Osteonecrosis of the external auditory canal secondary to bisphosphonates. Systematic review
Abstract Introduction and objective: Benign osteonecrosis of the external auditory canal (EAC) is a side effect pretty unknown due to bisphosphonate (BPs) therapy. Our aim is to describe the way of presentation and treatment of cases published in literature. Method: We did a systematic review of patients with diagnose of osteonecrosis of the external ear canal secondary to bisphosphonates from September 2003 till February 2019. We followed PRISMA criteria and evaluated PubMed database. Results: 7 articles were identified including a total of 17 patients with osteonecrosis of EAC. 76% were women and 24% men, within ages between 51 and 89. The duration time till complications appeared ranged from 15 months to 20 years. The most common presentation was as a unilateral ulceration with bone exposure in 41% of cases. Floor of the EAC was the initial place in 100%. Computed Tomography was performed in 47% of patients showing bone necrosis; and two biopsies with osteomyelitis signs. 9 patients (53%) were successfully treated with antibiotics and topical corticosteroids, while 8 cases (47%) needed surgical treatment in addition to the withdrawal of BFS. Discussion/Conclusions: Osteonecrosis of EAC is a rare side effect of BPs treatment. Painless ulceration on the EAC floor is the most common onset. Topical antibiotics and local debridement are frequently enough for complete healing.
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Bast F1, Fuss H, Schrom T. Bilateral bisphosphonate-associated osteonecrosis of the external ear canal: a rare case. HNO 2012;60:1127-9.
Bisphosphonates: osteonecrosis of the external auditory canal. Prescrire Int 2016 ;25:154.
Fleisch H, Russell RG, Straumann F. Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 1966;212:901-3.
Froelich K, Radeloff A, Kohler C, Mlynski R, Muller J, Hagen R et al. Bisphosphonate-induced osteonecrosis of the external ear canal: a retrospective study. Eur Arch Otolaryngol 2011; 268:1219-25.
Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA 2006;103:7829-34.
Kharazmi M1, Hallberg P, Persson U, Warfvinge G. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Oral Maxillofac Surg 2013;51:e285-7.
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479-91.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e1-34.
McCadden L, Leonard CG, Primrose WJ. Bisphosphonate-induced osteonecrosis of the ear canal: our experience and a review of the literature. Jour Otol Laryngol 2018;1-3.
McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126:13-20.
Polizzotto M, Cousins V, Schwarer A. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol 2006;132:114.
Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 2014;72:1938-56.
Russell RG. Bisphosphonates: the first 40 years. Bone 2011;49:2-19.
Salzman R, Hoza J, Perina V, Starek I. Osteonecrosis of the external auditory canal associated with oral bisphosphonate therapy: case report and literature review. Otol Neurotol 2013; 34:209-13.
Thorsteinsson AL1, Vestergaard P, Eiken P. External auditory canal and middle ear cholesteatoma and osteonecrosis in bisphosphonate-treated osteoporosis patients: a Danish national register-based cohort study and literature review. Osteoporos Int 2014;25:1937-44.
Wickham N, Crawford A, Carney AS, Goss AN. Bisphosphonate-associated osteonecrosis of the external auditory canal. J Laryngol Otol 2013 Jul;127 Suppl 2:S51-3.
Bisphosphonates: osteonecrosis of the external auditory canal. Prescrire Int 2016 ;25:154.
Fleisch H, Russell RG, Straumann F. Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 1966;212:901-3.
Froelich K, Radeloff A, Kohler C, Mlynski R, Muller J, Hagen R et al. Bisphosphonate-induced osteonecrosis of the external ear canal: a retrospective study. Eur Arch Otolaryngol 2011; 268:1219-25.
Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA 2006;103:7829-34.
Kharazmi M1, Hallberg P, Persson U, Warfvinge G. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Oral Maxillofac Surg 2013;51:e285-7.
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479-91.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e1-34.
McCadden L, Leonard CG, Primrose WJ. Bisphosphonate-induced osteonecrosis of the ear canal: our experience and a review of the literature. Jour Otol Laryngol 2018;1-3.
McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126:13-20.
Polizzotto M, Cousins V, Schwarer A. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol 2006;132:114.
Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 2014;72:1938-56.
Russell RG. Bisphosphonates: the first 40 years. Bone 2011;49:2-19.
Salzman R, Hoza J, Perina V, Starek I. Osteonecrosis of the external auditory canal associated with oral bisphosphonate therapy: case report and literature review. Otol Neurotol 2013; 34:209-13.
Thorsteinsson AL1, Vestergaard P, Eiken P. External auditory canal and middle ear cholesteatoma and osteonecrosis in bisphosphonate-treated osteoporosis patients: a Danish national register-based cohort study and literature review. Osteoporos Int 2014;25:1937-44.
Wickham N, Crawford A, Carney AS, Goss AN. Bisphosphonate-associated osteonecrosis of the external auditory canal. J Laryngol Otol 2013 Jul;127 Suppl 2:S51-3.
Lopez-Simon, E., Corriols-Noval, P., Castillo-Ledesma, N., & Morales-Angulo, C. (2019). Osteonecrosis of the external auditory canal secondary to bisphosphonates. Systematic review. Revista ORL, 10(4), 295–303. https://doi.org/10.14201/orl.20961
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