Several animal and human studies suggest pharmacological approaches may prevent steroid-induced osteonecrosis (ON). We asked whether the newly developed 3-hydroxymethyl-3-glutaryl-CoA (HMG-CoA) reductase inhibitor, pitavastatin, could prevent steroid-induced ON in rabbits. We injected 65 adult male Japanese white rabbits once with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were divided into two groups; one group of 35 rabbits received pitavastatins (PS), and the other group of 30 rabbits received no prophylaxis (CTR). Hematological examinations were performed just before the steroid injection (0 weeks) and at 1 and 2 weeks after steroid injection; both the femora and the humeri were histologically examined 2 weeks postinjection. The incidence of histologic changes consistent with early ON in the PS group (13 of 35; 37%) was lower in comparison to the CTR group (21 of 30; 70%). The size of the bone marrow fat cells in the PS group (56.6 +/- 10 microm) was smaller than those in the CTR group (60 +/- 4 microm). The data suggest pitavastatin has the potential to lower the incidence of steroid-induced ON in rabbits.