C-terminal telopeptide

In bone physiology, the C-terminal telopeptide (or more formally, carboxy-terminal collagen crosslinks, and known by the acronym CTX) is a telopeptide that can be used as a biomarker 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.<ref name="MarxCTX">Marx, RE, et al. Oral Bisphosphonate-Induced Osteonecrosis: Risk Factors, Prediction of Risk Using Serum CTX Testing, Prevention, and Treatment, J Oral Maxillofac Surg 2007;65:2397-2410</ref> The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to bone resorption than any other test currently available.<ref name="ROSEN">Rosen, HN, et al. Serum CTX. A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 2000;66:100</ref>

Bisphosphonate-associated osteonecrosis of the jaw

Main article: Bisphosphonate-associated osteonecrosis of the jaw

In the early 2000s, a link between bisphosphonate use and impaired bone physiology was noted.<ref>Marx, RE, et al. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 2003;61:1115</ref><ref>Ruggerio, SL, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg 2004;62:527</ref> The strong inhibition of osteoclast 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.<ref>Ruggiero, SL. Bisphosphonate-related Osteonecrosis of the Jaws. Compendium 2008;29(2):97–105.</ref>

Risk determination

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.<ref name="ROSEN"/>

Use of the CTX 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.<ref name="MarxCTX"/>

The CTX test measures for the presence and concentration of a crosslink peptide sequence of type I collagen, found, among other tissues, in bone. This specific peptide sequence relates to bone turnover because it is the portion that is cleaved by osteoclasts during bone resorption, and its serum levels are therefore proportional to osteoclastic activity at the time the blood sample is drawn.<ref name="MarxCTX"/> 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.<ref name="MarxCTX"/>

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.<ref>Ju, H, et al. Comparison of analytical performance and biological variability of three bone resorption assays. Clin Chem 1997;43:1570–1576</ref> In contrast, the monoclonal antibody 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.<ref name="ROSEN"/>

See also

N-terminal telopeptide

References

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