Abstract
There is increasing evidence suggesting that traditional antiepileptic drugs (AEDs) such as phenytoin, phenobarbital, valproic acid and carbamazepine decrease the bone mineral density (BMD), thus increasing the risk of osteoporosis and also bone fracture in patients with epilepsy. Perampanel is known as the latest AED approved in over 45 countries worldwide including Japan. Perampanel is used for the treatment of partial-onset seizures with or without secondary generalized and tonic-clonic seizures in patients. However, to the best of our knowledge, there have been no studies related to the effects of perampanel on bone metabolism. Therefore, in this study, we examined the effects of perampanel on the bone metabolism by examining the changes in BMD and to some extent by developing to the histomorphometrical study in compared with phenytoin, as a reference. Following daily oral administration of phenytoin (30 mg/kg) or perampanel (3.0 mg/kg) for 6 weeks, we examined bone analysis at the proximal tibial metaphysis using 6-week-old male C57BL/6 mice. As the results, the decreases in BMD and the marked damages in bone structure were observed as shown in the trabecular bone volume, trabecular thickness, and trabecular number of phenytoin-treated group. These deteriorations of bone structure due to the phenytoin were accompanied by a significant increase in the eroded surface per bone surface (ES/BS) and osteoclast number per bone surface (N.Oc/BS). These data are completely in line with the fact that phenytoin increases the risk of osteoporosis and also bone fracture in patients with epilepsy. On the other hand, in the perampanel-treated group, the significant change of BMD was not observed, in compared with that of control group. Moreover, the histomorphometrical findings are obtained that perampanel may suppress slightly bone formation and enhance bone resorption under certain conditions in this study. In case of further long-term use of perampanel or combined use with traditional AEDs, the progress of bone loss may be taken in consideration in clinical use of perampanel.
