Abstract
Bone is a dynamic tissue that undergoes constant remodeling, with removal by osteoclastic bone resorption and replacement via osteoblastic bone formation and mineralization. Deterioration of bone mass with aging leads to osteoporosis. Bisphosphonates are potent inhibitors of osteoclastic bone resorption. Genistein, an isoflavone, exerts a bone anabolic effect by suppressing osteoclastic bone resorption and stimulating osteoblastic bone formation. The present study was undertaken to investigate the anabolic effects of a combination of alendronate and genistein on osteoclastic differentiation. Preosteoclastic RAW267.4 cells were cultured with alendronate (0.1-100 µM) and/or genistein (0.1-100 µM) in vitro. Alendronate or genistein alone had no significant effect on the proliferation and death of RAW267.4 cells. Notably, the combination of the two agents was found to potently and synergistically repress the proliferation and death of RAW267.4 cells. Moreover, alendronate or genistein used separately at higher concentrations suppressed the osteoclastic differentiation of RAW267.4 cells induced by receptor activator of nuclear factor-κB ligand (RANKL) in vitro. However, combinations of the two agents (0.1-100 µM) synergistically suppressed the RANKL-induced osteoclastic differentiation. In conclusion, bisphosphonate and genistein combination therapy may provide a novel strategy for the prevention and treatment of osteoclastic bone resorption.