CTX and NTX are new markers of bone resorption used to diagnose osteoporosis and assess effect of bisphosphonate therapy

CTX and NTX are markers of bone resorption (degradation products). CTX and NTX are derived from the enzymatic hydrolysis of type 1 collagen, they are peptides related to regions of cross-linking with pyridinoline (PYD). Collagen type 1 represents over 90% of the protein in bone.

What is CTX?

CTX is an abbreviation for urinary or serum collagen type 1 cross-linked C-telopeptide (CTX).

C-telopeptides cross-links of bone Type I collagen are sensitive markers of bone resorption in osteolytic diseases such as osteoporosis and osteoarthritis.

High levels of CTX and NTX indicate excessive bone turnover and is a sign of osteoporosis. Levels of CXT and NT decrease with bisphosphonates therapy. Very low levels may indicate over-aggressive treatment of osteoporosis with bisphosphonates.

Women with high serum CTX (T score greater than 2) have a 25% probability of fracture over 5 years. Women with low BMD and high CTX have 54% probability of fracture over 5 years.

What is NTX?

NTX is an abbreviation for urinary collagen type 1 cross-linked N-telopeptide. NTX, the amino terminal cross-linked peptide of type I collagen, is released during bone resorption.

How to measure CTX and NTX peptides?

Rather than use the cross-links themselves as markers, there are assays based on specific antibodies against isolated collagen peptides containing cross-links.

The pyridinium cross-links and the collagen telopeptides involving the cross-linking sites are considered the best indices for the assessment of bone resorption. Serum CTX is the mostly commonly used measurement. Urine and serum CTX are used for following antiresorptive therapy.

For a 90% specificity to predict a positive BMD response (+3%), cut-offs, expressed as a percentage decrease from baseline, are as follows:

-Urine NTX and urine CTX, -45% to –65%
- Serum CTX, -35% to –55%

A change of greater than 30% is significant.

References:
C-Telopeptide Pyridinoline Cross-Links: Sensitive Indicators of Periodontal Tissue Destruction. Ann N Y Acad Sci. 1999 June 30; 878: 404–412.
Bisphosphonate-Related Osteonecrosis of the Jaw: Workup. eMedicine.
Utility of Bone Markers in Osteoporosis. eMedicine.
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. Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL. Calcif Tissue Int. 2000 Feb;66(2):100-3.
Illustration: Bone Remodeling. Obgyn.net.

Risk of esophageal cancer increased with 10 or more prescriptions for oral bisphosphonates over a 5 year period. http://goo.gl/m0fT
It is reasonable to stop bisphosphonates after 5 years of use and then to follow patients with markers of bone turnover http://goo.gl/YmNS9
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