Effect of atorvastatin on phenytoin-induced osteoporosis in adult albino rats: a pharmacological and light and electron microscopic study

ABSTRACT

Phenytoin, an antiepileptic drug [AED], might affect bone structure and mineralization. Epileptic patients who take AEDs are at increased risk for falls and fractures. Therefore, there is a need for a new approach to increase bone health in these patients. This study was conducted to assess the efficacy of statins in preventing bone loss associated with AEDs. Thirty male adult albino rats were divided into five equal groups. The animals, which received daily treatment by gastric gavage for 5 weeks, were classified into group I [the control group]; group II, in which the rats were given phenytoin 20 mg/kg bw; group III, in which rats received phenytoin as in group II with atorvastatin 5 mg/kg bw; group IV, in which rats were given phenytoin along with atorvastatin 10 mg/kg bw; and group V, in which they were given phenytoin along with atorvastatin 20 mg/kg bw. Biochemical assays, assessment of bone mineral density, light [LM] and scanning electron microscopic studies [SME], as well as morphometric and statistical studies were carried out. The present work demonstrated that atorvastatin in a dose-dependent manner significantly [P<0.001] prevented the decrease in serum and bone calcium and phosphorus and bone-specific alkaline phosphatase due to phenytoin administration. There was also a graded improvement in osteocalcin [a marker for 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 gradual improvement of the tibia bone with higher doses as there was a significant increase [P<0.05] in trabecular and cortical bone thickness and a significant decrease [P<0.05] in osteoclast numbers per area of bone surface in the metaphysis; compared with the phenytoin-only-treated group, an improvement was seen in the growth of the epiphyseal plate. Atorvastatin could be considered a beneficial drug for treatment of osteoporosis in epileptic patients on phenytoin