Effects of bisphosphonates on alkaline phosphatase activity, mineralization, and prostaglandin E(2) synthesis in the clonal osteoblast-like cell line MC3T3-E1

The effects of 3 bisphosphonates, AHBuBP, AHPrBP, and Cl(2)MBP on cell growth, alkaline phosphatase (ALP) activity, mineralization, and prostaglandin E(2) (PGE(2)) synthesis in the clonal osteoblast-like cell line MC3T3-E1 were studied. These bisphosphonates had essentially similar effects on growth and the osteoblastic functions of the cells, i.e., they had no inhibitory effects on cell growth except at higher concentrations, they increased ALP activity, and inhibited PGE(2) production. In the presence of AHBuBP, ALP activity was higher than that in the control after day 6 of culture. Lower concentrations of AHBuBP slightly facilitated mineralization by the cells. It is probable that bisphosphonates enhance the functions of osteoblasts in certain concentration and that the inhibition of endogenous PGE(2) production may be involved in the mechanism of action of bisphosphonates.