Effect of atorvastatin on phenytoin-induced osteoporosis inadult albino rats: a pharmacological and light and electronmicroscopic study

IntroductionPhenytoin, an antiepileptic drug (AED), might affect bone structure andmineralization. Epileptic patients who take AEDs are at increased risk for fallsand fractures. Therefore, there is a need for a new approach to increase bonehealth in these patients.Aim of the workThis study was conducted to assess the efficacy of statins in preventing boneloss associated with AEDs.Materials and methodsThirty male adult albino rats were divided into five equal groups. The animals,which received daily treatment by gastric gavage for 5 weeks, were classifiedinto: group I (the control group); group II, in which the rats were given phenytoin20 mg/kg bw; group III, in which rats received phenytoin as in group II withatorvastatin 5 mg/kg bw; group IV, in which rats were given phenytoin along withatorvastatin 10 mg/kg bw; and group V, in which they were given phenytoin alongwith atorvastatin 20 mg/kg bw. Biochemical assays, assessment of bone mineraldensity, light (LM) and scanning electron microscopic studies (SME), as well asmorphometric and statistical studies were carried out.ResultsThe present work demonstrated that atorvastatin in a dose-dependent mannersignificantly (P 0.001) prevented the decrease in serum and bone calciumand phosphorus and bone-specific alkaline phosphatase due to phenytoinadministration. There was also a graded improvement in osteocalcin (a markerfor osteoblastic activity) and TRAP (a marker for osteoclastic activity) levels.Moreover, atorvastatin significantly inhibited the loss in bone weight, volume,and density. On LM and SEM examination, atorvastatin showed a gradualimprovement of the tibia bone with higher doses as there was a significantincrease (P 0.05) in trabecular and cortical bone thickness and a significantdecrease (P 0.05) in osteoclast numbers per area of bone surface in themetaphysis; compared with the phenytoin-only-treated group, an improvementwas seen in the growth of the epiphyseal plate.ConclusionAtorvastatin could be considered a beneficial drug for treatment of osteoporosisin epileptic patients on phenytoin.