[3][4] 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.

In order to evaluate the risk of osteonecrosis for a patient taking bisphosphonates, use of the CTX biomarker was introduced in 2000 by Rosen.

[2] 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.

[1] The CTX test measures for the presence and concentration of a crosslink peptide sequence of type I collagen, found, among other tissues, in bone.

[6] 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.