2017 Volume 26 Issue 4 Pages 405-410
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 effects 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 histomorphometric 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 significant increase in the eroded surface per bone surface (ES/BS) and osteoclast number per bone surface (N.Oc/BS). In contrast, no significant change in bone structure parameters was observed in the perampanel group. However, compared to that in the control group, a significant decrease in bone formation parameters such as the osteoblast surface and mineral apposition rate occurred, additionally the ES/BS and N.Oc/BS were significantly increased in the perampanel group. These findings of this study suggest that perampanel may suppress bone formation and enhance bone resorption. Perampanel-induced failure of bone remodeling may have an adverse effect 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 effect of perampanel.
