Effect of bisphosphonates on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces

Purpose: This study investigated the effects of bisphosphonates (BPs) namely Alendronate (ALN) and Zoledronate (ZA) 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 in etiopathogenesis of painful disorders like BPrelated Osteonecrosis of the Jaw (BRONJ) following implant placement. Materials and Methods: MC3T3-E1 Subclone 4 cells were utilised in this study. Therapeutic doses of ALN and ZA were calculated based off reported peak plasma concentrations. The viability, proliferation, adhesion, and mineralisation potential of cells was assessed using a LIVE/DEAD stain, alamarBlue® assay, immunofluorescence microscopy, and Alizarin Red S staining respectively. Results: Therapeutic doses of ZA negatively affected cell viability, whereas therapeutic doses of ALN significantly enhanced cell differentiation and the amount of bone formation compared to the control. Conclusions: The findings of this study may provide some insight into the pathogenesis of BRONJ developing following implant placement in patients treated with ZA and may have promising implications towards improved wound healing and osseointegration in patients treated with ALN