Research ArticleBone

A degradation fragment of type X collagen is a real-time marker for bone growth velocity

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Science Translational Medicine  06 Dec 2017:
Vol. 9, Issue 419, eaan4669
DOI: 10.1126/scitranslmed.aan4669

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Detecting skeletal growth

During development, bone is created by a process called endochondral ossification, which results in the production of a fragment of type X collagen. Endochondral ossification also occurs during long bone growth and fracture healing. Coghlan et al. discovered that the type X collagen fragment could be isolated from blood and its concentration correlated with skeletal growth velocity. Fragment concentration was inversely correlated with age and fluctuated during fracture healing in adults. The authors developed an assay to quantify the fragment that could be useful as a real-time marker of skeletal growth in children and for monitoring response to treatment for growth and bone disorders.

Abstract

Despite its importance as a key parameter of child health and development, growth velocity is difficult to determine in real time because skeletal growth is slow and clinical tools to accurately detect very small increments of growth do not exist. We report discovery of a marker for skeletal growth in infants and children. The intact trimeric noncollagenous 1 (NC1) domain of type X collagen, the marker we designated as CXM for Collagen X Marker, is a degradation by-product of endochondral ossification that is released into the circulation in proportion to overall growth plate activity. This marker corresponds to the rate of linear bone growth at time of measurement. Serum concentrations of CXM plotted against age show a pattern similar to well-established height growth velocity curves and correlate with height growth velocity calculated from incremental height measurements in this study. The CXM marker is stable once collected and can be accurately assayed in serum, plasma, and dried blood spots. CXM testing may be useful for monitoring growth in the pediatric population, especially responses of infants and children with genetic and acquired growth disorders to interventions that target the underlying growth disturbances. The utility of CXM may potentially extend to managing other conditions such as fracture healing, scoliosis, arthritis, or cancer.

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