国际口腔医学杂志

国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (6): 717-724.doi: 10.7518/gjkq.2020106

• 综述 • 上一篇    下一篇

药物相关性颌骨坏死发病机制的研究进展

郭陟永1(),刘济远2(),李春洁1,唐休发1   

  1. 1.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院头颈肿瘤外科 成都 610041
    2.口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院口腔颌面外科 成都 610041
  • 收稿日期:2020-04-05 修回日期:2020-08-02 出版日期:2020-11-01 发布日期:2020-11-06
  • 通讯作者: 刘济远
  • 作者简介:郭陟永,住院医师,博士,Email： realzhiyongguo@qq.com
  • 基金资助:
    四川省科技厅重点研发项目(2017SZ0108)

Research progress on the pathogenesis of medication-related osteonecrosis of the jaw

Guo Zhiyong1(),Liu Jiyuan2(),Li Chunjie1,Tang Xiufa1   

  1. 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
    2. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2020-04-05 Revised:2020-08-02 Online:2020-11-01 Published:2020-11-06
  • Contact: Jiyuan Liu
  • Supported by:
    Key Research and Development Project of Sichuan Science and Technology Department(2017SZ0108)

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摘要：

药物相关性颌骨坏死（MRONJ）是一种只发生于颌骨的严重疾病,其发生与抗骨吸收药物和抗血管生成药物有关,如双膦酸盐、狄诺塞麦等。目前临床上缺乏有效的治疗手段。近年来,有关MRONJ发病机制的研究进展非常迅速,但是确切机制尚不清楚。目前有关MRONJ发生机制的主要假说包括骨重建抑制、血管生成抑制、口腔内微生物感染、免疫抑制等学说,还有软组织毒性、颌骨微裂纹等,且其发病可能是多因素协同作用的结果。本文就MRONJ发病机制的研究进展进行综述,以期为进一步的深入研究提供帮助。

关键词: 骨坏死, 双膦酸盐, 颌骨

Abstract:

Medication-related osteonecrosis of the jaw (MRONJ) is a severe bone disease unique to the jaw. It is closely related to antiresorptive drugs and antiangiogenic drugs, such as bisphosphonates and denosumab. The effect of current treatments on MRONJ is limited. Despite the rapid progression of the pathogenesis of MRONJ, the specific mechanism remains unclear. The hypotheses of MRONJ mainly include disrupted bone remodeling, suppression of angiogenesis, oral microbial infection, inhibition of immunity, toxicity of soft tissue, and microcracks. The pathogenesis of MRONJ may be influenced by multiple factors. The purpose of the current review is to summarize recent progress on MRONJ research.

Key words: osteonecrosis, bisphosphonates, jaw

中图分类号: 

