Long-term effects of bisphosphonates on mineralization of osteoblastic cell, MC3T3-E1

Bisphosphonates are potent inhibitors of bone resorption. Although the majority of studies have focused on the effects of bisphosphonates on osteoclasts, recent findings suggest that they may also have a direct action on osteoblasts. We studied the effects of long-term exposure to bisphosphonates, YM-529 and etidronate, on cell growth, alkaline phosphatase (ALP) activity and calcification of an osteoblastic cell line, MC3T3-E1 cells. The addition of 10-10M or 10-14M YM-529 increased the ALP activity in comparison with the control at 35 and 25 days after confluence respectively without marked effects on cell growth or appearance. The addition of 10-6M etidronate also increased the activity at 15 days after confluence. The result of calcium staining of the cells and matrices suggested that calcification was promoted at 35 days after confluence by exposure to 10-10 or 10-14M YM-529. These results suggest that proper concentrations of bisphosphonates promote calcification of osteoblastic cells and that bisphosphonates directly act on the function of osteoblasts as well as on osteoclasts.