Miconazole inhibits receptor activator of nuclear factor-κB ligand-mediated osteoclast formation and function

Osteoclasts are responsible for bone erosion in diseases as diverse as osteoporosis, periodontitis, and rheumatoid arthritis. Antifungal products have received recent attention as potential therapeutic and preventative drugs in human disease. Since little is known about the action of miconazole, an antifungal imidazole, on bone metabolism, we investigated the effects of miconazole on osteoclast formation using mouse bone marrow macrophages (BMMs). Miconazole inhibited RANKL-induced osteoclast formation in a dose-dependent manner without cytotoxicity. Furthermore, miconazole inhibited the bone resorptive activity of osteoclasts. Miconazole suppressed RANKL-induced expression of c-Fos and NFATc1, two essential transcription factors for osteoclast differentiation. Miconazole seemed to inhibit osteoclast formation MAPK pathways as well as Blimp1 through MafB expression. Miconazole also inhibited RANKL-induced expression of the pro-inflammatory cytokines, COX-2 and iNOS. In accordance with the in vitro study, miconazole reduced lipopolysaccharide-induced osteoclast formation in vivo. Therefore, miconazole exerted an inhibitory effect on osteoclast formation in vitro and in vivo. It could be useful for the treatment of bone diseases associated with excessive bone resorption.