The effects of zoledronate on the survival and function of human osteoblast-like cells

Background: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. Methods: In the current study, we hypothesized that zoledronate (ZOL) at the mu M level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. Results: Our results revealed that ZOL treatment dose-and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 mu M (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 mu M. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the mu M level had no effects on osteogenic differentiation of osteoblasts. Conclusion: We concluded that ZOL at the mu M level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the mu M level on skeletal disorders need to be investigated and clarified in the future researches.