Kanzaki Sho, Takada Yasunari, Ogawa Kaoru, Matsuo Koichi
Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan.
J Bone Miner Res. 2009 Jan;24(1):43-9. doi: 10.1359/jbmr.080812.
Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg(-/-) mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg(-/-) mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg(-/-) mice are unknown. We intraperitoneally injected Opg(-/-) mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg(-/-) mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg(-/-) mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg(-/-) mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.
包括锤骨、砧骨和镫骨在内的三块听小骨在中耳将声音从鼓膜传导至内耳。在缺乏骨保护素（OPG，一种破骨细胞生成细胞因子RANKL的可溶性诱饵受体）的Opg(-/-)小鼠中，听小骨被破骨细胞大量吸收。Opg(-/-)小鼠表现出进行性听力丧失，是青少年佩吉特病的模型。然而，抗吸收治疗对Opg(-/-)小鼠听小骨和听力功能的影响尚不清楚。我们每周5天、连续9周给Opg(-/-)小鼠腹腔注射双膦酸盐利塞膦酸盐。通过显微镜、放射学和组织学检查听小骨的形态。通过测量听性脑干反应（ABR）监测听力功能。对照Opg(-/-)小鼠的三块听小骨和胫骨均出现变薄。相比之下，利塞膦酸盐治疗显著抑制了Opg(-/-)小鼠听小骨以及长骨的骨质流失。治疗后镫骨与听囊之间连接处的骨融合减少。此外，ABR测量显示，利塞膦酸盐治疗显著改善了Opg(-/-)小鼠的听力。这些数据表明，双膦酸盐可能预防以听小骨过度吸收为特征的病理状态下的听力丧失。
