Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

描述(由申请人提供)： 在美国，影响数百万女性的骨质疏松性骨折的风险可能会因为慢性肾脏疾病(CKD)的共存而增加。这项跨学科的建议将阐明中度CKD对绝经后骨骼的骨量、微结构和强度的影响。我们将对患有和不患有CKD(60&GT；GFR&GT；30毫升/分钟)、有和没有脆性骨折病史的女性的骨密度(BMD)、微结构、促钙激素和重塑的生化标志物进行横断面深入分析。最先进的非侵入性技术，高分辨率外周计算机断层扫描(HRpQCT)和有限元分析(FEA)，将使我们能够区分小梁和皮质室，识别小梁微结构细节和模型骨强度。我们将比较患有CKD的妇女和患有原发性甲状旁腺功能亢进症(PHPT)的妇女，以进一步探讨PTH对绝经后骨骼的影响。我们假设，骨微结构和强度将根据CKD和骨折病史的不同而不同；CKD女性的生化变化将与微结构异常和强度降低相关；甲状旁腺素对皮质骨的分解代谢作用将在CKD和PHPT女性中看到。其具体目的是：1)比较骨折病史和慢性肾脏病妇女HRpQCT对骨量和微结构的面积和体积测量；2)通过有限元分析比较骨折病史和CKD妇女的骨机械能力(强度)；3)评估微结构和强度与甲状旁腺激素、其他促钙激素和重塑标志物之间的关系；以及4)评估绝经后PHPT妇女的骨量、微结构、强度和生化特征。这项建议包括一项为期5年的职业发展计划，涉及跨学科的指导和骨质量的结构、生物力学和生化评估方面的培训，并由正式课程提供支持。这项提案中描述的研究和培训将回答骨骼生理学中的重要问题，同时推进我成为代谢性骨骼疾病领域的独立研究员的目标。 公共卫生相关性：该项目将产生有关绝经后妇女肾功能轻度下降对骨骼的影响的信息。我们的发现将提高人们对绝经后骨质疏松症和慢性肾脏病患者中影响骨骼结构和力量的独特因素的认识。他们可能会强调将慢性肾脏病和继发性甲状旁腺功能亢进纳入绝经后骨质疏松症的诊断和治疗策略的重要性。

DESCRIPTION (provided by applicant): The risk of osteoporotic fracture, which affects millions of women in the United States, may be increased by the coexistence of chronic kidney disease (CKD). This interdisciplinary proposal will elucidate the effects of moderate CKD on bone mass, microarchitecture, and strength in the postmenopausal skeleton. We will use a cross-sectional, in-depth analysis of bone mineral density (BMD), microarchitecture, calciotropic hormones and biochemical markers of remodeling in women, with and without stage 3 CKD (60>GFR>30 ml/min) and with and without a history of fragility fracture. State of the art non-invasive techniques, high-resolution peripheral computed tomography (HRpQCT) and finite element analysis (FEA), will allow us to distinguish trabecular and cortical compartments, discern trabecular microstructural details and model bone strength. We will compare women with CKD to women with primary hyperparathyroism (PHPT) to further explore the effects of PTH on the postmenopausal skeleton. We hypothesize that bone microarchitecture and strength will differ based upon history of CKD and fracture; biochemical changes in women with CKD will be associated with abnormal microarchitecture and decreased strength; catabolic effects of PTH on cortical bone will be seen in women with CKD and PHPT. The specific aims are: 1) to compare areal and volumetric measurements of bone mass and microarchitecture by HRpQCT in women by fracture history and CKD; 2) to compare bone mechanical competence (strength) by FEA in women by fracture history and CKD; 3) to assess relationships between microarchitecture and strength with PTH, other calciotropic hormones, and remodeling markers; and 4) to assess bone mass, microarchitecture, strength and biochemical characteristics in postmenopausal women with PHPT. This proposal includes a 5-year career development plan involving interdisciplinary mentorship and training in structural, biomechanical and biochemical assessment of bone quality, supported by formal coursework. The research and training described in this proposal will answer important questions in skeletal physiology while advancing my goal of becoming an independent investigator in the field of metabolic bone diseases. PUBLIC HEALTH RELEVANCE: This project will generate information about the impact of mild declines in kidney function on the skeleton in postmenopausal women. Our findings will increase awareness of unique factors that affect skeletal structure and strength in the rapidly increasing population of postmenopausal women with osteoporosis and CKD. They may emphasize the importance of incorporating CKD and secondary hyperparathyroidism into diagnostic and treatment strategies for postmenopausal osteoporosis.