Idiopathic Osteoporosis in Pre-menopausal Women

描述(由申请人提供)： 这个应用程序的目标是支持我的专业发展，成为一名临床研究员，以及对以患者为中心的研究感兴趣的初级教职员工和研究员的导师。我的研究重点是深入研究各种疾病状态和药物及其对骨量、骨重塑和矿物质代谢的影响。这一建议源于已经开始阐明绝经前妇女特发性骨质疏松症(IOP)发病机制的初步工作。一小部分这样的妇女的TRANLIAC CREST骨活检显示出分离的重塑，骨恢复率增加，形成明显减少。这一假说认为绝经前妇女眼压是一种以骨骼微结构异常和重塑为特征的紊乱，存在形成和恢复的解偶联，失衡有利于恢复。我将在一项横断面研究中验证这一假设，在该研究中，绝经前患有眼压的女性将与正常女性进行比较。其他目标是调查眼压的病因和发病机制，并评估女性眼压患者的各种骨质量指标。五个具体目的是：1.描述其临床表型。2：确定中心和周围骨密度体积测量与骨折患病率之间的关系。3：利用定量组织形态计量学、Micro-CT、Micro-FE和FTIRI确定骨的发病机制异常。4：确定雌激素状态，5：阐明可能参与发病机制的生化特征。这一结果对绝经前妇女眼压的诊断和治疗具有重要的治疗意义。重要的是，该提案将提供许多机会来指导初级调查人员。作为一名导师，我取得了极大的成功，最近有两名K-23获奖者和16名前任或现任实习生。内分泌研究员以及其他学科的研究员和初级教员对我的研究非常感兴趣。医学部和GCRC对我作为一名临床研究员的发展做出了实质性的承诺。然而，我显然有必要减轻我的临床、行政和教学负担，以便有足够的时间从事临床研究，并培训和指导初级教员和研究员。K24奖是确保我作为一名导师和以患者为导向的研究人员继续取得成功所必需的支持的理想机制。

DESCRIPTION (provided by applicant): The goal of this application is to support my professional development as a clinical investigator and a mentor to junior faculty and fellows interested in patient-oriented research. My research has focused on the in depth investigation of various disease states and medications and their effects on bone mass, bone remodeling and mineral metabolism. This proposal stems from preliminary work that has begun to elucidate the pathogenesis of idiopathic osteoporosis (IOP) in pre-menopausal women. Transiliac crest bone biopsies from a small number of such women have revealed uncoupled remodeling, with increased bone resumption and markedly decreased formation. The hypothesis of this proposal is that IOP in premenopausal women is a disorder characterized by abnormal skeletal micro architecture and remodeling, in which there is uncoupling of formation from resumption, the imbalance favoring resumption. I will test this hypothesis in a cross-sectional study in which premenopausal women with IOP will be compared to normal women. Other goals are to investigate the etiology and pathogenesis and to assess various measures of bone quality in women with IOP. The five specific aims are to: 1. Describe the clinical phenotype. 2: Define the relationship between central and peripheral volumetric measurements of bone mineral density and fracture prevalence. 3: Define pathogenesis abnormalities in bone utilizing quantitative histomorphometry, micro-CT, micro-FE and FTIRI. 4: Characterize estrogen status, and 5: Elucidate biochemical characteristics that may contribute to the pathogenesis. The results should have important therapeutic implications for the diagnosis and management of IOP in premenopausal women. Importantly, the proposal will provide many opportunities to mentor beginning junior investigators. I have had excellent success as a mentor, with two recent K-23 awardees and 16 former or current trainees. There has been significant interest in my research from Endocrine Fellows and from Fellows and junior faculty in other disciplines. The Department of Medicine and the GCRC have made substantial commitments toward my development as a clinical investigator. However, it is clearly necessary for me to reduce my clinical, administrative and teaching loads in order to devote sufficient time to clinical research and to training and mentoring junior faculty and fellows. The K24 award is the ideal mechanism to ensure the support essential for my continued success as a mentor and patient-oriented investigator.