Phenytoin and sodium valproate but not levetiracetam induce bone alterations in female mice

Abstract

Adverse effects on the bone are amongst the potentially adverse clinical consequences with antiepileptic drugs (AEDs). This study compared the effects of 3 AEDs (phenytoin (PHT), sodium valproate (SVP), and levetiracetam (LTM)) on the bones of a Swiss strain of albino female mice. Drugs were administered daily for 4 months at doses that produced plasma concentrations corresponding to the clinically relevant therapeutic ranges. PHT and SVP (but not LTM) significantly lowered the bone mineral density (BMD) of lumbar vertebrae (L2-L4) as evaluated by dual-energy X-ray absorptiometry (DEXA) scan. The findings were supported by histopathology of vertebral (lumbar) bone and analysis of bone turnover markers. While both PHT and SVP reduced alkaline phosphatase (ALP) and hydroxyproline (HxP) in lumbar vertebrae, and elevated tartarate-resistant acid phosphatase (TRAP) and urinary excretion of calcium, LTM did not affect any of these markers of bone turnover, indicating that the drug might be a safer option in female epileptic patients prone to bone changes.

Keywords: alkaline phosphatase; bone mineral density; calcium urinaire; densité minérale de l’os; hydroxyproline; levetiracetam; lévétiracétam; phenytoin; phosphatase acide résistante au tartarate; phosphatase alcaline; phénytoïne; sodium valproate; tartarate-resistant acid phosphatase; urinary calcium; valproate de sodium.