Renal Osteodystrophy: A Fresh Approach

肾性骨营养不良：一种新方法

• 批准号: 8235920
• 负责人: Hartmut H Malluche
• 金额: $ 29.29万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235920
• 关键词: Address; Adult; Affect; Alkaline Phosphatase; Aluminum; Award; Awareness; Biochemical; Biochemical Markers; Biopsy; Blood; Blood Tests; Blood specimen; Bone Diseases; Bone Resorption; Cardiovascular system; Caring; Chronic Kidney Failure; Clinical Research; Clinical Sciences; Cost of Illness; DEXA; Detection; Development; Diagnosis; Dialysis procedure; Dual-Energy X-Ray Absorptiometry; Early identification; Foundations; Funding; Goals; Gold; Health; Health Care Costs; Histologic; Histology; International; Investigation; Kentucky; Kidney; Kidney Diseases; Laboratories; Letters; Link; Low Prevalence; Maintenance; Measurement; Measures; Medical; Minerals; Morbidity - disease rate; Osteogenesis; Osteoporosis; Outcome; Patients; Physiologic calcification; Prevalence; Prevention; Procedures; Procollagen; Protocols documentation; Quality of life; Renal Osteodystrophy; Resources; Serum Markers; Skeleton; TRANCE protein; Testing; Therapeutic; Time; Translational Research; Tumor necrosis factor receptor 11b; United States; United States National Institutes of Health; Universities; Vascular calcification; Vitamin D Analog; X-Ray Computed Tomography; base; bone; bone loss; bone mass; bone metabolism; bone turnover; burden of illness; calcification; cancer type; cerebrovascular; cohort; diagnosis standard; experience; follow-up; imaging modality; improved; inorganic phosphate; mineralization; mortality; novel; patient population; prevent; quality assurance; skeletal abnormality; tartrate-resistant acid phosphatase; Address; Adult; Affect; Alkaline Phosphatase; Aluminum; Award; Awareness; Biochemical; Biochemical Markers; Biopsy; Blood; Blood Tests; Blood specimen; Bone Diseases; Bone Resorption; Cardiovascular system; Caring; Chronic Kidney Failure; Clinical Research; Clinical Sciences; Cost of Illness; DEXA; Detection; Development; Diagnosis; Dialysis procedure; Dual-Energy X-Ray Absorptiometry; Early identification; Foundations; Funding; Goals; Gold; Health; Health Care Costs; Histologic; Histology; International; Investigation; Kentucky; Kidney; Kidney Diseases; Laboratories; Letters; Link; Low Prevalence; Maintenance; Measurement; Measures; Medical; Minerals; Morbidity - disease rate; Osteogenesis; Osteoporosis; Outcome; Patients; Physiologic calcification; Prevalence; Prevention; Procedures; Procollagen; Protocols documentation; Quality of life; Renal Osteodystrophy; Resources; Serum Markers; Skeleton; TRANCE protein; Testing; Therapeutic; Time; Translational Research; Tumor necrosis factor receptor 11b; United States; United States National Institutes of Health; Universities; Vascular calcification; Vitamin D Analog; X-Ray Computed Tomography; base; bone; bone loss; bone mass; bone metabolism; bone turnover; burden of illness; calcification; cancer type; cerebrovascular; cohort; diagnosis standard; experience; follow-up; imaging modality; improved; inorganic phosphate; mineralization; mortality; novel; patient population; prevent; quality assurance; skeletal abnormality; tartrate-resistant acid phosphatase

DESCRIPTION (provided by applicant): Patients with chronic kidney disease (CKD) present with abnormalities in mineral and bone metabolism, which are associated with high morbidity and mortality. The most relevant bone abnormalities encompass suppressed or extremely elevated bone turnover and bone loss. Both turnover abnormalities and bone loss are associated with progressive calcifications, explaining the high morbidity and mortality. Bone biopsies are the gold standard for the diagnosis of bone abnormalities but are rarely performed. Noninvasive means to diagnose renal bone disease are urgently needed for implementation of targeted therapy to reduce morbidity and mortality. The long-term goal of the proposed study is to improve survival and quality of life in CKD patients by noninvasive detection of abnormalities in bone turnover and prevention of bone loss. This will allow administration of specific therapies and should contribute to reduction of disease burden and cost of a pervasive health problem affecting over 20 million patients in the United States. The central hypothesis is that renal osteodystrophy (ROD) can be defined noninvasively. Specifically, we will test the following hypotheses: 1. a) Bone volume component of ROD (bone loss) can be assessed by dual energy X-ray absorptiometry (DXA) and by quantitative computed tomography (QCT); however, QCT is more sensitive in recognizing bone loss; and, b) Bone loss occurs in patients with high and low turnover. Among patients with bone loss, there are at least 20% with low bone turnover. 2. The turnover component of ROD can be assessed noninvasively by PTH combined with established and/or novel biochemical markers of bone resorption and formation. The following specific aims will be pursued: 1. Comparison of DEXA and QCT for diagnosis of bone loss in CKD-5 patients and determination of the prevalence of low bone turnover in CKD-5 patients with bone loss. 2. Identification of the optimal combination of noninvasive tests for definition of the turnover component of ROD: For this purpose, 230 patients will be followed prospectively over 2 years, bone mass will be determined by QCT and DXA annually to establish the most sensitive means of identifying bone loss. Patients with osteoporosis at baseline and patients who develop bone loss at 1 or 2 years will be offered to undergo bone biopsy and blood drawing to measure serum markers of bone turnover, formation, and resorption. The best marker or combination of markers for definition of the turnover component ROD will be identified. Attainment of these goals will allow implementation of specific therapies without the use of invasive work-up and will assist in reducing morbidity, increasing survival, and improving quality of life in this unfortunate patient population. PUBLIC HEALTH RELEVANCE: Cardiovascular and cerebrovascular calcifications are linked to abnormalities in bone turnover and bone loss resulting in high morbidity and mortality. Bone turnover abnormalities and bone loss occur in chronic kidney disease patients and bone biopsy (an invasive test) is considered essential for diagnosis of these bone abnormalities. The proposed studies will establish noninvasive means (a panel of blood tests and imaging methods) for recognition and characterization of these bone abnormalities which has significant implications, regarding diagnosis, prevention, treatment and a better understanding of the pathogenic mechanisms.

描述（由申请人提供）：患有矿物质和骨代谢异常的慢性肾脏疾病（CKD）患者，与高发病率和死亡率有关。最相关的骨骼异常包括抑制或极高的骨骼更新和骨质流失。失误异常和骨质流失都与进行性钙化有关，从而解释了高发病率和死亡率。骨骼活检是诊断骨异常的金标准，但很少进行。迫切需要诊断肾骨疾病的无创手段来实施靶向治疗以降低发病率和死亡率。拟议的研究的长期目标是通过非侵入性检测骨转换和预防骨质流失来改善CKD患者的生存和生活质量。这将允许给予特定的疗法，并应导致疾病负担减轻疾病负担和成本，而普遍存在的健康问题影响了美国超过2000万患者。中心假设是可以非侵入性地定义肾脏骨营养不良（ROD）。具体而言，我们将测试以下假设：1。a）可以通过双能X射线吸收仪（DXA）和定量计算机断层扫描（QCT）评估杆的骨体积成分（骨丢失）；但是，QCT在识别骨质流失方面更为敏感。并且，b）骨质流失发生在高离职率高和低的患者中。在骨质流失的患者中，至少有20％的骨骼更新。 2。可以通过PTH与骨吸收和形成的已建立和/或新颖的生化标志物相结合的PTH进行非侵入性评估。将追求以下具体目的：1。在CKD-5患者中诊断DEXA和QCT的比较，并确定CKD-5患有骨质流失的患者骨失误的患病率低。 2。鉴定非侵入性测试的最佳组合来定义ROD的营业额分量：为此，将有230名患者预期在2年的时间内遵循230名患者，骨骼质量将由QCT和DXA每年确定，以确定识别骨质流失的最敏感方法。将提供基线骨质疏松症的患者，并在1或2年期间出现骨质流失的患者进行骨骼活检和血液绘画，以测量骨骼更新，形成和吸收的血清标志物。将确定用于定义离职组件杆的最佳标记或组合。实现这些目标将允许在不使用侵入性检查的情况下实施特定的疗法，并有助于降低发病率，提高生存率和改善这种不幸的患者人群的生活质量。公共卫生相关性：心血管和脑血管钙化与骨转换和骨质流失的异常有关，导致高发病和死亡率。慢性肾脏疾病患者发生骨翻新异常和骨质流失，骨活检（侵袭性测试）被认为对于诊断这些骨异常至关重要。提出的研究将建立无创手段（血液测试和成像方法），以识别和表征这些骨异常，这对诊断，预防，治疗以及对致病机制有更好的理解具有重要意义。