THE INTERACTION OF THE MACROPHAGE AND THE OSTEOBLAST IN THE PATHOPHYSIOLOGY OF ASEPTIC LOOSENING OF JOINT REPLACEMENTS

Macrophage phagocytosis of cement particles with production of inflamm atory mediators is a component of the underlying mechanism of aseptic loosening of joint prostheses. Prostaglandin E2 (PGE2), a bone resorbi ng mediator, has been implicated in the loosening process. Investigati ons have shown that macrophage phagocytosis of cement particles leads to production of bone-resorbing mediators other than PGE2. In this stu dy, conditioned medium from macrophages exposed to crushed simplex cem ent particles stimulated osteoblasts to release radiolabeled arachidon ic acid and metabolites. Incubation of osteoblasts in conditioned medi um from macrophages exposed to cement particles small enough to be pha gocytized increased PGE2 release 80-fold over unexposed osteoblasts (P < 0.001). Incubation of osteoblasts in conditioned medium from macrop hages exposed to particles too large to be phagocytized, or to bone ce ment filtrate, did not stimulate PGE2 release. We propose that the rol e of the macrophage in aseptic loosening is primarily to recognize the mechanical failure of the cement mantle by phagocytosis of cement par ticles and subsequent production of small amounts of specific mediator s. These mediators stimulate surrounding osteoblasts to secrete PGE2, which then amplifies the inflammatory response and ultimately results in bone resorption and aseptic loosening.