Dose-dependent effects of phytoestrogens on bone.

Phytoestrogens have the potential to maintain bone health and delay or prevent osteoporosis. This review focuses on their dose-dependent effects on bone and their possible mechanisms of action. Phytoestrogens exert biphasic dose-dependent effects on osteoblasts and osteoprogenitor cells, stimulating osteogenesis at low concentrations and inhibiting osteogenesis at high concentrations. They inhibit osteoclast formation and activity. Recent data show that the balance between estrogen receptors and peroxisome proliferator-activated receptors, which are dose-dependently activated by phytoestrogens, determines their biological effects on bone. This review provides a new understanding of the mechanism of action of phytoestrogens and could be important for future studies to find precise beneficial doses in vivo and in clinical trials.