PR-4. HEARING LOSS AND OSTEOPOROSIS OF AUDITORY OSSICLES IN MICE
Sho Kanzaki
(Keio University
Hospital), Masako Ito (Nagasaki University Hospital), Kaoru Ogawa, Koichi Matsuo
(Keio University Hospital, Japan)
Objectives: Hearing loss and osteoporosis are both associated with aging, but whether osteoporosis can directly contribute to impaired auditory function is unclear. Mice lacking osteoprotegerin (Opg-/- mice) develop osteoporosis due to enhanced differentiation of osteoclasts. We therefore asked whether ossicles, the malleus, incus, and stapes are susceptible to enhanced osteoclastic bone resorption in Opg-/- mice, and whether these mice suffer from impaired auditory function.
Material and methods: A total sixteen each Opg-/- and heterozygous littermate mice were used to analyze morphology of ossicles and auditory functions.
1) Morphology
The shapes of the malleus, incus and stapes were microscopically compared between Opg-/- (osteoporotic) and heterozygous mice. Osteoclasts and resorption lacunae were visualized with tartrate-resistant acid phosphatase (TRAP) activity. Trabecular microstructure of isolated mallei from 8-week Opg-/- and heterozygous mice (n=5 each group) were evaluated using micro-computed tomography. In addition, tibial bone mineral density (BMD) of the same mice was measured by quantitative CT
2) Auditory brain stem responses (ABR)
Tone burst ABR test was performed at the four frequencies 2, 4 12, and 20 kHz at the ages of 6, 10 and 15 weeks.
Results: All three ossicles in Opg-/- mice showed apparent thinning, especially at the malleal manubrium, malleal processus brevis, and stapedial arch. Furthermore, ossicles from Opg-/- mice stained more extensively positive for TRAP activity than those from heterozygous controls indicating that osteoclastic bone resorption of ossicles was more prominent in Opg-/- mice. Radiological analysis using µCT showed that malleal bone thickness was decreased in Opg-/- mice, corresponding to the decrease in tibial bone mineral density measured by quantitative CT. Opg-/- mice showed progressive hearing loss over the frequency range tested (2–20 kHz). At the age of 15 weeks, mutant mice were more than 20 decibels (dB) less sensitive than wild-type controls at the highest frequency of 20 kHz.
Conclusion: These data demonstrate that auditory ossicles are susceptible to bone resorption by osteoclasts and that osteoporosis may be a risk factor for conductive hearing loss. The possible link between hearing loss and osteoporosis may provide a novel basis for prevention and therapy of age-related hearing loss.
* Contact person email: skan@sc.itc.keio.ac.jp