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Randomized Controlled Trial
. 2023 Sep 29;38(10):2131-2142.
doi: 10.1093/ndt/gfac315.

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

Karin Levy-Schousboe  1 , Peter Marckmann  2 , Marie Frimodt-Møller  3   4 , Christian D Peters  5 , Krista D Kjærgaard  5 , Jens D Jensen  5 , Charlotte Strandhave  6 , Hanne Sandstrøm  7 , Mette F Hitz  8   9 , Bente Langdahl  10   11 , Peter Vestergaard  12   13   14 , Claus L Brasen  15   16 , Anne Schmedes  15 , Jonna S Madsen  15   16 , Niklas R Jørgensen  9   17 , Jens B Frøkjær  14   18 , Niels E Frandsen  1 , Inge Petersen  19 , Ditte Hansen  4   9
Affiliations
Randomized Controlled Trial

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

Karin Levy-Schousboe et al. Nephrol Dial Transplant. .

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 multicentre, 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, ultradistal 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 g/cm2 [95% confidence interval (CI) -0.039 to -0.008]}, whereas the decrease in lumbar spine BMD seen in the placebo group was prevented [mean difference of changes between groups 0.050 g/cm2 (95% CI 0.015-0.085)]. 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.

Keywords: bone mineral density; chronic kidney disease; end-stage kidney disease; menaquinone-7; mineral and bone disorder.

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Conflict of interest statement

K.L.-S.’s salary was partially funded by Kappa Bioscience AS, the Danish Society of Nephrology and the Karen Elise Jensen Foundation during the RenaKvit trial. M.F.H. has received a research grant from Orkla Care AS. B.L. has received research grants from Amgen and honoraria for academic services from Amgen, UCB, Gilead, Astellas, AstraZeneca and Gedeon-Richter, unrelated to the RenaKvit trial. The remaining authors have nothing to declare.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
CONSORT flow diagram. GI, gastro intestinal; PTH, parathyroid hormone. aNumber of overall completing participants. bNumber of participants completing the 1/3 distal radius DXA (primary outcome).
Figure 2:
Figure 2:
Effects of 2-years of supplementation with vitamin K2 (MK-7, 360 μg daily) or placebo: Bone mineral density of the distal radius. Mixed effect model analysis of changes in bone mineral density of the distal radius. (A) The 1/3 distal radius. (B) Mid-distal radius. (C) Ultra-distal radius. (D) Total distal radius (n = 120baseline, 92year 1 and 62year 2). Variables are unadjusted and presented as mean and 95% confidence intervals (CI). Significant between-group differences *: P ≤ .005. BMD; bone mineral density.
Figure 3:
Figure 3:
Effects of 2-years of supplementation with vitamin K2 (MK-7, 360 μg daily) or placebo: Bone mineral density. Mixed effect model analysis of changes in bone mineral density. (A) Lumbar spine (n = 119baseline, 92year 1 and 62year 2). (B) Femoral neck (n = 118baseline, 91year 1 and 60year 2). (C) Whole body (n = 105baseline, 80year 1 and 55year 2). Variables are unadjusted and presented as mean and 95% confidence intervals (CI). Significant between group differences *: P ≤ 0.005. BMD, bone mineral density.
Figure 4:
Figure 4:
Effects of 2-year supplementation with vitamin K2 (MK-7, 360 μg daily) or placebo: Biochemical markers of vitamin K status. Mixed effect model analysis of changes in biochemical markers of vitamin K status. (A) vitamin K1 (n = 123baseline, 95year 1 and 65year 2). (B) MK-7 (n = 123baseline, 95year 1 and 65year 2). (C) total OC (n = 123baseline, 96year 1 and 60year 2). (D) dp-ucMGP (n = 123baseline, 96year 1 and 65year 2). (E) PIVKA-II (n = 122baseline, 96year 1 and 64year 2). Variables are unadjusted and presented as mean and 95% Confidence intervals (CI). Significant group differences (mean (95% CI)) at *P < .05, **P = 0.001, ***P < .001. dp-ucMGP, Dephosphorylated-uncarboxylated Matrix Gla Protein; MK-7, Menaquinone 7; P, Plasma; PIVKA-II, protein induced by vitamin K Absence-II; S, Serum.
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References

    1. Moe S, Drüeke T, Cunningham Jet al. . Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945–53. - PubMed
    1. Hansen D, Olesen JB, Gislason GHet al. . Risk of fracture in adults on renal replacement therapy: a Danish national cohort study. Nephrol Dial Transplant 2016;31:1654–62. - PubMed
    1. Tentori F, McCullough K, Kilpatrick RDet al. . High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int 2014;85:166–73. - PMC - PubMed
    1. Leonard MB, Wehrli FW, Ziolkowski SLet al. . A multi-imaging modality study of bone density, bone structure and the muscle - bone unit in end-stage renal disease. Bone 2019;127:271–9. - PubMed
    1. Iimori S, Mori Y, Akita Wet al. . Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-center cohort study. Nephrol Dial Transplant 2012;27:345–51. - PubMed

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