Investigating the Interrelationship of Vitamin K and Vitamin D Status on Bone Density: Results from the VITamin D and OmegA-3 TriaL

Sufficient intake of both vitamin D and K may be necessary for bone health. Although the synthesis of osteocalcin (OC) is stimulated by vitamin D, OC needs to be carboxylated, or activated, by vitamin K to deposit calcium into bone. In the VITamin D and OmegA-3 TriaL (VITAL), there were no differences in 2-yr changes in areal bone mineral density (aBMD) at the spine, hip, or whole body in 771 U.S. participants (687 with follow-up data) randomized to supplemental vitamin D3 (2000 IU/d) vs. placebo. In this ancillary study, we investigated whether baseline vitamin K status is associated with changes in bone density and structure and whether baseline vitamin K status modifies the effects of supplemental vitamin D on aBMD changes. Higher baseline vitamin K status, as assessed by blood levels of phylloquinone, percent undercarboxylated OC, and dephosphorylated undercarboxylated matrix Gla protein, was not associated with favorable 2-yr changes in aBMD at the spine, hip, or whole body as assessed by dual energy x-ray absorptiometry; Trabecular Bone Score; or volumetric BMD (vBMD) and bone architecture outcomes at the radius and tibia as assessed by peripheral quantitative computed tomography. The effects of supplemental vitamin D on aBMD were not modified by baseline measures of vitamin K. In VITAL, higher vitamin K status, even when accompanied by supplemental vitamin D, did not prevent bone loss.