
==== Front
World J Otorhinolaryngol Head Neck Surg
World J Otorhinolaryngol Head Neck Surg
10.1002/(ISSN)2589-1081
WJO2
World Journal of Otorhinolaryngology - Head and Neck Surgery
2095-8811
2589-1081
John Wiley and Sons Inc. Hoboken

10.1002/wjo2.146
WJO2146
Case Study
Case Study
Three cases of uncommon medication‐associated osteonecrosis of temporal bone
THREE CASES MED‐ASSOCIATED OSTEONECROSIS TEMP BONE
VANDOLAH et al.
VanDolah Hunter http://orcid.org/0000-0003-4302-5729
1
Crossley Jason R. 2 jrc270@georgetown.edu

Kim H. Jeffrey 2
1 Georgetown University School of Medicine Washington DC USA
2 Department of Otolaryngology–Head and Neck Surgery MedStar Georgetown University Hospital Washington DC USA
* Correspondence Jason R. Crossley, Department of Otolaryngology–Head and Neck Surgery, MedStar Georgetown University Hospital, 3800 Reservoir Rd NW, Washington DC 20007, USA.
Email: jrc270@georgetown.edu

03 12 2023
9 2024
10 3 10.1002/wjo2.v10.3 237240
18 9 2023
12 4 2023
02 10 2023
© 2023 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Abstract

Introduction

Medication‐related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti‐resorptive and biologic agents. Here, we present the first case of tyrosine‐kinase inhibitor‐related external auditory canal (EAC) osteonecrosis as well as two cases related to anti‐resorptive therapies.

Methods

A retrospective case series.

Results

Case one: an 84‐year‐old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly‐based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69‐year‐old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60‐year‐old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine‐kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.

Conclusion

Anti‐resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

bisphosphonates
denosumab
external auditory canal
imatinib
medication‐related osteonecrosis
osteonecrosis
temporal bone
tyrosine‐kinase Inhibitors
None source-schema-version-number2.0
cover-dateSeptember 2024
details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.4.8 mode:remove_FC converted:03.09.2024
VanDolah H , Crossley JR , Kim HJ . Three cases of uncommon medication‐associated osteonecrosis of temporal bone. World J Otorhinolaryngol Head Neck Surg. 2024;10 :237‐240. 10.1002/wjo2.146
==== Body
pmcINTRODUCTION

Osteonecrosis of the external auditory canal (OEAC) has been reported in the literature associated with anti‐resorptive agents as well as antiangiogenic agents. 1 We report three cases of medication‐related OEAC, two associated with anti‐resorptive agents as well as a case of tyrosine‐kinase inhibitor‐related OEAC.

CASE PRESENTATIONS

Case 1

A 69‐year‐old male was referred for evaluation of gradual asymmetric hearing loss for a 6‐month duration. He had no tinnitus, ear fullness, dizziness, or pain. A routine otologic exam incidentally showed anterior superficial ulceration and inferior bony ear canal erosion consistent with osteonecrosis. He had a remote history of left orchiectomy for testicular cancer and radiation therapy to the retroperitoneum 30 years ago. He had no history of diabetes. For a 15‐year history of osteopenia and osteoporosis, he was treated with alendronic acid for 4 years followed by zoledronic acid. His last dose of zoledronic acid was 6 years before presentation. Computed tomography (CT) scan of the temporal bone demonstrated osteonecrosis of the left temporal bone affecting the external auditory canal (EAC) floor (Figure 1). He is being managed conservatively with topical acetic acid otic solution after local debridement.

Figure 1 Computed tomography (CT) scan of the temporal bone. (A) Coronal CT scan with lateral bony external auditory canal erosion with presence of squamous debris. (B) Axial CT scan with lateral bony external auditory canal erosion with the presence of squamous debris.

Case 2

An 84‐year‐old female was referred for osteonecrosis of the bilateral EAC. She experienced bilateral ear pruritus and left otorrhea. She had a history of osteoporosis treated with denosumab for a 2‐year period and risedronic acid for an unknown time. She had no history of diabetes. She had completed multiple courses of topical antibiotics for culture‐positive bilateral bacterial chronic otitis externa and had previously undergone a left postauricular canalplasty with temporalis fascia graft without resolution to her symptoms. She subsequently underwent successful left EAC reconstruction using an inferiorly‐based pedicle periosteal flap while the right ear canal was managed conservatively. She returned to wearing her hearing aids in both ears 3 months after the procedure. At 4‐month follow‐up, there was no active infection in either ear with well‐healed reconstruction of the left EAC and crusting in the right EAC with a thin epithelial layer covering the previously exposed bone. Postoperatively, she developed delayed left tympanic membrane perforation. She continues to follow in our clinic for monitoring nearly 2 years postoperatively.

