The Protective Role of Simvastatin on Methotrexate-Induced Bone Injury in Adult Albino Rat

Abstract

Background: Methotrexate (MTX) is a folic acid antagonist and chemotherapeutic agent widely used in cancer treatment. It is used as first line therapy in treatment of rheumatoid arthritis (RA). MTX was known to cause bone defects in the form of reduced mineral density (BMD) and bone fractures. Simvastatin (SIM) is widely used for cardiovascular diseases.Aim of Work: To investigate the possible protective role of SIM on MTX induced bone injury in rats.Material and Methods: Forty adult male albino rats were divided into four groups; Control group, SIM-treated group, MTX group and MTX + SIM group. MTX was given by subcutaneous injection as 0.65 mg/kg/day for two separate 5 days. SIM was administered orally as 25 mg/kg/day one month prior to and during the MTX course. At the end of the experiment, blood samples were collected for levels of osteocalcin (OSC) and alkaline phosphatase (ALP). All rats were sacrificed and specimens from their femurs were examined.Results: examination of MTX group showed marked thinning of the periosteum, and widening of bone marrow spaces. There was an apparent decrease in the number of osteocytes, together with an apparent increase in the number of osteoclasts. There was a significant decrease in the serum level of OSC together with a highly significant increase in the serum level of ALP in the MTX group as compared to the control group. On administration of SIM with MTX, there was marked improvement in most of the histological and serological parameters.Conclusion: SIM could be used as a protective measure for MTX-induced bone defects.