menaquinone-6 and Fractures--Bone

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

Topics: Cardiovascular Diseases; Fractures, Bone; Humans; Kidney Transplantation; Neoplasms; Nutritional Status; Postoperative Complications; Preoperative Period; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Supplementation with calcium (Ca) and/or vitamin D (vitD) is key to the management of osteoporosis. Other supplements like vitamin K2 (VitK2) and magnesium (Mg) could contribute to the maintenance of skeletal health. This narrative review summarizes the most recent data on Ca, vitD, vitK2 and Mg supplementation and age-related bone and muscle loss. Ca supplementation alone is not recommended for fracture prevention in the general postmenopausal population. Patients at risk of fracture with insufficient dietary intake and absorption could benefit from calcium supplementation, but it needs to be customized, taking into account possible side-effects and degree of adherence. VitD supplementation is essential in patients at risk of fracture and/or vitD deficiency. VitK2 and Mg both appear to be involved in bone metabolism. Data suggest that VitK2 supplementation might improve bone quality and reduce fracture risk in osteoporotic patients, potentially enhancing the efficacy of Ca ± vitD. Mg deficiency could negatively influence bone and muscle health. However, data regarding the efficacy of vitK2 and Mg supplementation on bone are inconclusive.

Topics: Animals; Calcium; Dietary Supplements; Fractures, Bone; Humans; Magnesium; Osteoporosis; Vitamin D; Vitamin K 2; Vitamins

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day.

Topics: Bone and Bones; Bone Density; Female; Fractures, Bone; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K; Vitamin K 2; Vitamins

Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.

Topics: Absorptiometry, Photon; Bone Density; Female; Fractures, Bone; Humans; Incidence; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Randomized Controlled Trials as Topic; Vitamin K 2

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

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-TOP research consortium has been authorized at 2000 by the Japanese Society of Osteoporosis and assisted by Public Health Research Foundation in order to obtain the clinical evidences regarding osteoporosis treatment. Each clinical trial program was named as JOINT (Japanese Osteoporosis Intervention Trial), which was multi-center randomized open label trial and was registered into clinical trial registry. JOINT-02 was started at 2003 to confirm the effect of combination treatment of active vitamin D3 and alendronate in the prevention of osteoporotic bone fracture occurrence. This trial will be terminated at 2009 and the subsequent third clinical trial to obtain the evidence regarding the combination effects of risedronate and vitamin K2 as JOINT-03 project has been started from 2008. Each trial included around 2,000 participants mainly from practitioner and the registration of the cases in JOINT-02 has been finished within 3 years, suggesting that the participated practitioner would have sympathy with the research aims. The A-TOP research group would have carried out epidemiological studies regarding establishment of osteoporosis database (JOB study), which will contribute the additional knowledge of Japanese osteoporosis.

Topics: Alendronate; Bone Density Conservation Agents; Cholecalciferol; Drug Therapy, Combination; Evidence-Based Medicine; Fractures, Bone; Fractures, Spontaneous; Humans; Japan; Multicenter Studies as Topic; Osteoporosis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Societies, Medical; Vitamin K 2

Patients with neurological diseases such as Alzheimer's disease, stroke and Parkinson's disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of menatetrenone (vitamin K(2)) against non-vertebral and hip fractures in patients with neurological diseases.. A literature search was conducted on PubMed from January 1995 to July 2008 to identify randomized controlled trials (RCTs) of use of menatetrenone against non-vertebral and hip fractures in patients with neurological diseases. A meta-analysis of all RCTs meeting these criteria was then performed.. Three RCTs of patients with Alzheimer's disease (n = 178, mean age 78 years), stroke (n = 99, mean age 66 years) and Parkinson's disease (n = 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported with menatetrenone treatment.. The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases. Further larger placebo-controlled trials are needed to confirm the results of the present study.

