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。第一个是延长对密歇根州骨健康研究(MBHS)人群的随访，增加4次年度检查。这项为期10年的MBHS纵向研究始于1992年，研究了由于更年期和肥胖而导致荷尔蒙状态变化的女性(基线年龄为25-45岁)的肌肉骨骼状况及其变化的自然历史。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年来身体成分的变化率和以下指标：1)绝经前、围绝经期和绝经后的骨损率，包括骨密度(BMD)、骨宽度和骨矿物质浓度；2)橡树的发病率和患病率；以及3)身体机能的变化。B)描述卵巢的变化(即这些激素的变化与1)绝经前、围绝经期和绝经后骨质损失率有关，2)橡木树的发病率和患病率，以及3)中年女性身体机能的变化。C)通过评估夸大的炎症状态加上日益严重的胰岛素抵抗(如肥胖症)是否会增加BMD丢失、OA进展和更大的身体限制的可能性，来评估脂肪和瘦肉质量变化影响的潜在机制。在1992/93年至2002/3年期间(不包括1996/1997年)，每年收集604名参加医疗保健制度的人的数据十次。超过60%的研究人群在所有十项评估中进行了评估，84%的人口至少进行了十(10)项评估中的八(8)项。与三大成果有关的成果已在30多份出版物中发表。拟议的4项额外年度评估将涵盖13年，其中包括妇女到绝经后的生殖寿命。年度评估将包括骨密度、身体功能测量、静脉采血和尿液采集，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，以便在感兴趣的时间间隔内拍摄一系列4张手部和膝部照片。将对储存的样本(血清和尿液)进行分析，以在13年内对选定的激素、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背景，以评估与衰老相关的过程(更年期)和与环境有关的过程(日益肥胖)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贡献。

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.