Gold salts inhibit osteoclastic bone resorption in vitro

Abstract

Loss of bone mass is commonly associated with rheumatoid arthritis (RA) and is increasingly considered to be due to the increased activity of bone-resorbing osteoclasts. Gold salts such as auranofin (AF), aurothioglucose (ATG) and aurothiomalate (ATM) have beneficial therapeutic effects in RA, but their mechanisms(s) of action is not well understood. In the present study we have examined the effects of these 3 gold salts on osteoclastic bone resorption in vitro, using the bone slice assay where bovine cortical bone slices are resorbed by osteoclasts disaggregated from the long bones of neonatal rats. All 3 gold salts inhibited osteoclastic bone resorption with IC50 values of AF = 0.1 microgram/ml, ATG and ATM = 1 microgram/ml. All 3 compounds caused a decreased survival of osteoclasts on bone slices at high concentrations indicating a cytotoxic effect that was also observed in a cytotoxicity assay with osteoblast-like UMR-106 cells. Preincubation of bone slices with various concentrations of AF followed by extensive washing prior to use in the bone slice assay also resulted in an inhibition of bone resorption (IC50 = 4 micrograms/ml) and osteoclast survival on the bone slices preincubated with high concentrations of AF was decreased. Since these effects were obtained with therapeutic concentrations of gold salts, these results indicate that inhibition of osteoclastic bone resorption by gold salts may, at least in part, account for their beneficial effects in RA.