IDIOPATHIC OSTEOPOROSIS IN PREMENOPAUSAL WOMEN

描述（由申请人提供）：骨质疏松症目前影响着美国1000万至1200万人。虽然大多数是绝经后妇女，骨质疏松症影响中年男子和绝经前妇女，这一建议的主题。虽然许多年轻女性骨质疏松症有潜在的继发性骨质流失的原因，其他人有原发性或特发性骨质疏松症（IOP）。男性的类似综合征与低血清胰岛素样生长因子1和成骨细胞功能障碍有关。虽然绝经前妇女的数据很少，但少数受影响妇女的髂嵴骨活检显示了非偶联重塑的证据，骨吸收增加，骨形成明显减少。因此，该建议的中心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，其中存在形成与吸收的解偶联，不平衡有利于吸收。这一假设将在一项横断面病例对照研究中进行检验，其中绝经前lOP女性将与正常女性进行比较。本研究计划的其他目标是调查lOP的病因和发病机制，并评估患有这种疾病的女性的骨质量的各种指标。为了实现这些目标，我们将在临床、光密度和生化（性腺激素和促钙激素、骨转换标志物、骨吸收细胞因子）方面对lOP女性进行表征。将应用定量骨组织形态学、微型计算机断层扫描（micro-CT）、有限元分析（micro-FE）评估骨结构、重塑、连接性和强度。傅里叶变换红外光谱（FTIRI）将用于评估骨矿物质和基质的性质。我们计划在患有lOP的绝经前妇女中实现五个具体目标。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、micro-CT、micro-FE和FTIRI确定骨活检标本中的致病性异常。4：表征雌激素状态，5：阐明可能导致IOP发病机制的生化特征。这些研究的结果将对这种疾病的诊断和管理具有重要的治疗意义。

DESCRIPTION (provided by applicant): Osteoporosis currently affects 10-12 million people in the United States. Although the majority are postmenopausal women, osteoporosis affects middle-aged men and also premenopausal women, the subject of this proposal. Although many young women with osteoporosis have an underlying secondary cause of bone loss, others have primary or idiopathic osteoporosis (lOP). The equivalent syndrome in men has been associated with low serum insulin-like growth factor 1 and osteoblast dysfunction. Although few data are available in premenopausal women, transiliac crest bone biopsies from a small number of affected women have revealed evidence of uncoupled remodeling, with increased bone resorption and markedly decreased formation. The central hypothesis of this proposal, therefore, is that lOP in premenopausal women is a disorder characterized by abnormal skeletal microarchitecture and remodeling, in which there is uncoupling of formation from resorption, with the imbalance favoring resorption. This hypothesis will be tested in a crosssectional, case-control study in which premenopausal women with lOP will be compared to normal women. Additional goals of this research proposal are to investigate the etiology and pathogenesis of lOP and to assess various measures of bone quality in women with this disorder. To accomplish these goals, we will characterize women with lOP in clinical, densitometric, and biochemical (gonadal and calciotropic hormones, bone turnover markers, bone resorbing cytokines) terms. Quantitative bone histomorphometry, microcomputed tomography (micro-CT), finite element analysis (micro-FE) will be applied to assess bone structure, remodeling, connectivity and strength. Fourier transform infrared spectroscopy (FTIRI) will be applied to evaluate the properties of bone mineral and matrix. We plan to pursue five specific aims in premenopausal women with lOP. 1. To describe the clinical phenotype. 2: To define the relationship between central and peripheral volumetric measurements of bone mineral density and fracture prevalence. 3: To define pathogenetic abnormalities in bone biopsy specimens utilizing quantitative histomorphometry, micro-CT, micro-FE and FTIRI. 4: to characterize estrogen status, and 5: to elucidate biochemical characteristics that may contribute to the pathogenesis of lOP. The results of these studies will have important therapeutic implications for the diagnosis and management of this disorder.