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) 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. 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 caspase-3, caspase-9, and Bcl-2-associated X protein (BAX) immunohistochemical staining (p < 0.001) and increased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups (p < 0.001). In summary, the use of antiseizure medications adversely affected the expression of proteins critical to bone physiology in young non-epileptic rats, with varying degrees of impact.