The effects of bisphosphonates on osteoblasts in vitro

Objective. The purpose of this study was to test the effects of bisphosphonates on osteoblast viability and function. Study design. Primary rat osteoblasts were cultured in normal media or media containing increasing concentrations of 2 bisphosphonates, alendronate and zoledronate. Enzyme-linked immunoabsorbent assays (ELISAs) were used to measure interleukin (IL)-6, transforming growth factor (TGF) beta 1, and receptor activator of nuclear factor kappa B ligand (RANKL) expression in supernatants after 24, 48, and 72 h. Live and necrotic cell numbers were assessed with trypan blue assays. Results. As drug concentrations increased, cell viability decreased significantly. The ELISAs revealed significant increases in TGF-beta 1 in treatment groups, but no significant change in RANKL or IL-6. Conclusions. High concentrations of alendronate and zoledronate were cytotoxic, decreasing cell viability at 72 h. Transforming growth factor beta 1 increased even as viability decreased, suggesting a mechanism for bisphosphonate action. These data suggest that lower concentrations of bisphosphonates may have therapeutic benefits without the cytotoxic effects which may result in osteonecrosis.