Bisphosphonates are used clinically for the prevention of bone resorption in osteoporosis. Bisphosphonates are known to inhibit osteoclast recruitment at a local site in pressurized middle ear and to reduce calcium release by parathyroid hormone in mo...
Bisphosphonates are used clinically for the prevention of bone resorption in osteoporosis. Bisphosphonates are known to inhibit osteoclast recruitment at a local site in pressurized middle ear and to reduce calcium release by parathyroid hormone in mouse calvarial culture system. Recently, however, ototoxicity of bisphosphonates, has been described after intravenous injection in Paget's disease. In order to investigate ototoxicity of bisphosphonate, auditory brainstem response(ABR) changes and histopathologic changes of the inner ear were observed after application of pamidronate, alendronate, risedronate to the round window membrane(RWM) of guinea pjgs. ABR recordings were performed prior to bisphosphonate application, and at one hour, one day and one, two, three and four weeks after the application. The animals were sacrificed and cochlea was dissected. The organ of Corti was examined under light microscope. After pamidronate application onto the RWM, ABR threshold shift increased upto 13 dB at 4 weeks. After alendronate application onto the RWM, ABR threshold shift increased upto 48 dB at 2 weeks and then slowly returned to 38 dB at 4 weeks. After risedronate application onto the RWM, ABR threshold shift increased upto 33 dB at 3 weeks and then returned to 28 dB at 4 weeks. Surface preparations were showing that loss of the third row of the outer hair cells was noticed but the inner hair cells and the remainder of outer hair cells were intact.
In conclusion, reversible hearing loss was induced and a part of outer hair cells were partially missing after bisphosphonate application onto the RWM.