Urinary biomarkers to assess linear bone growth velocity

用于评估线性骨生长速度的尿液生物标志物

• 批准号: 8621082
• 负责人: WILLIAM A HORTON
• 金额: $ 19.64万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8621082
• 关键词: Achondroplasia; Address; Adult; Age; Amino Acid Sequence; Arthritis; Biochemical; Biological Assay; Biological Markers; Bone Growth; C-Type Natriuretic Peptide; Cartilage; Cartilage Matrix; Child; Childhood; Clinical; Clinical Management; Clinical Trials; Collagen; Collagen Type II; Collagen Type X; Coupled; Cyclophosphamide; Data; Data Reporting; Degenerative polyarthritis; Detection; Development; Endocrine; Endocrinology; Enzyme-Linked Immunosorbent Assay; Epiphysial cartilage; Evaluation; Future; Goals; Growth; Growth Disorders; Height; Hormone Responsive; Length; Measurement; Measures; Methods; Monitor; Nature; Peptide Hydrolases; Peptides; Process; Proteins; Protocols documentation; Proxy; Reference Values; Sampling; Serum; Severities; Somatotropin; Somatropin; Specimen; Testing; Therapeutic; Time; Turner' s Syndrome; Urine; articular cartilage; base; bone; chondrodysplasia; hormone therapy; novel strategies; public health relevance; response; skeletal; skeletal disorder; tool; urinary

Project Summary Measuring bone growth velocity is an essential but challenging part of managing disorders of skeletal growth due largely to the many months needed to accurately gauge incremental changes of bone length, which reflects the inherently slow nature of bone growth. While clearly less than ideal, the current practice is accepted because of the lack of methods that yield faster results. We propose a completely new approach that examines the bone growth process directly by analyzing its byproducts as biomarkers of bone growth. Because it addresses bone growth rather than the consequence of bone growth, it potentially offers a much shorter turn around time that could dramatically reduce the interval needed to clinically measure bone growth velocity. We will analyze cartilage turnover as a direct readout of endochondral ossification by measuring terminal degradation products of types II and X collagen in urine. Type II collagen fragments have been measured to assess severity of osteoarthritis in adults establishing proof-of-concept for this approach, but in growing children in whom arthritis is rare, results should reflect endochondral bone growth almost exclusively, especially when coupled with analysis of type X collagen fragments. We will develop the assays, correlate results with bone growth velocity to provide means to assess and monitor bone growth velocity and quantify deficient growth rate and its response to growth promoting therapies. More specifically, we will adapt commercial ELISA kits to measure a type II collagen neoepitope (CTX-II) and develop a comparable assay for type X collagen fragments, which we have designated CXM, and apply them to normally growing children in Aim 1. In Aim 2 we will correlate biomarker levels with growth (height) velocity over 1 yr in healthy children and develop norms that can be used clinically to gauge growth rate from biomarker measurements. Biomarker sampling and data reporting protocols will be optimized in this aim. Bone growth biomarkers will be assessed in children with chondrodysplasias and growth hormone-responsive forms of short stature and response of the latter group to growth hormone therapy will be monitored by biomarkers in Aim 3. We believe development of this novel approach to assessing linear bone growth velocity in a much shorter time frame than is currently possible will have a major impact on the evaluation and management of pediatric short stature.

项目摘要 测量骨骼生长速度是管理骨骼生长疾病的重要部分 在很大程度上是由于准确衡量骨长的增量变化所需的数月之际 反映了骨骼生长的固有缓慢性质。虽然显然不是理想的情况，但当前的做法是 由于缺乏产生更快结果的方法而被接受。 我们提出了一种全新的方法 通过将其副产品分析为骨骼生长的生物标志物直接检查骨骼生长过程。 因为它解决了骨骼生长而不是骨骼生长的结果，因此它可能提供了很多 较短的转折时间可能会大大减少临床测量骨骼生长所需的间隔 速度。 我们将通过测量来分析软骨转换，作为内向卷骨化的直接读数 尿液中II型和X胶原蛋白的末端降解产物。 II型胶原蛋白片段已经 测量以评估成人在建立这种方法概念概念的成年人中的严重程度，但 成长中关节炎的儿童很少，结果应几乎完全反映骨软骨的生长，几乎完全反映 特别是当与X型胶原蛋白片段的分析结合使用时。我们将开发分析，相关 骨生长速度的结果可提供评估和监测骨生长速度和量化的方法 不足的增长率及其对增长促进疗法的反应。更具体地说，我们会适应 商业ELISA套件，用于测量II型胶原蛋白新闻（CTX-II）并开发可比的测定法 X型胶原蛋白片段，我们已指定为CXM，并将其应用于通常成长的儿童 目标1。在目标2中，我们将在健康儿童中将生物标志物水平与1岁以上的生物标志物水平与增长（高度）速度相关联 制定可在临床上使用生物标志物测量来衡量生长速率的规范。 生物标志物 在此目的中将优化采样和数据报告协议。 将评估骨骼生长生物标志物 在软骨肿瘤和生长激素响应形式的矮小形式和反应的儿童中 AIM 3中的生物标志物将对后者进行生长激素治疗。我们认为 这种新颖的方法是评估线性骨生长速度的时间比目前要短得多的时间范围 可能会对小儿短身材的评估和管理产生重大影响。