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Biomarkers for Bisphosphonate‐Related Osteonecrosis of the Jaw
Author(s) -
Kim JinWoo,
Cha InHo,
Kim SunJong,
Kim MyungRae
Publication year - 2016
Publication title -
clinical implant dentistry and related research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.338
H-Index - 85
eISSN - 1708-8208
pISSN - 1523-0899
DOI - 10.1111/cid.12297
Subject(s) - medicine , bisphosphonate , rankl , osteonecrosis of the jaw , zoledronic acid , saline , analysis of variance , urology , biomarker , dentistry , gastroenterology , osteoporosis , receptor , chemistry , biochemistry , activator (genetics)
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 S prague‐ D awley 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 CT x, G lu‐ OC , TRACP 5b, RANKL , and OPG , were assessed at baseline ( T 0), at surgical intervention ( T 1), and at sacrifice ( T 2). 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 T 2, 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 . O c/ T . A r and N . O c/ B . A r 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 .