Involvement of platelet activation in experimental osteonecrosis in rabbits

Osteonecrosis (ON) was produced experimentally in rabbits by intravenous injection of platelet activating factor (PAF) in combination with lipopolysaccharides (LPS) on two occasions separated by a week-long interval. Eleven of 15 rabbits (73%), with administration of both LPS (50 microg/kg) and PAF (10 microg/kg), exhibited microcirculatory injuries including extravasation of erythrocytes into sinusoidal spaces and formation of microthrombi in arterioles near regions of erythrocyte extravasation. Seven of 15 rabbits (47%), which received both LPS (50 microg/kg) and PAF (10 microg/kg), exhibited necrosis of trabeculae and 8 of 15 (53%) exhibited bone marrow necrosis. In addition, PAF receptor antagonist (0.3 and 3.0 mg/kg) significantly reduced the incidence of trabecular necrosis (0%) in this model. The findings of the present study suggest that platelet activation may play an important role in inducible ON, and that suppression of platelet activation may contribute prevention of ON.