Medication Related Osteonecrosis of The Jaws (Mronj): Review

Abstract

Bisphosphonates are synthetic analogues of pyrophosphates

used for the treatment of hypercalcemia in patients with

malignancies and bone metastasis and for the treatment of

multiple myeloma, bone resorption in the case of metastatic

malignant diseases, and in the treatment of osteoporosis.

Bisphosphonates related osteonecrosis of the jaw cases

accelarated at the end of 2003. Due to some medications,

American Association of Oral and Maxillofacial Surgery

modified the concept as medication related osteonecrosis of

the jaw(MRONJ) in 2014. The aim of the present review was

to analyze the etiology, clinical manifestations, risk factors,

radiologic features and different treatment strategies of

MRONJ.

Keywords

• Bisphosphonates,Jaw Osteonecrosis,Medications

İlaca Bağlı Olarak Çene Kemiklerinde Görülen Osteonekroz (Mronj): Derleme

Abstract

Bifosfonatlar pirofosfatların sentetik analogları olup;

malignensilere bağlı olarak gelişen hiperkalsemi, multipl

myeloma, kemik metastazı tedavisinin yanında osteoporöz

tedavisi için kullanılan ilaçlardır. Bisfosfanat kullanımına

bağlı çenelerde görülen osteonekroz olguları 2003 yılının

sonlarından itibaren hızla artış göstermiştir. 2014 yılında

Amerikan Çene Yüz Cerrahisi Derneği tarafından tabloya

katılan bazı ilaçlarla tablo ilaç kullanımına bağlı olarak

çene kemiklerinde gelişen osteonekroz olarak değişmiştir.

Bu derlemenin amacı ilaç kullanımına bağlı olarak çene

kemiklerinde gelişen osteonekroz olgularının etiyolojisini,

klinik ve radyolojik bulgularını, risk faktörlerini ve farklı

tedavi seçeneklerini irdelemektir.

 

Keywords

• bifosfonat,çene osteonekrozu,ilaç

References

1. 1) Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.
2. 2) Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004; 62:527-34.
3. 3) 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 jaw - 2009 update. J Oral Maxillofac Surg 2009;67:2-12.
4. 4) Ruggiero SL, Dodson TB, Mehrotra B; American Association of Oral and Maxillofacial Surgeons on Medication-Related Osteonecrosis of the Jaw—2014 Update. J Oral Maxillofac Surg 2014;72:1938-56.
5. 5) Reid IR. Anti-resorptive therapies for osteoporosis. Seminars in Cell & Developmental Biology 2008;19:473-8.
6. 6) Marx RE. Oral & Intravenous Bisphosphonate-Induced Osteonecrosis of theJaws. History, Etiology, Prevention, and Treatment. Illinois: Quintessence Publishing Co, Inc; 2007.
7. 7) Soydan SS, Veziroğlu Şenel F, Araz K. Bisfosfonata bağlı olarak çene kemiklerinde gelişen osteonekrozun patogenezi ve tedavisi.Hacettepe Üni Diş Hek Fak Derg 2009;33:61-8.
8. 8) Crepin S,Laroche ML, Sarry B, Merle L.. Osteoecrosis of the jaws induced by clodronate, an alkylbisphosphonate: case report and literature review. Eur J Clin Pharmacol 2010;66:547-54.

