Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial

Abstract

Background Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis. Methods In a multicenter double-blind placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultra-distal, and total), femoral neck, lumbar spine (L1-L4), and whole body was assessed by Dual-energy X-ray Absorptiometry. Serum levels of vitamin K1 and MK-7, and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein, and Protein Induced by Vitamin K Absence-II were measured to assess vitamin K status. Results After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation (mean difference of changes relative to placebo -0.023 (95% CI (-0.039;-0.008)) g/cm2), whereas the decrease in lumbar spine BMD seen in the placebo group was prevented (mean difference of changes between groups 0.050 (95% CI (0.015;0.085)) g/cm2. No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7 supplemented participants. Conclusion Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis.

Efficacy of vitamin K on bone fragility: puzzling findings from which we should learn how to design a rigorous study

“…Results from a recent vitamin K intervention study in dialysis patients by Levy-Schousboe et al. published in this issue of NDT , should be interpreted against this background [ 16 ]. The investigators conducted a randomized placebo-controlled (RCT), double-blind study to evaluate the impact of vitamin K supplementation on BMD in dialysis patients.…”

“…MK supplementation reduced BMD loss at the lumbar spine but not at the femoral neck. VFs incidence and progression of vascular calcification, evaluated according to Kauppilla's method, did not differ between groups [ 16 ].…”