Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and...
Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and aggravation of BRONJ. Methods: Twenty seven rats were divided into 3 groups; Saline group (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got weekly intraperitoneal injection for 4 times and extraction of left maxillary and mandibular 1st, 2nd molars were followed. Consecutive injections were performed, and blood sampling for measurements of C-terminal crosslinked telopeptide of type I collagen and tartrate-resistant acid phosphate 5b rats were performed at the time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated clinically, radiologically and histologically. Results: 12/18 (66.6 %) of experimental group were diagnosed as BRONJ. There was no significant difference in incidence between zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll). Conclusions: Concurrent use of bisphosphonates and steroids increase incidence of BRONJ compared to saline group (l). Zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the rat treated with bisphosphonates and steroids can be considered a novel, reliable and reproducible model to understand pathology of BRONJ.
Background: The aim of this study is to develop a rat model of bisphosphonates-related osteonecrosis of the jaw (BRONJ) that would be verified with clinical, radiological and histological examination, and to confirm the influence of concurrent bisphosphonates and steroids use upon the occurrence and aggravation of BRONJ. Methods: Twenty seven rats were divided into 3 groups; Saline group (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got weekly intraperitoneal injection for 4 times and extraction of left maxillary and mandibular 1st, 2nd molars were followed. Consecutive injections were performed, and blood sampling for measurements of C-terminal crosslinked telopeptide of type I collagen and tartrate-resistant acid phosphate 5b rats were performed at the time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated clinically, radiologically and histologically. Results: 12/18 (66.6 %) of experimental group were diagnosed as BRONJ. There was no significant difference in incidence between zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll). Conclusions: Concurrent use of bisphosphonates and steroids increase incidence of BRONJ compared to saline group (l). Zoledronate alone group (ll) and concurrent use of zoledronate and dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the rat treated with bisphosphonates and steroids can be considered a novel, reliable and reproducible model to understand pathology of BRONJ.
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문제 정의
The concurrent use of bisphosphonates and steroids has definite clinical relevance with BRONJ, as many BRONJ patients being treated for multiple myeloma, breast cancer receive both drugs [13]. The purpose of this study focused on development of rat model of BRONJ to confirm how concurrent use of BPs and steroids can affect occurrence and aggravation of BRONJ.
However, it has not been defined, interaction between systemic risk factors, concurrent medications, and occurrence and aggravation of BRONJ. Thus, the authors aimed to develop a rat model of BRONJ, and to confirm how concurrent use of BPs and steroids can affect occurrence and aggravation of BRONJ in this study.
제안 방법
Blood samples are used on ELISA kit, to analyze CTX, TRACP 5b level. All the specimens were evaluated by clinical, radiological, histological examination.
All the specimens were reviewed to confirm incomplete oral mucosal coverage on necrotic alveolar bone and sequestra formation, then photographed, and preserved with 10 % buffered-formalin immediately.
I-HC conceived of the study, and participated in its design and coordination and helped to draft the manuscript. J-WK participated in the design of the study and performed the statistical analysis.
1 Time table of study is shown above. It takes 12 weeks, and 2,4,8 weeks after extraction, we sacrifice every 3 rats of control group, 2,2,5 rats of experimental group. We take blood samples at the same time
I-HC conceived of the study, and participated in its design and coordination and helped to draft the manuscript. J-WK participated in the design of the study and performed the statistical analysis. H-WJ carried out acquisition, analysis, and interpretation of data and drafting the manuscript.
대상 데이터
Twenty seven female Spraque-Dawley rats (250–300 g) were used and 54 sites (left maxilla and mandible).
Mean life of Spraque-Dawley rat is 24 months, 96 weeks. We used 8 week-rats, it takes 12 weeks to finish this study. So they are 20 weeks-old and still adolescent.
성능/효과
2) It has little chance of spontaneous BRONJ, resulting from concurrent use of bisphosphonates and steroids only, surgical stimulus, such as extraction plays important role as trigger factor, increasing incidence of BRONJ.
Seven of 10 rats, that were sacrificed 8 weeks after extraction, showed osteonecrosis of jaw, relatively high incidence of BRONJ(70 %). It explains that injection period can be a risk factor for BRONJ (Fig.
후속연구
There are many bone turn-over markers including TRACP 5b, but clinical use is not established yet. There should be more research for clinical use of TRACP 5b, predicting possibility of BRONJ incidence, staging and managing of BRONJ patients.
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