9. 9) Rogers MJ, Watts DJ,Russell RG.Overview of Bisphosphonates. Cancer 1997;80:1652-60.
10. 10) Naidu A, Dechow PC, Spears R, Wright JM, Kessler HP, Opperman LA. The effects of bisphosphonates on osteoblasts in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:5-13.
11. 11) Green JR. Antitumor Effects of Bisphosphonates. Cancer 2003; 97: 840-7.
12. 12) Santini D, Gentilucci UV, Vincenzi B, Picardi A, Vasaturo F, La Cesa A. ve ark. The antineoplastic role of bisphosphonates: from basic research to clinical evidence. Annals of Oncology 2003;14:1468–76.
13. 13) Diel IJ, Bergner R, Grötz KA.Adverse effects of bisphosphonates: current issues. J Support Oncol, 2007;5:475-82.
14. 14) Reid IR, Bolland MJ, Grey AB. Is bisphosphonate associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 2007;41:318-20.
15. 15) Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S, Sinha S, Garrett-Sinha L, Raghavan S. Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 2008;66:839-47.
16. 16) Diz P, López-Cedrún J L, Arenaz J, Scully C. Denosumab-related osteonecrosis of the jaw. Journal of the American Dental Association. 2012;143:981–4.
17. 17) Hamadeh I S, Ngwa B A, Gong Y. Drug induced osteonecrosis of the jaw. Cancer Treatment Reviews. 2015;41:455–64.
18. 18) Van Poznak CH, Temin S, Yee GC, et al. American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 2011;29:1221-7.
19. 19) Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova Jet al.Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma. J Clin Oncol 2011;29;1125-32.
20. 20) Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377:813–22.
21. 21) Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009;27:1564–71.
22. 22) Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007;25:4431–7.
23. 23) Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745–55.
24. 24) Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol 2012;23:1341–7.
25. 25) Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 2013;14:901-8.
26. 26) Street J, Lenehan B. Vascular endothelial growth factor regulates osteoblast survival – evidence for an autocrine feedback mechanism. J Orthop Surg Res 2009;4:19-31.
27. 27) Horner A, Bord S, Kelsall AW, Coleman N, Compston JE. Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone. Bone 2001;28:65–71.
28. 28) Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002; 2: 727-39.
29. 29) Bernold DM, Sinicrope FA. Advances in chemotherapy for colorectal cancer. Clin Gastroenterol Hepatol 2006;4:808-21.
30. 30) Herbst RS, O’Neill VJ, Fehrenbacher L, Belani CP, Bonomi FD, Hart L et al: Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non–small-cell lung cancer. J Clin Oncol 2007;25:4743-50.
31. 31) Saif MW, Elfiky A, Salem RR: Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 2007;14:1860-9.
32. 32) Kerr DJ. Targeting angiogenesis in cancer: clinical development of bevacizumab. Nat Clin Pract Oncol 2004;1:39-43.
33. 33) Milan NC, Poveda MJ, Cruz O, Mora J. Safety of bevacizumab in patients younger than 4 years of age. Clin Transl Oncol 2016;18:464-8.
34. 34) Guarneri V, Miles D, Robert N, Dieras V, Glaspy J, Smith I et al: 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;122:181-8.
35. 35) Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G, Huryn JM. Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 2008;26:4037–8.
36. 36) Ayllon J, Launay-Vacher V, Medioni J, Cros C, Spano JP, Oudard S. Osteonecrosis of the jaw under bisphosphonate and antiangiogenic therapies: cumulative toxicity profile? Ann Oncol 2009;20:600-1.
37. 37) Troeltzsch M, Woodlock T, Kriegelstein S, Steiner T, Messlinger K, Troeltzsch M. Physiology and pharmacology of nonbisphosphonate drugs implicated in osteonecrosis of the jaw. J Can Dent Assoc 2012;78:c85-91.
38. 38) Hoefert S, Eufinger H. Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw: presentation of three cases Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:463-9.
39. 39) Fleissig Y, Regev E, Lehman H. Sunitinib related osteonecrosis of jaw: a case report Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology2012;113:e1–3.
40. 40) Marx RE, Cillo JE, Ulloa JJ. Oral bisphosphonate induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral MaxillofacSurg 2007;65:2397-410.
41. 41) Sharma D, Ivanovski S, Slevin M, Hamlet S, Kop TS, Brinzaniuc C et al. Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect. Vasc Cell 2013;5:1–5.
42. 42) Fedele S, Porter SR, D’Aiuto F, Aljohani S, Vescovi P, Manfredi M et al. Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med 2010;123:1060–4.
43. 43) Chiandussi S, Biasotto M, Dore F, Cavalli F, Cova MA, Di Lenarda R. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 2006;35:236–43.
44. 44) Khan AA,Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F et al; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic reviewand international consensus. J Bone Miner Res 2015;30:3–23.
45. 45) Li G. Patient radiation dose and protection from cone-beam computed tomography. Imaging Sci Dent 2013;43:63–9.
46. 46) 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;104:249-58.
47. 47) Stockmann P, Hinkmann FM, LellMM, et al. 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;14:311–7.
48. 48) O'Ryan FS, Khoury S, Liao W, Han MM, Hui RL, Baer D et al. Intraoral bisphosphonate related osteonecrosis of the jaws; bone scintigraphy as an early indicator. J.Oral Maxillofac Surg 2009;67:1363-72.
