DISCUSSION
uraemia, ESKD, BMD loss of the 1/3 distal radius, osteoarthritis, kidney impairment, fractures, arteriovenous fistula
URAEMIA, STILL, OSTEOARTHRITIS, RECRUITMENT, AORTIC CALCIFICATION
In the present randomised, double-blind, placebo-controlled trial, the effects on bone of daily supplementation with 360 µg vitamin K2 (MK-7) were compared with placebo in 123 patients receiving chronic dialysis treatment. In the ITT analysis, an accelerated BMD loss of the 1/3 distal radius was observed with MK-7 supplementation compared with placebo, whereas the decrease in lumbar spine BMD observed in the placebo-supplemented participants was prevented with MK-7. The RenaKvit trial is the first to investigate the effect of vitamin K supplementation on BMD in patients on dialysis treatment.Surprisingly, we found the primary outcome, BMD of the 1/3 distal radius, to decrease ≈3% after 2 years of MK-7 supplementation compared with placebo, whereas BMD of the remaining distal radius sites was unaffected. However, these findings could not be confirmed in per protocol analysis. This may be because the participants able to complete the study represent only a subgroup of participants not randomly distributed between the groups. It may also be due to a type 1 statistical error in the ITT analysis. Four randomised studies, all in postmenopausal women with no kidney impairment, have examined the 2-year effect of vitamin K supplementation on distal radius BMD. One open-labelled study in 396 Japanese women examined the 1/3 distal radius and found a reduced BMD loss with supplements of vitamin K2 (MK-4) compared with no treatment [BMD of the lumbar spine decreased in the placebo group to a similar extent as reported in a previous 2-year observational study in patients on dialysis [In postmenopausal women without kidney impairment, the influence of vitamin K on lumbar spine BMD varies. Whereas three neither blinded nor placebo-controlled Japanese randomised 2-year studies [BMD of the femoral neck decreased in both study groups after 2 years, although to a lesser extent with MK-7 supplementation and with borderline significance between treatments groups. Four randomised, controlled trials in elderly Caucasian populations without kidney impairment investigated the 3-year effect of vitamin K supplementation on BMD of the femoral neck. Two studies observed increased BMD with supplements of MK-7 [In ESKD, low BMD predicts fractures [Similar to our findings, MK-7 supplementation had contrasting effects on trabecular and cortical bone as assessed by high-resolution peripheral quantitative computed tomography in a 3-year study of Caucasian postmenopausal women [Vitamin D regulates the expression of OC and appropriate vitamin D status may therefore be of importance for the effects of vitamin K supplementation on bone [In accordance with other studies [Even though markers of bone turnover may be affected by ESKD [In uraemia, this absence of convincing beneficial effects of MK-7 supplementation on bone might be explained by the profound disturbances in vitamin K lipoprotein distribution and metabolism as recently discussed by Kaesler This study has strengths and limitations. Being a randomised, placebo-controlled, double-blind study, important biases were eliminated. Also, the high adherence to study supplementation demonstrated both by tablet counting and blood concentrations of MK-7 and PIVKA-II was an important strength.According to our power calculation, we aimed at including 2 × 70 participants. Due to challenged recruitment, unfortunately we ended up with only 61 + 62 participants. Furthermore, the dropout rate in year 2 was higher than anticipated. For these reasons, only 30 + 32 patients contributed with 2-year primary outcome data, a number somewhat lower than required according to the power calculations (2 × 49). Nonetheless, we managed to detect significant changes in the primary outcome variable. It is possible that a larger sample size and a longer trial duration would have demonstrated more convincing differences in the response between treatment groups, and even other significant differences in outcomes as well.Previous studies have reported worsening of BMD on the arteriovenous fistula arm [Lumbar spine BMD may be increased by osteoarthritis, compression fractures, severe aortic calcification, which is common in the dialysis population, and intestinal deposition of phosphate binders [Finally, we cannot exclude a more pronounced effect if a higher dosage of MK-7 had been used, if vitamin K1 had been supplemented [In conclusion, 2 years of vitamin K (MK-7) supplementation may modify BMD site-specifically in patients receiving dialysis treatment, in addition to improvement in functional vitamin K status. Still, our findings do not support MK-7 supplementation to preserve bone in patients with ESKD receiving dialysis treatment.