vitamin-k-1 and Calcinosis

Vitamin K denotes a group of lipophilic vitamins determining post-translational modification of proteins. There are 2 main forms of vitamin K: vitamin K1 (phylloquinone, found in vegetables); vitamin K2 (menaquinone, produced by bacteria in the intestine and in fermented foods). Vitamin K stores are limited in humans, but it can be recycled. Vitamin K1 is principally transported to the liver, regulating the production of coagulation factors. Vitamin K2, instead, is also transported to extra-hepatic tissues, such as bone and arteries, regulating the activity of matrix Gla-protein (MGP) and osteocalcin [bone Gla-protein (BGP)]. In patients with chronic kidney disease (CKD), cardiovascular mortality is the first cause of death. Some pathogenetic mechanisms of vascular calcification (such as hyperparathyroidism, hyperphosphatemia, hypercalcemia, role of vitamin D) have been widely investigated, but the potential role of vitamin K is still uncertain. Vitamin K could play a key role, as it transforms glutamic acid residues into γ-carboxyglutamic acid, through a carboxylation process, makings both MGP (cMGP) and BGP (cBGP) biologically active. cMGP inhibits vascular calcifications (VC), while cBGP has an important role for a proper mineralization process. Uncarboxylated MGP and BGP (ucMGP and ucBGP) concentrations are indirect markers of vitamin K2 deficiency. The purpose of this review is to analyze the current literature to understand the relationship between vitamin K2 status, fragility fractures and VC in CKD patients. This analysis could be of help in planning investigations of Vitamin K status and its possible supplementation in CKD patients to avert fragility fractures and VC.

Topics: Animals; Calcinosis; Fractures, Bone; Humans; Kidney Failure, Chronic; Molecular Structure; Osteocalcin; Renal Dialysis; Vitamin K 1; Vitamin K 2

The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the

Topics: Animals; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Atrial Fibrillation; Calcinosis; Cells, Cultured; Disease Models, Animal; Epigenesis, Genetic; Gene Expression Regulation; Genes, Reporter; Heart Valve Diseases; Humans; Male; Mice, Inbred C57BL; Promoter Regions, Genetic; Recombinant Proteins; Rheumatic Heart Disease; RNA Interference; Snail Family Transcription Factors; Sus scrofa; Tumor Suppressor Protein p53; Vitamin K 1; Warfarin

A high dietary intake of vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) is thought to decrease cardiovascular disease risk by reducing vascular calcification. The objective of this study is to explore if there is a relationship between phylloquinone and menaquinones intake and risk of PAD.. We investigated the association between intake of phylloquinone and menaquinones with PAD in a prospective cohort with 36,629 participants. Occurrence of PAD was obtained by linkage to national registries. Baseline intake of phylloquinone and menaquinones was estimated using a validated food-frequency questionnaire. Multivariate Cox regression was used to estimate adjusted hazard ratio's for the association.. During 12.1 years (standard deviation 2.1 years) of follow-up, 489 incident cases of PAD were documented. Menaquinones intake was associated with a reduced risk of PAD with a hazard ratio (HR) of 0.71, 95% CI; 0.53-0.95 for the highest versus lowest quartile. A stronger association was observed (p interaction 0.0001) in participants with hypertension (HRQ4 versus Q1 0.59; 95% CI 0.39-0.87) or diabetes (HRQ4 versus Q1 0.56; 95% CI 0.18-1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk.. High intake of menaquinones was associated with a reduced risk of PAD, at least in hypertensive participants. High intake of phylloquinone was not associated with a reduced risk of PAD.

