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 BMD (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 was associated with changes in bone density and structure and whether baseline vitamin K status modified 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 DXA, trabecular bone score, or volumetric BMD (vBMD) and bone architecture outcomes at the radius and tibia as assessed by peripheral QCT. 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. Clinical Trial Registration No.: NCT04573946 (ClinicalTrials.gov).