Intraosseous infusion of prostaglandin E2 in the caprine tibia.

Abstract

We evaluated the effects of intraosseously administered prostaglandin E2 (PGE2) within the proximal metaphysis of the goat (caprine) tibia under intraosseous normotensive and hypertensive conditions. PGE2 was administered at 0.5 or 1.0 mg (1 ml vol) twice daily for 10 days via an Osteoport which had been surgically implanted within the proximal tibial metaphysis. Intraosseous hypertension was produced when venous outflow obstruction (VOO) was created by ligation of the popliteal vein, which drained the proximal tibia, and occlusion of the diaphyseal medullary space distally with bone cement. After VOO, the intraosseous pressure measured at the metaphysis increased significantly (p < 0.05) from a baseline mean of 14.9 +/- 4.2 mm Hg to 28.6 +/- 5.3 mm Hg. Serum radioimmunoassays indicated that VOO prolonged the venous drainage of PGE2 from the tibia after an infusion. Static histomorphometric analysis indicated a marked dose-dependent increase in new bone formation in all PGE2 groups at 30 days after the PGE2 infusion. Significant (p < 0.05) formation of new bone occurred, primarily at the subperiosteal and endocortical surfaces, and moderately increased the marrow cavity of cancellous new bone as compared with the VOO-only group and the controls. Bone remodeling indices were also increased by PGE2. The PGE2 infusion, combined with VOO, produced significantly more new bone formation than the PGE2 infusion alone. Intensive marrow fibrosis was associated with the active bone remodeling.