Topics: Adult; Aged; Calcinosis; Diet; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Peripheral Arterial Disease; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Surveys and Questionnaires; Vitamin K; Vitamin K 1; Vitamin K 2; Young Adult

In chronic kidney disease, vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein, are largely uncarboxylated indicating that functional vitamin K deficiency may contribute to uremic vascular calcification. Since the effects of uremia on the vitamin K cycle are unknown, we investigated the influence of uremia and vitamin K supplementation on the activity of the vitamin K cycle and extraosseous calcification. Uremia was induced in rats by an adenine-supplemented diet and vitamin K1 or K2 was administered over 4 and 7 weeks. After 4 weeks of adenine diet, the activity of the vitamin K cycle enzyme γ-carboxylase but not the activities of DT-diaphorase or vitamin K epoxide reductase were reduced. Serum levels of undercarboxylated matrix Gla protein increased, indicating functional vitamin K deficiency. There was no light microscopy-detectable calcification at this stage but chemically determined aortic and renal calcium content was increased. Vitamin K treatment reduced aortic and renal calcium content after 4 weeks. Seven weeks of uremia induced overt calcification in the aorta, heart, and kidneys; however, addition of vitamin K restored intrarenal γ-carboxylase activity and overstimulated it in the liver along with reducing heart and kidney calcification. Thus, uremic vitamin K deficiency may partially result from a reduction of the γ-carboxylase activity which possibly contributes to calcification. Pharmacological vitamin K supplementation restored the vitamin K cycle and slowed development of soft tissue calcification in experimental uremia.

Topics: Animals; Aorta; Calcinosis; Calcium-Binding Proteins; Carbon-Carbon Ligases; Extracellular Matrix Proteins; Kidney; Liver; Male; Matrix Gla Protein; NAD(P)H Dehydrogenase (Quinone); Rats; Rats, Wistar; Uremia; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

Topics: Calcinosis; Coronary Artery Disease; Diet; Factor Xa Inhibitors; Humans; Male; Middle Aged; Monckeberg Medial Calcific Sclerosis; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Warfarin

Eicosapentaenoic acid (EPA), a major n-3 polyunsaturated fatty acid, is reported to have various protective effects for cardiovascular disease. However, few studies have focused on the influence of EPA on vascular calcification.. Arterial medial calcification (AMC) was induced by administering warfarin (3 mg/g food) and vitamin K1 (1.5 mg/g food) for 2 weeks in Sprague-Dawley rats (control group), and EPA (1 g/kg/day) was administered for 2 weeks simultaneously with warfarin and vitamin K1 (EPA group) or after initiation of AMC (late EPA group). EPA showed a marked reduction of medial calcification in the EPA group, and showed a similar effect in the late EPA group. Immunohistochemical and RT-PCR analyses showed that EPA lowered the expression of osteogenetic markers, such as osteopontin, alkaline phosphatase and core binding factor-α1 in the aorta. Significant migration of macrophages with expression of matrix-metalloproteinase (MMP)-2 or MMP-9 was observed in the aortic adventitia around calcification. EPA also reduced macrophage infiltration, MMP-9 expression as well as gene expression of monocyte chemotactic protein (MCP)-1.. These observations indicate that EPA attenuates arterial medial calcification through an effect associated with the suppression of MMP-9 activity and inhibition of macrophage infiltration as well as osteogenic protein expression in warfarin-induced rat models.

Topics: Animals; Aorta; Calcinosis; Chemokine CCL2; Eicosapentaenoic Acid; Iliac Artery; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Vitamin K 1; Warfarin

Matrix Gla protein (MGP) is a small vitamin K-dependent protein containing five gamma-carboxyglutamic acid (Gla) residues that are believed to be important in binding Ca(2+), calcium crystals and bone morphogenetic protein. In addition, MGP contains phosphorylated serine residues that may further regulate its activity. In vivo, MGP has been shown to be a potent inhibitor of vascular calcification; however, the precise molecular mechanism underlying the function of MGP is not yet fully understood.. We investigated the effects of MGP in human vascular smooth muscle cell (VSMC) monolayers that undergo calcification after exposure to an increase in Ca(2+) concentration. Increased calcium salt deposition was found in cells treated with the vitamin K antagonist warfarin as compared to controls, whereas cells treated with vitamin K(1) showed decreased calcification as compared to controls. With conformation-specific antibodies, it was confirmed that warfarin treatment of VSMCs resulted in uncarboxylated (Gla-deficient) MGP. To specifically test the effects of MGP on VSMC calcification, we used full-length synthetic MGP and MGP-derived peptides representing various domains in MGP. Full length MGP, the gamma-carboxylated motif (Gla) (amino acids 35-54) and the phosphorylated serine motif (amino acids 3-15) inhibited calcification. Furthermore, we showed that the peptides were not taken up by VSMCs but bound to the cell surface and to vesicle-like structures.. These data demonstrate that both gamma-glutamyl carboxylation and serine phosphorylation of MGP contribute to its function as a calcification inhibitor and that MGP may inhibit calcification via binding to VSMC-derived vesicles.

