osteoprotegerin and Tinnitus

Presented here is a first-person account of the evolution of the practice of surgical neurootology to that of medical neurootology shaped mainly by results of treatment directed at underlying otosclerosis-like lesions of the otic capsule and metabolic factors. With new technologies and rapidly evolving concepts, the changing treatment algorithms did not remain constant to provide the usual evidence-based outcome analyses. However, the majority of the patients presenting with neurootological symptoms had undergone previous medical or surgical treatment before undergoing the medical management herein described. The underlying ongoing basic science findings over this period were linked to the clinical observations. On the basis of the more effective results of treating neurootological disorders, recommendations are made for future areas of investigation-mostly basic science-into developing an investigative foundation for future effective management of patients with a variety of neurootological disorders.

Topics: Animals; Blood Glucose; Bone Density Conservation Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Diabetes Mellitus, Type 2; Diphosphonates; Evidence-Based Medicine; Hair Cells, Auditory; Hearing Loss, Sensorineural; Humans; Insulin Resistance; Labyrinth Diseases; Meniere Disease; Mice; Mice, Knockout; Migraine Disorders; Osteoclasts; Osteoprotegerin; Otosclerosis; Tinnitus; Tumor Necrosis Factor-alpha

Otosclerosis is a bony dyscrasia characterized by histopathological findings of osteoclast production. Osteoclastogenesis explains the pathogenesis of otosclerosis. Basic science research in the experimental animal otic capsule has given insight into the process of evolution of otosclerosis. The normal otic capsule is preserved with very little bone turnover as a result of the production of osteoprotegerin (OPG) by the membranous inner ear that prevents the activation of osteoclasts. Animals genetically unable to produce OPG demonstrated the production of hearing loss and histopathology of the temporal bones consistent with that seen in otosclerosis. Applying the understanding of osteoclastogenesis to the treatment of otosclerosis has led to the clinical use of the class of drugs called bisphosphonates. The bisphosphonate group of drugs specifically targets osteoclasts by reducing production of osteoclasts and accelerating their early cell death. The rationale for use of bisphosphonates to treat the sensorineural hearing loss of otosclerosis is explained, with cases that illustrate the bisphosphonates treatment algorithms and the response to treatment.

Topics: Aged; Alendronate; Animals; Bone Density Conservation Agents; Bone Resorption; Cell Death; Combined Modality Therapy; Diphosphonates; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ear, Inner; Ear, Middle; Etidronic Acid; Follow-Up Studies; Hearing Aids; Hearing Loss, Sensorineural; Humans; Male; Middle Aged; Osteoclasts; Osteoprotegerin; Otosclerosis; Risedronic Acid; Speech Discrimination Tests; Speech Reception Threshold Test; Stapes Surgery; Tinnitus