Effects of the Antiepileptic Drug Vigabatrin on Bone Strength, Bone Mineral Density, and Bone Turnover in Rats.

First-generation antiepileptic drugs (AEDs) increase the risk of fracture in patients with epilepsy. Although phenytoin has been reported to adversely influence bone metabolism, little is known about the effects of recent AEDs. In this study, we examined the effects of vigabatrin, a second-generation AED, on bone metabolism in rats. Four-week-old male Wistar rats were treated orally with phenytoin (20 mg/kg) or vigabatrin (50 or 200 mg/kg) daily for 6 weeks. Bone histomorphometric analysis was performed, and bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, vigabatrin treatment did not affect bone strength or BMD. However, a significant decrease in bone microstructure parameters, such as the bone volume and number of trabeculae, were observed in the vigabatrin 200 mg/kg treated group as shown by bone histomorphometry. Moreover, the bone formation parameters, osteoid volume and mineralizing surface decreased after vigabatrin 200 mg/kg treatment, whereas the bone resorption parameters, eroded surface and osteoclast number increased. Our data suggest that vigabatrin-induced trabecular bone rarefaction, which is associated with decreased bone formation and enhanced bone resorption may affect bone strength after chronic exposure. Future studies should focus on the specific mechanisms underlying bone remodeling effect of vigabatrin. [ABSTRACT FROM AUTHOR]