The role of prostaglandins in bone in vivo.

Prostaglandins of the E series, primarily E2 and E1, have the greatest activity in bone. Following discovery of their potent ability to stimulate bone resorption in vitro, clinical investigations have placed prostaglandins at sites of localized bone resorption associated with inflammatory or space occupying lesions in vivo. These studies have shown that prostaglandin production at such sites may be increased by cytokines such as interleukin-1 but the mechanisms by which prostaglandins stimulate bone resorption are not yet known. Observation of periosteal bone formation in patients given, pharmacological doses of prostaglandin has led to investigation of its bone forming activity. Young, growing rats have increased metaphyseal bone formation and this is accompanied by increased periosteal and endocortical bone formation in older animals. In the mature animals there is a generalized activation of remodelling with increased formation in the remodeling cycle. This is also seen in oophorectomized rats and results in repletion of the lost bone in this model of osteoporosis. In animal models of localized disuse osteopenia, prostaglandins are found to be elevated at the site of bone loss and prostaglandin inhibitors at least partially protect against the exaggerated resorption that occurs. This is also seen in models of orthodontic tooth movement, periodontitis and osteomyelitis. Prostaglandin synthesis inhibitors have been shown to delay healing of bone and this has led to limitations on their use clinically in some situations. Exogenously administered prostaglandins have been found to enhance periosteal callus formation, but healing is not uniformly enhanced. Prostaglandins have also been associated with hypercalcemia in certain animal tumors that model human hypercalcemia of malignancy but are probably most important in this condition as mediators in the localized resorption of bone at tumor sites. These in vivo studies have shown that prostaglandins are involved with increases in both bone formation and bone resorption. In vitro studies have shown that prostaglandins stimulate osteoblasts as well as osteoclastic bone resorption but understanding these effects under in vivo conditions will require further investigation.