Cytochrome P4503A activity affects the gender difference in the development of steroid‐induced osteonecrosis in rabbits

Summary The aim of this study was to investigate cytochrome P 4503 A activity and its correlation with the development of osternecrosis (ON) among male and female steroid‐treated rabbits. Forty adult rabbits (male, n  = 20; female, n  = 20) were injected once with 20 mg/kg of methylprednisolone intramuscularly. Haematologically, cytochrome P 4503 A activity was measured by plasma 1′‐hydroxymidazolam‐to‐midazolam (1′‐ OH ‐ MDZ / MDZ ) ratio just before and 48 h after the steroid injection. We also measured the levels of oestradiol every week. Both femora and humeri were histopathologically examined for the presence of ON . Fifteen of 20 male rabbits (75%) developed ON , while 6 of 20 female rabbits (30%) did so. There was a significant difference in the rate of incidence of ON between male and female rabbits ( P  =   0.010). The 1′‐ OH ‐ MDZ / MDZ ratio in female rabbits just before, as well as 48 h after the steroid injection was significantly higher than that in male rabbits ( P  =   0.039 and P  =   0.001 respectively). In addition, 1′‐ OH ‐ MDZ / MDZ ratio in female rabbits significantly increased in 48 h after the steroid injection ( P  =   0.044), while that in male rabbits did not so ( P  =   0.978). The levels of oestradiol in female rabbits were significantly higher than those in male rabbits during the experimental period ( P  =   0.008). In conclusion, this study indicates that the gender difference in cytochrome P 4503 A activity may be one of the important factors for the development of steroid‐induced ON , possibly due to the effects of oestradiol.