Effects of the prostacyclin products, 6-keto prostaglandin E1 and 6-keto prostaglandin F1 alpha, on bone resorption in vitro.

Previous studies have suggested that prostacyclin (PGI2) can stimulate bone resorption in vitro. However, this effect required repeated administration, perhaps because PGI2 is rapidly degraded or converted to other products, including 6-keto prostaglandin F1 alpha (6K-PGF1 alpha) and possibly 6-keto prostaglandin E1 (6K-PGE1). We therefore tested the ability of 6K-PGF1 alpha and 6K-PGE1 to stimulate bone resorption as measured by the release of previously incorporated 45Ca from 19-day fetal rat long bone cultures and compared their effects with those of PGE1 and PGF1 alpha. As reported previously, PGE1 was the most potent of the monoenoic prostanoids. PGF1 alpha was somewhat less potent. Of the PGI2 products 6K-PGE1 was an effective stimulator, but less potent than PGE1 or PGF1 alpha. Thus, the potency ratios were approximately 100:10:1 for PGE1, PGF1 alpha and 6K-PGE1. In contrast, 6K-PGF1 alpha did not produce a maximal resorptive response and its effects were not dose-related. We conclude that 6K-PGE1 is an effective stimulator of bone resorption in vitro, while 6K-PGE1 alpha is only a partial agonist. The formation of these compounds might account for some of the effects of PGI2 reported previously.