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In [[physiology|bone physiology]], '''the C-terminal telopeptide''' (or more formally, '''carboxy-terminal collagen crosslinks''', and known by the [[acronym]] '''CTX''') is a [[wikt:telopeptide|telopeptide]] that can be used as a [[biomarker (medicine)|biomarker]] in the [[serum (blood)|serum]] to measure the rate of [[bone remodeling|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. <u>Oral Bisphosphonate-Induced Osteonecrosis: Risk Factors, Prediction of Risk Using Serum CTX Testing, Prevention, and Treatment</u>, ''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. <u>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</u>. ''Calcif Tissue Int'' 2000;66:100</ref>
{{DISPLAYTITLE:C-terminal telopeptide}}
==Bisphosphonate-associated osteonecrosis of the jaw==
== Overview ==
{{Main|Bisphosphonate-associated osteonecrosis of the jaw}}
The '''C-terminal telopeptide''' (CTX) is a biomarker used in the assessment of bone resorption. It is a fragment of type I collagen, which is the most abundant collagen in the human body and a major component of the bone matrix. CTX is released into the bloodstream during the process of bone degradation by [[osteoclast]]s.
In the early 2000s, a link between [[bisphosphonate]] use and impaired bone physiology was noted.<ref>Marx, RE, et al. <u>Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic</u>. ''J Oral Maxillofac Surg'' 2003;61:1115</ref><ref>Ruggerio, SL, et al. <u>Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases</u>. ''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. <u>Bisphosphonate-related Osteonecrosis of the Jaws</u>. ''Compendium'' 2008;29'''(2)''':97–105.</ref>
==Risk determination==
[[File:C-telopeptide.svg|thumb|right|Diagram of C-terminal telopeptide]]
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==
== Structure and Function ==
Although a number of [[surrogate endpoint|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"/>
Type I collagen is composed of three polypeptide chains that form a triple helix. The C-terminal telopeptide is a non-helical region at the end of the collagen molecule. During bone resorption, [[osteoclast]]s break down the bone matrix, releasing CTX into the circulation. The measurement of CTX levels in the blood or urine provides an indication of the rate of bone turnover.
The CTX test measures for the presence and concentration of a crosslink [[peptide]] sequence of [[Type-I collagen|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 [[osteoclast]]s 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 [[Kilogram#SI_multiples|pg]]/mL.
== Clinical Significance ==
CTX is commonly used in clinical practice to monitor bone health, particularly in conditions such as [[osteoporosis]]. Elevated levels of CTX indicate increased bone resorption, which can be a sign of bone loss. Monitoring CTX levels can help in assessing the effectiveness of treatments for osteoporosis and other metabolic bone diseases.
{{quotation|"Even though laboratory normal ranges are said to be between 50 pg/mL and 450 pg/mL, this normal range is not accurate related to the [[osteoporosis]] population. Actual normal values are usually well over 300 pg/mL and are most commonly 400 pg/mL to 550 pg/mL in patients not taking bisphosphonates. Lower values represent varying degrees of suppression of normal bone turnover, sometimes also called [[bone remodeling]] or bone renewal."<ref name="MarxCTX"/>}}
== Measurement ==
CTX can be measured in both serum and urine samples. The serum CTX test is often preferred due to its convenience and the stability of the biomarker in blood. The test is typically performed using immunoassays, which are sensitive and specific for the detection of CTX.
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"/>
== Related Pages ==
* [[Osteoclast]]
* [[Osteoporosis]]
* [[Bone resorption]]
* [[Type I collagen]]
Initially, urinary CTX levels were sought, but this proved to offer no greater value than urinary [[N-terminal telopeptide|NTX]] values—both tests suffered from large spontaneous fluctuations unrelated to therapy or intervention, and were therefore largely unreliable.<ref>Ju, H, et al. <u>Comparison
[[Category:Biomarkers]]
of analytical performance and biological variability of three bone resorption assays</u>. ''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 [[sensitivity and specificity|sensitive and specific]].<ref name="ROSEN"/>
The C-terminal telopeptide (CTX) is a biomarker used in the assessment of bone resorption. It is a fragment of type I collagen, which is the most abundant collagen in the human body and a major component of the bone matrix. CTX is released into the bloodstream during the process of bone degradation by osteoclasts.
Type I collagen is composed of three polypeptide chains that form a triple helix. The C-terminal telopeptide is a non-helical region at the end of the collagen molecule. During bone resorption, osteoclasts break down the bone matrix, releasing CTX into the circulation. The measurement of CTX levels in the blood or urine provides an indication of the rate of bone turnover.
CTX is commonly used in clinical practice to monitor bone health, particularly in conditions such as osteoporosis. Elevated levels of CTX indicate increased bone resorption, which can be a sign of bone loss. Monitoring CTX levels can help in assessing the effectiveness of treatments for osteoporosis and other metabolic bone diseases.
CTX can be measured in both serum and urine samples. The serum CTX test is often preferred due to its convenience and the stability of the biomarker in blood. The test is typically performed using immunoassays, which are sensitive and specific for the detection of CTX.