Topics: 1-Carboxyglutamic Acid; Adolescent; Adult; Amino Acid Sequence; Calcinosis; Calcium; Calcium-Binding Proteins; Cell Membrane; Cells, Cultured; Extracellular Matrix Proteins; Female; Humans; Male; Matrix Gla Protein; Middle Aged; Molecular Sequence Data; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Peptide Fragments; Phosphorylation; Protein Processing, Post-Translational; Protein Structure, Tertiary; Serine; Transport Vesicles; Vitamin K; Vitamin K 1; Warfarin

The activity of matrix Gla-protein (MGP), a potent inhibitor of vascular calcification, is dependent on carboxylation using vitamin K as a co-factor. In animals, low intake of total vitamin K has been shown to accelerate vascular calcification via the MGP mechanism. This has led to the hypothesis that low levels of dietary vitamin K intake may be a risk factor for accelerated vascular calcification in humans due to decreased MGP activity. Additionally, some authors have suggested that current recommended daily intake values for vitamin K might be insufficient to fully inhibit vascular calcification via the MGP mechanism. The aim of this study was to examine the relationship between dietary vitamin K1 (the most prevalent dietary form of vitamin K) intake and premature coronary artery calcification (CAC) in an asymptomatic screening population.. We conducted a prospective study of 807 consecutive active-duty US Army personnel, 39-45 years of age, without known coronary heart disease. Vitamin K1 intake was measured with the Block Dietary Questionnaire and CAC was identified using electron-beam computed tomography (EBCT).. We found no significant correlation between CAC score and vitamin K1 intake (r = 0.132, P = 0.106). Multivariate analysis with adjustment for cardiac risk factors showed no association between dietary vitamin K1 intake and CAC.. Dietary vitamin K1 (phylloquinone) intake appears to be unrelated to premature coronary calcification in a screening population. Further investigation into the relationship of vascular calcification and other forms of vitamin K1 (menaquinones) is indicated.

Topics: Adult; Calcinosis; Coronary Artery Disease; Female; Humans; Logistic Models; Male; Middle Aged; Military Personnel; Nutrition Surveys; Prospective Studies; Tomography, X-Ray Computed; Vitamin K 1

We sought to determine whether carbonic anhydrase (CA), which plays an important role in bone resorption, contributes to vascular mineral loss induced by an endothelin receptor antagonist.. Wistar rats were compared with rats receiving warfarin and vitamin K1 (WVK) for 8 weeks alone or in association with the endothelin receptor antagonist darusentan (30 mg/kg per day), the CA inhibitor acetazolamide (100 mg/kg per day), or both for the last 4 weeks. Rats were also treated with WVK for 5 or 6 weeks, and darusentan was added for the last week or last 2 weeks of treatment, respectively. Treatment with WVK produced medial elastocalcinosis in the aorta and carotid arteries. Immunohistochemistry revealed that CA II was already abundant in the adventitia and in calcified areas of aortic sections from WVK-treated rats. Darusentan did not significantly modify its abundance or distribution. In contrast, CA IV immunostaining, which was weak in WVK-treated rats, became apparent after 1 week of darusentan treatment and declined toward basal levels thereafter. These findings were confirmed by a parallel increase in CA IV protein abundance and activity in the aorta. The mineral loss induced by darusentan was blunted by acetazolamide treatment, confirming the functional relevance of the biochemical findings. Moreover, CA IV immunostaining was enhanced much later in the carotids, where darusentan did not cause regression of elastocalcinosis.. Vascular mineral loss induced by the blockade of endothelin receptors seems dependent on the activation of membrane-bound CA IV, suggesting that mineral loss may proceed via local changes in pH similar to that seen in bone resorption.

