Corticosteroid-induced avascular necrosis: an experimental study in rabbits.

New Zealand white rabbits were divided into 4 groups for the study of the etiology of corticosteroid-induced osteonecrosis (avascular necrosis). Group A and B received intramuscular injections of methylprednisolone acetate and methylprednisolone succinate respectively. Group C, on semirestricted diets, and Group D, on ad libitum diets, were controls. Osteocyte death, necrotic debris and intravascular fat emboli were evident in sections of proximal and distal femur by the 2nd week in experimental animals. Blood analysis revealed elevated lipid and prostaglandin levels. Osteoporosis was first observed at 6 weeks. Evidence of advanced osteonecrosis was present histologically at 18 weeks. It is concluded that osteonecrosis probably develops as the result of the interaction of several corticosteroid-induced alterations, including circulating fat emboli and inflammatory unbound free fatty acids or prostaglandins. Osteoporosis may also be a factor in explaining the sporadic nature of the disorder.