Prostaglandins are potent bone resorbing agents, the most potent of those tested being prostaglandin E2. The labile prostanofd, prostacylin, is also capable of resorbing bone, but its potency is not known. The responsiveness of rat bone and bone tumour cell adenylate cyclase has been used to assess the relative efficacies of a wide range of stable and labile prostaglandins, their metabolites and analogues upon bone. Prostaglandins may be important local regulators in bone, and it will be critical, therefore, to define the precise action of prostaglandin-like molecules on bone cells. There is ample evidence for a role for prostaglandins in the pathogenesis of malignant hypercalcaemia in a number of animal tumour models. Evidence is also accumulating in human cancers, suggesting that prostaglandin production may be important in the establishment of osseous metastases, and in generating excessive resorption adjacent to metastatic deposits in bone, particularly in breast and renal cortical carcinomas. The nature of the responsible proslaglandin-like molecules is undetermined, and this needs to be investigated by defining the pathways of arachidonic acid metabolism in tumours. When this has been achieved, drug therapy can be directed at the appropriate enzyme activities. The current application of cyclo-oxygenase inhibitors in these clinical syndromes is of little benefit.
- Bone Resorption
- Prostaglandin Synthetase Inhibitors
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism