Prostaglandins and hypercalcemia of cancer

The purpose of this article has been to briefly review the very convincing evidence that PGE is a bone-resorbing substance and that studies of two tumors that cause hypercalcemia in animals strongly indict PGE as the causative agent. The studies that have been reported from humans are less exhaustive for ethical reasons and consequently less conclusive. However, the three largest reported series of human dat have reported a total of 63 patients with this syndrome. Evidence for elevated endogenous PGE levels was found in 31 of these patients. All subjects with hypercalcemia and cancer did not respond to drugs that inhibit prostaglandin synthesis. However, it is important that there was a decrease in circulating calcium levels during therapy in all instances in which patients who had clear elevations of PGE were treated. Nonetheless, our understanding of the source and the role of PGE in hypercalcemia is far from complete. Moreover, the potential role of other products of arachidonic acid metabolism must be examined, as well as the interactions of arachidonic acid metabolites with substances such as osteoclast activating factor and others.