Pernicious anemia has recently been recognized as one of the risk factors for osteoporosis and bone fractures, but the underlying pathophysiologic mechanism is still unknown. To determine whether vitamin B12 has any direct effect on osteoblasts, we studied the effects of vitamin B12 on the proliferation and alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells (hBMSC) and UMR106 osteoblastic cells. Vitamin B12 at concentrations as low as 10(-12) mol/L significantly stimulated [3H]-thymidine incorporation in both types of cells, but concentrations higher than 10(-12) mol/L did not produce a greater effect. Vitamin B12 in the concentration range from 10(-12) to 10(-8) mol/L concentration-dependently increased alkaline phosphatase activity in both hBMSC and UMR106 cells. Based on these results, we suggest that a suppressed activity of osteoblasts may contribute to osteoporosis and fractures in patients with vitamin B12 deficiency.