Change in Bone, Arthritis, Function: Hormones & Obesity

骨骼、关节炎、功能的变化：激素

• 批准号: 7046172
• 负责人: MARYFRAN R SOWERS
• 金额: $ 51.2万
• 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/7046172
• 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); 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（申请人提供）：此申请有两个主要目标。首先是扩展密歇根骨健康研究（MBHS）人群的随访，以额外进行4次年度考试。 1992年发起的10年MBHS纵向研究表征了肌肉骨骼状况的自然历史及其在妇女中的改变（基线为25-45岁），其激素状态由于更年期和肥胖而发生了变化。其次，我们建议评估肥胖对肌肉骨骼状态和身体功能产生的代谢环境的影响，重点是氧化应激和炎症。目的是：a）描述人体成分的13年变化率以及以下内容：1）前，围绝经期和绝经后骨质损失率，包括骨矿物质密度（BMD），骨宽度和骨矿物质浓度，2）橡木的发生率和患病率以及3）的身体功能变化。 b）描述卵巢（即雌二醇'）和非卵巢激素浓度（即，雄激素）在13年内的变化，并将激素变化与1）前，绝经前和绝经后骨骨损失的发生率，2）oak的发生率和前进性，以及3）在身体上的发生变化。 c）通过评估夸张的炎症状态是否加上越来越更大的胰岛素抵抗（可见在肥胖症中），评估脂肪和瘦质量变化影响的潜在机制会增加BMD损失，OA进展和更大的身体限制的可能性。在1992/93至2002/3期间，每年从604名MBH的参与者中收集了数据，并排除了1996/1997。在所有十项评估中，已经评估了超过60％的研究人群，其中84％的人群在十（10）个评估中至少有8（8）个。与三个主要结果有关的结果已在30多个出版物中提出。拟议的4个年度评估将涵盖13年的期限，其中包括妇女的生殖寿命到绝经后。年度评估将包括BMD，身体功能的测量，静脉切开术和尿液收集，以评估激素和炎症标记。 X射线将在拟议时期的第二年第三年进行，在感兴趣的时间间隔内拥有一系列4手和膝盖胶片。将分析储存的标本（血清和尿液）在13年期间对选定的激素，炎症标记，葡萄糖和胰岛素进行替代年份。这项研究将提供一个独特的环境，以评估与衰老相关的过程（更年期）的影响以及与环境相关的过程（增加肥胖）对肌肉骨骼疾病的发育和进展以及它们有助于功能程度的潜力。