An Experimental Study on Bisphosphonates Ototoxicity

Park, Il Seok; Kim, Hyung Jong; Lim, Hyun Joon

Abstract

BACKGROUND AND OBJECTIVES: Bisphosphonates are known to inhibit bone resorption, and some researchs are also undergoing on their protective effect against localized bone resorprion in aural cholesteatoma. However, ototoxicity has been reported recently after pamidronate, a bisphophonate, is introduced intravenously. Functional and morphologic changes of the inner ear were observed after local application of bisphosphonates onto the round window membrane (RWM).
MATERIALS AND METHODS
Auditory brainstem response (ABR) changes and histopathologic changes of the inner ear were observed after application of pamidronate, alendronate, risedronate to the RWM of guinea pigs. ABR recordings were taken prior to the bisphosphonate application as well as one hour after the application. These recordings were also taken each day after the application, continuing upto four weeks. Cochleas were dissected at the fourth week, and the organ of Corti was examined under the light microscope and scanning electron microscope.
RESULTS
After pamidronate was applied onto the RWM, the hearing level was elevated upto 13 dB, and then returned to normal at 4 weeks. After the alendronate application, hearing level was lowered to 48 dB at 2 weeks. After the risedronate application, hearing level was elevated to 33 dB at 3 weeks. The surface preparations and the scanning electron microscopic examination revealed loss of the third row of the outer hair cells. The inner hair cells and the remainder of outer hair cells were intact.
CONCLUSION
Reversible or irreversible hearing loss was induced and the outer hair cells were partially missing after the local application of biphosphonates onto the RWM.