A study of cases of bisphosphonate-induced cholesteatoma of the external auditory canal

Although osteonecrosis of the external auditory canal has been known to be a serious side effect of bisphosphonates, there are still few case reports on this condition. Bisphosphonates, are bone resorption inhibitors that are a first-line drug for osteoporosis and metastatic bone cancer. In Japan, w...

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Published injibi to rinsho Vol. 67; no. 6; pp. 352 - 360
Main Authors NAKASHIMA, Toshiyuki, SHIN, Takemoto, SHUTO, Hiroyuki
Format Journal Article
LanguageJapanese
Published JIBI TO RINSHO KAI 20.11.2021
耳鼻と臨床会
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ISSN0447-7227
2185-1034
DOI10.11334/jibi.67.6_352

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Abstract Although osteonecrosis of the external auditory canal has been known to be a serious side effect of bisphosphonates, there are still few case reports on this condition. Bisphosphonates, are bone resorption inhibitors that are a first-line drug for osteoporosis and metastatic bone cancer. In Japan, where the population is rapidly aging, the number of people taking bisphosphonates will probably continue to increase. We experienced 10 cases of bisphosphonate-induced cholesteatoma of the external auditory canal. In addition, we compared our cases to 19 previously reported cases according to the clinical progression classification. In both groups, the condition most frequently developed in elderly women who had been treated with bisphosphonates for a long time. The degree of progression and the duration of administration showed an inverse correlation, and it was found that even if the duration of administration was long, the condition did not necessarily progress. Regardless of the degree of progression, there were many cases of unilateral onset, and there was a tendency for the condition to frequently develop on the inferior and anterior inferior walls of the external auditory canal. Epithelialization was obtained in all cases with local treatment only; however, in the previously reported cases, the post-treatment course was not constant according to the treatment or degree of progression. It is expected that the accumulation of further cases of bisphosphonate-induced cholesteatoma of the external auditory canal will lead to the establishment of medical guidelines; however, at the present time, otolaryngologists should check whether patients take bisphosphonates, strive for early detection and discuss treatment strategies as needed in collaboration with orthopedic surgeons or physicians.
AbstractList Although osteonecrosis of the external auditory canal has been known to be a serious side effect of bisphosphonates, there are still few case reports on this condition. Bisphosphonates, are bone resorption inhibitors that are a first-line drug for osteoporosis and metastatic bone cancer. In Japan, where the population is rapidly aging, the number of people taking bisphosphonates will probably continue to increase. We experienced 10 cases of bisphosphonate-induced cholesteatoma of the external auditory canal. In addition, we compared our cases to 19 previously reported cases according to the clinical progression classification. In both groups, the condition most frequently developed in elderly women who had been treated with bisphosphonates for a long time. The degree of progression and the duration of administration showed an inverse correlation, and it was found that even if the duration of administration was long, the condition did not necessarily progress. Regardless of the degree of progression, there were many cases of unilateral onset, and there was a tendency for the condition to frequently develop on the inferior and anterior inferior walls of the external auditory canal. Epithelialization was obtained in all cases with local treatment only; however, in the previously reported cases, the post-treatment course was not constant according to the treatment or degree of progression. It is expected that the accumulation of further cases of bisphosphonate-induced cholesteatoma of the external auditory canal will lead to the establishment of medical guidelines; however, at the present time, otolaryngologists should check whether patients take bisphosphonates, strive for early detection and discuss treatment strategies as needed in collaboration with orthopedic surgeons or physicians.
