Prospective biomarker evaluation in patients with osteonecrosis of the jaw who received bisphosphonates

Abstract

Bone biomarkers have been suggested for the risk assessment for osteonecrosis of the jaw, a serious complication associated with bisphosphonate (BP) use; however, no consensus has been reached. This study investigated the possible associations between bone biomarkers and the development of bisphosphonates-related osteonecrosis of the jaw (BRONJ). This is a case-control study of 37 patients with BRONJ (age, 73.6±11.2years) who had at least 1 sample available at diagnosis, out of which, 35 were taking BPs for osteoporosis and 2 patients for bone metastasis. Age- and gender-matched 37 patients who had been exposed to BPs for >24months and had no evidence of BRONJ after dentoalveolar surgery served as control group. The association between biomarkers (osteocalcin [OC], deoxypyridinoline [DPD], C-terminal telopeptide of collagen I [CTX], N-terminal telopeptides [NTX], bone-specific alkaline phosphatase [BAP], and parathyroid hormone [PTH]) and BRONJ development, the effects of BP discontinuation on biomarkers, and the performance of biomarkers for risk assessment were investigated. In our study, the PTH levels were found to be significantly higher in BRONJ patients compared to controls (P<0.05). But the OC, DPD, CTX, NTX, and BAP levels were not significantly different between the 2 groups (P>0.05). The CTX level in reference to a 150pg/mL cutoff was also not significant for BRONJ development (P>0.05). Among BRONJ patients who discontinued BP, in a linear mixed model, only CTX showed a significant increase over time (β=0.002, P=0.007). The cutoff PTH level was >41.52pg/mL (AUC=0.719, P=0.009), and that of CTX was ≤0.094ng/mL (AUC=0.619, P=0.069). In conclusion, there is insufficient evidence for the risk prediction for BRONJ of current bone biomarkers; additional research is necessary.