  • R782.3
[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.
doi: 10.1016/j.joms.2014.04.031 pmid: 25234529
[2] de Souza Tolentino E, de Castro TF, Michellon FC, et al. Adjuvant therapies in the management of me-dication-related osteonecrosis of the jaws: systematic review[J]. Head Neck, 2019,41(12):4209-4228.
pmid: 31502752
[3] Weber JB, Camilotti RS, Ponte ME. Efficacy of laser therapy in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ): a systematic review[J]. Lasers Med Sci, 2016,31(6):1261-1272.
doi: 10.1007/s10103-016-1929-4 pmid: 27025860
[4] Chang J, Hakam AE, McCauley LK. Current unders-tanding of the pathophysiology of osteonecrosis of the jaw[J]. Curr Osteoporos Rep, 2018,16(5):584-595.
doi: 10.1007/s11914-018-0474-4 pmid: 30155844
[5] Kimachi K, Kajiya H, Nakayama S, et al. Zoledronic acid inhibits RANK expression and migration of osteoclast precursors during osteoclastogenesis[J]. Naunyn Schmiedebergs Arch Pharmacol, 2011,383(3):297-308.
doi: 10.1007/s00210-010-0596-4 pmid: 21225243
[6] Sharma D, Ivanovski S, Slevin M, et al. Bisphosphonate- related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect[J]. Vasc Cell, 2013,5(1):1.
doi: 10.1186/2045-824X-5-1 pmid: 23316704
[7] Jobke B, Milovanovic P, Amling M, et al. Bisphos-phonate-osteoclasts: changes in osteoclast morpho-logy and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients[J]. Bone, 2014,59:37-43.
doi: 10.1016/j.bone.2013.10.024 pmid: 24211427
[8] Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates[J]. Cancer, 2000,88(12 Suppl):2961-2978.
doi: 10.1002/1097-0142(20000615)88:12+<2961::aid-cncr12>3.3.co;2-c pmid: 10898340
[9] Zara S, De Colli M, di Giacomo V, et al. Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts[J]. Clin Oral Investig, 2015,19(3):601-611.
pmid: 25055744
[10] Giannasi C, Niada S, Farronato D, et al. Nitrogen containing bisphosphonates impair the release of bone homeostasis mediators and matrix production by human primary pre-osteoblasts[J]. Int J Med Sci, 2019,16(1):23-32.
pmid: 30662325
[11] Manzano-Moreno FJ, Ramos-Torrecillas J, Me-lguizo-Rodríguez L, et al. Bisphosphonate modula-tion of the gene expression of different markers involved in osteoblast physiology: possible im-plications in bisphosphonate-related osteonecrosis of the jaw[J]. Int J Med Sci, 2018,15(4):359-367.
doi: 10.7150/ijms.22627 pmid: 29511371
[12] Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphos-phonate therapy[J]. N Engl J Med, 2009,360(1):53-62.
doi: 10.1056/NEJMoa0802633 pmid: 19118304
[13] 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.
doi: 10.1016/j.jcms.2016.07.015 pmid: 27519659
[14] Zhu SP, Yao F, Qiu H, et al. Coupling factors and exosomal packaging microRNAs involved in the regulation of bone remodelling[J]. Biol Rev Camb Philos Soc, 2018,93(1):469-480.
pmid: 28795526
[15] Hattner R, Epker BN, Frost HM. Suggested sequen-tial mode of control of changes in cell behaviour in adult bone remodelling[J]. Nature, 1965,206(983):489-490.
doi: 10.1038/206489a0 pmid: 5319106
[16] Shimizu E, Tamasi J, Partridge NC. Alendronate affects osteoblast functions by crosstalk through EphrinB1-EphB[J]. J Dent Res, 2012,91(3):268-274.
pmid: 22180568
[17] Di Salvatore M, Orlandi A, Bagalà C, et al. Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line[J]. Cell Prolif, 2011,44(2):139-146.
pmid: 21401755
[18] Lelièvre L, Clézardin P, Magaud L, et al. Comparative study of neoadjuvant chemotherapy with and without zometa for management of locally advanced breast cancer with serum VEGF as primary endpoint: the NEOZOL study[J]. Clin Breast Cancer, 2018,18(6):e1311-e1321.
pmid: 30098917
[19] Wehrhan F, Stockmann P, Nkenke E, et al. Differential impairment of vascularization and angiogenesis in bisphosphonate-associated osteonecrosis of the jaw-related mucoperiosteal tissue[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2011,112(2):216-221.
doi: 10.1016/j.tripleo.2011.02.028 pmid: 21664154
[20] Ferretti G, Fabi A, Carlini P, et al. Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients[J]. Oncology, 2005,69(1):35-43.
doi: 10.1159/000087286 pmid: 16088233
[21] Oteri G, Allegra A, Bellomo G, et al. Reduced serum levels of interleukin 17 in patients with osteonecrosis of the jaw and in multiple myeloma subjects after bisphosphonates administration[J]. Cytokine, 2008,43(2):103-104.
pmid: 18585926
