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.

项目总结