Topics: Aged; Bone Density Conservation Agents; Brain Diseases; Female; Fractures, Bone; Hip Fractures; Humans; Male; Randomized Controlled Trials as Topic; Vitamin K 2

Intervention studies and meta-analyses have shown that vitamin D(3) at 700-800 IU/day decreases the fracture incidence. Higher phylloquinone (vitamin K(1)) intake or "natto" intake was associated with lower fracture incidence. In contrast, current intake of vitamin D and K in Japanese is likely to be unsatisfactory for preventing fracture. The intake of fish, abundant in vitamin D(3) is encouraged. Regarding vitamin K, "natto" intake is strongly recommended, since it contains extraordinary amount of menaquinone-7. Phylloquinone in green vegetables would be efficiently absorbed when cooked with oil. Thus Japanese traditional foods seem to be appropriate for bone health.

Topics: Cholecalciferol; Dietary Fats; Female; Food Analysis; Fractures, Bone; Humans; Male; Risk; Solubility; Soy Foods; Vitamin K 1; Vitamin K 2

To determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women.. Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009.. Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1.. The electronic literature searches identified 1078 potentially relevant articles. Of these, 14 articles relating to five trials that compared vitamin K with a relevant comparator in postmenopausal women with osteoporosis or osteopenia met the review inclusion criteria. The double-blind ECKO trial compared 5 mg of phylloquinone (vitamin K1) with placebo in Canadian women with osteopenia but without osteoporosis. Four open-label trials used 45 mg of menatetrenone (vitamin K2) in Japanese women with osteoporosis; the comparators were no treatment, etidronate or calcium. The methodological quality of the ECKO trial was good; however, all four menatetrenone trials were poorly reported and three were very small (n < 100 in each group). Phylloquinone was associated with a statistically significant reduction in the risk of clinical fractures relative to placebo [relative risk 0.46, 95% confidence interval (CI) 0.22 to 0.99]; morphometric vertebral fractures were not reported. The smaller menatetrenone trials found that menatetrenone was associated with a reduced risk of morphometric vertebral fractures relative to no treatment or calcium; however, the larger Osteoporosis Fracture (OF) study found no evidence of a reduction in vertebral fracture risk. The three smaller trials found no significant difference between treatment groups in non-vertebral fracture incidence. In the ECKO trial, phylloquinone was not associated with an increase in adverse events. In the menatetrenone trials, adverse event reporting was generally poor; however, in the OF study, menatetrenone was associated with a significantly higher incidence of skin and skin appendage lesions. No published economic evaluations of vitamin K were found and a mathematical model was thus constructed to estimate the cost-effectiveness of vitamin K1. Comparators were alendronate, risedronate and strontium ranelate. Vitamin K1 and alendronate were markedly more cost-effective than either risedronate or strontium ranelate. The base-case results favoured vitamin K1, but this relied on many assumptions, particularly on the efficacy of preventing hip and vertebral fractures. Calculation of the expected value of sampled information was conducted assuming a randomised controlled trial of 5 years' duration comparing alendronate with vitamin K1. The costs incurred in obtaining updated efficacy data from a trial with 2000 women per arm were estimated to be a cost-effective use of resources.. There is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Fractures, Bone; Humans; Models, Econometric; Osteoporosis, Postmenopausal; Quality-Adjusted Life Years; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins

Vitamin K2 has been approved for the treatment of osteoporosis in Japan since 1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD. The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures. A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence. To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed.

Topics: Bone Density; Evidence-Based Medicine; Fractures, Bone; Humans; Meta-Analysis as Topic; Osteoporosis; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K 2

The incidence of osteoporotic fractures increases along aging and the importance of their prevention is more emphasized in the elderly. Although the major determinants for fragile fractures in the elderly are not only the lower bone strength but also frailty and fall, treatments with anti-resorbers are effective also in the elderly. On the other hands, nutritional agents such as active vitamin D3 and vitamin K2 are effective in reducing the fracture incidences in spite of their modest effects on bone mineral density. Recently, the effects of vitamin Ds on the reduction of fall events are noticed and the prevention of osteoporotic fractures in the elderly through extra-skeletal mechanisms seems promising.

