GOLD SALTS INHIBIT OSTEOCLASTIC BONE-RESORPTION IN-VITRO

Loss of bone mass is commonly associated with rheumatoid arthritis (RA ) and is increasingly considered to be due to the increased activity o f bone-resorbing osteoclasts. Gold salts such as auranofin (AF), aurot hioglucose (ATG) and aurothiomalate (ATM) have beneficial therapeutic effects in RA, hut their mechanisms(s) of action is not well understoo d. In the present study we have examined the effects of these 3 gold s alts on osteoclastic bone resorption in vitro, using the bone slice as say where bovine cortical bone slices are resorbed by osteoclasts disa ggregated from the long bones of neonatal rats. All 3 gold sails inhib ited osteoclastic bone resorption with IC50 values of AF = 0.1 mu g/ml , ATG and ATM = 1 mu g/ml. All 3 compounds caused 3 decreased survival of osteoclasts on bone slices at high concentrations indicating a cyt otoxic effect that was also observed in a cytotoxicity assay with oste oblast-like UMR-106 cells. Preincubation of bone slices with various c oncentrations of AF followed by extensive washing prior to use in the bone slice assay also resulted in an inhibition of bone resorption (IC 50 = 4 mu g/ml) and osteoclast survival on the bone slices preincubate d with high concentrations of AF was decreased. Since these effects we re obtained with therapeutic concentrations of gold salts, these resul ts indicate that inhibition of osteoclastic bone resorption by gold sa lts may, at least in part, account for their beneficial effects in RA.