Bisphosphonate and statin: adverse effects of co-medication on wound healing in in vitro models of periodontal tissues

OBJECTIVE: Bisphosphonates and statins may influence wound healing and are frequently prescribed to the same patient group. Bisphosphonates may induce osteonecrosis of the jaw; however, little information is available on the cellular mechanisms and biological effects of co-medication in oral tissues. The aim was to assess the effects of alendronate and simvastatin, both alone and combined, on osteoblasts and gingival fibroblasts in vitro. STUDY DESIGN: Primary human gingival fibroblasts and primary human osteoblasts were incubated with alendronate (5 µM) and simvastatin (1, 5 or 10 µM), alone or combined, for up to 14 days. Cells were assessed for viability by measuring lactate dehydrogenase activity and caspase-3 concentration in the cell culture media. Migration and proliferation potential was assessed by scratch-wound assay. Secreted levels of cytokines/chemokines were measured using Luminex 200 multianalytic profiling. RESULTS: High concentrations of simvastatin, both alone and combined with alendronate, affected the proliferation/migration potential and reduced scratch closure. The same exposure induced near abolishment of secreted levels of cytokines affecting angiogenesis, such as VEGF, IL-6, IL-8, and MCP-1, however little effect was found on cell viability. CONCLUSION: High concentrations of simvastatin, alone or combined with alendronate, may have a negative impact on angiogenetic markers and cell migration/proliferation, affecting wound healing and growth.