Topics: Accidental Falls; Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Diphosphonates; Estrogen Replacement Therapy; Fractures, Bone; Humans; Osteoporosis; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Vitamin K 2

Meta-analysis involving previous clinical studies showed that VK(2) decreased the incidence of fracture. In particular, the results based on the data on bone mineral density and fracture suggested that VK(2) improves bone quality. Preclinical studies regarding bone quality reported that VK(2) improved the trabecular microarchitecture (connectivity and width) in an ovariectomized model, and that VK(2) increased the bone strength without influencing the bone mineral content in a model fed a low-Mg diet and a vitamin C deficiency model, increasing the collagen level and proline hydroxylation. Thus, improvement in bone quality via actions on the bone geometry and collagen level/quality may be involved in a VK(2)-related decrease in the incidence of new fracture in clinical studies.

Topics: Animals; Bone and Bones; Bone Density; Collagen; Fractures, Bone; Humans; Hydroxyproline; Meta-Analysis as Topic; Proline; Vitamin K 2

Menatetrenone (MK-4) is a form of vitamin K(2) (VK(2)) which is utilized for the treatment of osteoporosis. MK4 has a grade B as a total recommendation rate in the Japanese guideline for the prevention and treatment of osteoporosis in 2006 based on the current clinical evidences. The effects of fracture prevention by MK-4 are assumed to be based on the increase of bone mineral density as well as the improvement of bone quality. Recent researches suggest that VK affects bone metabolism via nuclear receptor in addition to the carboxylation of VK dependent proteins.

Topics: Bone and Bones; Bone Density; Evidence-Based Medicine; Fractures, Bone; Humans; Meta-Analysis as Topic; Osteoporosis; Practice Guidelines as Topic; Vitamin K 2

In recent years, bone quality is thought to be an important factor in bone strength. Vitamin K(2) (VK(2))drugs inhibit bone fracture, although their effect of increasing bone mineral density (BMD)is lower compared to bisphosphonate. This suggests VK(2) analogs improve bone quality. Glucocorticoid-induced osteoporosis(GIOP)brings about a bone fracture even under the condition of high BMD. VK(2) drugs might be effective to prevent bone fracture in GIOP, because they increase bone strength independently of bone mineral density (BMD).

Topics: Bone and Bones; Fractures, Bone; Glucocorticoids; Humans; Osteoporosis; Vitamin K 2

Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesis of osteocalcin, osteonectin and other matrix bone proteins, in addition, new finding, in stem cell culture found osteoblast producing gene expression of collagen type 1, the other action, vitamin K(2) contains mild antiresorpion by inducing the osteoclastic apoptosis. Our study found that postmenopausal and elderly women have high risk of vitamin K(2) deficiency, comparing to the normal value of young, reproductive females. The efficacy of vitamin K(2) will be fulfill benefit after 6 months of administration, prolong use will enhance of bone quality that prevent fracture.

Topics: Apoptosis; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Calcium-Binding Proteins; Cells, Cultured; Collagen Type I; Extracellular Matrix Proteins; Female; Fractures, Bone; Humans; Male; Matrix Gla Protein; Osteoblasts; Osteocalcin; Osteoclasts; Vitamin K 2; Vitamin K Deficiency

Topics: Bone and Bones; Bone Density; Bone Density Conservation Agents; Diphosphonates; Drug Therapy, Combination; Evidence-Based Medicine; Fractures, Bone; Humans; Osteoporosis; Vitamin K 2

Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.. To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.. The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.. Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.. Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.. Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.. This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.

