华西口腔医学杂志 ›› 2021, Vol. 39 ›› Issue (3): 245-254.doi: 10.7518/hxkq.2021.03.001
• 专家论坛 • 下一篇
收稿日期:
2020-09-02
修回日期:
2021-04-08
出版日期:
2021-06-01
发布日期:
2021-05-26
通讯作者:
潘剑
E-mail:jianpancn@163.com
作者简介:
基金资助:
Received:
2020-09-02
Revised:
2021-04-08
Online:
2021-06-01
Published:
2021-05-26
Contact:
Pan Jian
E-mail:jianpancn@163.com
Supported by:
摘要:
药物相关性颌骨坏死(MRONJ)近年来发病率不断增高,目前认为其机制可能为骨重建抑制学说、血管生成抑制学说、口腔微生物感染学说、免疫抑制学说、细胞毒性、颌骨微裂纹形成及单核苷酸多态性等,但基于单机制进行防治效果均不理想。药物治疗前规范的口腔检查及相关疾病预处理,药物治疗期间定期口腔随访对MRONJ的预防具有重要意义。在MRONJ治疗过程中,准确判断其分期,根据指南进行标准化治疗的同时,也需考虑患者具体情况,进行个性化调整。本文将国内外最新相关研究及指南和四川大学华西口腔医院口腔颌面外科近年来对MRONJ诊治经验相结合,对其发病机制及防治策略展开阐述和讨论,供同行参考。
中图分类号:
潘剑, 刘济远. 药物相关性颌骨坏死的发病机制及其防治[J]. 华西口腔医学杂志, 2021, 39(3): 245-254.
Pan Jian, Liu Jiyuan. Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws[J]. West China Journal of Stomatology, 2021, 39(3): 245-254.
表 1
MRONJ的影像学检查特点及使用建议
检查方式 | 使用建议 |
---|---|
根尖片 | 可初步辅助判断,典型特征包括硬膜增厚、牙槽骨骨小梁密度增加、牙周膜间隙增宽等,但是使用较少 |
全景片 | 相对根尖片,可纳入判断的结构更多,表现为骨小梁密度增加、拔牙窝不完全愈合、骨片形成、下颌神经管或上颌窦底骨皮质增厚等,可以作为影像学检查选择之一 |
螺旋CT及CBCT | 典型病变包括弥漫性骨硬化、骨溶解区形成、骨皮质糜烂、骨膜增生、瘘管形成及拔牙牙槽窝不完全愈合。一般来说,该影像学显示区域大于临床暴露区域。在观察骨质改变上,螺旋CT及CBCT效果相当,但CBCT的辐射相对小得多 |
MRI | 在观察骨质改变上,与CT相当,在评估骨坏死早期骨髓变化以及围绕骨坏死区域的软组织变化方面占优势,在临床症状出现之前可出现骨髓信号强度的降低 |
闪烁扫描和PET | 有早期核素浓集,死骨形成后会有核素摄取下降的特点,对于检测早期疾病具有高灵敏度 |
1 | Russell RG. Bisphosphonates: the first 40 years[J]. Bone, 2011, 49(1): 2-19. |
2 | Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws[J]. J Oral Maxillofac Surg, 2007, 65(3): 369-376. |
3 | 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. |
4 | Wang Q, Liu J, Qi S, et al. Clinical analysis of medication related osteonecrosis of the jaws: a growing severe complication in China[J]. J Dent Sci, 2018, 13(3): 190-197. |
5 | 潘剑, 王杞章, 刘济远. 双膦酸盐相关性颌骨坏死[J]. 华西口腔医学杂志, 2017, 35(1): 29-36. |
Pan J, Wang QZ, Liu JY. Research progress on bisphosphonate-related osteonecrosis of the jaws[J]. West China J Stomatol, 2017, 35(1): 29-36. | |
6 | Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates[J]. Cancer, 2000, 88(12): 2961-2978. |
7 | David P, Nguyen H, Barbier A, et al. The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase[J]. J Bone Miner Res, 1996, 11(10): 1498-1507. |
8 | Fleisch H. Bisphosphonates: mechanisms of action[J]. Endocr Rev, 1998, 19(1): 80-100. |
9 | Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphosphonate the-rapy[J]. N Engl J Med, 2009, 360(1): 53-62. |
10 | Córdova LA, Guilbaud F, Amiaud J, et al. Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw[J]. J Craniomaxillofac Surg, 2016, 44(9): 1387-1394. |
11 | Hattner R, Epker BN, Frost HM. Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling[J]. Nature, 1965, 206(983): 489-490. |
