In reply
We thank Tamura and colleagues for pointing out the existence of an unpublished trial carried out by Eisai Co, Ltd, which did not show any fracture prevention benefits of large doses (45mg/d) of vitamin K2 (menaquinone-4). For reasons outlined by Tamura et al, these results were not available to us, but it is clearly important that the results of this large trial should be shared with the scientific community. We also agree that there is a need to implement international standards for trial registration and transparency of reporting as outlined in the recent Ottawa statement.1 With regard to the comment by Tamura et al on the lack of effect on BMD seen in a recent US trial, possible countervailing factors are the healthiness of the cohort compared with the studies that we analyzed and the relatively short treatment period. As raised in Sugiyama's letter, another consideration is that BMD may not be the most sensitive surrogate outcome measure for vitamin K effects.