Topics: Bone Density; Fractures, Bone; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K 1; Vitamin K 2; Vitamins

Vitamin K is a nutrient originally identified as an essential factor for blood coagulation. Recently, vitamin K has emerged as a potential protector against osteoporosis and hepatocarcinoma. Accumulated evidence indicates that subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues, particularly in bone, exists widely in the otherwise healthy adult population. Both vitamin K(1) and K(2) have been shown to exert protective effects against osteoporosis. Moreover, therapeutic potential of vitamin K(2) as an anti-hepatoma drug has been recently highlighted. Most of the new biological functions of vitamin K in bone and hepatoma cells are considered to be attributable to promotion of gamma-carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is shared by both vitamins K(1) and K(2). In contrast, vitamin K(2)-specific, gamma-carboxylation-unrelated functions have also been demonstrated. These functions include stimulation of steroid and xenobiotic receptor (SXR)-mediated transcription and anti-oxidant property. Thus, biological differences between vitamins K(1) and K(2), and a potential involvement of gamma-carboxylation-independent actions in the new roles of vitamin K remain open issues. Molecular bases of coagulation-unrelated pleiotropic actions of vitamin K and its implications in human health deserve further investigations.

Topics: 1-Carboxyglutamic Acid; Antioxidants; Carcinoma, Hepatocellular; Fractures, Bone; Humans; Liver Neoplasms; Osteoporosis; Pregnane X Receptor; Receptors, Steroid; Soy Foods; Transcription, Genetic; Vitamin K; Vitamin K 1; Vitamin K 2

Osteoporosis is the most frequent adverse effect of glucocorticoids. Management guidelines for glucocorticoid-induced osteoporosis have been established in the United States, the United Kingdom, and many other countries. The 2004 edition of the guidelines on the management and treatment of glucocorticoid-induced osteoporosis have been proposed by The Japanese Society for Bone and Mineral Research. The subjects were patients with using or planning to use oral glucocorticoids for 3 months or longer. The criterion for starting treatment was patients with prior fragility fracture and with new fractures during treatment, patients with less bone mineral density (BMD) than 80% of young adult mean, and patients with using as a dose of 5mg/day or higher (mean daily dose) as prednisolone equivalent. The bisphosphonates have been recommended as first-line drugs and active vitamin D(3) and vitamin K(2) have been recommended as second-line drugs.

Topics: Bone Density; Bone Density Conservation Agents; Cholecalciferol; Diphosphonates; Evidence-Based Medicine; Fractures, Bone; Glucocorticoids; Humans; Japan; Osteoporosis; Practice Guidelines as Topic; Prednisolone; Time Factors; Vitamin K 2

Most of the guidelines for management of glucocorticoid-induced osteoporosis (GIOP) recommend bisphosphonates as therapeutic agents. However, bisphosphonates have a gastrointestinal side effect, and a potential risk for pregnant women and children. Moreover, an efficacy of combination therapy with proved drugs for GIOP remains to be clarified. An analog of vitamin K(2) reduced the fracture risk independent from the bone mineral densities in GIOP. Since GIOP induced bone fracture even in the high bone mass, the vitamin K(2) analog should be an effective therapeutic agent for GIOP through increasing bone strength without an increase in bone mineral density.

Topics: Bone and Bones; Child; Female; Fractures, Bone; Glucocorticoids; Humans; Osteoporosis; Pregnancy; Tensile Strength; Vitamin K 2

Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment.

Topics: Animals; Bone and Bones; Bone Density; Diphosphonates; Disease Models, Animal; Drug Synergism; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Rats; Vitamin K 2; Vitamins

Osteoporosis is the most frequent adverse effect observed during glucocorticoids therapy. The 2004 edition of the guideline on the management and treatment of glucocorticoid-induced osteoporosis has been proposed by The Japanese Society for Bone and Mineral Research. The subjects were patients with using or planning to use oral glucocorticoids for 3 months or longer. The criterion for starting treatment consisted patients with prior fragility fracture and with new fractures during treatment, patients with less BMD than %YAM80, and patients with using as a dose of 5 mg/day or higher (mean daily dose) as prednisolone equivalent. The Bisphosphonates have been recommended as first-line drugs. Active vitamin D3 and vitamin K2 have been recommended as second-line drugs.

