TY - JOUR
T1 - Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw
AU - Kim, Jin Woo
AU - Cha, In Ho
AU - Kim, Sun Jong
AU - Kim, Myung Rae
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Bisphosphonate
KW - Osteonecrosis of the jaw
KW - Receptor activator of nuclear factor-κβ ligand
KW - Tartrate-resistant acid phosphatase
UR - http://www.scopus.com/inward/record.url?scp=84962861489&partnerID=8YFLogxK
U2 - 10.1111/cid.12297
DO - 10.1111/cid.12297
M3 - Article
C2 - 25726720
AN - SCOPUS:84962861489
SN - 1523-0899
VL - 18
SP - 281
EP - 291
JO - Clinical Implant Dentistry and Related Research
JF - Clinical Implant Dentistry and Related Research
IS - 2
ER -