Bone formation: Roles of genistein and daidzein

Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractures. Osteoporosis is most common in postmenopausal women, primarily due to the effects of hypoestrogenemia. In this chapter, the efficacy and mechanisms of action of phytoestrogens in promoting osteogenesis and the use of phytoestrogens as potential therapeutic agents for osteoporosis will be presented. Two phytoestrogens that have gained significant attention are daidzein and genistein. Overall, daidzein and genistein share many cellular effects to reverse the phenotypes observed in ovariectomized animals. Studies have shown that genistein effectively reduces the impacts of osteoporosis, while efficacy studies investigating daidzein have shown mixed results, which will be discussed. Several studies showed that daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. With regard to the molecular signaling that induces these phenotypic cell-specific effects, daidzein and genistein both act primarily through estrogen receptor dependent mechanisms at lower concentrations but may also act through different pathways at higher concentrations, which will be presented in this chapter. The importance of metabolites of daidzein and genistein and other phytoestrogens that may play a role in osteogenesis will also be addressed.