vitamin-k-semiquinone-radical and Hyperparathyroidism

Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

Topics: Calcium; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperparathyroidism; Osteocalcin; Phosphates; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Warfarin

Calcific arteriolopathy (CA), also known as " Calciphylaxis " describes a phenomenon of necrosis, mainly cutaneous and sometimes systemic, due to the obliteration of the arteriole's lumen. Initially there are under-intimal calcium deposits, and then the thrombosis occurs leading to the necrosis. CA affects mainly the renal insufficient hemodialysed patient, but not exclusively. We present 4 cases which illustrate well the etiologic spectrum of CA: terminal renal insufficiency, neoplasia, primary hyperparathyroidism, proteinuria, vitamin K inhibitors. We describe the AC's epidemiology, its cutaneous and systemic clinical presentations, its treatment. We make the hypothesis that CA is a strong risk marker in matter of cardiac mortality and we discuss this point.. In this article we describe the numerous breakthroughs that have been made in matter of research about calcification over the past few years: inhibitors of calcium phosphate deposition, vitamin D and PTH1R, protein-calcium complexes, cell death, induction of bone formation. These data are analysed from a clinical point of view with practical purposes. We present CA not only as a cutaneous disease but as a systemic pathology.. The CA epidemiology is an incentive to more diagnosis suspicion in front of organ infarct involving a patient likely to be concerned by CA. The scientific and therapeutic breakthroughs in matter of calcification enable a better prevention of the disease. Nevertheless it remains very difficult to cure when installed.

Topics: Aged; Arterioles; Biopsy; Calciphylaxis; Calcium; Coronary Artery Disease; Fatal Outcome; Female; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Neoplasms; Phosphates; Proteinuria; Skin; Vitamin K

Topics: Aged; Alkaline Phosphatase; Biomarkers; Bone Density; Calcium; Clinical Trials as Topic; Diphosphonates; Estrogen Replacement Therapy; Fractures, Bone; Humans; Hyperparathyroidism; Osteoporosis; Parathyroid Hormone; Selective Estrogen Receptor Modulators; Vitamin D; Vitamin K

Fat soluble vitamins (except vitamin K) are protein bounded with subsequent storage in the body. It is generally accepted that plasma level of vitamin A is increased in majority of patients with chronic renal insufficiency (CRI) including those on continuous ambulatory peritoneal dialysis (CAPD). Thus, there is no need to supplement this vitamin in CRI patients (pts). Plasma level of vitamin E in CRI pts may be elevated, normal or decreased. It seems to be justified to supplement this vitamin, in spite of its normal plasma level, in case platelet aggregation is increased. Both in dialyzed and nondialyzed CRI pts a normal serum level of vitamin K has been observed. Decreased or extremely low serum level of vitamin D following the gradual loss of renal tissue is to be observed in CRI pts. This deficit is regarded as the main factor leading to the decrease in serum level of calcium, the secondary hyperparathyroidism and bone changes. Treatment with 1.25(OH)2D3 (calcitriol) proved to be most successful in alleviation of symptoms resulting from the deficit of vitamin D3 in the body. Intravenous "pulsating" administration of calcitriol results in rapid normalization of serum PTH level. Treatment with 25(OH)D3 (calcidiol) given orally 3 times a week ("pulsating" method) revealed also fairly good results in this respect. During treatment with vitamin D3 hypercalcemia tends to develop, serum alkaline phosphatase normalizes, elevated PTH serum level decreases. Vitamin D metabolites are less active than 1.25(OH)2D3 being less hypercalcemic.

Topics: Avitaminosis; Calcitriol; Calcium; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Vitamin D; Vitamin E; Vitamin K

Topics: 1-Carboxyglutamic Acid; Adult; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteocalcin; Radioimmunoassay; Vitamin K

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer disease (AD), who are prone to falls and have osteoporosis. We previously found that vitamin K deficiency and low 25-hydroxyvitamin D (25-OHD) with compensatory hyperparathyroidism cause reduced bone mineral density (BMD) in female patients with AD. This may modifiable by intervention with menatetrenone (vitamin K2) and risedronate sodium; we address the possibility that treatment with menatetrenone, risedronate and calcium may reduce the incidence of nonvertebral fractures in elderly patients with AD. A total of 231 elderly patients with AD were randomly assigned to daily treatment with 45 mg of menatetrenone or a placebo combined with once weekly risedronate sodium, and followed up for 12 months. At baseline, patients of both groups showed high undercarboxylated osteocalcin (ucOC) and low 25-OHD insufficiency with compensatory hyperparathyroidism. During the study period, BMD in the treatment group increased by 5.7% and increased by 2.1% in the control group. Nonvertebral fractures occurred in 15 patients (10 hip fractures) in the control group and 5 patients (2 hip fractures) in the treatment group. The relative risk in the treatment group compared with the control group was 0.31 (95% confidence interval, 0.12-0.81). Elderly AD patients with hypovitaminosis K and D are at increased risk for hip fracture. The study medications were well tolerated with relatively few adverse events and effective in reducing the risk of a fracture in elderly patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Bone Density; Bone Density Conservation Agents; Etidronic Acid; Female; Hemostatics; Hip Fractures; Humans; Hyperparathyroidism; Male; Osteoporosis; Risedronic Acid; Vitamin D; Vitamin K; Vitamin K 2

We report a rapid, sensitive and reproducible method to measure free gamma-carboxyglutamic acid (GLA) in serum using precolumn derivatization with O-phthalaldehyde, reversed-phase chromatography and deproteinization of serum by ultrafiltration. Serum free GLA level in 62 healthy adults was 167 +/- 46 pmol/ml and was increased (302 +/- 195 pmol/ml) in 14 patients with primary hyper-parathyroidism, a disease characterized by an increased bone turnover. Peptide bound GLA averaged 413 pmol/ml. In rabbits receiving massive doses of warfarin during 6 days there was a time- and dose-dependent decrease of serum free GLA but a significant fraction was still measurable. These data indicate that free GLA circulates and originates both from the metabolism of the vitamin K-dependent clotting factors and from bone metabolism.

Topics: 1-Carboxyglutamic Acid; Animals; Bone and Bones; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Hyperparathyroidism; Male; Methods; Peptides; Protein Binding; Rabbits; Vitamin K; Warfarin

Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N = 9), primary hyperparathyroidism (N = 25), chronic renal failure (N = 20), and cancer involving bone (N = 5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.

Topics: Alkaline Phosphatase; Bone and Bones; Bone Diseases; Bone Neoplasms; Calcitonin; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteocalcin; Parathyroid Glands; Radioimmunoassay; Renal Dialysis; Vitamin K

Topics: Alkaline Phosphatase; Calcium; Ethanolamines; Humans; Hyperparathyroidism; Hypophosphatasia; Infant; Infant, Newborn; Male; Parathyroid Hormone; Prednisone; Vitamin K

Topics: Calcium; Calcium, Dietary; Celiac Disease; Diet; Diet Therapy; Drug Therapy; Glutens; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Osteitis Fibrosa Cystica; Potassium; Sprue, Tropical; Vitamin D; Vitamin K; Vitamins