Bisphosphonate-related osteonecrosis of the jaw: current state of the problem

Cover Page

Cite item


The article presents review of the literature on the current state of the problem of bisphosphonate-related osteonecrosis of the jaw. In Russia and abroad there are numerous reports of atypical lesions of the maxilla associated with taking medications on the basis of phosphorus or its analogues, in particular bisphosphonates. This is an issue: if earlier bisphosphonate treatment complications were limited to individual clinical observations, currently their frequency, according to different authors, reaches 8-27%. Bisphosphonate-related osteonecrosis of the jaw is characterized by unique etiopathogenic, clinical and diagnostic features that distinguish it from other inflammatory, degenerative and iatrogenic diseases of orofacial region, so it is reasonable to isolate it into an independent nosology, requiring a comprehensive study. According to current data, bisphosphonate-related osteonecrosis of the jaw is a complication of antiresorptive therapy, characterized by necrosis and exposure of bone area, which persists for more than 8 weeks, followed by the process progression in the absence of radiation therapy to the head area in history. Bisphosphonates are antiresorptive agents, potent inhibitors of bone tissue destruction, widely used for the treatment of bone metastasis, multiple myeloma, and hypercalcemia in cancer patients. However, the development of complications such as osteonecrosis of the jaw greatly reduces the positive effects of treatment, and extremely bothersome for patients. Osteonecrosis-related pyo-inflammatory processes of admaxillary tissue, the appearance of persistent sinus tracts on the skin and in the mouth, the risk of pathologic fracture of the jaw impair the quality of life of patients. Presented in the article analysis of currently known data about the bisphosphonate-related osteonecrosis of the jaw should attract the attention of dental surgeons, maxillofacial surgeons, endocrinologists, oncologists to this problem.

About the authors

E M Spevak

Stavropol State Medical University

Author for correspondence.

