Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw.
OBJECTIVE
The aim of this study was to investigate a possible biomarker for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an animal model.


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.
Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Yonsei University, Seoul, Korea.|Department of Oral and Maxillofacial Surgery, School of Medicine, Research Institute for Intractable Osteonecrosis of the Jaw, Ewha Womans University Medical Center, Ewha Womans University, Seoul, Korea.
Jin-Woo
JW
Kim
Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Yonsei University, Seoul, Korea.
In-Ho
IH
Cha
Department of Oral and Maxillofacial Surgery, School of Medicine, Research Institute for Intractable Osteonecrosis of the Jaw, Ewha Womans University Medical Center, Ewha Womans University, Seoul, Korea.
Sun-Jong
SJ
Kim
Department of Oral and Maxillofacial Surgery, School of Medicine, Research Institute for Intractable Osteonecrosis of the Jaw, Ewha Womans University Medical Center, Ewha Womans University, Seoul, Korea.
Myung-Rae
MR
Kim
D000818:Animals; D015415:Biomarkers; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw; D004195:Disease Models, Animal; D006801:Humans; D010010:Osteoclasts; D010020:Osteonecrosis; D053245:RANK Ligand / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase / Q000032:analysis*
D015415:Biomarkers; D053245:RANK Ligand; D000071681:Tartrate-Resistant Acid Phosphatase
biomarker; bisphosphonate; osteonecrosis of the jaw; receptor activator of nuclear factor-κβ ligand; tartrate-resistant acid phosphatase