Cobinamide inhibits osteoclastogenesis and alveolar bone resorption in periodontitis.

PURPOSE: Periodontitis is an inflammatory disease of the hard and soft tissues surrounding the teeth and is initiated by bacterial biofilms. Severe alveolar bone resorption often occurs because of marked increases in osteoclast number and activity, which can ultimately lead to tooth loss. Recent evidence suggests that reactive oxygen species (ROS) may act as a common mediator of both osteoclastogenesis and inflammation. METHODS: We examined the effect of the potent antioxidant cobinamide, a vitamin B₁₂ derivative, on osteoclast differentiation from mouse bone marrow macrophage (BMM) precursors in culture and on bone resorption and inflammation in a mouse model of ligature-induced periodontitis. RESULTS: At submicromolar concentrations, cobinamide significantly reduced receptor activator of nuclear factor κB ligand-dependent differentiation of osteoclasts from mouse BMM precursors. In addition, cobinamide rapidly and almost completely abrogated ROS generation and Ca²⁺ oscillations in differentiating osteoclasts, both of which are essential for osteoclastogenesis. Local application of cobinamide in a hydrogel significantly reduced alveolar bone resorption in the ligature-induced periodontitis model, concomitant with a marked reduction in osteoclast number and activity. Furthermore, cobinamide prevented ligature-induced oxidative tissue damage while simultaneously reducing T-cell and macrophage recruitment and the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α. CONCLUSIONS: These results indicate that cobinamide has anti-osteoclastogenic and anti-inflammatory effects in periodontitis, suggesting its potential clinical utility.