Onset of steroid-induced osteonecrosis in rabbits and its relationship to hyperlipaemia and increased free fatty acids

Abstract

Objectives. To clarify the initial onset time of osteonecrosis after the start of steroid treatment and its relation to the onset of abnormal lipid metabolism. Methods. Animal models were prepared by administering methylprednisolone to rabbits using five different steroid regimens. Results. A single, acute ischaemic event suggested by the frequency, size or number of necrotic foci within the proximal femur was not different among the groups. Histological evidence of osteonecrosis first occurred 1-2 weeks after initial steroid administration. At the same time there were significantly abnormal elevations in serum lipids, which persisted for between 1 and 2 weeks after the initial corticoid treatment. Triglycerides, total cholesterol and free fatty acids were markedly elevated in all groups; these lipid abnormalities were significantly present in the rabbits with osteonecrosis but not in the rabbits without osteonecrosis. Conclusions. This study shows that (i) osteonecrosis appears in rabbits shortly after corticoids are first administered, and (ii) osteonecrosis in rabbits is chronologically associated with the onset of hyperlipaemia and increased free fatty acids. This supports the occurrence of intraosseous fat embolism as a cause of osteonecrosis. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.