12 | Shimizu E, Tamasi J, Partridge NC. Alendronate affects osteoblast functions by crosstalk through EphrinB1-EphB[J]. J Dent Res, 2012, 91(3): 268-274. |
13 | Ziebart T, Koch F, Klein MO, et al. Geranylgeraniol-a new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw[J]. Oral Oncol, 2011, 47(3): 195-201. |
14 | Pabst AM, Krüger M, Ziebart T, et al. Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial progenitor cells after bisphosphonate therapy in vitro[J]. Clin Oral Investig, 2015, 19(7): 1625-1633. |
15 | Pabst AM, Krüger M, Blatt S, et al. Angiogenesis in the development of medication-related osteonecrosis of the jaws: an overview[J]. Dent J (Basel), 2016, 5(1): 2. |
16 | Pabst AM, Krüger M, Sagheb K, et al. The influence of geranylgeraniol on microvessel sprouting after bisphosphonate substitution in an in vitro 3D-angiogenesis assay[J]. Clin Oral Investig, 2017, 21(3): 771-778. |
17 | Lang M, Zhou Z, Shi L, et al. Influence of zoledronic acid on proliferation, migration, and apoptosis of vascular endothelial cells[J]. Br J Oral Maxillofac Surg, 2016, 54(8): 889-893. |
18 | Wang Q, Liu J, Guo T, et al. Epidermal growth factor reverses the inhibitory effects of the bisphosphonate, zoledronic acid, on human oral keratinocytes and human vascular endothelial cells in vitro via the epidermal growth factor receptor (EGFR)/Akt/phosphoinositide 3-kinase (PI3K) signaling pathway[J]. Med Sci Monit, 2019, 25: 700-710. |
19 | Zirk M, Wenzel C, Buller J, et al. Microbial diversity in infections of patients with medication-related osteonecrosis of the jaw[J]. Clin Oral Investig, 2019, 23(5): 2143-2151. |
20 | Hinson AM, Smith CW, Siegel ER, et al. Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary[J]. Int J Dent, 2014, 2014: 452737. |
21 | Russmueller G, Seemann R, Weiss K, et al. The association of medication-related osteonecrosis of the jaw with Actinomyces spp. infection[J]. Sci Rep, 2016, 6: 31604. |
22 | Silveira FM, Etges A, Correa MB, et al. Microscopic evaluation of the effect of oral microbiota on the development of bisphosphonate-related osteonecrosis of the jaws in rats[J]. J Oral Maxillofac Res, 2016, 7(4): e3. |
23 | Wolf AM, Rumpold H, Tilg H, et al. The effect of zoledronic acid on the function and differentiation of myeloid cells[J]. Haematologica, 2006, 91(9): 1165-1171. |
24 | Zhang Q, Atsuta I, Liu S, et al. Il-17-mediated M1/M2 macrophage alteration contributes to pathogenesis of bis-phosphonate-related osteonecrosis of the jaws[J]. Clin Cancer Res, 2013, 19(12): 3176-3188. |
25 | Movila A, Mawardi H, Nishimura K, et al. Possible pa-thogenic engagement of soluble Semaphorin 4D produ-ced by γδT cells in medication-related osteonecrosis of the jaw (MRONJ)[J]. Biochem Biophys Res Commun, 2016, 480(1): 42-47. |
