Human oral keratinocytes (OKF6) and fetal foreskin fibroblasts (HFFF2) were exposed to each drug at several concentrations and the effect on cell proliferation was assessed by counting the viable cells after different lengths of treatment. The effect on cell migration was examined using Transwell migration assays. An organotypic coculture model using keratinocytes and fibroblasts, which recapitulated the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation.
The 3 BPs affected the viability and proliferation of OKF6 and HFFF2 cells at concentrations in keeping with their known relative in聽vitro potencies. There was no effect on cell migration or tissue architecture in organotypic cultures at subtoxic concentrations.
The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that BP-related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility.