CHANGES IN SKELETAL MICROARCHITECTURE FOLLOWING RENAL TRANSPLANTATION

肾移植后骨骼微结构的变化

• 批准号: 7674591
• 负责人: Mary Beth Leonard
• 金额: $ 51.23万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674591
• 关键词: Address; Adult; Age; Architecture; Area; Biological Markers; Biopsy; Bone Density; Characteristics; Child; Chronic Kidney Failure; Data; Deformity; Deterioration; Diagnostic tests; Dialysis patients; Dialysis procedure; Dimensions; Discrimination; Disease; Dual-Energy X-Ray Absorptiometry; End stage renal failure; Fracture; Functional disorder; Glucocorticoids; Hip Fractures; Hyperparathyroidism; Image; Imaging Techniques; In Vitro; Individual; Intervention; Kidney Diseases; Kidney Failure; Kidney Transplantation; Lead; Living Donors; Magnetic Resonance Imaging; Measures; Metabolic Bone Diseases; Metabolism; Minerals; Multivariate Analysis; Normal Range; Parathyroid Hormones; Patients; Population; Porosity; Property; Receiver Operating Characteristics; Recovery; Relative (related person); Renal Osteodystrophy; Renal function; Research Personnel; Resolution; Risk; Schedule; Sclerosis; Sensitivity and Specificity; Solutions; Spinal Fractures; Structure; Therapeutic immunosuppression; Thick; Time; Transplant Recipients; Transplantation; Vitamin D; bone; bone loss; bone mass; bone strength; bone turnover; digital; high risk; human PTH protein; improved; inorganic phosphate; kidney allograft; muscle strength; programs; restoration; sex; skeletal; spine bone structure; substantia spongiosa; tibia; young adult

DESCRIPTION (provided by applicant): Renal osteodystrophy (ROD) is a universal disorder in end-stage renal disease (ESRD). Abnormal parathyroid hormone (PTH) secretion and mineral metabolism result in trabecular sclerosis, cortical thinning, and increased cortical porosity. Fracture rates in dialysis patients are markedly increased, and increase further following renal transplantation. The vast majority of studies of changes in bone mass following transplantation relied on DXA estimates of bone mineral density (BMD); however, DXA BMD does not distinguish between opposing disease effects on trabecular and cortical bone and does not predict fractures in dialysis patients. Quantitative CT (QCT) provides 3D measures of cortical BMD and bone dimensions (periosteal & endosteal circumferences) and bone strength is reliably estimated. Micro-MRI provides measures of trabecular microarchitecure and connectivity. The proposed study will examine tibia trabecular architecture using (MRI, and cortical BMD and dimensions using QCT in 60 young adults at the time of renal transplantation, and over the subsequent 12 months. We hypothesize that (1) cortical BMD and dimensions will be decreased and trabecular bone volume/total volume (BV/TV) will be increased relative to age and sex at the time of transplantation, (2) cortical BMD will increase after transplantation; however, cortical thickness, cross-sectional area and endosteal dimensions will not improve, (3) trabecular thickness and BV/TV will decrease in the first six months due to glucocorticoid therapy; (4) trabecular network connectivity will not recover after transplantation, and (5) QCT measures of cortical bone density and dimensions and (MRI estimates of trabecular connectivity will predict vertebral deformities and fractures. Multivariate analyses will address the effects of PTH levels, bone turnover, muscle strength, glucocorticoid therapy and renal allograft function on changes in bone structure. Secondary analyses will assess the diagnostic test characteristics of DXA, QCT and (MRI for fracture discrimination in ESRD. Bone histomorphometry and (CT will be used to compare QCT and (MRI measures of trabecular and cortical architecture in patients with high- and low- turnover disease, and to determine if bone turnover at baseline predicts changes in bone density and structure following transplantation. The determination of changes in bone density and structure after transplantation is necessary in order to identify appropriate interventions for this high-risk population.

描述(申请人提供)：肾性骨营养不良(Rod)是终末期肾病(ESRD)的一种普遍疾病。甲状旁腺激素(PTH)分泌和矿物质代谢异常导致小梁硬化、皮质变薄和皮质孔隙率增加。透析患者的骨折发生率显著增加，而且在肾移植后进一步增加。绝大多数移植后骨量变化的研究依赖于DXA对骨密度(BMD)的估计；然而，DXA骨密度不能区分疾病对骨小梁和皮质骨的影响，也不能预测透析患者的骨折。定量CT(QCT)提供了皮质骨密度和骨尺寸(骨膜和骨内周长)的三维测量，并可靠地估计了骨强度。Micro-MRI提供了小梁微结构和连通性的测量。这项拟议的研究将在肾移植时和随后的12个月内，使用MRI和QCT检查60名年轻人的胫骨小梁结构、皮质骨密度和尺寸。我们假设(1)移植时皮质骨密度和尺寸将减少，骨小梁体积/总体积(BV/TV)将随着年龄和性别的增加而增加，(2)移植后皮质骨密度将增加，但皮质厚度、横截面积和骨内膜尺寸不会改善，(3)由于糖皮质激素治疗，前六个月小梁厚度和BV/TV将减少；(4)移植后小梁网络连通性将无法恢复，(5)皮质骨密度和尺寸的QCT测量以及(5)小梁连通性的MRI估计将预测椎体变形和骨折。多变量分析将解决甲状旁腺素水平、骨转换、肌肉力量、糖皮质激素治疗和肾移植功能对骨结构变化的影响。二次分析将评估DXA、QCT和MRI在ESRD骨折鉴别诊断试验中的特点。骨组织形态计量学和(CT)将用于比较高周转率和低周转率疾病患者的骨小梁和皮质结构的QCT和(MRI)测量，并确定基线时的骨转换率是否预测移植后骨密度和结构的变化。有必要确定移植后骨密度和结构的变化，以便为这一高危人群确定适当的干预措施。