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Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw
Jin-Woo Kim1,2, In-Ho Cha1, Sun-Jong Kim2
1Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Yonsei University, Seoul, Korea.
Purpose:
The aim of this study was to investigate a possible biomarker for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an animal model.
Materials And Methods:
Forty-eight Sprague-Dawley rats were randomly divided into the bisphosphonate group (n = 36), who were injected once a week with zoledronic acid, and the control group (n = 12), who were injected once a week with saline. After 6 weeks, surgical intervention was performed, and 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 CTx, Glu-OC, TRACP 5b, RANKL, and OPG, were assessed at baseline (T0), at surgical intervention (T1), and at sacrifice (T2). Histomorphometric analysis for quantification of osteoclasts was performed.
Results:
Repeated measures analysis of variance revealed that TRACP 5b levels and the RANKL/OPG ratio were significantly decreased over time in the ONJ group compared with the non-ONJ group (p < .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 (29.6%) with lower intra-assay coefficient of variability (CV; 6.32%) and interassay CV (11.20%) compared with 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). N.Oc/T.Ar and N.Oc/B.Ar demonstrated significantly decreased number of osteoclasts in ONJ group versus non-ONJ group.
Conclusions:
These results show 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.
