cohort studies designed to assess the effects of certain diseases, drugs, and lifestyle differences on the incidence of fractures. "Sex Steroids, Growth Factors, and Bone Cell Function," the basic science component, focuses on sex steroid regulation of bone cell function. It will address two of the most important current issues in bone cell biology- the effect of changes in the concentration of the alpha and beta species of estrogen receptors on bone cell function and the identify of the major paracrine mediator of E on bone cells.