Vitamin K2 is a known vitamin to promote post-translational modification of vitamin K-dependent protein such as osteocalcin and blood coagulation factors. The effects of vitamin K2 on cortical bone mineral density in osteoporosis has been shown in the phase III DBT trial which had been reported several years ago. However, until now there is no available data regarding to the effect of vitamin K2 on vertebral bone mineral density (LBMD) and on fracture prevention. Thus, a two years randomized open trial to examine the effects of vitamin K2 on LBMD and the fracture prevention in a total of 167 osteoporotic patients had been carried out. The LBMD in vitamin K2 treated group was maintained for 2 years while, that in the control group was deceased to -3% during 2 years observation. The vertebral fracture incidence in the control group was 0.212 +/- 0.038 events/year and that in the treated group was 0.098 +/- 0.029 (p = 0.0186). Vitamin K2 treated group showed significantly lower Glu-osteocalcin level suggesting that vitamin K2 contributed to increase in post-translational modification of osteocalcin. When the treated group was divided into two groups: Group 1 showed low serum Glu-osteocalcin level and Group 2 maintained high Glu-osteocalcin level despite vitamin K2 administration. The LBMD in group 1 significantly higher than that in the Group 2. This may indicate that sufficient tissue supply of vitamin K2 is the limiting factor to increase in LBMD. Furthermore, patients with Apo E4 phenotype showed less response in LBMD comparing to that in the patients without Apo E4. In conclusion, vitamin K2 is effective to maintain trabecular BMD in osteoporosis and effectively prevent future fracture. However, some part of the patients didn't respond to vitamin K2 treatment. Therefore, we have to develop the more practical way(s) to predict the effectiveness of vitamin K2 treatment in osteoporosis.