Clinical Investigation of C-Terminal Cross-Linking Telopeptide Test in Prevention and Management of Bisphosphonate-Associated Osteonecrosis of the Jaws

Purpose

The aim of this study was to determine, in a clinical setting, the effectiveness of the C-terminal cross-linking telopeptide test (CTX) test in the prevention and management of osteonecrosis of the jaws (ONJ) in patients taking bisphosphonates.

Patients and Methods

A total of 348 patients underwent a fasted morning CTX test. Of these, 222 were patients at risk of ONJ who had been referred for extractions, 15 had ONJ, and 113 were controls.

Results

The 215 patients taking long-term oral bisphosphonates were older (71 ± 11.6 years), were predominantly women with osteoporosis, and were medically compromised. The average CTX value was 238 ± 144 pg/mL, with 98 having a value less than 200 pg/mL. One patient with a CTX value of 126 pg/mL developed ONJ after an extraction. Seven intravenous bisphosphonate patients underwent extractions with no cases of ONJ developing. The CTX value was 329 ± 354, with 4 less than 200 pg/mL. Fifteen patients developed ONJ, 12 after extractions and 3 spontaneously. Of these, 7, who were still taking a bisphosphonate at presentation, had a CTX value of 116 pg/mL. A CTX value of less than 150 pg/mL did not correlate with the clinical risk factors of age, gender, comorbidities, bone disease, or bisphosphonate duration. A statistically significant difference in the CTX value was found for those taking alendronate compared with those taking risedronate (P < .0001). If the bisphosphonate was ceased, the CTX value increased at approximately 25 pg/mL per month.

Conclusions

The CTX test is not predictive of the development of ONJ for an individual patient but does identify those in the “risk zone,” which is a value of less than 150 pg/mL to 200 pg/mL. If medically appropriate, the bisphosphonate can be ceased so that the CTX value increases to bring the patient out of the “risk zone.”