The effects of prostaglandin E2 in rapidly growing rats: depressed longitudinal and radial growth and increased metaphyseal hard tissue mass.

The effects of 0, 0.3, 1.0, 3.0, or 6.0 mg of prostaglandin E2 (PGE2)/kg/day administered subcutaneously for 3 weeks to triple fluorochrome-labeled weanling rats are reported. Microradiographs and undecalcified sections of proximal tibiae, tibial shafts, and seventh caudal vertebrae were evaluated by static and dynamic bone histomorphometry techniques. Significant changes were observed only at higher dose levels. Proximal tibial longitudinal growth rates were depressed in doses of 1, 3, or 6 mg PGE2/kg/day. Growth plate thickness and the size of hypertrophic cartilage cells were decreased in animals given 3 and 6 mg of PGE2/kg/day, but the calculated rate of cartilage cell production was unaffected. At doses of 6 mg PGE2/kg/day, periosteal bone apposition rates between Day -1 and Day +19 in both the tibial shafts and caudal vertebral cortices were depressed by less than 25%. Cortical bone mass and endosteal bone apposition rates in the tibial shaft and caudal vertebrae were unaffected. Hard tissue mass in the secondary spongiosa of the proximal tibial metaphysis increased dramatically (28%, 44%, and 60%, respectively) in rats treated with 1, 3, or 6 mg PGE2/kg/day. In addition, the secondary spongiosa contained numerous islands of woven trabecular bone along with an increased number of trabeculae. The study demonstrates that high doses of PGE2 stimulate new woven trabecular bone production and depress longitudinal and radial growth in rapidly growing rats.