Effect of antiseizure drugs on growing bone in prepubertal non-epileptic rats

To investigate the histologic effects of topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), lacosamide (LCM), clobazam (CLB), and zonisamide (ZNS) on rat bone. Seventy male Wistar-Albino rats (aged 21-24 days, weighing 46.4-55.3 g) were divided into 7 experimental groups with 10 rats each:(i) Control group, (ii) TPM group (40 mg/kg/day), (iii) LTG group (10 mg/kg/day), (iv) LEV group (200 mg/kg/day), (v) LCM group (30 mg/kg/day), (vi) CLB group (50 mg/kg/day), and (vii) ZNS group (100 mg/kg/day). All the drugs were administered by gavage for 90 days.The specimens were analyzed using apoptosis (TUNEL) and immunohistochemical staining. The number of osteoblasts and the thickness of femoral compact bone decreased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups. In osteoblasts, there was local atrophy in TPM, LEV, and LCM groups, while intense atrophy was observed in LTG, CLB, and ZNS groups. In all experimental groups, there were abnormally prominent enlargements in the Havers and Volkmann canals. The number of TUNEL-positive cells was higher in all experimental groups compared to the control group, and this difference was statistically significant in CLB and ZNS groups ( p<0.001 for both). The HSCORE increased significantly for C-3, C-9, and BAX immunohistochemical staining ( p<0.001) and increased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups ( p<0.001).