vitamin-k-semiquinone-radical and Bone-Diseases

Vitamins D and K are lipid-phase nutrients that are pleiotropic - endowed with versatile homeostatic capacities at the organ, tissue, and cellular levels. Their metabolic and physiologic roles overlap considerably, as evidenced in the bone and cardiovascular systems. Vitamin D₃ (cholecalciferol, D₃) is the prehormone for the vitamin D endocrine system. Vitamin D₃ undergoes initial enzymatic conversion to 25-hydroxyvitamin D (25D, calcidiol), then to the seco-steroid hormone 1alpha, 25-dihydroxyvitamin D (1,25D, calcitriol). Beyond its endocrine roles in calcium homeostasis, 1,25D likely has autocrine, paracrine, and intracrine effects. At least 17 tissues likely synthesize 1,25D, and 35 carry the vitamin D receptor (VDR). Vitamin D functional deficiency is widespread in human populations. Vitamin K₁ (phylloquinone) is more abundant in foods but less bioactive than the vitamin K₂ menaquinones (especially MK-4, menatetrenone). Menadione (vitamin K₃) has minimal K activity. Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically re-reduced. Warfarin inhibits this vitamin K reduction, necessitating K supplementation during anticoagulation therapy. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, facilitate bone mineralization, inhibit vessel wall calcification, support endothelial integrity, are involved in cell growth control and tissue renewal, and have numerous other effects. This review updates vitamin D and K skeletal and cardiovascular benefits and evidence for their synergy of action.

Topics: Bone and Bones; Bone Density; Bone Diseases; Calcification, Physiologic; Cardiovascular Diseases; Cardiovascular System; Cholecalciferol; Fractures, Bone; Humans; Nutritional Physiological Phenomena; Osteoblasts; Osteocytes; Vitamin D Deficiency; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; Vitamin K Deficiency

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in up to 85% of adult patients and osteoporosis in 10% to 34%. In children, study results are discordant probably because of comparisons to different control populations and corrections for bone size in growing children. Malnutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period for bone mineralization and requires a careful follow-up to achieve optimal bone peak mass. Strategies for optimizing bone health, such as monitoring bone mineral density (BMD) and providing preventive care are necessary from childhood through adolescence to minimize CF-related bone disease in adult CF patients.

Topics: Adult; Bone Density; Bone Diseases; Bone Remodeling; Calcification, Physiologic; Calcium; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Puberty; Vitamin K

Diabetes mellitus is considered as a risk factor for fractures, and there are some reports showing that metabolic effects of poor glycemic control resulted in lower bone turnover. Previous studies have revealed that this reduction of bone turnover increases bone fragility, independently of bone mineral density, so that the mechanisms of diabetic osteopahty seem to be more closely related to bone quality than bone quantity. The mechanisms of the preventive effect on fractures by vitamin K treatment should be related to amelioration of bone quality via increasing amounts of carboxylated osteocalcin. Therefore, administration of vitamin K(2) (menatetrenone) to the patients with diabetic osteopathy will be beneficial in order to improve the impaired bone quality and to reduce fracture risk.

Topics: Animals; Bone Diseases; Diabetes Complications; Humans; Rats; 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

To summarize the clinical features and bone complications in a patient from a large family with X-linked congenital adrenocortical hypoplasia (AHC) and evaluate the efficacy of different treatment regimens on the prognosis of secondary osteoporosis caused by AHC at a 5-year follow-up.. A large family with AHC was recruited, and the causative gene mutation was identified by Sanger sequencing in the proband. Clinical features as well as radiological examinations and laboratory indices of osteoporosis secondary to AHC were analyzed in this study. Meanwhile, the proband was treated with classical antiresorptive drugs (bisphosphonates) for 2 years and switched to a vitamin K. The proband was identified as carrying a homozygous insertion mutation (p. Thr193GlyfsX13) in the. Secondary osteoporosis induced by AHC deserves clinical attention. Unlike in primary osteoporosis, the curative effect of bisphosphonates was unsatisfactory and was more likely to cause atypical femoral fractures in long-term treatment. It is suggested that bone anabolic drugs may be better alternatives.

Topics: Bone Diseases; Diphosphonates; Femoral Fractures; Humans; Mutation; Osteoporosis; Vitamin K

Bone disease has become an increasingly recognized complication of cystic fibrosis (CF). Although causes of CF bone disease are multifactorial, there has been recent interest in the role of vitamin K in CF bone disease.. A questionnaire survey of all UK paediatric CF centre dietitians and centre directors was carried out to ascertain current practice with regard to vitamin K prescribing and bone health surveillance.. The survey had a 97% response rate representing 3414 CF children. Twenty-three centre directors and 19 dietitians responded, and at least moderate agreement was noted with kappa scores >0.41 for all but one question assessed. Ninety-three per cent centres report that >90% pancreatic insufficient patients receive vitamins A, D and E, yet only 18% centres routinely supplement vitamin K. The majority (60%) report that <10% of their CF patients receive vitamin K, whilst vitamin K dosage varied from 0.3-0.5 to 10 mg day(-1). Only one centre undertook no bone health surveillance, and vitamin D levels are measured in 89%, calcium intake assessed in 82% and dual-energy X-ray absorptiometry scans performed in 61% centres.. Heterogeneity in both vitamin K prescribing practices and bone health surveillance in CF across the UK were noted, underlining the need for a national consensus on bone health management, as well as acting as a call for longitudinal research into the clinical effectiveness of vitamin K therapy in CF.

Topics: Absorptiometry, Photon; Adult; Bone and Bones; Bone Density; Bone Diseases; Child; Cystic Fibrosis; Dietetics; Female; Humans; Male; Pediatrics; Practice Patterns, Physicians'; Surveys and Questionnaires; United Kingdom; Vitamin K

Topics: Bone Diseases; Humans; Nutritional Requirements; Osteocalcin; Vitamin K

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: Ascorbic Acid; Blood Glucose; Blood Proteins; Bone Diseases; Celiac Disease; Cholesterol; Esophageal Diseases; Fats; Feces; Female; Gastrectomy; Gastrointestinal Motility; Glucose Tolerance Test; Hemostasis; Humans; Intestinal Absorption; Iodine; Jejunum; Malabsorption Syndromes; Male; Nitrogen; Radiography; Vitamin A Deficiency; Vitamin K; Water-Electrolyte Balance; Xylose

Topics: Alkaline Phosphatase; Biopsy; Blood; Blood Protein Disorders; Bone Diseases; Calcium Metabolism Disorders; Carbohydrate Metabolism; Folic Acid; Glutens; Humans; Hypocalcemia; In Vitro Techniques; Iron; Lipid Metabolism; Malabsorption Syndromes; Osteomalacia; Proteins; Radiography; Urine; Vitamin D; Vitamin K

Topics: Bone Diseases; Disease; Multiple Sclerosis; Osteitis Deformans; Skull; Thiamine Pyrophosphate; Vitamin A; Vitamin K; Vitamins