Effect of prostaglandin endoperoxides and metabolites on bone resorption in vitro

Abstract

PROSTAGLANDINS are potent bone resorbers¹ which have been implicated as mediators of bone loss and hypercalcaemia in disease^2–6, but the specific products in the pathway of prostaglandin synthesis and degradation which are responsible have not yet been identified in vivo. Although PGE₂ is the most potent stimulator of bone resorption among the prostaglandins thus far tested in vitro¹, in animal tumour models, the increase in immunoreactive PGE₂ concentrations does not correlate well with the development of hypercalcaemia². We therefore tested the early products of arachidonic acid metabolism via the cyclo-oxygenase pathway, the prostaglandin endoperoxides (PGG₂ and PGH₂) and some of the 13,14-dihydro (H-PGE₂ and Ha-PGE₂) and 15-keto-13,14-dihydro metabolites of prostaglandins (15K-H₂-PGE₂ and 15K-H-PGF_2α) for their effects on the release of previously incorporated ⁴⁵Ca from cultured foetal rat long bones. The endoperoxides were found to cause a rapid transient increase in the release of previously incorporated ⁴⁵Ca from bone, but did not stimulate prolonged resorption. H₂-PGE₂ and H₂-PGE₁ were almost as potent as the parent compounds. 15K-H₂-PGE₂ and 15K-H-PGF_2α were much less potent, but did stimulate resorption at 10⁻⁵ M.