Topics: Animals; Aorta; Aortic Diseases; Calcinosis; Calcium; Carbonic Anhydrase II; Carbonic Anhydrase IV; Carotid Arteries; Endothelin Receptor Antagonists; Enzyme Activation; Hemodynamics; Male; Phenylpropionates; Pyrimidines; Rats; Rats, Wistar; Remission Induction; Vitamin K 1; Warfarin

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Topics: Aortic Diseases; Arteriosclerosis; Calcinosis; Cholesterol; Cholesterol, HDL; Coronary Disease; Diet; Energy Intake; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Netherlands; Odds Ratio; Prospective Studies; Risk Factors; Sex Characteristics; Vitamin K 1; Vitamin K 2

We have previously shown that an endothelin receptor antagonist can regress medial arterial calcification in a rat model. The aim of this study was to characterize the phenotypic changes of vascular smooth muscle cells during calcification and mineral loss, in order to understand better the underlying mechanisms. Control Wistar rats were compared with rats treated only with warfarin/ vitamin K1 (15 mg/kg per day) for 8 weeks, or in combination with darusentan (30 mg/kg per day) for the final 4 weeks. Vascular smooth muscle cell, bone cell and macrophage phenotypes were evaluated by the local expression of alpha-actin, tartrate-resistant acid phosphatase and ED-1, respectively. Proteins involved in the modulation of bone resorption like osteopontin and osteoprotegerin were also evaluated by immunohistochemistry. The warfarin/vitamin K1 treatment increased medial arterial calcification ninefold (P < 0.05). At sites of calcification, there was a decrease in alpha-actin localization, and an appearance of osteopontin immunostaining. Histochemical and immunostaining for osteoclast and macrophage markers, as well as for osteoprotegerin, were negative. Although the extent of calcification foci was reduced by darusentan, protein localization in the calcified areas was not modified. Thus, the development of medial arterial calcification produces a phenotypic change in vascular smooth muscle cells that does not appear to be normalized in regions remaining calcified during mineral loss.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Macrophages; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteoclasts; Osteopontin; Osteoprotegerin; Phenotype; Phenylpropionates; Pyrimidines; Rats; Rats, Wistar; Receptors, Endothelin; Vitamin K 1; Warfarin

Isolated systolic hypertension is the predominant form of hypertension in the elderly population. Reduction of arterial compliance appears to contribute to the elevation of pulse pressure (PP) and among potential mechanisms, gradual vascular calcification, fragmentation of elastic lamellae, and augmentation of rigid component like collagen could contribute to increase aortic stiffening. Few experimental models of the disease are currently available.. To induce large artery calcification, rats were treated with warfarin and vitamin K(1) (WK) for 4 and 8 weeks, to inhibit the maturation of matrix Gla protein. The impact of chronic PP elevation was determined on large artery and cardiac remodeling and on aortic endothelial function.. The WK treatment led to aortic medial calcification and a proportional elevation of PP, attributable mainly to a selective elevation of systolic blood pressure. The chronic treatment also increased collagen, whereas elastin decreased in the aorta. Pulse wave velocity, an index of aortic stiffening, increased in rats treated with WK. However, indices of left ventricular and aortic hypertrophy and remodeling remained normal. In addition, the WK treatment did not modify the vasoconstriction to norepinephrine and endothelin-1, and the vasodilatory response to acetylcholine and sodium nitroprusside.. Chronic treatment with WK represents a new model of isolated systolic hypertension with several characteristics of the human disease. The relative ease to induce calcification in this model may help to foster more fundamental research, which is lacking in this type of hypertension.

Topics: Animals; Anticoagulants; Antifibrinolytic Agents; Aorta; Calcinosis; Calcium; Collagen; Disease Models, Animal; Drug Administration Schedule; Elastin; Hemodynamics; Hypertension; Male; Rats; Rats, Wistar; Renin; Systole; Vascular Diseases; Vasomotor System; Vitamin K 1; Warfarin

