PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION

因为它的高发病率和它的破坏性 社会经济后果，退化性骨质疏松症是 影响人口老龄化的重要疾病。疾病引起的 每年130万次骨折，其中包括24万次髋部骨折。 65岁以上的女性中有近三分之一患有脊椎病 骨折。女性患髋部骨折的终生风险为15%，女性为5% 男人。50%的幸存者事后无法独立行走， 25%至50%的人致力于长期疗养院护理。总括 骨质疏松症的成本估计为每年70亿至100亿美元。 美国。为了治疗和预防这种疾病，我们需要 1)了解骨细胞调节的基本生理机制 功能，2)阐明细胞调控紊乱的机制 骨质疏松症中的骨细胞功能，3)更准确地界定临床 骨折的危险因素，以及4)寻找安全有效的治疗方法 预防将被普遍用于老龄化的普通人群 女人。实现这些目标是我们的总目标。该计划 该项目包含四个独立的研究组件和一个 行政和生物统计学核心。项目1，“儿童的病理生理学” 骨质疏松症“是临床研究的组成部分。它测试 假设这种疾病是由几种物质的生产受损引起的 全身和局部骨细胞调节因子或来自受损 对他们的回应。我们将寻找全身性的异常 调节因素，并通过测试培养的人类骨骼细胞，将 评估可能存在的局部骨细胞调节异常 在骨质疏松症的研究中尚属首次。项目2，“记录研究 髋部骨折“是流行病学的组成部分。它以一系列 独特的基于人群的回顾(非当前、历史)队列 旨在确定髋关节和其他各种疾病发病率的研究 与年龄相关的骨折，并确定其风险因素。在指定的 队列中有危险因素的患者，骨折的发生率会 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 科学部分。它利用细胞生物学和分子生物学 评价性行为的作用和机制的技术 类固醇和生长因子对培养的正常人成骨样细胞的影响 细胞。项目4，“钙预防疗法”，是临床 试用组件。它被设计用来确定老年人是否有骨丢失 妇女可以通过原样补充钙来预防或减少 根据我们的初步数据显示。

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.