Topics: Bone and Bones; Bone Density; Cholecalciferol; Diphosphonates; Fractures, Bone; Glucocorticoids; Humans; Osteocalcin; Osteoporosis; Practice Guidelines as Topic; Prednisolone; Randomized Controlled Trials as Topic; Risk; Vitamin K 2

In the WHO technical report, vitamin D metabolites have been suggested to have a role as an adjunctive therapy when given with an antiresorptive agent. Beneficial effects on BMD have been reported following the addition of calcitriol to alendronate, etidronate, and HRT, but no data on fracture rates are available. Here we summarize our clinical study on the concurrent therapy and review reports on the concurrent treatments.

Topics: Aged; Bone Density; Cholecalciferol; Clinical Trials as Topic; Diphosphonates; Drug Therapy, Combination; Estrogen Replacement Therapy; Etidronic Acid; Female; Fractures, Bone; Humans; Male; Multicenter Studies as Topic; Osteoporosis; Vitamin K 2

Vitamin K2 (menatetrenone) treatment was reported to significantly prevent new clinical fracture (chi2 = 10.935;p = 0.0273) in a 2-year group comparison study of patients with osteoporosis, although it only maintained the baseline bone mineral density. This result strongly suggested that another factor was involved in promoting bone strength apart from an increase in bone mineral density. With respect to the therapeutic effect of menatetrenone treatment on corticosteroid-induced osteoporosis over 2 years, the incidence of a new vertebral fracture was 13.3% in the menatetrenone treatment group versus 41% in the control group, indicating that this treatment could prevent fractures. Multivariate logistic regression analysis was performed to investigate independent risk factors for new vertebral fractures, and treatment with menatetrenone showed a preventive effect on fracture with an odds ratio of 0.03 and a risk rate of 0.003.

Topics: Animals; Bone and Bones; Bone Density; Fractures, Bone; Humans; Osteoporosis; Vitamin K 2

Topics: Animals; Bone Density; Fractures, Bone; Humans; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K 2

Topics: Alendronate; Bone Density; Cholecalciferol; Clinical Trials as Topic; Estrogen Replacement Therapy; Etidronic Acid; Fractures, Bone; Humans; Hydroxycholecalciferols; Osteoporosis; Raloxifene Hydrochloride; Vitamin K 2

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; 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To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women.. This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups.. A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol.. Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women.

Topics: Aged; Alkaline Phosphatase; Bone Density; Bone Density Conservation Agents; Calcium; Double-Blind Method; Female; Fractures, Bone; Humans; Hydroxycholecalciferols; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Phosphorus; Treatment Outcome; Vitamin K 2

Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.. This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by -1.28% and -1.22% (p = 0.84) (difference of -0.06%; 95% confidence interval [CI] -0.67% to 0.54%) at the lumbar spine and -0.69% and -0.88% (p = 0.51) (difference of 0.19%; 95% CI -0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.. Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers.. ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241).

Topics: Adult; Aged; Aged, 80 and over; Bone Density; Bone Diseases, Metabolic; Dietary Supplements; Double-Blind Method; Female; Fractures, Bone; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Treatment Outcome; Vitamin D; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Corresponding Author, Yoshihiro Sato, and the co-authors have been informed.\ \ Dr. Sato wishes to retract this article on the grounds that it contains fabricated clinical trial data, which he was responsible for producing. In addition, Dr. Sato claims he listed all of the named co-authors without their consent. The co-authors were therefore unaware of the presence of fabricated data in this publication and their participation in the publication. This retraction was initiated by Dr. Sato, and the Editor-in-Chief of Bone was informed by the author directly.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Bone Density; Calcium; Ergocalciferols; Female; Fractures, Bone; Humans; Vitamin K 2

