Chronic Kidney Disease and PTH: Effects on the Postmenopausal Skeleton

慢性肾脏病和 PTH：对绝经后骨骼的影响

• 批准号: 8311824
• 负责人: Emily Margaret Stein
• 金额: $ 14.98万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311824
• 关键词: Affect; Awareness; Biochemical; Biochemical Markers; Biomechanics; Bone Density; Bone remodeling; Calcitriol; Characteristics; Chronic Kidney Failure; Competence; Data Set; Development Plans; Diagnostic; Dual-Energy X-Ray Absorptiometry; End stage renal failure; Finite Element Analysis; Fracture; General Population; Goals; Hip Fractures; Hormones; Hyperparathyroidism; Image; Individual; Instruction; Measurement; Measures; Mechanics; Medical center; Mentorship; Metabolic Bone Diseases; Modeling; Osteoporosis; Parathyroid gland; Patients; Peripheral; Phenotype; Physiology; Population; Postmenopausal Osteoporosis; Postmenopause; Principal Investigator; Recording of previous events; Renal function; Reporting; Research Personnel; Research Proposals; Research Training; Resolution; Risk; Scanning; Secondary Hyperparathyroidism; Serum; Site; Skeleton; Staging; Structure; Techniques; Training; United States; Universities; Woman; X-Ray Computed Tomography; base; bone; bone mass; bone quality; bone strength; career development; experience; instrument; interdisciplinary approach; meetings; new technology; older women; osteoporosis with pathological fracture; programs; skeletal; tomography; tool; treatment strategy

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.

影响美国数百万女性的骨质疏松性骨折的风险可能会增加 慢性肾脏病（CKD）并存。这项跨学科提案将阐明以下因素的影响： 中度 CKD 对绝经后骨骼的骨量、微结构和强度的影响。我们将使用 对骨矿物质密度 (BMD)、微结构、促钙激素的横断面深入分析 以及女性重塑的生化标志物，无论是否患有 3 期 CKD (60>GFR>30 ml/min) 以及 有或没有脆性骨折病史。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 小梁和皮质区室，辨别小梁微观结构细节并模拟骨强度。 我们将比较患有 CKD 的女性与患有原发性甲状旁腺功能亢进 (PHPT) 的女性，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 根据 CKD 和骨折史而有所不同；患有 CKD 的女性的生化变化将 与微结构异常和强度下降有关； PTH 对皮质的分解代谢作用 患有 CKD 和 PHPT 的女性会出现骨头。具体目标是：1）比较面积和体积 根据骨折史和 CKD，通过 HRpQCT 测量女性骨量和微结构； 2） 通过 FEA 根据骨折史和 CKD 比较女性的骨机械能力（强度）； 3）到 评估微结构和强度与 PTH、其他促钙激素之间的关系，以及 重塑标记； 4) 评估骨量、微结构、强度和生化指标 绝经后妇女 PHPT 的特征该提案包括 5 年职业发展 涉及结构、生物力学和生物化学方面的跨学科指导和培训的计划 骨质量评估，由正式课程支持。本节中描述的研究和培训 该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 代谢性骨疾病领域的独立研究者。 相关性（参见说明）： 该项目将生成有关肾功能轻度下降对骨骼的影响的信息 绝经后妇女。我们的研究结果将提高人们对影响骨骼结构的独特因素的认识 患有骨质疏松症和慢性肾病的绝经后妇女人数迅速增加。 他们可能会强调将 CKD 和继发性甲状旁腺功能亢进症纳入其中的重要性 绝经后骨质疏松症的诊断和治疗策略。