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作为一个临床研究者和导师的初级教师和研究员感兴趣的病人为导向的研究。我的研究重点是深入调查各种疾病状态和药物及其对骨量，骨重建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。少数此类女性的髂嵴骨活检显示非偶联重建，骨恢复增加，骨形成明显减少。该建议的假设是，绝经前女性的IOP是一种以异常骨骼微结构和重塑为特征的疾病，其中存在形成与恢复的解偶联，不平衡有利于恢复。我将在一项横断面研究中检验这一假设，在这项研究中，绝经前患有IOP的妇女将与正常妇女进行比较。其他目标是研究病因和发病机制，并评估各种措施的骨质疏松症妇女。五个具体目标是：1.描述临床表型。2：确定骨密度的中心和外周体积测量与骨折患病率之间的关系。3：利用定量组织形态学、显微CT、显微FE和FTIRI确定骨中的发病机制异常。4：描述雌激素状态，5：阐明可能导致发病机制的生化特征。该结果对绝经前妇女IOP的诊断和治疗具有重要意义。重要的是，该提案将为初级调查员提供许多指导机会。作为导师，我取得了巨大的成功，最近有两名K-23获奖者和16名前任或现任学员。内分泌研究员、其他学科的研究员和初级教师对我的研究产生了浓厚的兴趣。医学系和GCRC对我作为临床研究者的发展做出了实质性的承诺。然而，我显然有必要减少我的临床，行政和教学负担，以便投入足够的时间进行临床研究和培训，指导初级教师和研究员。K24奖是一个理想的机制，以确保我作为一个导师和以病人为导向的研究者继续取得成功所必需的支持。

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.