Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

影响美国数百万女性的骨质疏松性骨折风险可能会增加 慢性肾脏病(CKD)并存。这项跨学科的提案将阐明 中度慢性肾脏病对绝经后骨骼的骨量、微结构和强度的影响。我们将使用 对骨密度(BMD)、微结构、促钙激素进行横断面深入分析 和生化标记物的重塑，有和没有CKD 3期(60；GFR和GT；30毫升/分钟)和 有和没有脆性骨折的病史。最先进的非侵入性技术，高分辨率 外围计算机断层扫描(HRpQCT)和有限元分析(FEA)将使我们能够区分 骨小梁和皮质室，识别骨小梁的微结构细节和模型骨强度。 我们将比较患有CKD和原发性甲状旁腺功能亢进症(PHPT)的女性，以进一步探索 甲状旁腺素对绝经后骨骼的影响我们假设骨骼的微结构和强度 将根据慢性肾脏病和骨折病史的不同而不同；慢性肾脏病女性的生化变化将是 与微结构异常和强度下降有关；甲状旁腺素对皮质的分解代谢作用 骨质可见于患有慢性肾脏病和PHPT的女性。具体目标是：1)比较面积和体积 用HRpQCT测量骨折病史和慢性肾脏病妇女的骨量和微结构 通过有限元分析比较骨折病史和慢性肾脏病女性的骨力学能力(强度)；3) 评估微结构和强度与甲状旁腺素、其他促钙激素和 重建标志物；以及4)评估骨量、微结构、强度和生化 绝经后妇女甲状旁腺功能亢进的特点这份提案包括5年的职业发展。 涉及结构、生物力学和生化方面的跨学科指导和培训的计划 对骨骼质量的评估，由正规课程提供支持。本文件中描述的研究和培训 提案将回答骨骼生理学中的重要问题，同时推进我成为一名 代谢性骨病领域的独立研究员。 相关性(请参阅说明)： 这个项目将产生关于肾功能轻微下降对骨骼的影响的信息 绝经后的女性。我们的发现将提高人们对影响骨骼结构的独特因素的认识 在迅速增长的绝经后骨质疏松症和慢性肾脏病的人口中的力量。 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症合并到 绝经后骨质疏松症的诊断和治疗策略。

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. RELEVANCE (See instructions): 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.