PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION

老龄化人群骨代谢的生理学

• 批准号: 2442206
• 负责人: B. LAWRENCE RIGGS
• 金额: $ 129.45万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442206
• 关键词: aging; osteoporosis

Osteoporosis is one of the most important diseases associated with aging and is also one of the most important issues affecting women's health. Fractures due to osteoporosis exact a staggering toll in disability and expense. For a 50-yr-old white women, the lifetime risk of having one or more fractures associated with osteoporosis is 40% to 50% and is about one- third of this for white men or black women. Each year in the United States, there are at least 1.3 million fractures due to osteoporosis, which cost the healthcare system between $10 and $20 billion and, unless the disease is controlled, these will double over the next 25 yrs because of continued aging of the population. The long-range goal of this Program Project is to understand better the causes of age-related bone loss in osteoporosis an, by so doing, to develop effective strategies for its treatment and prevention. The Program Project contains 4 independent research components, each representing a different research discipline, and an administrative and biostatistical core. "Pathophysiology of Involutional Osteoporosis,' is the clinical investigative component. In this project, normal women will be studied to understand better the two most important causes of involutional bone loss -- estrogen deficiency and age-related processes. Also, women with postmenopausal osteoporosis will be studied to determine if their greater levels of bone turnover and rates of bone loss are due to unique processes that differ substantially from those in comparable women without osteoporosis. All studies will be made in a metabolic ward and will combine traditional physiologic methods with state-of-the-art techniques. "Record Studies of Hip Fractures," is the epidemiology component. It features a series of unique population-based, retrospective (noncurrent, historical) cohort studies designed to assess the effects of certain diseases, drugs, and lifestyle differences on the incidence of fractures. Also, secular changes in age-adjusted fracture rates over the last 20 yrs will be assessed. "Regulation of Bone Cell Function," is the basic science component. It uses cell biology and molecular biology techniques to evaluate the effects of estrogen on the differentiation and expression of growth factors on cultured normal osteoblast-like cells derived from bone or bone marrow and on a unique new cell line derived from normal undifferentiated fetal osteoblast-like cells immortalized with a temperature sensitive/regulated SV-40 large T antigen. Also, estrogen regulation of osteoblast-derived paracrine factors that regulate osteoclastic activity will be identified and characterized. "Preventive Therapy with Calcium," is an ongoing clinical trial, which will require a 1-yr extension to complete. It is designed to determine if bone loss in elderly women can be prevented or reduced by calcium supplementation.

骨质疏松症是与衰老有关的最重要的疾病之一 也是影响女性健康的最重要问题之一。 由于骨质疏松症导致的骨折造成了惊人的残疾和 费用。对于50岁的白人女性来说，生一个孩子或 更多与骨质疏松症相关的骨折是40%到50%，大约是1- 其中三分之一是针对白人男性或黑人女性的。每年在美国 在美国，至少有130万人因骨质疏松而骨折，其中 医疗保健系统的成本在100亿至200亿美元之间，除非 疾病得到了控制，在接下来的25年里，这一数字将翻一番 人口持续老龄化。这项计划的长远目标 项目是为了更好地了解与年龄相关的骨丢失的原因 骨质疏松症，通过这样做，为其制定有效的策略 治疗和预防。该计划项目包含4个独立的 研究组成部分，每个组成部分代表不同的研究学科，以及 一个行政和生物统计学核心。“病理生理学” 退化性骨质疏松症“是临床研究的组成部分。在……里面 本项目中，将对正常女性进行研究，以更好地了解两者 导致退化性骨丢失的最重要原因--雌激素缺乏和 与年龄相关的过程。此外，患有绝经后骨质疏松症的女性将 被研究以确定他们更高的骨转换水平和比率 是由于独特的过程造成的，这种过程与 在没有骨质疏松的可比女性中也是如此。所有的研究都将进行 在新陈代谢病房，将结合传统的生理方法和 最先进的技术。《髋部骨折的记录研究》是 流行病学部分。它以一系列独特的基于人口的、 回溯性(非当前的、历史的)队列研究旨在评估 某些疾病、药物和生活方式的差异对 骨折发生率。此外，年龄调整后骨折的长期变化 将评估过去20年的费率。“骨细胞的调控” 是基础科学的组成部分。它利用细胞生物学和 用分子生物学技术评价雌激素对小鼠卵巢功能的影响 生长因子在正常培养细胞中的分化和表达 成骨样细胞来源于骨或骨髓，并在一个独特的新的 正常胎儿未分化成骨样细胞来源的细胞系 用温度敏感/调节的SV-40大T抗原永生。 此外，雌激素对成骨细胞衍生的旁分泌因子的调节作用 调节破骨细胞活动将被识别和表征。 “钙预防疗法”是一项正在进行的临床试验，它将 需要延期1年才能完成。它被设计用来确定骨骼是否 钙可以预防或减少老年妇女的骨质流失 补充。