Change in Bone, Arthritis, Function: Hormones & Obesity

骨骼、关节炎、功能的变化：激素

• 批准号: 6921105
• 负责人: MARYFRAN R SOWERS
• 金额: $ 50.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6921105
• 关键词: X ray; acute phase protein; androstenedione; blood chemistry; body composition; bone density; clinical research; electrical impedance; estradiol; female; hormone regulation /control mechanism; human middle age (35-64); human subject; inflammation; insulin sensitivity /resistance; interleukin 6; interview; knee; longitudinal human study; menopause; obesity; osteoarthritis; osteoporosis; oxidative stress; photon absorptiometry; postmenopause; tumor necrosis factor alpha; urinalysis; women' s health; young adult human (21-34)

DESCRIPTION (provided by applicant): This application has two major goals. The first is to extend follow-up in the Michigan Bone Health Study (MBHS) population for an additional 4 annual examinations. The 10-year MBHS longitudinal study, initiated in 1992, has characterized the natural history of musculoskeletal status and its alteration among women (aged 25-45 at their baseline) whose hormone status is changing because of menopause and obesity. Secondly, we propose to evaluate the influence of the metabolic environment generated by obesity on musculoskeletal status and physical functioning with a focus on oxidative stress and inflammation. The aims are to: A) Describe the 13-year rate of change in body composition and the following: 1) rate of pre, perimenopausal and postmenopausal bone loss including bone mineral density (BMD), bone width, and bone mineral concentration, 2) incidence and prevalence of OAK, and 3) change in physical functioning. B) Describe changes in ovarian (i.e.. estradiol') and non-ovarian hormone concentrations (i.e., androstenedione) over a 13-year period and relate the hormone changes to 1) rate of pre, perimenopausal and postmenopausal bone loss, 2) incidence and prevalence of OAK, and 3) change in physical functioning in mid-aged women. C) Evaluate the potential mechanisms for the impact of change in fat and lean mass by assessing whether an exaggerated inflammatory state coupled with increasingly greater insulin resistance (seen in obesity) increases the likelihood of greater BMD loss, OA progression, and greater physical limitation. Data has been collected annually from the 604 enrollees of MBHS ten times over the period 1992/93 to 2002/3 and excluding 1996/1997. More than 60% of the study population has been assessed at all ten evaluations and 84% of the population had at least eight (8) of the ten (10) evaluations. Results related to the three major outcomes have been presented in more than 30 publications. The proposed 4 additional yearly assessments will cover a 13-year period that includes the reproductive life span of women to the postmenopause. Annual assessments will include BMD, measures of physical functioning, phlebotomy and urine collection to allow assessment of hormones and inflammation markers. X-rays will be taken in the 2nd-3nd year of the proposed time period to have a series of 4 hand and knee films over the time interval of interest. Stored specimens (serum and urine) will be assayed to have alternative year measures of selected hormones, inflammation markers, glucose and insulin over the 13-year period. This study will provide a unique setting to evaluate the impact of an aging related process (menopause) and an environmentally related process (increasing obesity) on the development and progression of musculoskeletal disease and their potential for contributing to degree of functioning.

描述（由申请人提供）：该申请有两个主要目标。第一个是扩大密歇根骨骼健康研究 (MBHS) 人群的随访范围，进行额外 4 次年度检查。这项为期 10 年的 MBHS 纵向研究始于 1992 年，描述了女性（基线年龄为 25-45 岁）肌肉骨骼状态的自然史及其变化，这些女性的激素状态因更年期和肥胖而发生变化。其次，我们建议评估肥胖产生的代谢环境对肌肉骨骼状态和身体功能的影响，重点关注氧化应激和炎症。目的是： A) 描述 13 年身体成分的变化率以及以下内容：1) 绝经前、围绝经期和绝经后骨质流失率，包括骨矿物质密度 (BMD)、骨宽度和骨矿物质浓度，2 ) OAK 的发病率和患病率，以及 3) 身体机能的变化。 B) 描述 13 年期间卵巢（即雌二醇）和非卵巢激素浓度（即雄烯二酮）的变化，并将激素变化与 1) 绝经前、围绝经期和绝经后骨质流失率，2) 发生率联系起来和 OAK 患病率，以及 3) 中年女性身体机能的变化。 C) 通过评估过度的炎症状态与日益增强的胰岛素抵抗（在肥胖中可见）是否会增加 BMD 损失更大、OA 进展和身体限制更大的可能性，来评估脂肪和瘦体重变化影响的潜在机制。 1992/1993 年至 2002/3 年期间（不包括 1996/1997 年），每年从 MBHS 的 604 名注册者收集数据十次。超过 60% 的研究人群在所有十项评估中均接受过评估，并且 84% 的人群在十 (10) 项评估中至少进行了八 (8) 项评估。与这三项主要成果相关的结果已在 30 多种出版物中发表。拟议的 4 次额外年度评估将涵盖 13 年期间，其中包括妇女的生殖寿命到绝经后。年度评估将包括骨密度、身体机能测量、放血和尿液收集，以评估激素和炎症标志物。将在建议时间段的第二年至第三年拍摄 X 光片，以便在感兴趣的时间间隔内拍摄一系列 4 张手部和膝盖片。将对储存的样本（血清和尿液）进行分析，以对 13 年期间选定的激素、炎症标志物、葡萄糖和胰岛素进行替代年份测量。这项研究将提供一个独特的环境来评估衰老相关过程（更年期）和环境相关过程（肥胖增加）对肌肉骨骼疾病发生和进展的影响及其对功能程度的贡献潜力。