The purpose of the present preclinical study was to determine whether vitamin K(2) would promote bone healing in a rat femoral osteotomy model with or without glucocorticoid (GC) treatment. Thirty-eight 6 week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation and then were randomized into four groups that received the following treatment schedules: vehicle, vitamin K(2), GC + vehicle, and GC + vitamin K(2). GC (prednisolone, 2.5 mg/kg) was administered subcutaneously twice a week. Vitamin K(2) (menatetrenone, 30 mg/kg) was administered orally five times a week. After 8 weeks of treatment, the wires were removed and a bone histomorphometric analysis was performed on the bone tissue inside the callus. Vitamin K(2) administration to GC-untreated rats decreased the osteoclast surface/bone surface (OcS/BS), osteoblast surface (ObS)/BS, eroded surface (ES)/BS, and bone formation rate (BFR)/BS and increased the lamellar area/bone area. Although GC treatment increased the ES/BS and decreased the ObS/BS, BFR/BS, and lamellar area/bone area, vitamin K(2) administration to GC-treated rats decreased the OcS/BS and prevented an increase in the ES/BS and a decrease in the lamellar area/bone area. These results suggested that vitamin K(2) downregulated bone turnover and stimulated lamellar bone formation in GC-untreated rats and prevented an increase in bone resorption while maintaining bone formation and prevented a decrease in lamellar bone formation in GC-treated rats. Thus, vitamin K(2) appears to be effective for promoting bone healing in a rat femoral osteotomy model with or without GC treatment.

Topics: Animals; Antifibrinolytic Agents; Bone Regeneration; Bone Resorption; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Femur; Fractures, Bone; Glucocorticoids; Internal Fixators; Osteoblasts; Osteoclasts; Osteotomy; Prednisolone; Rats; Rats, Sprague-Dawley; Treatment Outcome; Vitamin K 2; Wound Healing

It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis. However, there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density (BMD) or fractures in Japan. The objectives were to evaluate the association between plasma phylloquinone (K1) or menaquinone (MK-4 and MK-7) concentration and BMD or fracture in Japanese women prospectively. A total of 379 healthy women aged 30-88 years (mean age, 63.0 years) were consecutively enrolled. Plasma K1, MK-4, MK-7, and serum undercarboxylated osteocalcin (ucOC) concentrations, BMD, and incidence of vertebral fractures were evaluated. In stepwise multiple linear regression analyses, L2-4 BMD and a bone turnover marker, log K1, concentrations were independently correlated with vertebral fracture incidence. When subjects were divided into low and high K1 groups by plasma K1 concentration, the incidence of vertebral fracture in the low K1 group (14.4%) was significantly higher than that in the high K1 group (4.2%), and its age-adjusted RR was 3.58 (95% CI, 3.26-3.93). L2-4 BMD was not different between the two groups. These results suggest that subjects with vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Asian People; Female; Fractures, Bone; Humans; Incidence; Japan; Middle Aged; Spinal Injuries; Vitamin K 1; Vitamin K 2

Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K1) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with gamma-carboxylation of the osteocalcin molecule.. The objectives were to measure the circulating concentrations of K1, MK-4, and MK-7 in women and to ascertain whether each form of vitamin K is significantly associated with bone metabolism.. Plasma concentrations of K1, MK-4, MK-7, undercarboxylated osteocalcin (ucOC; measured by using the new electrochemiluminescence immunoassay), intact osteocalcin (iOC), calcium, and phosphorus; bone-derived alkaline phosphatase activity; and concentrations of urinary creatinine, N-terminal telopeptide, and deoxypyridinoline were measured in healthy women (n = 396).. On average, MK-7 and MK-4 were the highest and lowest, respectively, of the 3 vitamers in all age groups. K1 and MK-7 correlated inversely with ucOC, but associations between nutritional basal concentration of MK-4 and ucOC were not observed. Multiple regression analysis indicated that not only K1 and MK-7 concentrations but also age were independently correlated with ucOC concentration and the ratio of ucOC to iOC. The plasma K1 or MK-7 concentration required to minimize the ucOC concentration was highest in the group aged > or =70 y, and it decreased progressively for each of the younger age groups.. The definite role of ucOC remains unclear. However, if submaximal gamma-carboxylation is related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Bone and Bones; Bone Density; Carboxylic Acids; Female; Fractures, Bone; Humans; Japan; Middle Aged; Nutritional Requirements; Nutritional Status; Osteocalcin; Risk Factors; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Vitamins