Risk Factors Playing A Role on Medication Related Osteonecrosis of The Jaws And Clinical, Radiographic Characteristics

Abstract

Medication-related osteonecrosis of the jaws develops with bone necrosis and progressive bone destruction as a result of impaired blood supply in the maxilla and mandible. Bisphosphonates used in the treatment of many bone metabolism diseases and malignancies play a major role in the etiology of osteonecrosis. It has been found that various drugs caused to osteonecrosis in the jaws, apart from bisphosphonates. In the literature, it has been reported that osteonecrosis is also encountered in patients who do not use bisphosphonates, besides the use of other drugs other than bisphosphonates, the presence of some systemic diseases that suppress the immune system such as diabetes, surgical dental procedures, local factors such as the use of prosthesis and some genetic factors pose a risk in the formation of osteonecrosis. Since it is difficult to treat and a progressive condition, early diagnosis is important in terms of prognosis. The aim of this review is to give actual information about the risk factors, clinical and radiographic features of medication-related osteonecrosis of the jaws.

Keywords

• Bisphosphonates
• Jaw
• Osteonecrosis

İlaç Kullanımına Bağlı Çene Kemiklerinin Osteonekrozunun Ortaya Çıkmasında Rol Oynayan Risk Faktörleri Ve Klinik, Radyografik Özellikleri

Abstract

Çene kemiklerinde ilaç kullanımına bağlı gelişen osteonekroz, maksilla ve mandibulada kan desteğinin bozulması sonucunda kemik nekrozu ve ilerleyici kemik yıkımı ile gelişir. Etiyolojisinde kemik metabolizması hastalıklarının birçoğu ve malignitelerin tedavisinde kullanılan bifosfanatlar büyük rol oynar. Bifosfonatların dışında çeşitli ilaçların da çene kemiklerinde osteonekroza neden olduğu belirlenmiştir. Literatürde bifosfonat kullanmayan hastalarda da osteonekroza rastlanıldığı bildirilmiş, bu hastalarda bifosfonat dışında başka ilaçların kullanımının yanında diyabet gibi immün sistemi baskılayan bazı sistemik hastalıkların varlığı, cerrahi dental uygulamalar, protez kullanımı gibi lokal faktörler ile bazı genetik faktörlerin osteonekroz oluşumunda risk oluşturduğu belirtilmiştir. Tedavisi zor ve ilerleyici bir durum olduğundan, erken teşhis prognoz açısından önemlidir. Bu derlemenin amacı çene kemiklerinde ilaç kullanımına bağlı gelişen osteonekrozun oluşumunda rol oynayan risk faktörlerine dikkat çekmek, klinik ve radyografik özellikleri hakkında güncel bilgiler vermektir.

Keywords

• Bifosfonat
• çene
• osteonekroz

References

1. Biçer AZY. Bifosfonatlar ve çenelerde görülen osteonekroz. Acta Odontologica Turcica 2013;30(1):35-8.
2. Ertaş ET, Atıcı MY. Bifosfonatlar ve çene kemiğinde görülen osteonekroz. Selcuk Dental Journal, 2015; 2: 91-100.
3. Yazıcı T, Şentürk MF, Koçer G. İlaca Bağlı Olarak Görülen Çene Kemiklerinde Görülen Osteonekroz (Mronj): Derleme. Sdü Sağlık Bilimleri Enstitüsü Dergisi 2017(1).
4. Schiodt M, Vadhan-Raj S, Chambers MS, Nicolatou-Galitis O, Politis C, Coropciuc R, Fedele S, Jandial D, Zhang J, Ma H, Saunders DP. A multicenter case registry study on medication-related osteonecrosis of the jaw in patients with advanced cancer. Support Care Cancer. 2018 Jun;26(6):1905-1915.
5. Duygu Çapar G , Cabbar F , Yalçın M , Özcakır Tomruk C . İlaçlara Bağlı Çene Kemiği Osteonekrozu: Derleme. Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi. 2016; 25(13): 0-0.
6. Tozoğlu S, Şimşek Kaya G. Çenelerde Görülen Bifosfonatlarla İlişkili Osteonekrozlar. Turkiye Klinikleri J Oral Maxillofac Surg-Special Topics. 2016;2(2):131-42.
7. Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59.
8. Soğur D, Önem D, Baksı P. Bisfosfanat kullanımına bağlı çene kemiğinde gelişen osteonekroz: etyoloji, risk faktörleri, tanı kriterleri ve tedavi alternatifleri. Atatürk Üniversitesi Diş Hekimliği Fakültesi Dergisi. 2012; 2012(1): 95-83.

9. Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos I, Gika D, Moulopoulos LA, Bamia C, Terpos E, Tsionos K, Bamias A. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica. 2006 Jul;91(7):968-71.
10. Guarneri V, Miles D, Robert N, Diéras V, Glaspy J, Smith I, Thomssen C, Biganzoli L, Taran T, Conte P. Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res Treat. 2010 Jul;122(1):181-8.
11. Chiu CT, Chiang WF, Chuang CY, Chang SW. Resolution of oral bisphosphonate and steroid-related osteonecrosis of the jaw--a serial case analysis. J Oral Maxillofac Surg. 2010 May;68(5):1055-63.
12. Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007 Dec;65(12):2397-410.
13. Öztürk E, Saruhan N. İlaca Bağlı Olarak Çene Kemiklerinde Görülen Osteonekroz (Mronj) J Biotechnol and Strategic Health Res. 2019;3(1):8-20.
14. Bagan JV, Jiménez Y, Gómez D, Sirera R, Poveda R, Scully C. Collagen telopeptide (serum CTX) and its relationship with the size and number of lesions in osteonecrosis of the jaws in cancer patients on intravenous bisphosphonates. Oral Oncol. 2008 Nov;44(11):1088-9.
15. Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000 Feb;66(2):100-3.
16. Kwon YD, Kim DY, Ohe JY, Yoo JY, Walter C. Correlation between serum C-terminal cross-linking telopeptide of type I collagen and staging of oral bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2009 Dec;67(12):2644-8.
17. Kwon YD, Kim YR, Choi BJ, Lee DW, Kim DY. Oral bisphosphonate-related osteonecrosis of the jaws: favorable outcome after bisphosphonate holiday. Quintessence Int. 2009 Apr;40(4):277-8.
18. Sindel D, Gula G. Osteoporozda Kemik Mineral Yoğunluğunun Değerlendirilmesi. Turk J Osteoporos 2015;21(1):23-29.
19. Baim S, Miller PD. Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw. J Bone Miner Res. 2009 Apr;24(4):561-74.
20. Ersan N. Çenelerin İlaç Kullanımına Bağlı Nekrozu (MRONJ): Hangi Noktadayız?. İlgüy D, editör. Ağız Hastalıkları. Ankara: Türkiye 2018. p.86-97.
21. Kalra S, Jain V. Dental complications and management of patients on bisphosphonate therapy: A review article. J Oral Biol Craniofac Res. 2013 Jan-Apr;3(1):25-30.
22. Viera-Negrón YE, Ruan WH, Winger JN, Hou X, Sharawy MM, Borke JL. Effect of ovariectomy and alendronate on implant osseointegration in rat maxillary bone. J Oral Implantol. 2008;34(2):76-82.
23. Campisi G, Di Fede O, Musciotto A, Lo Casto A, Lo Muzio L, Fulfaro F, Badalamenti G, Russo A, Gebbia N. Bisphosphonate-related osteonecrosis of the jaw (BRONJ): run dental management designs and issues in diagnosis. Ann Oncol. 2007 Jun;18 Suppl 6:vi168-72. Review.
24. Onur ÖD, Kurtuluş B, Çevik P. Bifosfonat Kullanan Hastalarda Oral Cerrahi Uygulamalarda Karşilaşilabilecek Sorunlar Ve Tedavisi Oral Complications And Treatments In Patients Receiving Bisphosphonates. Journal of Istanbul University Faculty of Dentistry 2009;43: 113-22.
25. Doğan Onur Ö, Atalay B. Anti-rezorptif İlaç Tedavisinin Ağızda Yarattığı Sorunlara Güncel Yaklaşım. Ünür M, editör. Ağız Kanserlerinin Tanı, Tedavi ve Prognozu. 1. Baskı. Ankara: Türkiye Klinikleri; 2019. p.34-9.
26. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005 Dec 1;23(34):8580-7.
27. Spinelli G, Torresetti M, Lazzeri D, Zhang YX, Arcuri F, Agostini T, Grassetti L. Microsurgical reconstruction after bisphosphonate-related osteonecrosis of the jaw: our experience with fibula free flap. J Craniofac Surg. 2014 May;25(3):788-92.
28. Zavras AI, Zhu S. Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis? J Oral Maxillofac Surg. 2006 Jun;64(6):917-23.
29. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014 Oct;72(10):1938-56.
30. Jadu F, Lee L, Pharoah M, Reece D, Wang L. A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients. Ann Oncol. 2007 Dec;18(12):2015-9.
31. Yamamoto D, Tsubota Y, Utsunomiya T, Sueoka N, Ueda A, Endo K, Yoshikawa K, Kon M. Osteonecrosis of the jaw associated with everolimus: A case report. Mol Clin Oncol. 2017 Feb;6(2):255-257.