A N Tsymbal

Stavropol Regional Clinical Consultative and Diagnostic Center



  1. Жабина А.С. Роль бисфосфонатов для профилактики и лечения метастазов в кости. Практ. онкол. 2011; 12 (3): 124-131.
  2. Заславская Н.А., Дробышев А.Ю., Волков А.Г. Опыт лечения остеонекрозов челюстей у пациентов, получающих антирезорбтивную терапию (бисфосфонаты, «Деносумаб»). Cathedra. 2014; (47): 32-34.
  3. Кондратьев В.Б., Мартынюк В.В., Ли Л.А. Метастазы в кости: осложнённые формы, гиперкальциемия, синдром компрессии спинного мозга, медикаментозное лечение. Практ. онкол. 2000; (2): 41-45.
  4. Слетов А.А., Сирак С.В., Давыдов А.Б. и др. Аппаратный метод лечения переломов нижней челюсти при бисфосфонатных остеонекрозах. Стоматология для всех. 2014; (2): 32-36.
  5. Сулейманов A.M., Мингазов Г.Г., Саляхова Г.А. Бисфосфонатные остеонекрозы челюстей. Мед. вестн. Башкортостана. 2012; 7 (2): 112-115.
  6. Тарасенко С.В., Дробышев А.Ю., Шипкова Т.П. и др. Тактика лечения больных с бисфосфонатным остеонекрозом челюстей. Рос. стоматол. 2012; (2): 3-13.
  7. Торопцова Н.В., Беневоленская Л.И. Бисфосфонаты: приверженность терапии - залог успешного лечения остеопороза. Соврем. ревматол. 2008; (1): 78-81.
  8. Agrillo A. Avascular necrosis of the jaws: New therapeutic protocol in the treatment of 30 clinical cases. J. Cranio-maxillofacial Surg. 2006; 34 (9): 197. doi: 10.1016/S1010-5182(06)60763-4
  9. Allen M.R., Ruggiero S.L. Higher bone matrix density exists in only a subset of patients with bisphosphonate-related osteonecrosis of the jaw. J. Oral. Maxillofac. Surg. 2015; 13: 212. doi: 10.1186/s12967-015-0568-z
  10. Bashutski J.D., Eber R.M., Kinney J.S. et al. Teriparatide and osseous regeneration in the oral cavity. N. Engl. J. Med. 2010; 363: 2396-2405. doi: 10.1056/NEJMoa1005361
  11. Bocanegra-Perez S., Vicente-Barrero M., Knezevic M. et al. Use of platelet-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw. Int. J. Oral. Maxillofac. Surg. 2012; 41: 1410-1415. doi: 10.1016/j.ijom.2012.04.020
  12. Bottler T., Keller O., Kuttenberger J. Treament of bisphosphonate- associated osteonecrosis of the jaf. Less is more? J. Craniomaxillofacial Surg. 2006; 34 (9): 171. doi: 10.1016/S1010-5182(06)60661-6
  13. Calvo de Mora J. Maxillary necrosis associated with bisphosphonates. Diagnostic, clinical aspects and treatment. J. Craniomaxillofacial Surg. 2006; 34 (9): 195. doi: 10.1016/S1010-5182(06)60751-8
  14. Cella L., Oppici A., Arbasi M. et al. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw. Head Face Med. 2011; 7: 16. doi: 10.1186/1746-160X-7-16
  15. Demers L., Costa L., Lipton A. Biochemical marker and skeletal metastases. Clin. Orthop. 2003; 415: 138-147. doi: 10.1097/01.blo0000092979.12414.54
  16. Epstein M.S., Wicknick F.W., Epstein J.B. et al. Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod. 2010; 110: 593-596. doi: 10.1016/j.tripleo.2010.05.067
  17. 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. Int. J. Oral. Maxillofac. Surg. 2015; 44 (5): 568. doi: 10.1016/j.ijom.2015.01.026
  18. Haidar A., Jonler M., Folkmar T.B., Lund L. Bisphosphonate (zoledronic acid)-induced osteonecrosis of the jaw. Scand. J. Urol. Nephrol. 2009; 43: 442-444. doi: 10.3109/00365590903295193
  19. Kalyan S., Wang J., Quabius E.S. et al. Systemic immunity shapes the oral microbiome and susceptibility to bisphosphonate-associated osteonecrosis of the jaw. J. Transl. Med. 2015; 13: 212. doi: 10.1186/s12967-015-0568-z
  20. Kos M. Incidence and risk predictors for osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J. Arch. Med. Sci. 2015; 11 (2): 319-324. doi: 10.5114/aoms.2015.50964
  21. Kyrgidis A., Vahtsevanos K., Koloutsos G. et al. Bisphosphonate-related osteonecrosis of the jaws: a case-control study of risk factors in breast cancer patients. J. Clin. Oncol. 2008; 26: 4634-4638. doi: 10.1200/JCO.2008.16.2768
  22. Lesclous P., Abi N.S., Carrel J.P. et al. Bisphosphonate-associated osteonecrosis of the jaw: a key role of inflammation? Bone. 2009; 45: 843-852. doi: 10.1016/j.bone.2009.07.011
  23. Marx R.E. Pamidronate (Aredia) and Zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J. Oral. Maxillofac. Surg. 2003; 61: 1115-1117. doi: 10.1016/S0278-2391(03)00720-1
  24. Marx R.E., 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: 1567-1575. doi: 10.1016/j.joms.2005.07.010
  25. Merigo E., Manfredi M., Meleti M. et al. Bone necrosis of the jaws associated with bisphosphonate treatment: a report of twenty-nine cases. Acta Biomed. 2006; 77 (1): 109-117.
  26. Miyazaki H., Nishimatsu H., Kume H. et al. Leukopenia as a risk factor for osteonecrosis of the jaw in metastatic prostate cancer treated using zoledronic acid and docetaxel. BJU Int. 2012; 110: 520-525. doi: 10.1111/j.1464-410X.2012.11205.x
  27. Nicolatou-Galitis O., Papadopoulou E., Sarri T. et al. Osteonecrosis of the jaw in oncology patients treated with bisphosphonates: prospective experience of a dental oncology referral center. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod. 2011; 112: 195-202. doi: 10.1016/j.tripleo.2011.02.037
  28. Ortega C., Montemurro F., Faggiuolo R. et al. Osteonecrosis of the jaw in prostate cancer patients with bone metastases treated with zoledronate: a retrospective analysis. Acta Oncol. 2007; 46: 664-668. doi: 10.1080/02841860601185917
  29. Ripamonti C.I., Cislaghi E., Mariani L., Maniezzo M. Efficacy and safety of medical ozone (O(3)) 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: 185-190. doi: 10.1016/j.oraloncology.2011.01.002
  30. Rollason V., Laverrière A., MacDonald L.C. et al. Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ). Cochrane Database Syst. Rev. 2016; 26: 2. CD008455. doi: 10.1002/14651858
  31. Ruggiero S.L., Dodson T.B., Fantasia J. et al. 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; 72 (10): 1938-1956. doi: 10.1016/j.joms.2014.04.031
  32. Stockmann P., Hinkmann F.M., Lell M.M. 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: 311-317. doi: 10.1007/s00784-009-0293-1
  33. Tennis P., Rothman K.J., Bohn R.L. et al. Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiol. Drug. Saf. 2012; 21: 810-817. doi: 10.1002/pds.3292
  34. Torres S.R., Chen C.S., Leroux B.G. et al. Fractal dimension evaluation of cone beam computed tomography in patients with bisphosphonate-associated osteonecrosis. Dentomaxillofac. Radiol. 2011; 40: 501-505. doi: 10.1259/dmfr/14636637
  35. Vitte C., Fleisch H., Guenthes H.L. Bisphosphonates induce osteoblasts to secrete an inhibitor ofosteoclastic mediated resorption. Endocrinology. 1996; 137: 2324-2333.
  36. Watts N.B., Marciani R.D. Osteonecrosis of the jaw. South Med. J. 2008; 101: 160-165. doi: 10.1097/SMJ.0b013e31816127d9

© 2017 Spevak E.M., Tsymbal A.N.

Creative Commons License

This work is licensed
under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies