Hearing function in older patients may be related to bone structure. We conducted an experiment to evaluate the effect of zoledronic acid on osteoporotic middle ear ossicles in an animal model. Our subjects were 19 female New Zealand white rabbits (38 ears) weighing 2 to 4 kg. We divided the rabbits into three groups: one group consisted of 6 rabbits with osteoporotic ears that were treated with zoledronic acid; the second group was made up of 8 rabbits with osteoporotic ears that were not treated; a control group included 5 rabbits with normal ears that were untreated. After an oophorectomy, the 6 study rabbits were administered 0.1 ml/kg of zoledronic acid intravenously. All rabbits were sacrificed 16 weeks later, and the middle ear ossicles were removed for investigation under light microscopy. Although osteoporosis enhanced the osteoclastic bone resorption of the ossicles, zoledronic acid enhanced osteoblastic activity on osteoporotic middle ear ossicles. The incidence of osteoporosis was 93.8% in the untreated osteoporosis group and 33.3% in zoledronic acid group-a statistically significant difference (OR: 0.24; 95% CI: 0.09 to 0.58; p < 0.001). Osteoporosis appears to increase the resorption of the middle ear ossicles, a process that can be avoided with zoledronic acid administration. Prevention of the effects of osteoporosis in humans may help decrease the irreversible changes in the middle ear ossicles.