32. Japanese Allied Committee on Osteonecrosis of the Jaw, Yoneda T, Hagino H, Sugimoto T, Ohta H, Takahashi S, Soen S, Taguchi A, Nagata T, Urade M, Shibahara T, Toyosawa S. Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw. J Bone Miner Metab. 2017 Jan;35(1):6-19.
33. Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, Watts NB, Brandi ML, Peters E, Guise T, Eastell R, Cheung AM, Morin SN, Masri B, Cooper C, Morgan SL, Obermayer-Pietsch B, Langdahl BL, Al Dabagh R, Davison KS, Kendler DL, Sándor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan;30(1):3-23.
34. Ruggiero SL. Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Clin Cases Miner Bone Metab. 2007 Jan;4(1):37-42. Sigua-Rodriguez EA, da Costa Ribeiro R, de Brito AC, Alvarez-Pinzon N, de Albergaria-Barbosa JR. Bisphosphonate-related osteonecrosis of the jaw: a review of the literature. Int J Dent. 2014;2014:192320.
35. Sigua-Rodriguez EA, da Costa Ribeiro R, de Brito AC, Alvarez-Pinzon N, de Albergaria-Barbosa JR. Bisphosphonate-related osteonecrosis of the jaw: a review of the literature. Int J Dent. 2014;2014:192320.
36. Bianchi SD, Scoletta M, Cassione FB, Migliaretti G, Mozzati M. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Aug;104(2):249-58.
37. Bedogni A, Blandamura S, Lokmic Z, Palumbo C, Ragazzo M, Ferrari F, Tregnaghi A, Pietrogrande F, Procopio O, Saia G, Ferretti M, Bedogni G, Chiarini L, Ferronato G, Ninfo V, Lo Russo L, Lo Muzio L, Nocini PF. Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Mar;105(3):358-64.
38. Elad S, Gomori MJ, Ben-Ami N, Friedlander-Barenboim S, Regev E, Lazarovici TS, Yarom N. Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation. Clin Oral Investig. 2010 Feb;14(1):43-50.
39. Taguchi A, Akiyama H, Koseki T, Shimizutani K. Recognition of bisphosphonate-related osteonecrosis of the jaw among oral and maxillofacial radiologists: results from a questionnaire-based survey in Japan. Oral Radiology 2013;29(2):98-104.
40. Stockmann P, Hinkmann FM, Lell MM, Fenner M, Vairaktaris E, Neukam FW, Nkenke E. Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study. Clin Oral Investig. 2010 Jun;14(3):311-7.
41. Torres SR, Chen CS, Leroux BG, Lee PP, Hollender LG, Santos EC, Drew SP, Hung KC, Schubert MM. Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 May;113(5):695-703.
42. Wilde F, Heufelder M, Lorenz K, Liese S, Liese J, Helmrich J, Schramm A, Hemprich A, Hirsch E, Winter K. Prevalence of cone beam computed tomography imaging findings according to the clinical stage of bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec;114(6):804-11.
43. Krishnan A, Arslanoglu A, Yildirm N, Silbergleit R, Aygun N. Imaging findings of bisphosphonate-related osteonecrosis of the jaw with emphasis on early magnetic resonance imaging findings. J Comput Assist Tomogr. 2009 Mar-Apr;33(2):298-304.
44. Catalano L, Del Vecchio S, Petruzziello F, Fonti R, Salvatore B, Martorelli C, Califano C, Caparrotti G, Segreto S, Pace L, Rotoli B. Sestamibi and FDG-PET scans to support diagnosis of jaw osteonecrosis. Ann Hematol. 2007 Jun;86(6):415-23.
45. Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Oct;102(4):433-41.
46. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws--2009 update. J Oral Maxillofac Surg. 2009 May;67(5 Suppl):2-12.
47. Dixon RB, Tricker ND, Garetto LP. Bone turnover in elderly canine mandible and tibia. J Dent Res 1997;76:336.
48. Hino S, Murase R, Terakado N, Shintani S, Hamakawa H. Response of diffuse sclerosing osteomyelitis of the mandible to alendronate: follow-up study by 99mTc scintigraphy. Int J Oral Maxillofac Surg. 2005 Jul;34(5):576-8.
49. Soydan SS, Veziroğlu Şenel F, Araz K. Bisfosfonata bağlı olarak çene kemiklerinde gelişen osteonekrozun patogenezi ve tedavisi. Hacettepe Üni Diş Hek Fak Derg 2009;33(3):61-8.