**8. Conclusion**

replacement was confirmed in a randomized trial in women on continuous dialysis, receiving hormone therapy (estradiol and cyclic norethisterone) for 1 year. At the end of the study, the active group showed an increase in bone mineral density at the lumbar spine. This difference between the active and control group (receiving cinacalcet) was significant at all measure‐ ment sites [67]. Active vitamin D analogs, calcimimetics administration and phosphate‐binders are widely used to suppress iPTH and thus bone specific alkaline phosphatase, as a marker of

Kohlmeier et al. were the first to show an independent association between serum concentra‐ tion of phylloquinone <1.2 nmol/l or less (poor vitamin K status) and an increased risk of bone fracture in patients with end‐stage renal disease [68]. This observation was confirmed by Fusaro et al. [69] in 2013, showing that hemodialysis patients treated by warfarin for longer than 1 year had an increased risk of vertebral fractures, compared with patients not on warfarin. McCabe et al. enrolling 172, stage 3–5 CKD patients without dialysis treatment, showed that intake of vitamin K was insufficient in more than 50–60% of individuals on a given diet, if measures of ucOC were conducted (>20% ucOC), and 97% if evaluation was done by the prothrombin induced by vitamin K absence‐II (PIVKA‐II) assessment (>2 nmol/l) [70, 71]. After establishment of dialysis as a therapeutic intervention, Cranenburg et al. showed in a study of 40 chronic hemodialysis patients from 2012 that the dietary intake of vitamin K1 and K2, in general, was insufficient. This was reflected by analyses of plasma levels of desphospho‐ undercarboxylated (dp‐uc) MGP (matrix‐GLA protein), which was increased over the normal range by some 82.5% with elevated PIVKA‐II values 3.81.4–12.4 ng/ml, reference value <2 ng/ ml. [72]. Elevated dp‐ucMGP levels suggest insufficient vitamin K2 levels on the vascular site,

A 6 weeks randomized controlled trial on hemodialysis patients evaluated the response of biomarkers of vitamin K status (dp‐ucMGP, PIVKA‐II and ucOC) to the ingestion of 45, 135, 360 μg/day of MK‐7. The study confirmed that most patients displayed a functional deficiency at baseline, and that MK‐7 supplementation decreased dp‐ucMGP and PIVKA‐II. However,

In osteoporosis, the main treatment aims at inhibiting osteoclastic bone resorption. The osteoclast and osteoblast are functionally tightly coupled, and the mechanism of this reciprocal link is now very well known. By the discovery of MK‐7, which is able to play a role in the prevention of bone loss from most sites of the skeleton, there is hope for efficient treatment. MK‐7 has been shown to stimulate osteoblastic bone formation, as well as suppressing osteoclastic bone resorption *in vitro* and in humans, as showed by Knapen et al. [57]. MK‐7 suppresses the activation of NF‐κB signaling pathways in both osteoblasts and osteoclasts. These treatments have not yet been enrolled side by side with vitamin D analogs in CKD patients. Unfortunately, vitamin K2 is rare in Western diets, but in CKD patients, vitamin K2 levels are very low due to recommended restriction of potassium and phosphate in the diet.

New trials enrolling CKD and chronic dialysis patients treated with MK‐7 supplementation are presently being conducted to fully evaluate the effect of MK‐7 on atherosclerosis and bone

while high ucOC reflects insufficient vitamin K2 on bone or osseous sites.

only the highest doses brought about a significant decrease in ucOC [73].

enhanced bone turnover.

116 Vitamin K2 - Vital for Health and Wellbeing

mineral density.

In the near future, the dose, bioavailability and potency of the vitamin K2 subfamily member menaquinone MK‐7, will most probably make it possible to improve on the bone building process, yielding enhanced bone strength and resilience in several bone‐losing patient categories, such as those suffering from osteoporosis of different etiologies, and patients presenting with low bone mass (osteopenia).
