TY - JOUR

T1 - Vitamin K supplementation and bone mineral density in dialysis

T2 - results of the double-blind, randomised, placebo-controlled RenaKvit trial

AU - Levy-Schousboe, Karin

AU - Marckmann, Peter

AU - Frimodt-Møller, Marie

AU - Peters, Christian D.

AU - Kjaergaard, Krista D.

AU - Jensen, Jens D.

AU - Strandhave, Charlotte

AU - Sandstrom, Hanne

AU - Hitz, Mette F.

AU - Langdahl, Bente

AU - Vestergaard, Peter

AU - Brasen, Claus L.

AU - Schmedes, Anne

AU - Madsen, Jonna S.

AU - Jorgensen, Niklas R.

AU - Frokjaer, Jens B.

AU - Frandsen, Niels E.

AU - Petersen, Inge

AU - Hansen, Ditte

PY - 2023

Y1 - 2023

N2 - 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 mu g 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/cm(2) [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/cm(2) (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.

AB - 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 mu g 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/cm(2) [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/cm(2) (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.

KW - bone mineral density

KW - chronic kidney disease

KW - end-stage kidney disease

KW - menaquinone-7

KW - mineral and bone disorder

KW - HEMODIALYSIS-PATIENTS

KW - POSTMENOPAUSAL WOMEN

KW - REPLACEMENT THERAPY

KW - ELDERLY-MEN

KW - FRACTURE

KW - OSTEOCALCIN

KW - CLASSIFICATION

KW - TURNOVER

KW - GEOMETRY

KW - INDEXES

U2 - 10.1093/ndt/gfac315

DO - 10.1093/ndt/gfac315

M3 - Journal article

C2 - 36460034

VL - 38

SP - 2131

EP - 2142

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

ER -