Osteonecrosis (ON) was produced experimentally in rabbits by intravenous in
jection of platelet activating factor (PAF) in combination with lipopolysac
charides (LPS) on two occasions separated by a week-long interval. Eleven o
f 15 rabbits (73%), with administration of both LPS (50 mug/kg) and PAF (10
mug/kg), exhibited microcirculatory injuries including extravasation of er
ythrocytes into sinusoidal spaces and formation of microthrombi in arteriol
es near regions of erythrocyte extravasation. Seven of 15 rabbits (47%), wh
ich received both LIPS (50 mug/kg) and PAF (10 mug/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 inc
idence of trabecular necrosis (0%) in this model. The findings of the prese
nt study suggest that platelet activation may play an important role in ind
ucible ON, and that suppression of platelet activation may contribute preve
ntion of ON.