PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION

老龄化人群骨代谢的生理学

• 批准号: 3090941
• 负责人: B. LAWRENCE RIGGS
• 金额: $ 80.77万
• 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 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3090941
• 关键词: aging; osteoporosis

Because of its high incidence and because of its devastating socioeconomic consequences, involutional osteoporosis is one of the most important disorders affecting the aging population. The disease causes 1.3 million fractures, including 240,000 hip fractures, each year. Almost one-third of women over age 65 years will have had vertebral fractures. The lifetime risk of hip fracture is 15% in women and 5% in men. Fifty percent of survivors cannot walk independently afterwards, and 25 to 50% are committed to long-term nursing home care. Overall costs of osteoporosis are estimated as $7 to $10 billion annually in the United States. In order to treat and to prevent this disorder we need 1) to know more about basic physiologic mechanisms regulating bone cell function, 2) to elucidate the mechanisms of disordered regulation of bone cell function in osteoporosis, 3) to define more sharply clinical risk factors for fractures, and 4) to find a safe and effective means of prevention that would be widely used by the general population of aging women. To accomplish these aims is our overall goal. The Program Project contains four independent research components and an administrative and biostatistical core. Project 1, "Pathophysiology of Osteoporosis," is the clinical investigation component. It tests the hypothesis that the disease results from impaired production of several systemic and local bone cell regulatory factors or from impaired response to them. We will search for abnormalities of systemic regulatory factors and, by testing cultured human bone cells, will assess possible local abnormalities of bone cell regulation for the first time in the study of osteoporosis. Project 2, "Record Studies of Hip Fractures" is the epidemiology component. It features a series of unique population-based retrospective (non-current, historical) cohort studies designed to determine the incidence of hip and various other age-related fractures and identify risk factors for them. In specified cohorts of patients with the risk factor, the incidence of fracture will be compared with the expected incidence rates in the community population. Project 3, "Regulation of Bone Cell Function," is the basic science component. It uses cell biology and molecular biology techniques to evaluate the effect and mechanism of action of sex steroids and growth factors on cultured normal human osteoblast-like cells. Project 4, "Preventive Therapy with Calcium," is the clinical trial component. It is designed to determine if bone loss in elderly women can be prevented or reduced by calcium supplementation as is suggested by our preliminary data.

由于其发病率高、破坏性大 社会经济后果中，渐进性骨质疏松症是最严重的疾病之一 影响人口老龄化的重要疾病。 该病引起 每年有 130 万例骨折，其中包括 24 万例髋部骨折。 65 岁以上女性中，近三分之一患有脊椎病 骨折。 女性终生髋部骨折的风险为 15%，男性为 5% 男人。 百分之五十的幸存者事后无法独立行走， 25% 至 50% 致力于长期疗养院护理。 全面的 据估计，骨质疏松症每年造成的损失为 7 至 100 亿美元 美国。 为了治疗和预防这种疾病，我们需要 1）了解更多调节骨细胞的基本生理机制 功能，2）阐明紊乱调节的机制 骨质疏松症中的骨细胞功能，3) 更清晰地定义临床 骨折的危险因素，以及4）找到安全有效的方法 一般老年人口将广泛使用的预防措施 女性。 实现这些目标是我们的总体目标。 该计划 项目包含四个独立研究部分和一个 行政和生物统计核心。 项目 1，“病理生理学 骨质疏松症”是临床研究的组成部分。它测试 假设该疾病是由几种细胞产生受损引起的 全身和局部骨细胞调节因子或受损 回应他们。 我们将寻找系统性异常 调节因素，并通过测试培养的人骨细胞，将 评估骨细胞调节可能的局部异常 首次参与骨质疏松症研究。 项目 2，“记录研究” 髋部骨折”是流行病学部分。它具有一系列 独特的基于人群的回顾性（非当前、历史）队列 旨在确定髋关节和其他各种疾病发生率的研究 与年龄相关的骨折并确定其危险因素。 在指定的 具有危险因素的患者队列中，骨折的发生率将 与社区的预期发病率进行比较 人口。 项目3“骨细胞功能的调节”是基础 科学成分。 它利用细胞生物学和分子生物学 评估性的影响和作用机制的技术 类固醇和生长因子对培养的正常人成骨细胞样细胞的影响 细胞。 项目 4“钙预防治疗”是临床 试用组件。 它旨在确定老年人是否骨质流失 女性可以通过补钙来预防或减少 根据我们的初步数据建议。