Treatment with Antiepileptic Agent Perampanel Suppresses Bone Formation and Enhances Bone Resorption: A Bone Histomorphometric Study in Mice

Traditional antiepileptic drugs (AEDs) such as phenytoin, decrease bone mineral density (BMD) and increase the risk of bone fracture in patients with epilepsy. In this study, we examined the eff ects of perampanel, a novel antiepileptic drug, on bone metabolism by bone histomorphometry. Following daily oral administration of either phenytoin (30 mg/kg) or perampanel (3.0 mg/kg) for 6 weeks, we performed bone histomorphom etric analysis at the proximal tibial metaphysis of 6-week-old male C57BL/6 mice. A significant decrease in bone structure parameters such as the trabecular bone volume, trabecular thickness, and trabecular number was observed in the phenytoin group. These deteriorations of bone structure due to the administration of phenytoin were accompanied by a signifi cant increase in the eroded surface per bone surface (ES/BS) and osteoclast number per bone surface (N.Oc/BS). In contrast, no signifi cant change in bone structure parameters was observed in the perampanel group. However, compared to that in the control group, a signifi cant decrease in bone formation parameters such as the osteoblast surface and mineral apposition rate occurred, additionally the ES/BS and N.Oc/BS were signifi cantly increased in the perampanel group. These fi ndings of this study suggest that perampanel may suppress bone formation and enhance bone resorption. Perampanel-induced failure of bone remodeling may have an adverse eff ect on bone volume with further long-term use. In the future, it would be necessary to conduct research studies to elucidate the detailed mechanism underlying the bone remodeling eff ect of perampanel.