Change in Bone, Arthritis, Function: Hormones & Obesity

描述（由申请人提供）：该应用程序有两个主要目标。第一个是在密歇根州骨健康研究（MBHS）人群中延长随访，增加4次年度检查。1992年开始的为期10年的MBHS纵向研究，描述了由于绝经和肥胖而导致激素状态发生变化的女性（基线年龄为25-45岁）的肌肉骨骼状态及其变化的自然史。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，重点是氧化应激和炎症。其目的是：A）描述13年身体组成的变化率和以下内容：1）绝经前、围绝经期和绝经后骨丢失率，包括骨矿物质密度（BMD）、骨宽度和骨矿物质浓度，2）OAK的发生率和患病率，3）身体功能的变化。B）描述卵巢的变化（即。雌二醇）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丢失率，2）OAK的发病率和患病率，以及3）中年妇女身体功能的变化联系起来。C）通过评估过度的炎症状态加上越来越大的胰岛素抵抗（见于肥胖症）是否增加了更大的BMD损失、OA进展和更大的身体限制的可能性，来评估脂肪和瘦体重变化的影响的潜在机制。在1992/1993年至2002/2003年期间（不包括1996/1997年），每年从604名MBHS登记者中收集10次数据。超过60%的研究人群在所有10项评价中接受了评估，84%的人群至少接受了10项评价中的8项。30多份出版物介绍了与这三项主要成果有关的结果。拟议的4次额外年度评估将涵盖13年的时间，包括妇女的生殖寿命至绝经后期。年度评估将包括BMD、身体功能测量、抽血和尿液收集，以评估激素和炎症标志物。将在拟定时间段的第2 - 3年拍摄X线片，以在关注的时间间隔内拍摄一系列4张手部和膝关节X线片。将对储存的标本（血清和尿液）进行分析，以在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，以评估衰老相关过程（绝经）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及其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.