Dose effects of corticosteroids on the development of osteonecrosis in rabbits.

OBJECTIVE: The relationship between dose of corticosteroids and the prevalence of osteonecrosis (ON) has not been established. We examined the dose effects of corticosteroids on the development of ON in a rabbit model. METHODS: Rabbits were injected once intramuscularly with 1 (12 rabbits), 5 (12 rabbits), 20 (20 rabbits), and 40 (25 rabbits) mg/kg of methylprednisolone acetate (MPSL) into the right gluteus medius muscle. Four weeks after the MPSL injection, the proximal and distal parts of both the femora and humeri were histopathologically examined for the presence of ON. Hematological examinations were performed before and after the corticosteroid injection. RESULTS: In rabbits with 1, 5, 20, and 40 mg/kg MPSL, the incidence of ON was 0, 42%, 70%, and 96%, respectively. The dose of MPSL showed a significant association with the incidence of ON. Histologically, reparative tissues around the ON sites were observed in the rabbits with 5 mg/kg MPSL, but not observed in rabbits with 20 and 40 mg/kg MPSL. On hematological examination, hyperlipidemia and thrombocytopenia were most apparent in the rabbits receiving 40 mg/kg MPSL. CONCLUSION: The study suggested that the dose of corticosteroids plays an important role in the development of ON in rabbits. The repair process was also found to be influenced by the dose of corticosteroids. Corticosteroid-induced hyperlipidemia and thrombocytopenia seemed to be associated with the incidence of ON.

Effects of tacrolimus (FK506) on the development of osteonecrosis in a rabbit model.

The present study examined the effects of tacrolimus (FK506) on the development of osteonecrosis in rabbits. In Experiment A, rabbits were given FK506, and also given a single dose of steroid. Control rabbits were given the same dose of steroid only. In Experiment B, rabbits were given FK506 and a reduced dose of steroid. The results showed that addition of FK506 did not change the number of rabbits with osteonecrosis when an identical steroid dose was given. When the steroid dose was reduced, the osteonecrosis incidence significantly decreased (p < 0.01). These results suggest that the clinically reported decrease in the osteonecrosis incidence following the introduction of FK506 is most likely attributable to the lower doses of steroids.

Effects of cyclosporin A on the development of osteonecrosis in rabbits.

BACKGROUND: Osteonecrosis (ON) of the femoral head is a serious complication in patients who have undergone organ transplantation. Introduction of cyclosporin A has resulted in lower-dosage steroid treatment and a decrease in the occurrence of ON. We examined the effect of cyclosporin A on the development of ON in rabbits. METHODS: In experiment A, rabbits were given cyclosporin A and 20 mg/kg methylprednisolone acetate. The control group was given 20 mg/kg methylprednisolone acetate only. Experiment B was then performed to mimic the clinical situation in which the use of cyclosporin A and lower steroid doses resulted in a decrease in occurrence of ON. In Experiment C, the effects of treatment with cyclosporin A only on development of ON were examined. 4 weeks after injection, bilateral femora and humeri were examined histopathologically for ON. RESULTS: Cyclosporin A increased the incidence of ON in rabbits when given in combination with steroid (p = 0.04). No ON lesions were observed in rabbits treated with cyclosporin A alone. INTERPRETATION: Our findings suggest that the clinically reported reduction in occurrence of ON following the use of cyclosporin A is probably attributable to the lower steroid doses used.

Brodie's abscess of the proximal femoral epiphysis in an adult woman with systemic lupus erythematosus.

We report an unusual case of pathologically proved femoral head Brodie's abscess mimicking avascular necrosis of bone in a 51-year-old woman with a 2-year history of corticosteroid treatment for systemic lupus erythematosus. On plain radiographs, a rounded lucency and thin sclerotic margins together with subchondral collapse and a lytic region were observed in the femoral head. The histopathologic examination revealed a central abscess formation surrounded by fibrous tissue with the aggregation of neutrophils and plasma cells. To our knowledge, this is the first case report describing a Brodie's abscess which had developed within the proximal femoral epiphysis in an adult.

Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats.

Rheumatoid arthritis (RA), a systemic inflammatory disease of unknown etiology, mainly affects synovial joints. Although angiogenic growth factors, including fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), may play a critical role in the development and progression of RA joint disease, little information is now available regarding their exact role in initiation and/or progression of RA. In this study, we show that both polypeptides were up-regulated in the rat joint synovial tissue of an adjuvant-induced model of arthritis (AIA), as well as human subjects with RA. FGF-2 overexpression via Sendai virus-mediated gene transfer significantly worsened clinical symptoms and signs of rat AIA, including hind paw swelling and radiological bone destruction, as well as histological findings based on inflammatory reaction, synovial angiogenesis, pannus formation, and osteocartilaginous destruction, associated with up-regulation of endogenous VEGF. FGF-2 gene transfer to non-AIA joints was without effect. These findings suggested that FGF-2 modulated disease progression, but did not affect initiation. Reverse experiments using anti-FGF-2-neutralizing rabbit IgG attenuated clinical symptoms and histopathological abnormalities of AIA joints. To our knowledge, this is the first report indicating direct in vivo evidence of disease-modulatory effects of FGF-2 in AIA, as probably associated with endogenous VEGF function. FGF-2 may prove to be a possible therapeutic target to treat subjects with RA.