唑来膦酸剂量与颌骨坏死相关性的实验研究

doi:10.19438/j.cjoms.2017.02.004

中国口腔颌面外科杂志 ›› 2017, Vol. 15 ›› Issue (2): 115-120.doi: 10.19438/j.cjoms.2017.02.004

唑来膦酸剂量与颌骨坏死相关性的实验研究

沈亚俊^{1, 2}, 杜明燕², 关键^{2*, *}, 李矛³, 赵彦涛⁴, 葛成¹

1.解放军第307医院口腔科,北京 100071;
2.佳木斯大学口腔医学院,黑龙江佳木斯 154000;
3.解放军第306医院骨科,北京 100101;
4.解放军总医院第一附属医院骨科研究所,北京 100051

收稿日期:2016-06-13 出版日期:2017-03-20 发布日期:2017-04-13
通讯作者: 葛成,E-mail：gechengde@163.com;关键,E-mail：guanjian1207@163.com。^*共同通信作者
作者简介:沈亚俊（1990-）,男,硕士研究生,E-mail：190212913@qq.com

Relationship between different doses of zoledronic acid and bisphosphonate-related osteonecrosis of jaw: an experiment study in rats

SHEN Ya-jun^{1, 2}, DU Ming-yan², GUAN Jian², LI Mao³, ZHAO Yan-tao⁴, GE Cheng¹

1.Department of Oral and Maxillofacial Surgery, The 307th Hospital of Military Medical Sciences. Beijing 100071;
2.Jiamusi University School of Stomatology. Jiamusi 154000, Heilongjiang Province;
3.Department of Orthopaedics, The 306th Hospital of PLA. Beijing 100101;
4.Research Institution of Orthopaedics, First Affiliated Hospital of PLA General Hospital. Beijing 100051, China

Received:2016-06-13 Online:2017-03-20 Published:2017-04-13
Contact: 北京市自然科学基金（7152110）

摘要/Abstract

摘要： 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、132 μg/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、132 μg/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。

关键词: 唑来膦酸, 剂量, 下颌骨, 骨坏死

Abstract: PURPOSE : To investigate the relationship between different doses of zoledronic acid (ZA) and bisphosphonate-related osteonecrosis of jaw (BRONJ) by establishing the model of osteonecrosis of jaw in rats with different doses of ZA. METHODS : Forty SD rats were divided into 4 groups (ten rats in each group), the rats in 4 groups were injected intraperitoneally with 33, 66 and 132 μg/kg ZA or normal saline (control), respectively, three times a week for 12 weeks, and the weight was measured weekly. In the ninth week, all rats was subjected to extraction of the first left mandibular molar. After the last injection, all rats were sacrificed. The jaws were clinically, radiologically and histopathologically examined. Independent samples t test was performed using SPSS19.0 software package. RESULTS : The weight of rats in the experimental groups was significantly lower than that in the control group after extraction (P<0.05). 86.7% rats in the experimental group were observed with unclosed mucosa; however, mucosa on extraction sites in the control group healed completely (P<0.05). Radiological examination revealed radiolucent areas on the extraction sites in the experimental groups were significantly greater than those in the control group (P<0.05). Histopathological examination showed 70% rats in the experimental group developed osteonecrosis,especially in higher dose group,while osteonecrosis was not found in the control group (P<0.05). CONCLUSION : The study showed severe BRONJ was closely associated with high dose of ZA. Low dose of ZA just induces minor BRONJ, or is unable to induce BRONJ. Thus, Patients treated with high dose of ZA are facing great risk of developing BRONJ.

Key words: Zoledronic Acid, Dose, Jaw, Osteonecrosis

中图分类号:

R782

沈亚俊, 杜明燕, 关键, 李矛, 赵彦涛, 葛成. 唑来膦酸剂量与颌骨坏死相关性的实验研究[J]. 中国口腔颌面外科杂志, 2017, 15(2): 115-120.

SHEN Ya-jun, DU Ming-yan, GUAN Jian, LI Mao, ZHAO Yan-tao, GE Cheng. Relationship between different doses of zoledronic acid and bisphosphonate-related osteonecrosis of jaw: an experiment study in rats[J]. China J Oral Maxillofac Surg, 2017, 15(2): 115-120.

参考文献

[1] Ruggiero SL, Dodson TB, Fantasia J, et al. American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw-2014 update [J]. J Oral Maxillofac Surg, 2014, 72(10):1938-1956.
[2] Guarneri V, MilesD, Robert N, et al. Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer [J]. Breast Cancer Res Treat, 2010, 122(1): 181-188.
[3] Barasch A, Cunha-Cruz J, Curro FA, et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN [J]. J Dent Res, 2011, 90(4): 439-444.
[4] Yamazaki T, Yamori M, Ishizaki T, et al. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study [J]. Int J Oral Maxillofac Surg, 2012, 41(11): 1397-1403.
[5] Allen MR. The effects of bisposphonates on jaw bone remodeling, tissue proprieties, and extraction healing [J]. Odontology, 2011, 99(1): 8-17.
[6] Aghaloo TL, Kang B, Sung EC, et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat[J]. J Bone Miner Res, 2011, 26(8): 1871-1882.
[7] Jabbour Z, El-Hakim M, Henderson JE, et al. Bisphosphonates inhibit bone remodeling in the jaws bones of rats and delay healing following tooth extractions [J]. Oral Oncol, 2014, 50(5): 485-490.
[8] Aghaloo TL, Kang B, Sung EC, et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat [J]. J Bone Miner Res, 2011, 26(8): 1871-1882.
[9] Kang B, Cheong S, Chaichanasakul T, et al. Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice [J]. Bone Miner Res, 2013, 28(7): 1631-1640.
[10] Sonis ST, Watkins BA, Lyng GD, et al. Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients [J]. Oral Oncol, 2009, 45(2): 164-172.
[11] Li CL, Seneviratne CJ, Huo L, et al. Impact of Actinomyces naeslundii on bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats with periodontitis[J]. J Cranio maxillofac Surg, 2015, 43(8): 1662-1669.
[12] Roelofs AJ, Thompson K, Gordon S, et al. Molecular mechanisms of action of bisphosphonates: current status [J]. Clin Cancer Res, 2006, 12(20 Pt 2): 6222s-6230s.
[13] Vasconcelos AC, Berti-Couto SA, Azambuja AA, et al. Comparison of effects of clodronate and zoledronic acid on the repair of maxilla surgical wounds histomorphometric, receptor activator of nuclear factor-kB ligand, osteoprotegerin, von Willebrand factor, and caspase-3 evaluation[J]. J Oral Pathol Med, 2012, 41(9): 702-712.
[14] Mavrokokki T, Cheng A, Stein B, et al. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia [J]. J Oral Maxillofac Surg, 2007, 65(3): 415-423.
[15] Ersan N, van Ruijven LJ, Bronckers AL, et al. Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model [J]. Dentomaxillofac Radiol, 2014, 43(1): 20130144.
[16] Cankaya AB, Erdem MA, Isler SC, et al. Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws in an experimental rat model [J]. Int J Med Sci, 2011, 8(8): 667-672.
[17] Ma YL, Bryant HU, Zeng Q, et al. New bone formation with teriparatide [human parathyroid hormone-(1-34)] is not retarded by long-term pretreatment with alendronate, estrogen, or raloxifene in ovariectomized rats [J]. Endocrinology, 2003, 144(5): 2008-2015.

唑来膦酸剂量与颌骨坏死相关性的实验研究

Relationship between different doses of zoledronic acid and bisphosphonate-related osteonecrosis of jaw: an experiment study in rats

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