To provide a rational basis for recommended daily allowances (RDA) of dietary phylloquinone (vitamin K1) and menaquinone (vitamin K2) intake that adequately supply extrahepatic (notably vascular) tissue requirements.. Vitamin K has a key function in the synthesis of at least two proteins involved in calcium and bone metabolism, namely osteocalcin and matrix Gla-protein (MGP). MGP was shown to be a strong inhibitor of vascular calcification. Present RDA values for vitamin K are based on the hepatic phylloquinone requirement for coagulation factor synthesis. Accumulating data suggest that extrahepatic tissues such as bone and vessel wall require higher dietary intakes and have a preference for menaquinone rather than for phylloquinone.. Tissue-specific vitamin K consumption under controlled intake was determined in warfarin-treated rats using the vitamin K-quinone/epoxide ratio as a measure for vitamin K consumption. Immunohistochemical analysis of human vascular material was performed using a monoclonal antibody against MGP. The same antibody was used for quantification of MGP levels in serum.. At least some extrahepatic tissues including the arterial vessel wall have a high preference for accumulating and using menaquinone rather than phylloquinone. Both intima and media sclerosis are associated with high tissue concentrations of MGP, with the most prominent accumulation at the interface between vascular tissue and calcified material. This was consistent with increased concentrations of circulating MGP in subjects with atherosclerosis and diabetes mellitus.. This is the first report demonstrating the association between MGP and vascular calcification. The hypothesis is put forward that undercarboxylation of MGP is a risk factor for vascular calcification and that the present RDA values are too low to ensure full carboxylation of MGP.

Topics: Arteriosclerosis; Calcinosis; Calcium; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Muscle, Smooth, Vascular; Osteocalcin; Vitamin K; Vitamin K 1

Sprague-Dawley rats were given daily subcutaneous doses of sodium warfarin (100 mg/kg) and vitamin K1 (10 mg/kg) for up to 12 weeks, starting on the day after birth. This dosing regimen creates an extrahepatic vitamin K deficiency while preserving the vitamin K-dependent processes of the liver. Control rats received either vitamin K1 only or were untreated. All rats survived without any signs of hemorrhage. The warfarin-treated rats developed a marked maxillonasal hypoplasia associated with a 11-13% reduction in the length of the nasal bones compared with controls. The length of the posterior part of the skull was not significantly different from controls. In the warfarin-treated rats, the septal cartilage of the nasal septum showed large areas of calcification, not present in controls, and abnormal calcium bridges in the epiphyseal cartilages of the vertebrae and long bones. The ectopic calcification in the septal cartilage may have been the cause of the reduced longitudinal growth of the nasal septum and the associated maxillonasal hypoplasia. It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K-dependent matrix gla protein in the embryo.

Topics: Animals; Animals, Newborn; Calcinosis; Cartilage Diseases; Female; Growth Plate; Male; Maxilla; Models, Biological; Nasal Bone; Nasal Septum; Rats; Rats, Sprague-Dawley; Skull; Species Specificity; Vitamin K 1; Vitamin K Deficiency; Warfarin

Vitamin K promotes the formation of gamma-carboxylated glutamic acid (Gla) residues within different protein classes such as vitamin K-dependent clotting factors, bone Gla-protein (BGP or osteocalcin), and atherocalcin. Gla-containing proteins have a high affinity for the Ca2+ ion. In addition to bone and atheromatous plaques they are also regularly found in ectopic calcifications, but not in uncalcified soft tissue. In the present study we investigate the possibility that vitamin K and BGP, in addition to previously recognized factors, may play a role in soft tissue calcification of chronic hemodialysis patients. Patients without radiovisible ectopic calcifications (group A) are compared to patients with such Ca deposits (group B). Both patient groups have comparable values of predialysis plasma Ca, P, alkaline phosphatases, parathyroid hormone (PTH) and 25 hydroxyvitamin D. The CaxP product is slightly higher in group B than in group A patients. Plasma vitamin K1 levels of group B patients are increased to more than twice the values observed in group A patients. Plasma BGP, even though not significantly different, shows a trend towards decreased levels in group B patients. A positive correlation exists between plasma vitamin K1 and BGP for patient group A alone, but not for group B alone. A correlation is also observed between plasma PTH and BGP (all patients) and between serum alkaline phosphatases and plasma BGP (all patients). Taken together, these results favor the hypothesis that in addition to an increased CaxP product a vitamin K excess may induce soft tissue calcification in hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Calcinosis; Calcium; Calcium-Binding Proteins; Connective Tissue Diseases; Female; Humans; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Renal Dialysis; Uremia; Vitamin K; Vitamin K 1