Comparison of the effects of auranofin, gold sodium thiomalate, and penicillamine on resorption of cultured fetal rat long bones.

We compared three antirheumatic agents: auranofin (Aur), gold sodium thiomalate (GST), and penicillamine (Pen) for their effect on resorption in control unstimulated cultures of fetal rat long bones and in cultures stimulated by parathyroid hormone (PTH), prostaglandin E2 (PGE2), and murine interleukin-1 (mIL-1). Aur (3 X 10(-6) M) and GST (10(-4) M) inhibited PTH-stimulated bone resorption by 39 and 42%, respectively. The same concentrations of Aur and GST inhibited PGE2-stimulated bones by 72 and 44, respectively, and mIL-1-stimulated bones by 74 and 50%, respectively. Pen (10(-4) M) was not effective against any of the stimulators. Dose-response curves showed that Aur was at least 10 times more potent than GST. Inhibition by Aur was sustained after removal of the drug, while there was full recovery from GST. Aur inhibited 3H-thymidine and 3H-proline incorporation into bones, while GST had no effect. Aur and GST decreased beta-glucuronidase activity to undetectable levels at five days of culture. Part of the therapeutic effectiveness of Aur and GST may reside in their ability to inhibit periarticular destruction by inhibiting PGE2- and IL-1-mediated osteoclastic bone resorption.