BISPHOSPHONATES IN BONE-CEMENT INHIBIT PMMA PARTICLE-INDUCED BONE-RESORPTION

Objective - Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previo usly been shown that macrophages, in response to polymethylmethacrylat e (PMMA) particles, differentiate into bone resorbing osteoclasts, and that this process is inhibited by a bisphosphonate, etidronate (EHDP) . The aim of this study was to determine whether incorporating EHDP in bone cement could reduce PMMA associated bone resorption. Methods - T wo concentrations of EHDP were mixed with PMMA monomer before polymeri sation, Particles of PMMA (1-10 mu m) were generated then added to mou se monocytes cocultured with UMR106 rat osteoblast-like cells and the extent of osteoclast differentiation was determined by assessing the e xtent of tartrate resistant acid phosphatase (TRAP) staining and measu ring the amount of lacunar bone resorption. Results - The addition of PMMA to monocyte-UMR106 cocultures resulted in a marked increase in th e number of TRAP positive osteoclast-like cells and a significant incr ease in the number of lacunar resorption pits compared with control cu ltures to which no particles had been added. After the addition of par ticles of PMMA + 20 mg EHDP, significantly fewer lacunar pits (p = 0.0 0006) and fewer TRAP positive cells were noted compared with coculture s containing PMMA particles alone. Conclusions - These results indicat e that by mixing a bisphosphonate with bone cement, it is possible to inhibit PRIMA particle induced bone resorption. This bisphosphonate in hibition of PMMA biomaterial wear particle containing macrophage-osteo clast differentiation and bone resorption may provide a possible thera peutic strategy to prevent or to control the osteolysis of aseptic loo sening.