26 | Tseng HC, Kanayama K, Kaur K, et al. Bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation[J]. Oncotarget, 2015, 6(24): 20002-20025. |
27 | Grassi F, Manferdini C, Cattini L, et al. T cell suppression by osteoclasts in vitro[J]. J Cell Physiol, 2011, 226(4): 982-990. |
28 | Jung J, Park JS, Righesso L, et al. Effects of an oral bis-phosphonate and three intravenous bisphosphonates on several cell types in vitro[J]. Clin Oral Investig, 2018, 22(7): 2527-2534. |
29 | Hoefert S, Schmitz I, Tannapfel A, et al. Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of sym-ptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings[J]. Clin Oral Investig, 2010, 14(3): 271-284. |
30 | Guo Z, Cui W, Que L, et al. Pharmacogenetics of medication-related osteonecrosis of the jaw: a systematic review and meta-analysis[J]. Int J Oral Maxillofac Surg, 2020, 49(3): 298-309. |
31 | Sarasquete ME, García-Sanz R, Marín L, et al. Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis[J]. Blood, 2008, 112(7): 2709-2712. |
32 | Arduino PG, Menegatti E, Scoletta M, et al. Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws[J]. J Oral Pathol Med, 2011, 40(6): 510-515. |
33 | Di Martino MT, Arbitrio M, Guzzi PH, et al. A peroxisome proliferator-activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid-related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling[J]. Br J Haematol, 2011, 154(4): 529-533. |
34 | Choi H, Lee JH, Kim HJ, et al. Genetic association between VEGF polymorphisms and BRONJ in the Korean population[J]. Oral Dis, 2015, 21(7): 866-871. |
35 | Beth-Tasdogan NH, Mayer B, Hussein H, et al. Interventions for managing medication-related osteonecrosis of the jaw[J]. Cochrane Database Syst Rev, 2017, 10(10): CD012432. |
36 | Scottish Dental Clinical Effectiveness Programme. Oral health management of patients at risk of medication-related osteonecrosis of the jaw[J]. Br Dent J, 2017, 222(12): 930. |
37 | Drudge-Coates L, Van den Wyngaert T, Schiødt M, et al. Preventing, identifying, and managing medication-related osteonecrosis of the jaw: a practical guide for nurses and other allied healthcare professionals[J]. Support Care Cancer, 2020, 28(9): 4019-4029. |
38 | Fliefel R, Tröltzsch M, Kühnisch J, et al. Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review[J]. Int J Oral Maxillofac Surg, 2015, 44(5): 568-585. |
39 | 王杞章, 刘济远, 潘剑. 药物性颌骨坏死的研究进展[J]. 华西口腔医学杂志, 2018, 36(5): 568-572. |
Wang QZ, Liu JY, Pan J. Progress on medication-related osteonecrosis of the jaw[J]. West China J Stomatol, 2018, 36(5): 568-572. | |
40 | Dodson TB. CTX and its role in managing patients exposed to oral bisphosphonates [J]. J Oral Maxillofac Surg, 2010, 68(2): 487-489. |
41 | 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. |
