The Vessels-Bone Axis: Iliac Artery Calcifications, Vertebral Fractures and Vitamin K from VIKI Study

Abstract

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as >20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL; p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL; p < 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.

Prevalence and Correlates of Cardiovascular Calcification and Its Prognostic Effects Among Patients With Chronic Kidney Disease: Results From the C-STRIDE Study

“…Bone mineral disorders may infer conditions that foster VC, in turn, calcifying vessels may release several circulating factors which affect bone metabolism ( 18 ). Osteoporosis, fractures, and VC are highly prevalent in CKD patients and closely interrelated ( 19 ). This is particularly true for hemodialysis patients.…”

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

“…Moreover, in a cohort of 188 HD patients, patients with more severe degrees of VC as assessed by Adragao and total calcification score had significantly lower plasma dp-cMGP levels, whereas dp-ucMGP was not correlated with the extent of VC [ 72 ]. Fusaro et al conducted a multicenter, cross-sectional study (VIKI) that included 387 HD patients from eighteen Italian dialysis centers; they found that HD patients with calcification of the iliac arteries exhibited significantly decreased circulating levels of vitamin K2 and MK-7, while no difference was found regarding vitamin K1 and MK-4 levels [ 73 ]. Furthermore, a close link between vitamin K deficiency and calciphylaxis has been suggested as well.…”

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data

“…Similarly, women with CVD have been shown to have increased risk of FF [14]. Recently, a relationship between iliac arteries calcifications and abdominal aortic calcifications on one side and the risk for vertebral fractures on the other has been demonstrated in hemodialysis patients, even more so after adjusting for vitamin K, a major player both in bone and vascular health [15].…”