Bisphosphonates inhibit IL-6 production by human osteoblast-like cells

Since bisphosphonates prevent bone loss in osteoporosis and rheumatoid arthritis, diseases in which the osteoclastogenic and inflammatory cytokine interleukin-6 plays a pathophysiologic role, we studied whether these drugs regulate the production of this cytokine by osteoblasts. Spontaneous and IL-1 + TNF-alpha stimulated IL-6 release was measured in supernatants of cultures of human osteoblastic osteosarcoma cells MG-63, pretreated for 4 hours with different doses of etidronate, clodronate or alendronate using a specific bioassay. Etidronate (from 10(-4) to 10(-8) M) or alendronate (From 10(-6) to 10(-11) M) inhibited in a dose-dependent manner the cytokine-induced IL-6 secretion (60 +/- 9.5% at 10(-5) M and 65 +/- 12% at 10(-7) M, respectively; p < 0.01). Though significant, the inhibitory effect of clodronate was less (35 +/- 7% at 10(-5) M, p < 0.05). These in vitro observations might have in vivo relevance in explaining at least in part the mechanisms by which bisphosphonates inhibit systemic and periarticular bone resorption.