| Summary: | Introduction Osteonecrosis of the jaws is a potential complication of bisphosphonate therapy. The underlying mechanism(s) remain unclear. While most research has concentrated on the effects of bisphosphonates on osteoclast and osteoblast function, the disease is diagnosed and classified on the basis of mucosal breakdown, suggesting that oral soft tissues may be involved in its pathogenesis. Aims To determine the effect of three different bisphosphonate drugs (aledronate, zoledronate and clodronate) on the function of oral keratinocytes and fibroblasts. Methods 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 co-culture model using keratinocytes and fibroblasts, which recapitulates the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation. Results The three bisphosphonates affected the viability and proliferation of OKF6 and HFFF2 cells at concentrations in keeping with their known relative in vitro potencies. There was no effect on cell migration or tissue architecture in organotypic cultures at subtoxic concentrations. Discussion The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that bisphosphonate related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility.
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