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相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。 骨质疏松症引起的骨折造成了惊人的残疾和死亡人数 费用。 对于 50 岁的白人女性来说，一生中患上一种或多种疾病的风险 与骨质疏松症相关的骨折占 40% 至 50%，大约为 1- 其中三分之一是白人男性或黑人女性。 每年在美国 美国至少有 130 万例骨折是由于骨质疏松症造成的 医疗保健系统的成本在 10 至 200 亿美元之间，除非 疾病得到控制，这些数字将在未来 25 年翻倍，因为 人口持续老龄化。 本计划的长期目标 该项目旨在更好地了解与年龄相关的骨质流失的原因 骨质疏松症，并通过这样做，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 行政和生物统计核心。 “病理生理学 “退化性骨质疏松症”是临床研究的组成部分。 在 这个项目将对正常女性进行研究，以更好地了解这两者 更年期骨质流失的最重要原因——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会 进行研究以确定他们的骨转换水平和速率是否更高 骨质流失是由于独特的过程造成的，这些过程与 那些没有骨质疏松症的可比女性。 所有研究都将进行 在代谢病房，将传统的生理方法与 最先进的技术。 “髋部骨折的记录研究”是 流行病学成分。 它具有一系列独特的基于人口的、 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 骨折的发生率。 此外，年龄调整骨折的长期变化 将评估过去 20 年的利率。 《骨细胞的调节 功能”是基础科学组成部分。它利用细胞生物学和 分子生物学技术评估雌激素对 正常培养物中生长因子的分化和表达 源自骨或骨髓的成骨细胞样细胞，采用独特的新方法 源自正常未分化胎儿成骨细胞样细胞的细胞系 用温度敏感/调节的 SV-40 大 T 抗原永生化。 此外，雌激素对成骨细胞衍生的旁分泌因子的调节 调节破骨细胞活性将被识别和表征。 “钙预防疗法”是一项正在进行的临床试验，它将 需要延长 1 年才能完成。 它旨在确定是否有骨骼 钙可以预防或减少老年妇女的损失 补充。