In this study, therapeutic effects of Vitamin K2, Raloxifene and their co-administration on bone, uterus, blood and weight profiles were investigated with an ovariectomized rat model. Forty Wistar rats were divided into five groups (n = 8): Raloxifene (R), Vitamin K2 (K), Raloxifene + Vitamin K2 (R + K), ovariectomized controls (OVX) and Sham-operated controls (Sham). Treatment began 3 months after ovariectomy. Vitamin K2 and Raloxifene were administered 30 and 1.5 mg/kg/day separately and in combination five times per week for 12 weeks. All treatment groups had significantly higher ultimate strength and energy absorption capacity (P < 0.05) than ovariectomized controls in both femur and tibia. Histological results showed that treatment groups had healthy lumen structure, whereas OVX had degeneration. Adverse effects which were seen in individual treatments (myometrium weakening in K, endometrium weakening in R, and ALP increase in group R) were not observed in the R + K group implying a synergistic effect of these two agents when they are co-administered. According to blood analysis, ALP values were significantly high in Raloxifene-only group (P < 0.0001). This effect is suppressed in the co-administered group. In summary, the groups R. K and R + K had significantly higher ultimate strength and less susceptibility to fracture than ovariectomized controls. In summation, Vitamin K2 treated groups (either in single or combined with Raloxifene) had considerable biomechanical performance and reproductive tissue profile indicating that this agent is prospectively effective in osteoporosis management. (C) 2011 Elsevier B.V. All rights reserved.