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Effect of Chemical Sympathectomy With 6-Hydroxydopamine on Osteoclast Activity in the Gerbilline Middle Ear Bulla

Hypothesis Chemical sympathectomy with 6-hydroxydopamine (HDA) increases middle ear bulla bone resorption in the Mongolian gerbil. Background Many diseases of the middle ear have pathologic processes linked to abnormal bone remodeling. Numerous factors controlling bone remodeling have been identified. An understanding of these factors and their role in pathologic remodeling is therefore essential. Sympathectomy, induced both surgically and pharmaceutically, is known to increase middle ear bone resorption, suggesting a role for the central nervous system in bone metabolism. This effect, however, may be confounded by hemodynamic changes induced by hemicranial surgical sympathectomy or by uncertainty in the action of pharmaceutical agents on the sympathetic nervous system. In this experiment, a third modality with unique properties, chemical sympathectomy with HDA, was used to quantify further the effect of sympathectomy on middle ear bone remodeling. Methods Eight gerbils designated experimental received intraperitoneal injections of HDA (75 mg/kg) for 1 week, whereas eight animals designated control received similar injections of saline. One week after injections, the animals were euthanized and bulla bone samples were analyzed histomorphometrically to determine osteoclastic activity. In addition, to assess for any direct effects on bone metabolism, the activity of HDA was determined in vitro using the calvarial calcium release assay. Results The in vitro study found HDA to have no direct stimulatory activity on calcium release. The in vivo study showed HDA to increase osteoclastic activity significantly in middle ear bone. Conclusion HDA-induced sympathectomy increases bone resorption in gerbilline middle ear bone.