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

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  • Kanda Junkichi
    Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
  • Izumo Nobuo
    General Health Medical Center, Yokohama University of Pharmacy
  • Kobayashi Yoshiko
    Department of Radiation Science, Yokohama University of Pharmacy
  • Onodera Kenji
    Department of Clinical Pharmacotherapy and Pharmacy, Bethel Epilepsy Centre
  • Shimakura Taketoshi
    Niigata Bone Science Institute
  • Yamamoto Noriaki
    Niigata Bone Science Institute Division of Orthopedic Surgery, Niigata Rehabilitation Hospital
  • Takahashi Hideaki E
    Niigata Bone Science Institute
  • Wakabayashi Hiroyuki
    Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences

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<p>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.</p>

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