Azithromycin suppresses human osteoclast formation and activity in vitro

Abstract

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.

Effect of Periodontal Debridement Plus Systemic Azithromycin v/s Periodontal Debridement as Unique Therapy in Subjects with Periodontitis: A Randomized Controlled Clinical Trial.

“…This coincides with some previous studies [16,26,27] that perceived a signi cant reduction of BoP in the AZM group at 3 and 6 months, unlike earlier results [13,18,20]. Accounting for the fact that BoP is considered a negative predictor [8], these results are consistent with those obtained for PPD since both indicate periodontal stability and are related to the anti-in ammatory role of azithromycin [10,12,25]. Furthermore, O'Rourke [5] suggested investigating the use of AZM as a complement to NSPT, especially in patients who did not achieve resolution of BoP and PPD.…”

“…Concerning CAL, although there was a reduction in this variable and CAL gain in both groups, being more evident in AZM group, no signi cant differences were observed (Table 2)..This is consistent with that reported by other researchers [8,10,13,19,23] who evaluated patients at 3 months post NSPT. It is thought that NSPT by itself is successful in the long term for most patients, since it generates a biocompatible surface that allows for periodontal repair [30].…”

“…The administration of azithromycin adjunctive to NSPT has led to different results depending on the baseline PPD [20]. Moreover, it has been demonstrated to be more effective in patients with severe periodontitis than in those who have a moderate manifestation [8,10,22,23]. Particularly, it was suggested there is a greater clinical bene t in the deeper initial pockets (≥ 6 mm) where in most cases, these sites need surgical treatment for their resolution, which could be modi ed with the application of AZM.…”

Clinical effect of azithromycin as an adjunct to non‐surgical treatment of chronic periodontitis: a meta‐analysis of randomized controlled clinical trials

“…Although systemic azithromycin is well known for its antibacterial properties, it has also been shown to possess additional anti‐inflammatory and immune‐modulating effects . By influencing the production of cytokines, it has a dampening effect on the proinflammatory response .…”

“…It is shown to be efficacious against periodontal pathogens, such as Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans . In addition, azithromycin has a direct suppressive effect on human osteoclast function in vitro . The use of adjunctive azithromycin in SRP may be effective for periodontal tissue regeneration .…”