Change in Bone, Arthritis, Function: Hormones & Obesity

描述（由申请人提供）：本申请有两个主要目标。首先是延长密歇根骨骼健康研究（MBHS）人群的随访时间，每年再进行4次检查。这项始于1992年的长达10年的MBHS纵向研究，描述了因绝经和肥胖而导致激素水平发生变化的女性（基线年龄为25-45岁）肌肉骨骼状态的自然历史及其变化。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年的身体组成变化率，以及以下内容：1)绝经前、围绝经期和绝经后的骨质流失率，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；3)身体功能的变化。B)描述卵巢的变化(即……雌激素')和非卵巢激素浓度（即雄烯二酮），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)OAK的发病率和流行率以及3)中年妇女身体功能的变化联系起来。C)评估脂肪和瘦肉质量变化影响的潜在机制，通过评估过度的炎症状态是否与越来越大的胰岛素抵抗（见肥胖）相结合，增加了骨密度损失、骨性关节炎进展和更大身体限制的可能性。在1992/93年至2002/3年期间（不包括1996/1997年），每年对604名MBHS参保人进行10次数据收集。超过60%的研究人群接受了所有10项评估，84%的人群至少接受了10项评估中的8项。与这三个主要成果有关的结果已发表在30多份出版物中。拟议增加的4项年度评估将涵盖13年期间，包括妇女的生殖寿命至绝经后。年度评估将包括骨密度、身体功能测量、采血和尿液收集，以评估激素和炎症标志物。x射线将在提议的时间的第二到第三年拍摄在感兴趣的时间间隔内拍摄一系列4张手和膝盖照片。将对储存的标本（血清和尿液）进行分析，以便在13年期间对选定的激素、炎症标志物、葡萄糖和胰岛素进行替代年度测量。本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）对肌肉骨骼疾病的发展和进展的影响，以及它们对功能程度的潜在影响。

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.