Kanda Junkichi, Izumo Nobuo, Kobayashi Yoshiko, Onodera Kenji, Shimakura Taketoshi, Yamamoto Noriaki, E Takahashi Hideaki, Wakabayashi Hiroyuki
Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences.
General Health Medical Center, Yokohama University of Pharmacy.
Biomed Res. 2017;38(5):297-305. doi: 10.2220/biomedres.38.297.
Long-term treatment with antiepileptic drugs (AED) is associated with an elevated risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has been shown to affect bone metabolism adversely, whereas newly developed AEDs have not been studied. This study evaluated the effects of topiramate and lamotrigine on bone metabolism in rats. Five-week-old male Sprague-Dawley rats were treated orally with phenytoin (20 mg/kg), topiramate (5 or 20 mg/kg), or lamotrigine (2 or 10 mg/kg) daily for 12 weeks. Phenytoin reduced bone strength, measured by maximum load to failure of the femoral mid-diaphysis, along with reduced femur total BMD. Serum tartrate-resistant acid phosphatase-5b levels significantly increased after phenytoin treatment, while serum osteocalcin levels decreased after topiramate 20 mg/kg treatment. Furthermore, osteoblast surface and bone mineralizing surface were significantly lowered by topiramate. Lamotrigine treatment did not affect bone strength, BMD, or bone turnover. We demonstrated that phenytoin treatment significantly increased bone resorption and lowered BMD and bone strength. Since lamotrigine did not affect bone metabolism, it can be concluded that lamotrigine is safety medicine for bone health. Topiramate was associated with decreased bone formation, which may affect bone strength and BMD with chronic use. Thus, patients taking topiramate should be monitored for changes in BMD to avoid risk of fracture.
抗癫痫药物（AED）的长期治疗与骨矿物质密度（BMD）降低导致的骨折风险升高有关。已证实苯妥英会对骨代谢产生不利影响，而新开发的AED尚未进行相关研究。本研究评估了托吡酯和拉莫三嗪对大鼠骨代谢的影响。将5周龄雄性Sprague-Dawley大鼠每日口服给予苯妥英（20mg/kg）、托吡酯（5或20mg/kg）或拉莫三嗪（2或10mg/kg），持续12周。苯妥英降低了通过股骨中骨干骨折最大负荷测量的骨强度，同时降低了股骨总骨密度。苯妥英治疗后血清抗酒石酸酸性磷酸酶-5b水平显著升高，而托吡酯20mg/kg治疗后血清骨钙素水平降低。此外，托吡酯显著降低了成骨细胞表面和骨矿化表面。拉莫三嗪治疗未影响骨强度、骨密度或骨转换。我们证明苯妥英治疗显著增加了骨吸收，降低了骨密度和骨强度。由于拉莫三嗪不影响骨代谢，因此可以得出结论，拉莫三嗪对骨骼健康是安全的药物。托吡酯与骨形成减少有关，长期使用可能会影响骨强度和骨密度。因此，服用托吡酯的患者应监测骨密度变化以避免骨折风险。
