Vitamin K2,
raloxifene, and
bisphosphonates, such as
etidronate,
alendronate, and
risedronate, are widely used in the treatment of
postmenopausal osteoporosis in Japan. A meta-analysis study has demonstrated the efficacy of anti-resorptive agents:
raloxifene and
etidronate have been shown to reduce the incidence of vertebral fractures, and
alendronate and
risedronate have been shown to reduce the incidence of both vertebral and
hip fractures. Furthermore, a report of the World Health Organization (WHO) has provided evidence from a randomized controlled trial suggesting that
vitamin K2, which may stimulate bone formation via gamma-carboxylation of
osteocalcin and/or
steroid and
xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Based on the weight of the currently available evidence, it is recommended that
alendronate and
risedronate, rather than
vitamin K2, should be chosen initially for the treatment of
postmenopausal osteoporosis, because these agents have been shown to be the most efficacious for reducing the incidence of both vertebral and
hip fractures among the current range of commercially available agents. However, the more potent anti-fracture efficacy of combined treatment with the anti-resorptive and commercially available
anabolic agents may need to be established. Some studies have shown that combined treatment with a
bisphosphonate and
vitamin K2 may be more effective than treatment with a
bisphosphonate alone in preventing vertebral fractures. On the other hand, the results of a preclinical study do suggest the possible efficacy of combined treatment with
vitamin K2 and
raloxifene in the prevention of vertebral and
hip fractures in postmenopausal women, although no clinical studies have reported on the effects of combined treatment with
vitamin K2 and
raloxifene in postmenopausal women with
osteoporosis.
Vitamin K deficiency, as indicated by high serum levels of undercarboxylated
osteocalcin, has been shown to contribute to the occurrence of
hip fractures in elderly women. Thus, we propose that the important role of
vitamin K2 used in combination with
bisphosphonates or
raloxifene should not be underestimated in the prevention of fractures in postmenopausal women with
osteoporosis with
vitamin K deficiency.