Mediators of bone resorption around implants.

An important cause of prosthetic loosening is bone resorption that results from the interaction of macrophages with implant surfaces and particulate debris. The mediators involved in this bone resorption were investigated in vitro. Medium conditioned by macrophages interacting with foreign materials was assayed for bone resorption stimulation and inhibition, and for prostaglandin E2 (PGE2). In some experiments, the medium was dialyzed, and in others indomethacin was added. Macrophages were found to release stimulators and inhibitors of bone resorption. The relative amount of these was variable. When macrophages interacted with foreign surfaces, their stimulatory effect was ten times their inhibitory effect. Further activation by phagocytosis caused a further 15-fold increase in stimulation, with no change in inhibition. It is probable that before macrophages encounter foreign materials their stimulatory and inhibitory effects are the same so that they do not cause net bone resorption. Important stimulatory and inhibitory mediators were not dialyzable and so were probably cytokines or possibly collagenase. Prostaglandins were neither important stimulators nor inhibitors. There was only enough PGE2 released to account for 2% of the bone resorption that was stimulated.