42 | Di Fede O, Panzarella V, Mauceri R, et al. The dental management of patients at risk of medication-related osteonecrosis of the jaw: new paradigm of primary prevention[J]. Biomed Res Int, 2018, 2018: 2684924. |
43 | Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus[J]. J Bone Miner Res, 2015, 30(1): 3-23. |
44 | Bermúdez-Bejarano EB, Serrera-Figallo MÁ, Gutiérrez-Corrales A, et al. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates[J]. J Clin Exp Dent, 2017, 9(1): e141-e149. |
45 | Yoneda T, Hagino H, Sugimoto T, et al. Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons[J]. J Bone Miner Metab, 2010, 28(4): 365-383. |
46 | Lerman MA, Xie W, Treister NS, et al. Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes[J]. Oral Oncol, 2013, 49(9): 977-983. |
47 | Beth-Tasdogan NH, Mayer B, Hussein H, et al. Interventions for managing medication-related osteonecrosis of the jaw[J]. Cochrane Database Syst Rev, 2017, 10(10): CD012432. |
48 | Peleg M, Lopez EA. The treatment of osteoradionecrosis of the mandible: the case for hyperbaric oxygen and bone graft reconstruction[J]. J Oral Maxillofac Surg, 2006, 64(6): 956-960. |
49 | Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful[J]. Mediators Inflamm, 2004, 13(1): 3-11. |
[1] | 刘晓琳, 任群, 白九平, 康培, 任贵云, 李向军, 冯晓伟. 基于锥形束CT的1 138颗多生牙影像学特征分析[J]. 华西口腔医学杂志, 2023, 41(6): 671-677. |
[2] | 张晓玲, 薛宁宁, 阮敏慧, 曾昕. 口腔黏膜溃疡损害出现短暂自愈的朗格汉斯细胞组织细胞增生症1例[J]. 华西口腔医学杂志, 2023, 41(5): 592-598. |
[3] | 王铁彪, 周五超, 肖寅, 程家龙, 欧阳洲城, 程晨, 习伟宏. 改良关节盘锚固术在颞下颌关节盘穿孔、破裂治疗中的应用[J]. 华西口腔医学杂志, 2023, 41(4): 434-442. |
[4] | 蔡美娟, 向绍雯, 谢成婕, 欧阳楚红, 童方丽. 意向性牙再植治疗下颌第二磨牙根管治疗失败病例1例[J]. 华西口腔医学杂志, 2023, 41(4): 471-477. |
[5] | 郑艳, 闫柳清, 华成舸, 梁新华, 杨征. 四川省口腔医疗机构和口腔综合治疗台配置现状分析[J]. 华西口腔医学杂志, 2023, 41(3): 333-340. |
[6] | 杨靖梅, 周子亮, 吴亚菲, 聂敏. 基于网络药理学和分子对接技术探究姜黄素治疗牙周炎的作用机制[J]. 华西口腔医学杂志, 2023, 41(2): 157-164. |
[7] | 李成蹊, 宋卫健. 上颌侧切牙Ⅱ型和ⅢA型双牙内陷根管治疗1例[J]. 华西口腔医学杂志, 2023, 41(2): 232-236. |
[8] | 蒋鸿杰, 李茂, 唐月阳, 汤亚玲. 淋巴上皮囊肿恶变1例[J]. 华西口腔医学杂志, 2023, 41(2): 237-242. |
[9] | 贾婷婷, 张达, 戚向敏, 王彩娇, 颜世果. 口腔疣状黄瘤伴口腔扁平苔藓1例[J]. 华西口腔医学杂志, 2023, 41(1): 104-109. |
[10] | 冯志强, 安金刚, 张益, 贺洋. 晚期药物相关性颌骨坏死的手术治疗[J]. 华西口腔医学杂志, 2023, 41(1): 43-51. |
[11] | 刘磊, 向中正, 李一, 郭伟, 杨凯, 王军, 孙志军, 任国欣, 张建国, 孙沫逸, 冉伟, 黄桂林, 唐瞻贵, 李龙江. 头颈部鳞癌免疫检查点抑制剂治疗专家共识[J]. 华西口腔医学杂志, 2022, 40(6): 619-628. |
[12] | 李煌, 武秀萍, 黄兰, 徐晓梅, 康娜, 韩向龙, 李宇, 赵宁, 江凌勇, 谢贤聚, 郭杰, 李志华, 莫水学, 刘楚峰, 胡江天, 施洁珺, 曹猛, 胡炜, 曹阳, 宋锦璘, 汤旭娜, 白丁. 正畸根尖区牙根外吸收的风险因素及其临床处理建议的专家共识[J]. 华西口腔医学杂志, 2022, 40(6): 629-637. |
[13] | 杨雯君, 韩佳佳, 王逸尘, 李凤翔, 杜启涛. 不同方法去除根管内充填材料的效果评价[J]. 华西口腔医学杂志, 2022, 40(6): 685-689. |
[14] | 郑琛, 苏吉梅, 梁鑫, 吴娟, 顾伟忠, 赵雄. 先天性颗粒细胞龈瘤的临床病理分析[J]. 华西口腔医学杂志, 2022, 40(6): 710-715. |
[15] | 王显文, 陈谦明, 江潞. 1例表现为非典型性血管增生的放射性口腔黏膜炎[J]. 华西口腔医学杂志, 2022, 40(6): 721-726. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||