N-terminal telopeptide of type 1 collagen (NTX) in Urine and serum
25% (urine) 12% (serum)
At present, the N- and C-terminal telopeptides, known as NTX and CTX, respectively, are the most sensitive and specific markers of bone resorption. These fragments are formed by the activity of cathepsin K and appear in significant amounts, both in blood and urine, where they can be measured by specific immunoassays. In bone resorption processes, osteoclasts release minerals and fragments of collagen. Some of these peptide fragments of the terminal amino or carboxyl ends do not have the helical structure typical of the collagen fiber, the telopeptide regions, which bind to the pyridinium bridges, pass into circulation.
Hydroxyproline is a non-essential amino acid that comes from the hydroxylation of proline and constitutes 10% of the mature collagen content. Most of the techniques used for its quantification present high variability (coefficient of variation between 10 to 12%). It can be determined by HPLC (high efficiency liquid chromatography), a technique limited to research purposes, rather than a massive clinical use. Its primary use is in the monitoring of Paget's disease. In osteoporosis it presents low sensitivity and although the determination of urinary hydroxyproline was the marker of historical resorption, with time it has been replaced by other more sensitive and specific bone
I believe that there is no single best marker, and its always good to use more than one, or choose it acording to the type of experimental design. If drugs are tested, the variability of the bone markers will also differ in relationship to the compound main mode of action.
I feel NTX is the best marker to detect bone resorption. This marker is considered to be more specific and sensitive. NTX can be detected at very early stage of resoprtion and in both serum and urine.
The IOF in a 2011 Position paper reviewed all the infotrmation and felt that serum CTx was the best marker of bow resorption and the propeptide of type I N terminal procollagen was the best marker of bone formation. Most clinical trials, now, use these two markers.
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