What is C-terminal telopeptide?

Updated: Feb 18, 2020
  • Author: Carlos Solano Loran, MD; Chief Editor: Eric B Staros, MD  more...
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Degradation products derived from the enzymatic hydrolysis of type 1 collagen, particularly peptides related to regions of cross-linking with PYD, are the best markers of bone resorption. Released collagen fragments are responsible for many bone markers, since more than 90% of protein in bone consists of collagen type 1.

Although urinary hydroxyproline was previously one of the primary bone resorption markers used, specificity and sensitivity were lacking in this assay. A component of bone collagen, hydroxyproline is released into the serum during degradation of bone, reaching the urine in free and bound forms. However, because it is derived from the degradation of newly synthesized collagens, from collagens of nonbone tissues, and from diet, serum hydroxyproline is now considered to be a nonspecific marker of bone turnover. Urinary hydroxyproline has consequently been replaced by more specific techniques.

The pyridinium compounds PYD and DPD, as well as hydroxypyridinium cross-links collagen, are among the more specific markers. Formed during the extracellular maturation of fibrillar collagens, PYD and DPD are released when mature collagens degrade. PYD and DPD measurement values do not change in association with the degradation of newly synthesized collagens and are not influenced by dietary sources.

Testing can also be performed without directly using cross-links as markers. Assays have been developed based on specific antibodies raised in an immune response against isolated collagen peptides containing cross-links. Detected by radioimmunoassay technique, fragments exist for C-telopeptide of type 1 collagen (CTX, CrossLaps) and cross-linked N-terminal telopeptide of type 1 collagen by ELISA technique (NTX, Osteomark). [2]

The NTX assay employs a monoclonal antibody directed against a urinary pool of collagen cross-links (originating from a patient with Paget disease). Serum CrossLaps assay measures only β-isomer of CTX, while the urine CrossLaps assay measures α- and β-isomers of CTX. Urine from healthy individuals has produced a detectable reaction from these assays, and elevated turnover has produced large increases.

The 2 categories of C-telopeptide methods are C-telopeptide of type 1 collagen (CTX) and type 1 collagen cross-linked C-telopeptide (ICTP). They differ with regard to which segment domains they recognize in the C-terminal telopeptide region of the α1 chain of type 1 collagen and also differ in their response to bone metabolic processes.

CTX shows remarkable response to antiresorptive therapies, while serum ICTP is insensitive to osteoporosis and other normal metabolic bone processes. However, in bone pathologic conditions such as bone metastasis and rheumatoid arthritis, serum ICTP may be a marker of bone degradation. [3]

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