Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw

Jin Woo Kim, Inho Cha, Sun Jong Kim, Myung Rae Kim

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)281-291
Number of pages11
JournalClinical Implant Dentistry and Related Research
Volume18
Issue number2
DOIs
Publication statusPublished - 2016 Apr 1

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Bisphosphonate-Associated Osteonecrosis of the Jaw
zoledronic acid
Biomarkers
Diphosphonates
Osteoclasts
Sensitivity and Specificity
Signal-To-Noise Ratio
Area Under Curve
Sprague Dawley Rats
Analysis of Variance
Animal Models
Control Groups
Injections
Serum
Research

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Dentistry(all)

Cite this

Kim, Jin Woo ; Cha, Inho ; Kim, Sun Jong ; Kim, Myung Rae. / Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw. In: Clinical Implant Dentistry and Related Research. 2016 ; Vol. 18, No. 2. pp. 281-291.
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abstract = "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.",
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Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw. / Kim, Jin Woo; Cha, Inho; Kim, Sun Jong; Kim, Myung Rae.

In: Clinical Implant Dentistry and Related Research, Vol. 18, No. 2, 01.04.2016, p. 281-291.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Biomarkers for Bisphosphonate-Related Osteonecrosis of the Jaw

AU - Kim, Jin Woo

AU - Cha, Inho

AU - Kim, Sun Jong

AU - Kim, Myung Rae

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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.

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