[Experimental study on avascular necrosis of femoral head induced by methylprednisolone combined with lipopolysaccharide in rabbits].

OBJECTIVE: To establish a stable animal model for glucocorticoid-induced avascular necrosis of femoral head in rabbits.

METHODS: Thirty-six adult New Zealand rabbits were randomly divided into four groups: ten were injected twice with lipopolysaccharide (group A), ten were treated with a combination of lipopolysaccharide and methylprednisolone (group B), ten were injected three times with methylprednisolone (group C), and six were injected normal saline as a control (group D). MR imaging was performed in the rabbits before the first injection of lipopolysaccharide or methylprednisolone, and at 2, 4, and 6 weeks after the last injection of lipopolysaccharide or methylprednisolone. Histopathological changes in the femoral heads were observed by light microscope and transmission electron microscope at the end of six weeks after the injection. Vascular infusion with Chinese ink was made to evaluate the morphological changes of blood vessels in the femoral head. The percentage of trabecular bone area and empty lacunae and microvascular density were measured. According to the histological and MR imaging appearance of the femoral heads in all groups, the incidence of osteonecrosis of every group was calculated.

RESULTS: Listlessness, blepharal hyperemia, less activity and reduced diet were found in the rabbits of groups A and B after injected with lipopolysaccharide. At 3 weeks after the final injection, the body weight of groups B and C was decreased. At 4 weeks after the final injection, the body weight of groups A and D was increased. No abnormal signal could be detected on MR images in rabbits of all groups before injection and at 2 weeks after the injection. At 4 weeks and 6 weeks after the last injection, irregular low signal on T1-weighted images and irregular low or highsignal on T2-weighted images could be detected on MR images in rabbits of groups B and C, no abnormal signal could be detected on MR images in rabbits of groups A and D. At 6 weeks after the last injection, the trabecular bone of group B became thin and sparse, some were broken. The percentages of empty lacunae were 11.8% +/- 4.7%, 34.4% +/- 6.2%, 20.0% +/- 4.7% and 9.3% +/- 4.6%; the percentages of trabecular bone area were 59.2% +/- 6.8%, 40.1% +/- 6.0%, 51.5% +/- 5.6% and 63.2% +/- 8.3%; and the microvascular densities were 14.3% +/- 2.7%, 4.5% +/- 2.1%, 10.2% +/- 3.1% and 15.4% +/- 4.1% in groups A, B, C and D respectively. There were statistically significant differences between group B and groups A, C, D (P <0.01). The fatty tamponade accumulated in the medullary cavity and intramedullary vascular sinusoids were pressed by the lipocytes and became narrow. Limposomes were found in osteocytes and vascular endothelia of group B and group C. Osteocytes of group B crimpled and pyknosis or karyolysis of chromatin were observed in these osteocytes, nuclear membrane of the osteocytes was discontinous. Vascular endothelia became swollen and the cell junctions widened or were destroyed in groups A and B. The incidence of osteonecrosis in group B (88.9%) was higher than that in group C (22.2%, P < 0.05). There was no osteonecrosis occurred in groups A and D. Conclusion Methylprednisolone combined with lipopolysaccharide can induce typical rabbit model for early avascular necrosis of femoral head.