Purpose: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD).
Methods: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae.
Results: 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812-3584) vs 1182 (235-2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: - 0.02 [- 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: - 2.06 [- 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo.
Conclusion: Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044.
Keywords: Arterial calcification; Bone mineral density; Cardiovascular disease; Randomized controlled clinical trial; Type 2 diabetes; Vitamin K.