[22] Yamada J, Tsuno NH, Kitayama J, et al. Anti-angio-genic property of zoledronic acid by inhibition of endothelial progenitor cell differentiation[J]. J Surg Res, 2009,151(1):115-120.
doi: 10.1016/j.jss.2008.01.031 pmid: 18619615
[23] Hasmim M, Bieler G, Rüegg C. Zoledronate inhibits endothelial cell adhesion, migration and survival through the suppression of multiple, prenylation-dependent signaling pathways[J]. J Thromb Haemost, 2007,5(1):166-173.
doi: 10.1111/j.1538-7836.2006.02259.x pmid: 17059425
[24] 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.
pmid: 27344431
[25] Hoefert S, Eufinger H. Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw: presentation of three cases[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010,110(4):463-469.
pmid: 20692189
[26] Gnant M, Baselga J, Rugo HS, et al. Effect of everolimus on bone marker levels and progressive disease in bone in BOLERO-2[J]. J Natl Cancer Inst, 2013,105(9):654-663.
doi: 10.1093/jnci/djt026 pmid: 23425564
[27] Magremanne M, Lahon M, De Ceulaer J, et al. Unusual bevacizumab-related complication of an oral in-fection[J]. J Oral Maxillofac Surg, 2013,71(1):53-55.
doi: 10.1016/j.joms.2012.03.022 pmid: 22705223
[28] Misso G, Porru M, Stoppacciaro A, et al. Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid[J]. Cancer Biol Ther, 2012,13(14):1491-1500.
pmid: 22990205
[29] Gao SY, Zheng GS, Wang L, et al. Zoledronate sup-pressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB[J]. PLoS One, 2017,12(6):e0179248.
doi: 10.1371/journal.pone.0179248 pmid: 28594896
[30] Ohlrich EJ, Coates DE, Cullinan MP, et al. The bis-phosphonate zoledronic acid regulates key angio-genesis-related genes in primary human gingival fibroblasts[J]. Arch Oral Biol, 2016,63:7-14.
doi: 10.1016/j.archoralbio.2015.11.013 pmid: 26658366
[31] Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a syste-matic review and international consensus[J]. J Bone Miner Res, 2015,30(1):3-23.
pmid: 25414052
[32] Sanchez BC, Chang C, Wu CG, et al. Electron trans-port chain is biochemically linked to pilus assembly required for polymicrobial interactions and biofilm formation in the gram-positive actinobacterium Actinomyces oris[J]. mBio, 2017,8(3):e00399-e00317.
doi: 10.1128/mBio.00399-17 pmid: 28634238
[33] Kaplan I, Anavi K, Anavi Y, et al. The clinical spec-trum of Actinomyces-associated lesions of the oral mucosa and jawbones: correlations with histomor-phometric analysis[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2009,108(5):738-746.
doi: 10.1016/j.tripleo.2009.06.019 pmid: 19748292
[34] Pushalkar S, Li X, Kurago Z, et al. Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw[J]. Int J Oral Sci, 2014,6(4):219-226.
doi: 10.1038/ijos.2014.46 pmid: 25105817
[35] Hinson AM, Smith CW, Siegel ER, et al. Is bisphos-phonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary[J]. Int J Dent, 2014: 452737.
[36] 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.
doi: 10.1038/srep31604 pmid: 27530150
[37] Sedghizadeh PP, Yooseph S, Fadrosh DW, et al. Metagenomic investigation of microbes and viruses in patients with jaw osteonecrosis associated with bisphosphonate therapy[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2012,114(6):764-770.
doi: 10.1016/j.oooo.2012.08.444 pmid: 23159114
[38] Kalyan S, Quabius ES, Wiltfang J, et al. Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy[J]. J Bone Miner Res, 2013,28(4):728-735.
doi: 10.1002/jbmr.1769 pmid: 22991330
[39] 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.
doi: 10.5037/jomr.2016.7403 pmid: 28154747
[40] Ono T, Okamoto K, Nakashima T, et al. IL-17-producing γδ T cells enhance bone regeneration[J]. Nat Commun, 2016,7:10928.
doi: 10.1038/ncomms10928 pmid: 26965320
[41] 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.
pmid: 16956814
[42] Orsini G, Failli A, Legitimo A, et al. Zoledronic acid modulates maturation of human monocyte-derived dendritic cells[J]. Exp Biol Med (Maywood), 2011,236(12):1420-1426.
doi: 10.1258/ebm.2011.011168
[43] Zhang QZ, Atsuta I, Liu SY, et al. IL-17-mediated M1/M2 macrophage alteration contributes to patho-genesis of bisphosphonate-related osteonecrosis of the jaws[J]. Clin Cancer Res, 2013,19(12):3176-3188.
doi: 10.1158/1078-0432.CCR-13-0042 pmid: 23616636
