The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

telopeptide of fibrillar

collagens Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

such as

collagen type I Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers. It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endo ...

and type II. It is used as a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

in the serum to measure the rate of bone turnover. It can be useful in assisting clinicians to determine a patient's nonsurgical treatment response as well as evaluate a patient's risk of developing complications during healing following surgical intervention. The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nucleated ...

than any other test currently available.

Biomarker discovery

In the early 2000s, a link between

bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...

use and impaired bone physiology was noted. The strong inhibition of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

function precipitated by bisphosphonate therapy can lead to inhibition of normal bone turnover, leading to impaired wound healing following trauma (such as dental surgery) or even spontaneous non-healing bone exposure. Because bisphosphonates are preferentially deposited in bone with high turnover rates, it is possible that the levels of bisphosphonate within the jaw bones are selectively elevated. With the advent of implant dentistry, more dental patients are undergoing therapies in the oral cavity that involve bone healing, such as surgical implant placement and bone grafting procedures. In order to evaluate the risk of osteonecrosis for a patient taking bisphosphonates, use of the CTX biomarker was introduced in 2000 by Rosen.

Use as a biomarker

Although a number of surrogate biomarkers exist for measuring the metabolic products of bone resorption, the serum CTX marker was chosen because it is both highly correlated to bone turnover rate and already available for detection in a laboratory test carried out by a major lab testing corporation. The CTX test measures for the presence and concentration of a crosslink

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

sequence of

type I collagen Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers. It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endomy ...

, found, among other tissues, in bone. This specific peptide sequence relates to bone turnover because it is the portion that is cleaved by

s during bone resorption, and its serum levels are therefore proportional to osteoclastic activity at the time the blood sample is drawn. Serum levels in healthy patients not taking bisphosphonates tends to hover above 300 pg/mL. Patients who are placed on a 6-month drug holiday exhibit marked improvements in their serum CTX values; in one study, patients showed an improvement of 155.3 pg/mL over 6 months or a rate of 25.9 pg/mL each month. Initially, urinary CTX levels were sought, but this proved to offer no greater value than urinary NTX values—both tests suffered from large spontaneous fluctuations unrelated to therapy or intervention, and were therefore largely unreliable. In contrast, the

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

test for detecting serum CTX levels features minimal spontaneous disruption yet remarkable change to antiresorptive therapy, making the serum CTX assay both highly sensitive and specific.

References

{{reflist Biomarkers Bones Chemical pathology Collagens Peptides

Biomarker discovery

Use as a biomarker

See also

References