Macrolide antibiotics have been found to possess not only antimicrobial properties, but also modulate inflammation. In this review the multi-faceted properties of azithromycin are discussed. Due to the unique anti-inflammatory and antimicrobial properties, macrolides, and especially azithromycin, are currently used for a number of conditions which have both an inflammatory and microbial component. For the same reason, azithromycin may be of value as an adjunct in the management of periodontitis which, although driven by an infectious component, is largely a result of uncontrolled chronic inflammation.

Azithromycin is an antibiotic with anti‐inflammatory properties used as an adjunct to treat periodontitis, a common inflammatory mediated condition featuring pathologic alveolar bone resorption. This study aimed to determine the effect of azithromycin on human osteoclast formation and resorptive activity in vitro. Osteoclasts were generated from peripheral blood mononuclear cells stimulated with macrophage colony stimulating factor (M‐CSF) and receptor activator of nuclear factor kappa B (RANK) ligand. The effects of azithromycin at concentrations ranging from 0.5 to 40 µg/ml were tested. Osteoclast formation and activity, acidification, actin ring formation and expression of mRNA, and protein encoding for key osteoclast genes were assessed. The results demonstrated that azithromycin reduced osteoclast resorptive activity at all concentrations tested with osteoclast formation being significantly reduced at the higher concentrations (20 and 40 µg/ml). mRNA and protein expression of key osteoclast transcription factor Nuclear Factor of Activated T cells (NFATc1) was significantly reduced by azithromycin at later stages of osteoclast development (day 17). Azithromycin also reduced tumor necrosis factor receptor associated factor‐6 (TRAF6) mRNA expression at day 14, and cathepsin K mRNA expression at days 14 and 17. Integrin β3 and MMP‐9 mRNA expression was reduced by azithromycin at day 17 in osteoclasts cultured on dentine. The osteoclast proton pump did not appear to be affected by azithromycin, however formation of the actin ring cytoskeleton was inhibited. This study demonstrates that azithromycin inhibits human osteoclast function in vitro, which may account for at least some of the beneficial clinical effects observed with azithromycin treatment in periodontitis. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.