Biological or Clinical Significance:
Bone resorption is a function of osteoclasts. These cells remove the mineral from bone and break down the organic matrix that is primarily comprised of type I collagen. Collagen is a cross-linked fibrous protein that forms the fabric of bone and most other connective tissues. Bone contains three polypeptide chains wound together in a helical structure. The ends of these chains (known as telopeptides) provide the intermolecular cross-linking that gives collagen its strength and resiliency. As these cross-linked domains from bone and other skeletal connective tissues are broken down, the pyridinoline cross-linking domains are released and ultimately excreted into the urine in the form of small peptides bound to pyridinoline (70%) and free pyridinoline (30%). One type of peptide-bound pyridinoline is the cross-linked N-telopeptide (NTX) which is unique to type I bone collagen. NTX can be used to identify fast losers of bone, to monitor therapy, to measure dose response, or to determine patient compliance with therapeutic prescription(s).
A growing body of clinical studies has shown that urinary NTx provides a sensitive marker of human bone resorption. Its specificity is based on originating solely from type I collagen, being particularly enriched as a cross-linking structure in bone type I collagen and being produced directly as a proteolytic neoepitope by osteoclast activity during bone resorption. Analysis of urine specimens has certain advantages, including ease of collection and reduced biohazard precautions for clinical laboratory personnel than with bloodbased specimens. However, the obtained results need to be normalized to creatinine.
Principle of Test Method:
The NTX assay is a competitive, enzyme-linked immunosorbent assay (ELISA) for the quantitative measurement of the NTX in human urine. NTX is reported as a normalized ratio to urinary creatinine in order to account for variations in urine flow rate. Therefore NTX and urine creatinine are preferably tested from the same aliquot.
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Ju HS, Leung S, Brown B, Stringer MA, Leigh S, Scherrer C, Shepard K, Jenkins D, Knudsen J, Cannon R. Comparison of analytical performance and biological variability of three bone resorption assays. Clin Chem. 1997; 43:1570-1576.