STRUCTURAL EFFECTS OF RENAL OSTEODYSTROPHY DURING GROWTH

肾性骨营养不良对生长过程的结构影响

• 批准号: 6895172
• 负责人: Mary Beth Leonard
• 金额: $ 53.51万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895172
• 关键词: adolescence (12-20); bone density; bone development; dialysis therapy; disease /disorder proneness /risk; growth /development; homologous transplantation; human subject; immunosuppressive; kidney disorder; kidney transplantation; longitudinal human study; middle childhood (6-11); morphology; muscle strength; pathologic bone resorption; patient oriented research; photon absorptiometry; renal failure; renal rickets; tomography

DESCRIPTION (provided by applicant): Renal osteodystrophy (ROD) is a multifactorial disorder of bone metabolism in renal disease, resulting in thinning of cortical bone. Despite the widespread use of treatments to decrease bone resorption, fracture rates in young adults on dialysis are 100-fold greater than in the general population. Skeletal development is characterized by marked expansion and accumulation of bone. The growing skeleton may be particularly vulnerable to the structural effects of ROD, resulting in irreversible deficits in skeletal architecture and peak bone mass. Unlike traditional densitometric measures of bone mass, peripheral quantitative computed tomography (pQCT) permits the discrete assessment of trabecular and cortical bone density and dimensions, and bone strength can be reliably estimated. Therefore, pQCT is an ideal tool to study the structural effects of ROD during growth. Accurate characterization of the structural bone deficits and the risk factors for poor skeletal development in pediatric renal disease have not been addressed and are the focus of this study. The hypotheses are (a) cortical dimensions and strength are impaired in children with renal failure, (b) the bone deficit is associated with delayed growth and development, and with the underlying renal disease and therapies, and (c) the recovery and reconstitution of bone structure following renal transplantation is modulated by skeletal maturation, immunosuppressive therapies, and allograft function. In healthy children, bone mass is highly correlated with growth and maturation; therefore, to understand the extent of bone deficits in children with renal disease, these analyses will require a contemporary control group of similar age, gender, and ethnicity. This study is a multi-center prospective cohort study of bone accretion (dimensions, density and strength) in children with mild-to-severe renal failure, in dialysis patients, and in renal transplant recipients, compared to healthy controls. The study will be conducted in the pediatric GCRC facilities of the Children's Hospital of Philadelphia and the Children's Hospital Medical Center of Cincinnati. These sites both have large clinical pediatric nephrology programs and have extensive experience in studies of bone mineralization in childhood. The protocol will examine the effects of renal disease severity, delayed bone age, faltering growth, decreased muscle strength, hyperparathyroidism, immunosuppression (glucocorticoids, cyclosporine, tacrolimus), and ROD therapies. The protocol will also examine baseline measures of bone turnover as predictors of bone mineral accretion during growth and will examine the utility of routine dual energy x-ray absorptiometry in the assessment of ROD in children. The accurate characterization of the structural effects of ROD is necessary in order to identify and evaluate appropriate therapies to optimize peak bone mass and decrease fracture risk in a population that will continue to require renal replacement therapies throughout adulthood.

描述（由申请人提供）：肾性骨营养不良（ROD）是一种 肾病中的多因素骨代谢紊乱，导致 皮质骨变薄。尽管广泛使用的治疗，以减少 接受透析的年轻人的骨吸收、骨折率是 高于一般人群。skeleton的发展特点是 骨骼明显膨胀和堆积不断增长的骨骼可能是 特别容易受到ROD的结构性影响，导致 骨骼结构和峰值骨量的不可逆缺陷。不像 传统的骨密度测量，外周定量 计算机断层扫描（pQCT）允许对小梁和 皮质骨密度和尺寸以及骨强度可以可靠地 估算因此，pQCT是研究结构效应的理想工具。 生长期间的ROD。结构性骨缺损的准确表征 以及儿童肾脏疾病中骨骼发育不良的危险因素 这些问题尚未得到解决，也是本研究的重点。 假设是（a）皮质尺寸和强度受损， 肾衰竭儿童，（B）骨缺损与延迟 生长和发育，以及潜在的肾脏疾病和治疗， 和（c）肾移植后骨结构的恢复和重建 移植受骨骼成熟、免疫抑制 治疗和同种异体移植物功能。在健康儿童中， 与生长和成熟相关;因此，要了解 肾脏疾病儿童的骨缺损，这些分析将需要 年龄、性别和种族相似的当代对照组。 本研究是一项关于骨增长的多中心前瞻性队列研究 （尺寸、密度和强度） 在透析患者和肾移植受者中， 健康对照本研究将在儿科GCRC机构进行 费城儿童医院和儿童医院医疗中心 辛辛那提的中心。这两个站点都有大型临床儿科肾病 项目，并在骨矿化研究方面拥有丰富的经验， 童年.该方案将检查肾脏疾病严重程度的影响， 骨龄延迟，生长迟缓，肌肉力量下降， 甲状旁腺功能亢进，免疫抑制（糖皮质激素，环孢霉素， 他克莫司）和ROD疗法。该方案还将检查基线 测量骨转换作为生长期间骨矿物质增加的预测因子 并将检查常规双能X射线吸收测定法在 评估儿童的ROD。结构的准确表征 ROD的影响是必要的，以确定和评估适当的 在人群中优化峰值骨量和降低骨折风险的疗法 在整个成年期都需要肾脏替代治疗。