Idiopathic Osteoporosis in Premenopausal Women

描述（由申请人提供）：此更新申请的目标是为我的指导计划提供持续的支持，为对患者导向研究（POR）感兴趣的初级教师和研究员。在我的第一个K24，2初级教师完成了K奖，一个收到了R 01和4被授予新的K23，一个非常成功的记录。我未来的研究目标是进行高质量的POR，阐明与绝经后骨质疏松症，绝经前妇女特发性骨质疏松症（IOP）和其他与骨骼不良反应相关的疾病相关的骨强度不足的细胞和结构机制。我的指导目标是利用目前和新资助的项目，为POR的新临床研究者提供高质量的指导和培训。在研究期间，我们定义了IOP女性骨质量的一致性微结构异常：皮质薄、骨小梁丢失、连接性降低、僵硬和矿化。尽管存在一些异质性，但大多数患者的重塑程度较低或正常。在更新中，我们将检验以下假设：患有IOP的绝经前妇女的微结构异常与骨细胞（特别是成骨细胞）的异常形成、功能或寿命有关，以及骨合成代谢剂PTH（1-34）可以逆转我们所定义的结构和动力学异常。我们将使用骨骼宏观和微观成像和细胞生物学的成熟和新方法，这将为IOP中骨丢失的机制提供新的见解，并为其治疗提供合理的基础。这个建议，以及数据库，生物标本和成像数据，从其他目前和新资助的项目，将为我提供很多机会，指导初级研究人员在POR，也将为我提供保护的时间，专注于培训和指导。通过调查IOP的原因和治疗，改善不明原因骨折的年轻女性的健康状况，并允许我将更多的时间用于POR以及培训和指导POR的初级教师和研究员，该提案解决了NIH的几个关键任务。

DESCRIPTION (provided by applicant): The goal of this renewal application is to provide continued support for my mentoring program for junior faculty and fellows interested in patient- oriented research (POR). During my first K24, 2 junior faculty completed K awards, one received an R01 and 4 were awarded new K23s, a highly successful record. My future research goals are to conduct high quality POR elucidating cellular and structural mechanisms that underlie deficits in bone strength associated with postmenopausal osteoporosis, idiopathic osteoporosis (IOP) in premenopausal women, and other diseases associated with adverse effects on the skeleton. My mentoring goals are to use currently and newly funded projects to provide high quality mentoring and training for new clinical investigators in POR. During the grant, we defined consistent microarchitectural abnormalities of bone quality in women with IOP: thin cortices, trabecular loss, decreased connectivity, stiffness and mineralization. Despite some heterogeneity, the majority had low or normal remodeling. In the renewal, we will test the hypotheses that microarchitectural abnormalities in premenopausal women with IOP are related to abnormal formation, function or lifespan of bone cells, particularly osteoblasts and that PTH(1-34), a bone anabolic agent, can reverse the structural and dynamic abnormalities we have defined. We will use established and novel approaches to skeletal macro- and micro-imaging and cell biology that will provide novel insights into mechanisms of bone loss in IOP and a rational basis for its therapy. This proposal, as well as databases, biological specimens and imaging data from other currently and newly funded projects, will provide me with many opportunities to mentor junior investigators in POR and will also provide me with protected time to focus on training and mentoring. By investigating the causes and therapy of IOP, improving the health of young women with unexplained fractures, and permitting me to devote more time to POR and to training and mentoring junior faculty and fellows in POR, this proposal addresses several key missions of NIH.