Although osteonecrosis of the external auditory canal has been known to be a serious side effect of bisphosphonates, there are still few case reports on this condition. Bisphosphonates, are bone resorption inhibitors that are a first-line drug for osteoporosis and metastatic bone cancer. In Japan, where the population is rapidly aging, the number of people taking bisphosphonates will probably continue to increase. We experienced 10 cases of bisphosphonate-induced cholesteatoma of the external auditory canal. In addition, we compared our cases to 19 previously reported cases according to the clinical progression classification. In both groups, the condition most frequently developed in elderly women who had been treated with bisphosphonates for a long time. The degree of progression and the duration of administration showed an inverse correlation, and it was found that even if the duration of administration was long, the condition did not necessarily progress. Regardless of the degree of progression, there were many cases of unilateral onset, and there was a tendency for the condition to frequently develop on the inferior and anterior inferior walls of the external auditory canal. Epithelialization was obtained in all cases with local treatment only; however, in the previously reported cases, the post-treatment course was not constant according to the treatment or degree of progression. It is expected that the accumulation of further cases of bisphosphonate-induced cholesteatoma of the external auditory canal will lead to the establishment of medical guidelines; however, at the present time, otolaryngologists should check whether patients take bisphosphonates, strive for early detection and discuss treatment strategies as needed in collaboration with orthopedic surgeons or physicians. ビスホスホネート製剤(以下、BP 製剤)の重大な副作用として外耳道骨壊死・外耳道真珠腫が知られているが、症例報告数はいまだに少ない。BP 製剤は強力な骨吸収抑制作用を有しており、骨粗鬆症や骨転移を有する癌患者に対する第一選択薬であるため、高齢化著しい本邦では今後ますます BP 製剤使用者は増加すると予想される。今回、われわれは BP 製剤が原因と考えられる外耳道真珠腫 10 例を経験した。また、本症例と渉猟し得た既報告 19 例との臨床的な進展度分類による比較検討を行ったが、両報告共に多くは高齢女性に発症し、いずれも長期間にわたり BP 製剤を使用していた。進展度と投与期間は逆の相関を示しており、投与期間が長くても必ずしも病状が進行するとは限らないことが分かった。進展度に関係なく、片側発症例が多く、外耳道下壁から前下壁に好発する傾向があった。本症例は全例、局所処置のみで上皮化を得たが、既報告例では治療別や進展度別にみた治療後経過は一定ではなかった。今後、症例数の蓄積により診療方針が定まるのを期待したいが、現時点では BP 製剤使用の有無の確認を怠らずに、外耳道真珠腫・骨壊死の早期発見に努め、必要に応じて整形外科や内科と連携し治療方針を検討することが重要である。
Author NAKASHIMA, Toshiyuki
SHIN, Takemoto
SHUTO, Hiroyuki
Author_FL 首藤 洋行
中島 俊之
進 武幹
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  fullname: SHUTO, Hiroyuki
  organization: Department of Otorhinolaryngology, Koyanagi Memorial Hospital
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References 11) 奥田 匠 他 : 臨床所見に基づいた外耳道真珠腫の進展度分類案.Otol Jpn 24 : 175-180,2014
10) 大道亮太郎 他 : 耳漏を主訴に来院した扁桃周囲膿瘍の 1 例.日本耳鼻感染症研会誌 31 : 175-178,2012
13) Marx RE : Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws − A growing epidemic −. J Oral Maxillofac Surg 61 : 1115-1117, 2003.
14) 高岡一樹 他 : 骨吸収抑制関連顎骨壊死 (ARONJ) の現状と今後の課題.日薬理誌 153 : 22-27,2019
2) 片岡祐子 他 : ビスホスホネート製剤投与が原因と考えられた外耳道骨壊死.日耳鼻 121 : 905-911,2018
15) 米田俊之 他 : 骨吸収抑制薬関連顎骨壊死の病態と管理.顎骨壊死検討委員会ポジションペーパー 2016 : 1-16,2016
8) Salzman R et al : Osteonecrosis of the external auditory canal associated with oral bisphosphonate therapy − Case report and literature review −. Otol Neurotol 34 : 209-213, 2013.
5) Polizzotto MN et al : Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol 132 : 114-117, 2006.
9) Wickham N et al : Bisphosphonate-associated osteonecrosis of the external auditory canal. J Laryngol Otol 127 : S51-53, 2013.
6) Froelich K et al : Bisphosphonate-induced osteonecrosis of the external ear canal − A retrospective study −. Eur Arch Otorhinolaryngol 268 : 1219-1225, 2011.
12) 厚生労働省 : 2019 年 国民生活基礎調査の概況 (Ⅳ介護の状況). http://www.mhlw.go.jp/toukei/saikinn/hw/k-tyosa/k-tyosa19/dl/05.pdf (2020.7.17)
18) Marx RE et al : Oral bisphosphonate-induced osteonecrosis − Risk factors, prediction of risk using serum CTX testing, prevention, and treatment −. J Oral Maxillofac Surg 65 : 2397-2410, 2007.
21) 橋本 研 他 : 慢性腎不全・血液透析患者に発症した外耳道真珠の検討.日耳鼻 117 : 1179-1187,2014
7) Kharazmi M et al : Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Oral Maxillofac Surg 51 : 285-287, 2013.
4) 小出千秋 他 : ビスホスホネートの副作用と考えられた外耳道骨壊死の 1 例.耳喉頭頸 89 : 355-359,2017
20) Barasch A et al : Risk factors for osteonecrosis of the jaws − A case-control study from the CONDOR dental PBRN −. J Dent Res 90 : 439-444, 2011.
16) Thorsteinsson AL et al : 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 25 : 1937-1944, 2014.
19) Chiu WY et al : The risk of osteonecrosis of the jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene. J Clin Endocrinol Metab 99 : 2729-2735, 2014.
3) 金沢弘美 他 : ビスホスホネート製剤長期投与歴のある外耳道真珠腫の臨床像 − 保存的治療効果から見た検討 −.日耳鼻 121 : 783-790,2018
22) Takamori T et al : Denosumab-induced osteonecrosis of external auditory canal. Auris Nasus Larynx 48 : 1199-1203, 2021.
