双膦酸盐相关性颌骨坏死9例临床分析

中国口腔颌面外科杂志 ›› 2016, Vol. 14 ›› Issue (5): 449-454.

双膦酸盐相关性颌骨坏死9例临床分析

张学伟¹, 刘浩¹, 陈瑞扬², 张萍¹, 杨立¹, 吴炜³, 严颖彬¹

1.天津市口腔医院口腔颌面外科,
2.口腔病理科, 天津 300041;
3.天津医科大学总医院口腔科,天津 300052

收稿日期:2016-02-03 出版日期:2016-09-20 发布日期:2016-10-14
通讯作者: 严颖彬,E-mail: Yingbinyan@qq.com
作者简介:张学伟(1984-),女,硕士,主治医师,E-mail:zhangxuewei225@163.com
基金资助:
国家自然科学（青年）基金（81300901）; 天津市自然科学（青年）基金（14JCQNJC12500）; 天津市卫生局面上项目（2012KY18）

Bisphosphonate-related osteonecrosis of the jaw: report of 9 cases

ZHANG Xue-wei¹, LIU Hao¹, CHEN Rui-yang², ZHANG Ping¹, YANG Li¹, WU Wei³, YAN Ying-bin¹

1. Department of Oral and Maxillofacial Surgery,
2. Department of Oral Pathology, Tianjin Stomatological Hospital. Tianjin 300041;
3.Department of Stomatology, Tianjin Medical University General Hospital. Tianjin 300052, China

Received:2016-02-03 Online:2016-09-20 Published:2016-10-14

摘要/Abstract

摘要： 目的: 探讨双膦酸盐相关性颌骨坏死（bisphosphonate-related osteonecrosis of the jaw, BRONJ）的临床特点及治疗效果。方法: 分析2013年1月—2015年4月诊治的9例BRONJ患者的临床数据及影像学资料。结果: 9例患者均为静脉给药,平均用药时间42.7个月。用药期间7例有拔牙史,2例有义齿局部刺激。除3例首次就诊即确诊外,其余6例经2家以上医疗机构方确诊。出现口腔症状至确诊时间间隔平均6.9个月。临床表现包括局部疼痛、间隙感染、拔牙创不愈合及死骨外露。影像学表现包括骨密度增高、骨膜反应、死骨形成及弥漫性骨质破坏。9例患者中,0期1例,Ⅱ期4例,Ⅲ期4例。保守治疗4例,手术治疗5例,平均随访10.3个月。3例临床Ⅲ期患者长期存在软组织慢性炎症并伴有感染急性发作,其余6例患者痊愈或病情稳定。结论: BRONJ的临床表现与影像学表现无特异性,询问双膦酸盐用药史是诊断的关键。BRONJ的疗效不佳,临床Ⅲ期患者倾向于难以治愈和病情易于反复。

关键词: 双膦酸盐, 骨坏死, 颌骨

Abstract: PURPOSE: To summarize the clinical features and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: A total of 9 patients diagnosed and treated as BRONJ in our hospital from January 2013 to April 2015 were included. Their clinical data and imaging findings were analyzed. RESULTS: All patients received intravenous infusion of bisphosphonates with the average treatment duration of 42.7 months. During bisphosphonate treatment, seven patients had a history of tooth extraction, and the other 2 patients used removable dentures. Three patients were diagnosed as BRONJ at the first clinical visit; however, the other 6 patients got the confirmed diagnosis after visiting more than 2 medical institutions. The average time from the occurrence of oral symptoms to diagnosis was 6.9 months. The clinical manifestations of BRONJ included local pain, facial space infection, non-healing of extraction sockets, and exposure of sequestrum. The imaging findings of BRONJ included increased bone mineral density, periosteal reaction, sequestrum formation and diffused bone destruction. Of the 9 patients, one patient was classified into stage 0, 4 patients stage Ⅱ, and 4 patients stage Ⅲ. Five patients underwent surgery, four cases received conservative treatment. The average follow-up time was 10.3 months. Three patients in stage Ⅲ had long-standing chronic inflammation of soft tissue with acute attack of infection, while the remaining 6 patients were cured or in stable condition during the follow-up period. CONCLUSIONS: Due to lack of characteristic clinical manifestations and imaging findings, medical history of bisphosphonate treatment is the key to making a diagnosis of BRONJ. The outcome of BRONJ is generally poor, and patients in stage Ⅲ tend to be difficult to cure and easy to relapse.

Key words: Bisphosphonates, Osteonecrosis, Jaw

中图分类号:

R782.3

张学伟, 刘浩, 陈瑞扬, 张萍, 杨立, 吴炜, 严颖彬. 双膦酸盐相关性颌骨坏死9例临床分析[J]. 中国口腔颌面外科杂志, 2016, 14(5): 449-454.

