PROSTAGLANDIN E(1)-INDUCED HYPEROSTOSIS - CLINICOPATHOLOGICAL CORRELATIONS AND POSSIBLE PATHOGENETIC MECHANISMS

Prostaglandin E(1) (PGE(1)) causes skeletal hypertrophy, a Phenomenon noted when it is administered for several weeks to maintain ductus art eriosus patency in neonates with congenital heart disease. This effect , a dose-dependent and reversible hyperostosis, was described radiolog ically as bone within bone, but skeletal histopathology was not studie d. We compared postmortem gross, radiological, and histological bone f indings for untreated controls and term gestation infants after 4, 27, and 56 days of continuous 0.1-0.2 mu g/kg/min PGE(1). Bone was not si gnificantly different from controls after 4 days of PGE(1). Radiograph s were negative after 27 days, but femoral colter showed early periost eal osteoblast proliferation. At 56 days of PGE(1), there was severe, radiologically apparent neocortex formation in tubular, rib and scapul ar bones. Corresponding sections of femoral shaft revealed distinctive histopathology with thickened periosteum and fibrocartilage-like tiss ue covering an exuberant neocortex of closely aligned, gracile, woven bone trabeculae. Paratrabecular stroma contained ectatic capillaries o rthogonally oriented to the periosteum, suggesting that a vascular rea ction to PGE(1) is important in the observed effect. The native cortex was partially resolved; because it is stress shielded by the neocorte x and no inflammation was present, this was interpreted as a secondary effect. We conclude that PGE(1)-associated paracortical bone hypertro phy is distinct from inflammatory processes and that its early stage m ay not be apparent radiologically. Moreover, the time course of PGE(1) -induced osteoblast proliferation and mineralization suggests that exp erimental use for 4-8 weeks may benefit conditions such as united frac tures.