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

基本信息

批准号：
8737013
负责人：
WILLIAM A HORTON
金额：
$ 16.36万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-18 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8737013
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&apos s Syndrome Urine articular cartilage base bone chondrodysplasia hormone therapy novel strategies public health relevance response skeletal skeletal disorder tool urinary

项目摘要

DESCRIPTION (provided by applicant): 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 i 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.

描述（由申请人提供）：测量骨骼生长速度是管理骨骼生长疾病的重要部分，这在很大程度上是由于准确衡量骨长的额度变化所需的许多月，这反映了骨骼生长的固有缓慢性。虽然显然不是理想的，但由于缺乏更快的结果的方法而接受了当前的实践。我们提出了一种全新的方法，该方法通过将其副产品作为骨骼生长的生物标志物分析直接检查骨骼生长过程。因为它解决了骨骼的生长而不是骨骼生长的结果，因此它可能会提供更短的时间，这可能会大大减少临床测量骨骼生长速度所需的间隔。我们将通过测量尿液中II型和X胶原蛋白的末端降解产物来分析软骨周转率，作为对内软骨骨化的直接读数。已经测量了II型胶原蛋白片段以评估成年人的骨关节炎的严重程度，为这种方法建立了概念概念，但是在成长中的儿童中，关节炎很少见，结果应几乎完全反映了内侧的骨骼生长，尤其是当与X类胶原型片段的分析结合时。我们将开发分析，将结果与骨骼生长速度相关联，以提供评估和监测骨骼生长速度并量化不足的生长速度及其对生长促进疗法的反应的方法。更具体地说，我们将调整商业ELISA套件来测量II型胶原蛋白新EPITOPE（CTX-II），并为X型X胶原片段的可比测定法进行了可比的测定，我们已将其指定为CXM，并将其应用于AIM 1的正常成长的儿童，并在AIM 2中。生物标志物测量。生物标志物采样和数据报告协议将在此目标中进行优化。 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.