Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits

Objectives: To investigate in vivo effects of lovastatin on inhibition of adipogenesis, an important mechanism of steroid-induced osteonecrosis, and on prevention of occurrence of steroid-induced osteonecrosis in rabbits. Methods: Fifty-four rabbits were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL). Then, they were divided into two groups: lovastatin was given in Group I and placebo was given in Group II. And another 16 rabbits were injected with physiologic saline (PS) as a control (Group III). Hematological examination was performed for serum lipid levels. Both the femora and the humeri were histopathologically examined for the presence of osteonecrosis before the injection and 1, 2, 4 and 12 weeks after the injection. Results: The serum lipid levels were significantly higher in Group II than in Groups I and III 1, 2 and 4 weeks after the injection. The incidence of osteonecrosis was significantly higher in Group II (69%) than in Group I (36%) and Group III (0%). Pathological examination showed less serious adipogenesis and bone death in Group I than in Group II. The size and area of the fat cells in the bone marrow were significantly smaller in Group I (47.5 +/- 1.3 mu m, 25%) and Group III (41.7 +/- 1.6 mu m, 12%) than in Group II (59.8 +/- 6.3 mu m, 51%) (P < 0.001). Conclusion: Lovastatin can prevent development of steroid-induced osteonecrosis in rabbits by inhibiting adipogenesis. Future evaluation on the effectiveness of lovastatin in the clinical practice is still necessary. (C) 2008 Elsevier Masson SAS. All rights reserved.