Our recent report indicated that the crude extract from stem bark of Erythrina variegata L. (Leguminosae) (EV) exerted beneficial effects against osteoporosis induced by estrogen deficiency in vivo. Followup phytochemical study has isolated genistein-derivatives mainly in the form of prenylgenistein from this extract, including 6-prenylgenistein, 8-prenylgenistein, and 6, 8-diprenylgenistein. The present study was performed to investigate the structure-function relationship of these compounds on osteoblastic proliferation, differentiation and mineralization in UMR 106 cells. Our results showed that genistein did not stimulate cell growth while 8-prenylgenistein promoted cell growth significantly by 10$sim$23%. In contrast, the treatment by 6-prenylgenistein for 48 h reduced UMR 106 cell proliferation when compared to cells treated with genistein. The proliferation of 6,8-diprenylgenistein-treated cells was greater than those treated by 6-prenylgenistein at all testing concentrations. For ALP activity, significant increase was found in cells treated by either 8-prenylgenistein or 6,8-diprenylgenistein for 48 h at the concentration of $10^{-10}M$. In mineralization study, the content of Ca and P in extracellular matrix were significantly increased in 8-prenylgenistein treated cells. The results showed that genistein derivatives isolated from EV demonstrated stimulatory effects on osteogenesis in UMR 106 cells. Based on the study of structure-activity relationship, it appears that prenylation at C-8, but not at C-6, could increase the bone-protective effect of genistein.