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: 7026543
• 负责人: Mary Beth Leonard
• 金额: $ 46.98万
• 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 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7026543
• 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(申请人提供)：肾性骨营养不良症(Rod)是一种 肾脏疾病中骨代谢的多因素紊乱，导致 皮质骨变薄。尽管广泛使用治疗方法来减少 接受透析的年轻人的骨吸收、骨折发生率为100倍 比一般人群中的要多。骨骼发育的特点是 通过骨骼的显著膨胀和堆积。不断增长的骨架可能是 特别容易受到杆状结构的影响，导致 不可逆的骨骼结构和峰值骨量缺陷。不像 骨量的传统密度测量方法，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 估计。因此，pQCT是研究结构效应的理想工具。 生长过程中的杆状物。对结构性骨缺陷的准确描述 儿童肾脏疾病骨骼发育不良的危险因素 都没有得到解决，也是本研究的重点。 这些假设是：(A)大脑皮质的大小和强度在 儿童肾功能衰竭，(B)骨缺陷与延迟 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、免疫抑制的调节 治疗和同种异体移植的功能。在健康的儿童中，骨量高度 与成长和成熟相关的；因此，要了解 肾脏疾病儿童的骨缺陷，这些分析将需要 年龄、性别和种族相近的当代对照组。 本研究是一项多中心前瞻性队列研究。 (大小、密度和强度)与儿童轻至重度肾脏 在透析患者和肾移植受者中，与 健康对照组。这项研究将在GCRC儿科设施中进行 费城儿童医院和儿童医院医疗 辛辛那提市中心。这两个部位都有较大的儿科肾病临床病例。 在骨矿化研究方面有丰富的经验 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， 甲状旁腺机能亢进症、免疫抑制(糖皮质激素、环孢素A、 他克莫司)和Rod疗法。该方案还将检查基线 骨转换指标作为生长过程中骨矿物质积累的预测指标 并将检验常规的双能x射线吸收测量法在 儿童Rod的评估。对结构的准确刻画 为了识别和评估适当的效果，杆的效果是必要的 优化人群峰值骨量和降低骨折风险的治疗方法 这将继续需要在整个成年期间进行肾脏替代治疗。

项目成果

Changes in bone structure and the muscle-bone unit in children with chronic kidney disease.

患有慢性肾脏疾病儿童的骨结构和肌肉骨单位的变化。

• DOI: 10.1038/ki.2012.347
• 发表时间: 2013-03
• 期刊: Kidney international
• 影响因子: 19.6

Vitamin D deficiency is common in children and adolescents with chronic kidney disease.

• DOI: 10.1038/ki.2011.431
• 发表时间: 2012-04
• 期刊: Kidney international
• 影响因子: 19.6

Mechanical loads and cortical bone geometry in healthy children and young adults.

健康儿童和年轻人的机械载荷和皮质骨几何形状。

• DOI: 10.1016/j.bone.2011.01.005
• 发表时间: 2011
• 期刊: Bone
• 影响因子: 4.1
• 作者: Wetzsteon,RachelJ;Zemel,BabetteS;Shults,Justine;Howard,KristaM;Kibe,LucyW;Leonard,MaryB
• 通讯作者: Leonard,MaryB

Assessment of dual-energy X-ray absorptiometry measures of bone health in pediatric chronic kidney disease.

• DOI: 10.1007/s00467-012-2116-x
• 发表时间: 2012-07
• 期刊: Pediatric nephrology (Berlin, Germany)
• 作者: Griffin LM;Kalkwarf HJ;Zemel BS;Shults J;Wetzsteon RJ;Strife CF;Leonard MB
• 通讯作者: Leonard MB

Volumetric bone mineral density and bone structure in childhood chronic kidney disease.

• DOI: 10.1002/jbmr.427
• 发表时间: 2011-09
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Wetzsteon, Rachel J.;Kalkwarf, Heidi J.;Shults, Justine;Zemel, Babette S.;Foster, Bethany J.;Griffin, Lindsay;Strife, C. Frederic;Foerster, Debbie L.;Jean-Pierre, Darlene K.;Leonard, Mary B.
• 通讯作者: Leonard, Mary B.