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Biomarker detection in bisphosphonate-related osteonecrosis of the jaw

Authors
 김진우 
Issue Date
2015
Description
Departement of Dental Science/석사
Abstract
Various bone biomarkers have been suggested for the risk assessment for osteonecrosis of the jaw, an oral complication associated with bisphosphonate (BP) use; however, no consensus has been established. The aim of this thesis was to investigate a possible biomarker for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an animal model.Forty eight Sprague-Dawley rats were randomly divided into the two groups; bisphosphonate group (n=36) treated with weekly zoledronic acid injection and control group (n=12) treated with weekly saline injection. After 6 weeks, surgical intervention was performed, and weekly 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 serum CTx, Glu-OC, TRACP 5b, RANKL, and OPG, were assessed at baseline (T0), at surgical intervention (T1; 8 weeks) and at sacrifice (T2; 14 weeks). Histomorphometric analysis for quantification of osteoclasts was performed.TRACP 5b levels and the RANKL/OPG ratio were significantly decreased over time in the ONJ group compared to the non-ONJ group (P < 0.05). 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 (LSC; 29.6%) with lower intra-assay coefficient variability (CV; 6.32%) and inter-assay CV (11.20%) compared to 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). Moreover, N.Oc/T.Ar and N.Oc/B.Ar demonstrated significantly decreased number of osteoclasts in ONJ group versus non-ONJ group. (P < 0.05)These results demonstrated 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.
Files in This Item:
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Appears in Collections:
2. College of Dentistry (치과대학) > Others (기타) > 2. Thesis
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/145589
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