Effect of concomitant administration of eicosapentaenoic acid and alendronate on bone changes due to methylprednisolone in rats

One of the main limitations of glucocorticoid therapy is its negative effects on bones. The aim of this study was to determine the effects of concurrent administration of eicosapentaenoic acid (EPA) and alendronate on bone changes induced by glucocorticoid treatment in rats. Thirty six male Wistar rats, who were 2.5 months of age, were divided equally into six groups and treated with normal saline (controls), 7 mg/kg methylprednisolone (MP), MP with 20 µg/kg alendronate, MP with alendronate and 80 mg/kg EPA, MP with alendronate and 160 mg/kg EPA, and MP with alendronate and 320 mg/kg EPA for a six-week period. At the end of the experiment, serum and urine samples were collected and the left tibia and femur were removed from each animal for histomorphometric studies.
There were no significant differences with regards to the levels of serum calcium, phosphorus, creatinine, osteocalcin, carboxy-terminal telopeptide of collagen type I (CTX), alkaline phosphatase, urinary calcium and creatinine, and the phosphorus:creatinine ratios among all groups. Epiphyseal and metaphyseal trabecular widths, and the area of epiphyseal bone and the entire femur in the MP group decreased significantly in comparison to the control group (p<0.001). There were no significant differences in the cortical parameters of the tibial bone between these groups. The groups treated with alendronate and alendronate with 80 mg/kg EPA had increased epiphyseal trabecular widths compared to the MP group (p<0.001) that were statistically similar in both groups. The groups treated with alendronate with 80 mg/kg EPA and alendronate with 320 mg/kg EPA had increased metaphyseal trabecular widths compared to the MP group (p<0.001). The groups with alendronate treatment alone and alendronate with 80 mg/kg EPA had significantly increased bone areas and tissue areas compared to the MP group (p<0.001). In conclusion, concomitant administration of EPA and alendronate may improve the known beneficial effects of alendronate on changes in the bone due to MP administration in rats.