Case 3

A 60‐year‐old male was referred for evaluation of 2 months of right otalgia without otorrhea. He had a history of BCR‐ABL positive chronic myelogenous leukemia, now in remission with imatinib treatment for the past 3 years. He had no history of diabetes. Physical examination and CT without contrast demonstrated right inferior EAC osteonecrosis. Subsequent biopsy of the lesion showed acute and chronic inflammation with hyperkeratosis without evidence of malignancy. After failing conservative therapy, he underwent right EAC reconstruction using a postauricular, periosteal vascular pedicle flap without complication (Figure 2). The patient experienced complete resolution of his otalgia and otorrhea at the 2‐month follow‐up. He follows up with our clinic yearly.

Figure 2 Right external auditory canal reconstruction. (A) Pre‐intervention canal granulation with exposed bone. (B) Osteonecrosis of external auditory canal. (C) External auditory canal after drilling sequestrated bone. (D) Reconstructed external auditory canal with a vascularized pedicle vascular flap.

DISCUSSION

Osteonecrosis is defined as the necrosis of bone cells and can be caused by a variety of pathologies including lack of vascular supply, radiation, and medications. Radiation‐associated injury is the most common cause of OEAC with an incidence of 8.5%, however, medications such antiresorptive or antiangiogenic agents may cause osteonecrosis. 2

The pathogenesis of medication‐related osteonecrosis involves inhibition of the differentiation of osteoclast precursors, the functioning of mature osteoclasts, and the normal processes of angiogenesis. 3 This is most frequently associated with administration of anti‐resorptive agents, including bisphosphonates, which reduce osteoclast activation and disrupt the normal cytokine‐mediated signaling between osteoclasts and osteoblasts. 3 Tyrosine‐kinase inhibitors like imatinib function via the inhibition of the differentiation of osteoclast precursors into mature osteoclasts as well as alteration of vascular endothelial growth factor‐independent angiogenesis. 3 , 4 Bisphosphonates and tyrosine‐kinase inhibitors are frequently used in the treatment of benign conditions such as osteoporosis and in the treatment of malignancies, respectively. With a significant number of patients at risk, clinicians should have a high degree of suspicion for nonradiation‐associated osteonecrosis in patients with temporal bone lesions. In all three cases, diagnosis was made after a review of the patient's past medical and medication history with a physical examination revealing exposed and eroded bone in the external auditory canal(s).

Initial management of this condition should aim to treat associated pain and otorrhea, provide topical antibiotic therapy, and debridement of squamous debris and sequestrated bone. In the cases detailed above, topical antibiotic therapy was prescribed to treat associated superimposed infection and inflammation. Surgery may provide a more definitive treatment of recalcitrant symptoms not responding to conservative medical therapy. In two of our cases of OEAC, a surgical excision of sequestrated bone with reconstruction using a vascularized pedicle periosteal flap provided an excellent outcome. 5

AUTHOR CONTRIBUTIONS

Hunter VanDolah: Literature review, manuscript preparation, and editing. Dr. Jason R. Crossley: Manuscript preparation and editing. Dr. H. Jeffrey Kim: Clinical evaluation and care of patients, operative surgeon, and manuscript editing.

CONFLICTS OF INTEREST STATEMENT

Professor H. Jeffrey Kim is a member of the World Journal of Otorhinolaryngology‐Head & Neck Surgery (WJOHNS) editorial board and is not involved in the peer review process of this article. Other authors declare no conflict of interest. [Correction added on 31 July 2024, after first online publication: Conflict of Interest is updated.]

ETHICS STATEMENT

This manuscript is exempt from IRB approval from the Georgetown University Institutional Review Board given that it consists of a case report of three cases. A copy of this exemption is available for review on the Office of Research Oversight/Regulatory Affairs website, and we have supplied a weblink for easy review. https://georgetown.box.com/s/e5mkqi7xnu7r51vbtrp4.

ACKNOWLEDGMENTS

The authors have no funding to report.

DATA AVAILABILITY STATEMENT

Data is available at reasonable request to the author.
==== Refs
REFERENCES

1 Canzano F , Di Lella F , Manuguerra R , Vincenti V . Osteonecrosis of the external auditory canal associated with oral sorafenib therapy: sorafenib and temporal bone osteonecrosis. Otol Neurotol. 2019;40 :e812‐e815.31356482
2 Morrissey D , Grigg R . Incidence of osteoradionecrosis of the temporal bone. ANZ J Surg. 2011;81 :876‐879.22507412
3 Alemán JO , Farooki A , Girotra M . Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies. Endocr Relat Cancer. 2014;21 :R247‐R259.24478055
4 Raimondi C , Fantin A , Lampropoulou A , Denti L , Chikh A , Ruhrberg C . Imatinib inhibits VEGF‐independent angiogenesis by targeting neuropilin 1‐dependent ABL1 activation in endothelial cells. J Exp Med. 2014;211 :1167‐1183.24863063
5 Ramsey MJ , Merchant SN , McKenna MJ . Postauricular periosteal‐pericranial flap for mastoid obliteration and canal wall down tympanomastoidectomy. Otol Neurotol. 2004;25 :873‐878.15547414
