Follicle Stimulating Hormone and Bone Loss in Postmenopausal Women

项目摘要 骨密度和质量下降是美国和全球发病率和死亡率的主要来源。与 随着人口老龄化，骨质疏松症的疾病负担预计将急剧增加。冲突 卵泡刺激素（FSH）水平与骨之间存在雌激素非依赖性相关性的证据 从体内研究和观察性研究中均观察到损失。虽然有生物学原理 和横截面证据的建议协会，没有纵向研究探讨了 FSH与绝经后妇女骨丢失的关系此外，从来没有一个 关于FSH与任何年龄组骨折风险之间关系的研究。理解这一 绝经后妇女之间的关联是至关重要的，因为目前的治疗和预防选择， 骨质疏松症是有限的。因此，确定与骨丢失进展相关的生物学过程， 绝经后妇女将为进一步的流行病学和药理学研究打开大门。 区这项研究的长期目标是更好地了解雌激素非依赖性的作用， FSH在伴随绝经的骨降解过程中。这项建议的目的是 研究血清FSH与骨过程相关的多种结局之间的关系， 衰老，包括骨矿物质密度（BMD）的变化和低骨量、骨质疏松症，以及 骨折我们推测，在绝经后妇女中，血清FSH水平和BMD之间存在负相关。 绝经后妇女以及增加的风险事件低骨量，骨质疏松症和骨折， FSH水平较高的人。我们将使用685名绝经后妇女的样本数据来完成这一点 在布法罗骨质疏松症和牙周病研究（一项前瞻性辅助研究， 妇女健康倡议）。这个绝经后妇女的队列是唯一适合于这些评估 相关性，因为它包括基线时测量的BMD、低骨量、骨质疏松症、FSH和五项 年随访访视，以及超过22年随访的骨折诊断。分析将是 在FSH和其他激素之间复杂的垂体负反馈机制的背景下进行， 内源性激素，该数据集包含雌二醇、性激素结合球蛋白和 睾酮.拟议的项目将大大扩大我的流行病学培训，包括交叉- 分段和纵向方法。此外，还包括对复杂系统的强大培训和理解 内源性激素与骨形成的内分泌反馈机制， 再吸收我提出的培训计划将是双管齐下的，以帮助我在流行病学和生物学 培训作为一个研究人员，而拟议的研究将填补空白的文献FSH和骨密度， 绝经后妇女。

PROJECT SUMMARY Decreased bone density and quality is a major source of morbidity and mortality in the U.S. and globally. With an aging population, the disease burden of osteoporosis is expected to drastically increase. Conflicting evidence of an estrogen independent association between follicle stimulating hormone (FSH) levels and bone loss has been observed from both in vivo studies and observational research. While there is biological rationale and cross-sectional evidence for the proposed association, no longitudinal studies have explored the relationship between FSH and bone loss in postmenopausal women. Additionally, there has never been a study pertaining to the relationship between FSH and fracture risk in any age group. Understanding this association among postmenopausal women is critical because current treatment and prevention options for osteoporosis are limited. Therefore, identifying biologic processes related to the progression of bone loss in postmenopausal women will open the door to further epidemiological and pharmacological research into this area. The long term goal of the proposed research is to better understand the estrogen-independent role of FSH in the process of bone degradation which accompanies menopause. The purpose of this proposal is to investigate the association between serum FSH and multiple outcomes associated with the process of bone aging, including changes in bone mineral density (BMD) and incident low bone mass, osteoporosis, and fracture. We hypothesize that there will be an inverse association between serum FSH levels and BMD in postmenopausal women as well as increased risk of incident low bone mass, osteoporosis and fracture in those with higher FSH levels. We will accomplish this using data from a sample of 685 postmenopausal women within the Buffalo Osteoporosis and Periodontal Disease Study (a prospective ancillary study within the Women's Health Initiative). This cohort of postmenopausal women is uniquely suited to the evaluation of these associations as it includes measures of BMD, low bone mass, osteoporosis, FSH, taken at baseline and a five year follow up visit, in addition to diagnoses of fracture over 22 years of follow up. The analyses will be conducted within the context of the complex pituitary negative feedback mechanism between FSH and other endogenous hormones, this dataset contains measures of estradiol, sex hormone binding globulin, and testosterone. The proposed project will greatly expand my epidemiologic training by incorporating both cross- sectional and longitudinal methods. Also included is robust training and understanding of the complex endocrine feedback mechanism between endogenous hormones and osteoclastic bone formation and resorption. My proposed training plan will be two-pronged to assist me in both my epidemiologic and biologic training as a researcher, while the proposed research will fill a gap in literature on FSH and BMD in postmenopausal women.