49. 49) Dimopoulos MA, Kastritis E, Anagnostopoulos A,Melakopoulos I, Gika D, Moulopoulos LA et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006;91:968–71.
50. 50) Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M et al. Frequency and risk factors associatedwithosteonecrosisofthejawincancerpatientstreated with intravenous bisphosphonates. J Bone Miner Res 2008;23: 826–6.
51. 51) Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG,et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 2009;27:5356–62.
52. 52) 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;18:2015–9 .
53. 53) KhamaisiM,RegevE, YaromN, Avni B, Leitersdorf E, Raz Ietal.Possibleassociationbetween diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab 2007;92:1172–5.
54. 54) Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005;63:1567–75.
55. 55) Woo S, Hellentein JW, Kalmar JR. Sytmeatic review: bisphosphonates and osteonecrosis of the jaws. Annals of International Medicine 2006;16:753-61.
56. 56) Coleman R, Woodward E, Brown J, Cameron D, Bell R, Dodwell D et al: Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer. Breast Cancer Res Treat 2011;127:429-38.
57. 57) Mauri D, Valachis A, Polyzos IP, Polyzos NP, Kamposioras K, Pesce LL. Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: a meta-analysis. Breast Cancer Res Treat 2009;116:433-9.
58. 58) Grbic JT, Black DM, Lyles KW, Reid DM, Orwoll E, McClung M, et al: The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program. J Am Dent Assoc 2010;141:1365-70.
59. 59) BamiasA, KastritisE, BamiaC, MoulopoulosLA, MelakopoulosI, BozasG, etal.
60. 60) Chiu CT, Chiang WF, Chuang CY, Chang SW. Resolution of oral bisphosphonates and steroid-related osteonecrosis of the jaw—a serial case analysis. J Oral Maxillofac Surg 2010;68:1055–63.
61. 61) Mücke Y,Mitchel AD. Local and microvascular free flaps in patients with medication-related osteonecrosis of the jaw. İn: Otto S (ed.) Medicaton-Related Osteonecrosis of the Jaws: Bisphosphonates, Denosumab, and New Agents. 1st ed. Springer, Berlin Heidelberg 2015.
62. 62) Carey JJ, Palomo L. Bisphosphonates and osteonecrosis of the jaw: innocent association or significant risk? Cleve Clin J Med2008;75: 871-9.
63. 63) Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 2009;20:137-45.
64. 64) Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009;20:117-20.
65. 65) Bagan JV, Jimenez Y, Murillo J, Hernandez S, Poveda R, Sanchis JM, et al. Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its relationship to teeth extractions. Study of 20 cases. Oral Oncol 2006; 42:327-9.
66. 66) Damm DD, Jones DM: Bisphosphonate-related osteonecrosis of the jaws: a potential alternative to drug holidays. Gen Dent 2013;61:33-8.
67. 67) Ristow O, Otto S, Troeltzsch M, Hohlweg-Majert B, Pautke C. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J Craniomaxillofac Surg 2015;43:290-3.
68. 68) Lerman MA, Xie W, Treister NS, Richardson PG, Weller EA, Woo SB. Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes. Oral Oncol 2013;49:977-83.
69. 69) Melea PI, Melakopoulos I, Kastritis E, Tesseromatis C, Margaritis V, Dimopoulos MA, et al. Conservative treatment of bisphosphonate- related osteonecrosis of the jaw in multiple myeloma patients. Int J Dent 2014;2014:427273, 7 pages.
70. 70) Vescovi P, Merigo E, Meleti M, Manfredi M, Fornaini C,Nammour S, et al. Conservative surgical management of stage I bisphosphonate-related osteonecrosis of the jaw. Int J Dent 2014; 2014:107690, 8 pages.
71. 1) Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M. Efficacy and safety of medical ozone (O3) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study. Oral Oncol 2011;47:185-90.
72. 2) Freiberger JJ, Padilla-Burgos R, McGraw T, Suliman HB, Kraft KH, Stolp BW, et al. What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg 2012;70:1573-83.
73. 3) Atalay B, Yalcin S, Emes Y, Aktas I, Aybar B, Issever H, et al. Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery? Lasers Med Sci 2011;26:815-23.
74. 4) Magremanne M, Reychler H. Pentoxifylline and tocopherol in the treatment of yearly zoledronic acid-related osteonecrosis of the jaw in a corticosteroid-induced osteoporosis. J Oral Maxillofac Surg 2014;72:334-7.
75. 5) Rugani P, Acham S, Kirnbauer B, Truschnegg A, Obermayer- Pietsch B, Jakse N. Stage-related treatment concept of medicationrelated osteonecrosis of the jaw-a case series. Clin Oral Investig 2015;19:1329-38.
76. 6) Curi MM, Cossolin GS, Koga DH, Zardetto C, Christianini S, Feher O, et al. Bisphosphonate-related osteonecrosis of the jaws an initial case series report of treatment combining partial bone resection and autologous platelet-rich plasma. J Oral Maxillofac Surg 2011;69:2465-72.
77. 7) Cella L, Oppici A, Arbasi M, Moretto M, Piepoli M, Vallisa D, et al. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw. Head Face Med2011;7:16-21.
78. 8) Kim JW, Kim SJ, Kim MR. Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study. Br J Oral Maxillofac Surg 2014;52:854-9.
79. 9) Cheung A, Seeman E. Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med 2010;363:2473-4.
80. 10) Neuprez A, Rompen E, Crielaard JM, Reginster JY. Teriparatide therapy for denosumab-induced osteonecrosis of the jaw in a male osteoporotic patient. Calcif Tissue Int 2014;95:94-6.