Phytoestrogens, such as Glycinol, have recently gained significant attention as an alternative therapy for osteoporosis due to their structural similarity to estradiol and their bone-generating potential. METHODS AND RESULTS: The osteogenic effects of Glycinol were investigated in human bone marrow mesenchymal stem cells (BMSCs) derived from older (>50 years old) and younger subjects (<25 years old). BMSCs isolated from older donors demonstrated reduced osteogenesis. 17β-estradiol and Glycinol exposure rescued the age-related reduction in osteogenic differentiation of BMSCs. These results correlated with the induction of osteogenic genes and estrogen receptor-α (ER-α) following Glycinol treatment. ER antagonist studies further support that Glycinol promotes osteogenesis through ER signaling. CONCLUSIONS: The results from these studies support investigating Glycinol as a potential preventive or treatment for osteoporosis.