[44] Movila A, Mawardi H, Nishimura K, et al. Possible pathogenic engagement of soluble semaphorin 4D produced by γδT cells in medication-related osteone-crosis of the jaw (MRONJ)[J]. Biochem Biophys Res Commun, 2016,480(1):42-47.
doi: 10.1016/j.bbrc.2016.10.012 pmid: 27720716
[45] Park S, Kanayama K, Kaur K, et al. Osteonecrosis of the jaw developed in mice: disease variants regulated by γδ t cells in oral mucosal barrier immunity[J]. J Biol Chem, 2015,290(28):17349-17366.
doi: 10.1074/jbc.M115.652305 pmid: 26013832
[46] Hagelauer N, Pabst AM, Ziebart T, et al. In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes[J]. Clin Oral Investig, 2015,19(1):139-148.
pmid: 24668343
[47] Jin HM, Kee SJ, Cho YN, et al. Dysregulated osteo-clastogenesis is related to natural killer T cell dys-function in rheumatoid arthritis[J]. Arthritis Rheumatol, 2015,67(10):2639-2650.
pmid: 26097058
[48] 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]. Oncotar-get, 2015,6(24):20002-20025.
[49] Grassi F, Manferdini C, Cattini L, et al. T cell sup-pression by osteoclasts in vitro[J]. J Cell Physiol, 2011,226(4):982-990.
doi: 10.1002/jcp.22411
[50] Ziebart T, Halling F, Heymann P, et al. Impact of soft tissue pathophysiology in the development and maintenance of bisphosphonate-related osteonecrosis of the jaw (BRONJ)[J]. Dent J (Basel), 2016,4(4):E36.
[51] Pabst AM, Ziebart T, Koch FP, et al. The influence of bisphosphonates on viability, migration, and apo-ptosis of human oral keratinocytes: in vitro study[J]. Clin Oral Investig, 2012,16(1):87-93.
doi: 10.1007/s00784-010-0507-6 pmid: 21225298
[52] Jung J, Park JS, Righesso L, et al. Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro[J]. Clin Oral Investig, 2018,22(7):2527-2534.
doi: 10.1007/s00784-018-2349-6 pmid: 29388023
[53] Landesberg R, Cozin M, Cremers S, et al. Inhibition of oral mucosal cell wound healing by bisphosphonates[J]. J Oral Maxillofac Surg, 2008,66(5):839-847.
doi: 10.1016/j.joms.2008.01.026 pmid: 18423269
[54] Li J, Mashiba T, Burr DB. Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage[J]. Calcif Tissue Int, 2001,69(5):281-286.
pmid: 11768198
[55] Allen MR, Burr DB. Mandible matrix necrosis in beagle dogs after 3 years of daily oral bisphosphonate treatment[J]. J Oral Maxillofac Surg, 2008,66(5):987-994.
doi: 10.1016/j.joms.2008.01.038 pmid: 18423290
[56] 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 symptomatic and non-symptomatic os-teonecrosis of the jaw based on scanning electron microscopy findings[J]. Clin Oral Investig, 2010,14(3):271-284.
doi: 10.1007/s00784-009-0300-6 pmid: 19536569
[57] Kim JW, Landayan ME, Lee JY, et al. Role of micro-cracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw[J]. Clin Oral Investig, 2016,20(8):2251-2258.
doi: 10.1007/s00784-016-1718-2
[58] Guo Z, Cui W, Que L, et al. Pharmacogenetics of medication-related osteonecrosis of the jaw: a syste-matic review and meta-analysis[J]. Int J Oral Maxil-lofac Surg, 2020,49(3):298-309.
[59] Sarasquete ME, García-Sanz R, Marín L, et al. Bis-phosphonate-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.
doi: 10.1182/blood-2008-04-147884 pmid: 18594024
[60] 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.
pmid: 21251073
[61] Di Martino MT, Arbitrio M, Guzzi PH, et al. A peroxisome proliferator-activated receptor gamma (PPARG) polymorphism is associated with zole-dronic acid-related osteonecrosis of the jaw in multi-ple myeloma patients: analysis by DMET microarray profiling[J]. Br J Haematol, 2011,154(4):529-533.
pmid: 21517810
[62] 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.
pmid: 26086871
[63] Holtmann H, Lommen J, Kübler NR, et al. Patho-genesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials[J]. J Int Med Res, 2018,46(10):4277-4296.
doi: 10.1177/0300060518788987 pmid: 30091399
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[2] 汤庆奋,王学侠. 17β-雌二醇对人类阴道和口腔颊粘膜的渗透性[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 潘劲松. 颈总动脉指压和颈内动脉球囊阻断试验在大脑血液动力学中的不同影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 王昆润. 后牙冠根斜形牙折的治疗[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 杨锦波. 嵌合体防龋疫苗的研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 王昆润. 下颔骨成形术用网状钛板固定植骨块[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 汪月月,郭莉莉. 口腔机能与老化—痴呆危险因素流行病学研究[J]. 国际口腔医学杂志, 1999, 26(04): .
[8] 丁刚. 应用硬组织代用品种植体行丰颏术[J]. 国际口腔医学杂志, 1999, 26(04): .
[9] 田磊. 局部应用脂多糖后结合上皮反应性增生的变化[J]. 国际口腔医学杂志, 1999, 26(04): .
[10] 戴青. 口腔念珠菌病的新分类[J]. 国际口腔医学杂志, 1999, 26(04): .