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目的 :建立双膦酸盐相关性颌骨坏死的大鼠模型,分析双膦酸盐剂量与颌骨坏死发生之间的关系。方法 :40只SD大鼠随机平均分为4组,腹腔注射剂量分别为33、66、132μg/kg的唑来膦酸,对照组腹腔注射生理盐水,连续注射12周,每周3次,每周称重。第9周,拔除所有大鼠左侧下颌第一磨牙,第12周处死所有大鼠,取左侧下颌骨,进行影像学和组织病理学分析。采用SPSS19.0软件包对数据进行独立样本t检验。结果:实验组大鼠在拔牙后,体重显著低于对照组(P<0.05),且X线片显示的拔牙创骨质密度也显著低于对照组(P<0.05);实验组86.7%的大鼠拔牙创黏膜未完全愈合,而对照组所有大鼠拔牙创黏膜均完全愈合(P<0.05)。组织学检测发现,实验组70%的大鼠发生骨坏死,其中66、132μg/kg骨坏死程度更为严重,而对照组组织学观察均未见骨坏死(P<0.05)。结论:BRONJ的发生和唑来膦酸的剂量有明显的相关性,低剂量唑来膦酸治疗只引起程度较轻的颌骨坏死,甚至不发生骨坏死,而高剂量唑来膦酸可引起严重骨坏死。
OBJECTIVE: To establish a rat model of bisphosphonate-associated osteonecrosis of the jaw and to analyze the relationship between the dose of bisphosphonates and the occurrence of jaw necrosis. Methods: Forty Sprague-Dawley rats were randomly divided into 4 groups. The animals were injected intraperitoneally with the doses of 33, 66 and 132μg / kg of zoledronic acid. The control group were injected with normal saline intraperitoneally for 12 weeks and 3 times a week Week weighing. At the 9th week, all the left mandibular first molar were removed and all the rats were sacrificed on the 12th week. The left mandibular was taken for imaging and histopathological analysis. SPSS19.0 software package for independent sample t-test data. Results: After tooth extraction, the body weight of the experimental group was significantly lower than that of the control group (P <0.05), and the bone density of the experimental group was significantly lower than that of the control group (P <0.05). In the experimental group, 86.7% The tooth mucosa did not heal completely during tooth extraction, while the mucosa of all rats in the control group healed completely (P <0.05). Histological examination found that 70% of the rats in the experimental group had osteonecrosis, of which 66,132μg / kg had more severe bone necrosis than the control group (P <0.05). CONCLUSIONS: The incidence of BRONJ is significantly related to the dose of zoledronic acid. Low-dose zoledronic acid treatment causes only mild necrosis of the jaw without osteonecrosis, whereas high doses of zoledronic acid can cause Severe bone necrosis.