Objective To investigate the effect of metformin (Met) administrated at different doses and duration on bone mineral density (BMD) in SD rats treated with dexamethasone (Dex) as well as the underlying mechanism. Methods Seventy-two 3-month-old female SD rats were randomly divided into six groups (n =12 per group): control group (Con), Dex group, Met 100 mg group (Met 100), Met 200 mg group (Met 200), Met 300 mg group (Met 300), Met 500 mg group (Met 500). Each group was injected with 5 mg/kg Dex intramuscularly twice a week except for Con group. Each Met group was given corresponding dose of Met by gavage once a day. These rats were treated with the experimental protocol for 12 weeks. The body weights were determined at the initiation of the experiment, and monitored once every two weeks to adjust the dosage of the drug. BMD and body composition were measured regularly. After 12 weeks, blood was collected to test indicators such as C-telopeptide of type I collagen (CTX-I) and osteocalcin (OCN). Results At the initiation of the experiment and after 4 weeks, there was no significant difference for BMD among each group (all P>0.05). After 8 weeks, the BMD in Dex group was lower compared with Con group (P<0.05), while there was no significant difference for BMD between Dex group and each Met groups (all P>0.05). After 12 weeks, compared with Dex group, the BMD in Con, Met100 and Met200 groups were higher (all P<0.05), while the BMD in Met300 and Met500 groups were not significantly different when compared with Dex group (all P>0.05). After 12 weeks, compared with Dex group, CTX-I was lower in Con, Met100, Met200 and Met300 group (all P<0.05), while OCN was higher (all P<0.05). Conclusion Our findings suggested that Met could improve the BMD of SD rats treated with Dex by stimulating bone formation and inhibiting bone absorption, which was associated with the dosage and treatment duration of Met. |