Effect of Bisphosphonates on the Osteogenic Activity of Osteoprogenitor Cells Cultured on Titanium Surfaces

Purpose: This study investigated the effects of bisphosphonates, namely, alendronate and zoledronate, on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces at therapeutic doses in order to assess if altered osteoblastogenesis could compromise osseointegration and contribute to etiopathogenesis of painful disorders such as bisphosphonates-related osteonecrosis of the jaw (BRONJ) following implant placement. Materials and Methods: MC3T3-E1 Subclone 4 cells were utilized in this study. Therapeutic doses of alendronate and zoledronate were calculated based on reported peak plasma concentrations. The viability, proliferation, adhesion, and mineralization potential of cells was assessed using a LIVE/DEAD stain, alamarBlue assay, immunofluorescence microscopy, and Alizarin Red S staining, respectively. Results: Therapeutic doses of zoledronate negatively affected cell viability, whereas therapeutic doses of alendronate significantly enhanced cell differentiation and the amount of bone formation compared with the control. Conclusion: The findings of this study may provide some insight into the pathogenesis of BRONJ development following implant placement in patients treated with zoledronate and may have promising implications toward improved wound healing and osseointegration in patients treated with alendronate. Keywords: alendronate, bisphosphonates, dental implants, osseointegration, osteoblasts, zoledronate