ZHANG Xue-wei, LIU Hao, CHEN Rui-yang, ZHANG Ping, YANG Li, WU Wei, YAN Ying-bin. Bisphosphonate-related osteonecrosis of the jaw: report of 9 cases[J]. China J Oral Maxillofac Surg, 2016, 14(5): 449-454.

参考文献

[1] Burr D, Russell G. Foreword: bisphosphonates [J]. Bone, 2011, 49(1): 1.
[2] Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic [J]. J Oral Maxillofac Surg, 2003, 61(9): 1115-1117.
[3] Boonyapakorn T, Schirmer I, Reichart PA, et al. Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies [J]. Oral Oncol, 2008, 44(9): 857-869.
[4] 郭玉兴, 王佃灿, 安金刚, 等. 二膦酸盐颌骨骨髓炎24例临床特点分析 [J]. 中华口腔医学杂志, 2014, 49(9): 517-520.
[5] 黄如冰, 吴晓林, 俞娟. 双膦酸盐相关性颌骨坏死12例临床分析 [J].中华口腔医学研究杂志(电子版), 2012, 6(4): 353-357.
[6] 黄伟, 曾宪涛, 冷卫东, 等. 双膦酸盐相关性颌骨坏死的循证治疗:附3例报道 [J]. 中国口腔颌面外科杂志, 2013, 11(3): 221-228.
[7] 罗晨, 赵燕平, 马绪臣. 25例双膦酸盐相关颌骨坏死病例分析 [J].现代口腔医学杂志,2015, 29(2): 84-90.
[8] Abu-Id MH, Warnke PH, Gottschalk J, et al. "Bis-phossy jaws" - high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw [J]. J Craniomaxillofac Surg, 2008, 36(2): 95-103.
[9] 沈娇乡, 苏宇雄, 廖贵清. 双膦酸盐性颌骨坏死: 病例报告及文献复习 [J]. 中国口腔颌面外科杂志, 2009, 7(3): 286-288.
[10] Ruggiero SL, Dodson TB, Assael LA, et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws-2009 update [J].J Oral Maxillofac Surg, 2009, 67(5 Suppl): 2-12.
[11] Colella G, Campisi G, Fusco V. American Association of Oral and Maxillofacial Surgeons position paper: bisphosphonate-related osteonecrosis of the jaws-2009 update: the need to refine the BRONJ definition [J]. J Oral Maxillofac Surg, 2009, 67(12): 2698-2699.
[12] Gill SB, Valencia MP, Sabino ML, et al. Bisphosphonate-related osteonecrosis of the mandible and maxilla: clinical and imaging features [J].J Comput Assist Tomogr, 2009, 33(3): 449-454.
[13] Junquera L, Gallego L, Cuesta P, et al. Clinical experiences with bisphosphonate-associated osteonecrosis of the jaws: analysis of 21 cases [J]. Am J Otolaryngol, 2009, 30(6): 390-395.
[14] 李儒煌, 蔡志刚. 二膦酸盐相关性颌骨坏死研究进展 [J].口腔医学研究, 2012, 28(11): 1197-1199, 1202.
[15] Diel IJ, Fogelman I, Al-Nawas B, et al. Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw: is there a diverse relationship of amino- and non-aminobisphosphonates? [J].Crit Rev Oncol Hematol, 2007, 64(3): 198-207.
[16] Wilkinson GS, Kuo YF, Freeman JL, et al. Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis [J].J Natl Cancer Inst, 2007, 99(13): 1016-1024.
[17] Kos M, Kuebler JF, Luczak K, et al. Bisphosphonate-related osteonecrosis of the jaws: a review of 34 cases and evaluation of risk [J].J Craniomaxillofac Surg, 2010, 38(4): 255-259.
[18] 贺捷, 邱蔚六. 二膦酸盐与颌骨骨坏死 [J].中国口腔颌面外科杂志, 2010, 8(4): 370-375.
[19] 冯驭驰, 赵燕. 双膦酸盐类药物相关颌骨坏死发病机制及治疗研究进展 [J]. 中国骨质疏松杂志, 2014, 20(8): 998-1002.
[20] Kühl S S, Walter C, Acham S, et al. Bisphosphonate-related osteonecrosis of the jaws-a review [J].Oral Oncol, 2012, 48(10): 938-947.
[21] Heufelder MJ, Hendricks J, Remmerbach T, et al. Principles of oral surgery for prevention of bisphosphonate-related osteonecrosis of the jaw [J].Oral Surg Oral Med Oral Pathol Oral Radiol, 2014, 117(6): e429-435.
[22] Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment [J]. J Oral Maxillofac Surg, 2007, 65(12): 2397-2410.