Regulation of osteoclasts is required to maintain morphology and function of ossicles in middle ear

Little is known about how bone-resorbing osteoclasts play a role in the vibration of auditory ossicles. Osteoclasts are specialized multinuclear macrophages that resorb bone. Once bones develop through endochondral and intramembranous ossification (bone modeling), osteoclastic bone resorption in adults is usually followed and balanced by osteoblastic bone formation through “coupling” mechanisms, which maintain bone integrity (bone remodeling). Turnover of temporal bones including the otic capsule and ossicles is much slower than that of the long bones because the former contain high levels of osteoprotegerin (Opg), which inhibits osteoclast formation. We analyzed hearing function and morphology of ossicles in both osteoporotic and osteopetrotic mice. Ossicles in Opg deficient (Opg ^−/−) mice are massively resorbed by abundant osteoclasts, resulting in impaired hearing function. In Opg ^−/− mice, the ligament at the junction of the stapes and the otic capsule is lost by bony ankylosis. In addition, administration of the anti-resorptive drug bisphosphonate prevents not only erosion of auditory ossicles but also progression of hearing loss, suggesting that excessive bone resorption underlies impaired hearing in Opg ^−/− mice. Conversely, osteopetrotic mice, which lack osteoclasts due to either c-Fos or RANKL deficiency, show a smaller volume of the tympanic cavity but larger ossicles compared to controls. The malleal processus brevis thus touches the medial wall of the tympanic in osteopetrotic mice. These data demonstrate that regulation of osteoclastic bone resorption is required to maintain morphology of ossicles and normal hearing function.