17) Ruggiero SL et al : American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg 72 : 1938-1956, 2014.
1) ビスホスホネート系薬 : 外耳道骨壊死の非常にまれな報告.医薬品安全性情報 Vol. 14 (03) : 4-7. http://www.nihs.go.jp/dig/sireport/weekly14/03160210.pdf (2016.2.10)
References_xml – reference: 14) 高岡一樹 他 : 骨吸収抑制関連顎骨壊死 (ARONJ) の現状と今後の課題.日薬理誌 153 : 22-27,2019.
– reference: 16) Thorsteinsson AL et al : 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 25 : 1937-1944, 2014.
– reference: 20) Barasch A et al : Risk factors for osteonecrosis of the jaws − A case-control study from the CONDOR dental PBRN −. J Dent Res 90 : 439-444, 2011.
– reference: 4) 小出千秋 他 : ビスホスホネートの副作用と考えられた外耳道骨壊死の 1 例.耳喉頭頸 89 : 355-359,2017.
– reference: 6) Froelich K et al : Bisphosphonate-induced osteonecrosis of the external ear canal − A retrospective study −. Eur Arch Otorhinolaryngol 268 : 1219-1225, 2011.
– reference: 18) Marx RE et al : Oral bisphosphonate-induced osteonecrosis − Risk factors, prediction of risk using serum CTX testing, prevention, and treatment −. J Oral Maxillofac Surg 65 : 2397-2410, 2007.
– reference: 7) Kharazmi M et al : Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Oral Maxillofac Surg 51 : 285-287, 2013.
– reference: 12) 厚生労働省 : 2019 年 国民生活基礎調査の概況 (Ⅳ介護の状況). http://www.mhlw.go.jp/toukei/saikinn/hw/k-tyosa/k-tyosa19/dl/05.pdf (2020.7.17)
– reference: 9) Wickham N et al : Bisphosphonate-associated osteonecrosis of the external auditory canal. J Laryngol Otol 127 : S51-53, 2013.
– reference: 21) 橋本 研 他 : 慢性腎不全・血液透析患者に発症した外耳道真珠の検討.日耳鼻 117 : 1179-1187,2014.
– reference: 17) Ruggiero SL et al : American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg 72 : 1938-1956, 2014.
– reference: 5) Polizzotto MN et al : Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol 132 : 114-117, 2006.
– reference: 11) 奥田 匠 他 : 臨床所見に基づいた外耳道真珠腫の進展度分類案.Otol Jpn 24 : 175-180,2014.
– reference: 13) Marx RE : Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws − A growing epidemic −. J Oral Maxillofac Surg 61 : 1115-1117, 2003.
– reference: 19) Chiu WY et al : The risk of osteonecrosis of the jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene. J Clin Endocrinol Metab 99 : 2729-2735, 2014.
– reference: 22) Takamori T et al : Denosumab-induced osteonecrosis of external auditory canal. Auris Nasus Larynx 48 : 1199-1203, 2021.
– reference: 15) 米田俊之 他 : 骨吸収抑制薬関連顎骨壊死の病態と管理.顎骨壊死検討委員会ポジションペーパー 2016 : 1-16,2016.
– reference: 3) 金沢弘美 他 : ビスホスホネート製剤長期投与歴のある外耳道真珠腫の臨床像 − 保存的治療効果から見た検討 −.日耳鼻 121 : 783-790,2018.
– reference: 1) ビスホスホネート系薬 : 外耳道骨壊死の非常にまれな報告.医薬品安全性情報 Vol. 14 (03) : 4-7. http://www.nihs.go.jp/dig/sireport/weekly14/03160210.pdf (2016.2.10)
– reference: 8) Salzman R et al : Osteonecrosis of the external auditory canal associated with oral bisphosphonate therapy − Case report and literature review −. Otol Neurotol 34 : 209-213, 2013.
– reference: 2) 片岡祐子 他 : ビスホスホネート製剤投与が原因と考えられた外耳道骨壊死.日耳鼻 121 : 905-911,2018.
– reference: 10) 大道亮太郎 他 : 耳漏を主訴に来院した扁桃周囲膿瘍の 1 例.日本耳鼻感染症研会誌 31 : 175-178,2012.
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Snippet Although osteonecrosis of the external auditory canal has been known to be a serious side effect of bisphosphonates, there are still few case reports on this...
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SubjectTerms ビスホスホネート製剤
外耳道真珠腫
外耳道骨壊死
骨吸収抑制剤関連顎骨壊死(ARONJ)
Title A study of cases of bisphosphonate-induced cholesteatoma of the external auditory canal
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