Biomarker detection in bisphosphonate-related osteonecrosis of the jaw

Abstract

Various bone biomarkers have been suggested for the risk assessment for osteonecrosis of the jaw, an oral complication associated with bisphosphonate (BP) use; however, no consensus has been established. The aim of this thesis was to investigate a possible biomarker for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an animal model.Forty eight Sprague-Dawley rats were randomly divided into the two groups; bisphosphonate group (n=36) treated with weekly zoledronic acid injection and control group (n=12) treated with weekly saline injection. After 6 weeks, surgical intervention was performed, and weekly injections were continued up to 8 weeks. Rats in the bisphosphonate group were then further classified to the ONJ group and the non-ONJ group, and biomarkers, including serum CTx, Glu-OC, TRACP 5b, RANKL, and OPG, were assessed at baseline (T0), at surgical intervention (T1; 8 weeks) and at sacrifice (T2; 14 weeks). Histomorphometric analysis for quantification of osteoclasts was performed.TRACP 5b levels and the RANKL/OPG ratio were significantly decreased over time in the ONJ group compared to the non-ONJ group (P < 0.05). At T2, the area under the curve was 0.807 for TRACP 5b (sensitivity: 88.9%, specificity 66.7% at cutoff) and 0.765 for the RANKL/OPG ratio (sensitivity: 77.8%, specificity 62.9% at cutoff). TRACP 5b showed a lower least significant change (LSC; 29.6%) with lower intra-assay coefficient variability (CV; 6.32%) and inter-assay CV (11.20%) compared to those of the RANKL/OPG ratio (39.27%) and showed a higher signal-to-noise ratio (2.76) than that of the RANKL/OPG ratio (1.62). Moreover, N.Oc/T.Ar and N.Oc/B.Ar demonstrated significantly decreased number of osteoclasts in ONJ group versus non-ONJ group. (P < 0.05)These results demonstrated that serum TRACP 5b and the RANKL/OPG ratio were possible biomarkers for BRONJ. These data may provide useful additional information for future ONJ research. Further studies are needed to validate these results in humans with ONJ.