text: BACKGROUND: The purpose of this study was to investigate the effects of the combination of vitex agnus castus extract, as a source of phytoestrogens, plus magnesium supplementation on osteogenic and angiogenic factors and callus formation in women with long bone fracture. MATERIAL AND METHODS: In a double-blind randomized placebo controlled trial, 64 women with long bone fracture, 20-45 years old, were randomly allocated to receive 1) one Agnugol tablet (4 mg dried fruit extract of vitex agnus castus) plus 250 mg magnesium oxide (VAC + Mg group (n = 10)), 2) one Agnugol tablet plus placebo (VAC group (n = 15)), 3) placebo plus 250 mg magnesium oxide (Mg group (n = 12)), or 4) placebo plus placebo (placebo group (n = 14)) per day for 8 weeks. At baseline and endpoint of the trial, serum alkaline phosphatase, osteocalcin, and vascular endothelial growth factor (VEGF) were measured together with radiological bone assessment. RESULTS: There were no significant differences in the characteristic aspects of concern between the four groups at baseline. Despite the increased level of alkaline phosphatase in the VAC group (188.33    16.27 to 240.40    21.49, P = 0.05), administration of VAC + Mg could not increase alkaline phosphatase activity. However, treatment with VAC + Mg significantly enhanced the osteocalcin level. The serum concentration of VEGF was increased in the VAC group (269.04    116.63 to 640.03    240.16, P < 0.05). Callus formation in the VAC + Mg group was higher than the other groups but the differences between the four groups were not significant (P = 0.39). No relevant side effect was observed in patients in each group. CONCLUSION: Our results suggest that administration of vitex agnus castus plus magnesium may promote fracture healing. However, more studies need to further explore the roles of vitex agnus castus in fracture repair processes.