vitamin-k-semiquinone-radical and Osteoporosis

Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4-MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.

Topics: Animals; Humans; Kinetics; Osteoporosis; Vitamin K; Vitamin K 1; Vitamin K 2

The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.

Topics: Aged; Blood Coagulation; Female; Humans; Neoplasms; Osteoporosis; Ovarian Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2

Calcium is involved in bone metabolism, regulation of nerve signaling, and release of neurotransmitters. Phosphorus is a structural component of ATP, participates in metabolic energy regulation, and ensures stability to biological membranes and cells. Vitamin D and vitamin K are important for intestinal absorption and renal excretion of calcium and phosphorus. Vitamin D plays a regulatory role in bone formation, carbohydrate metabolism, immune responses, and cardiovascular regulation. Research has linked vitamin D deficiency to the development of diabetes mellitus, hypertension, cancer, and osteoporosis. Vitamin K has been associated with a reduced risk of osteoporosis, cancer, and cardiovascular diseases (due to improved vascular elasticity). This review highlights the importance of vitamins D and K in the metabolism of calcium and phosphorus and explores various molecular mechanisms that help maintain the system's mineral homeostasis. Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity.

Topics: Calcium; Calcium, Dietary; Dietary Supplements; Humans; Osteoporosis; Phosphorus; Subtilisins; Vitamin D; Vitamin K; Vitamin K 2; Vitamins

As a common systemically muscular-skeleton disorder of aging, osteoporosisis is characterized by the uninterrupted deconstruction in osseous microarchitecture. Osteoporosis can consequently lead to a significantly high risk of osteoporotic fractures, such as Osteoporotic Vertebral Compressive Fractures [OVCF] in the spine and osteoporotic femoral neck fractures in the hip joint, which can significantly increase the numbers of mortality and morbidity in elderly people, especially in postmenopausal women.. In addition, vitamin K has been demonstrated to play a key role in inhibiting osteoporotic fractures among postmenopausal women, but its long-term benefits, potential harms, and side effects of the combination between vitamin K and other anti-osteoporosis medicines, such as bisphosphonates or teriparatide still remain to be extensively studied. Therefore, the present study aimed to systematically reviewed previously published literature on the role of vitamin K in the treatment of osteoporosis. We currently, via multiple query strategies, searched the relevant literature in Cochrane and PubMed from January 2010 to December 2019.. Subsequently, we conducted the systematic review according to the standard guideline of Preferred Reporting Item for Systematic Reviews and Meta-Analyses [PRISMA].. Finally, ten relevant studies met our current criteria for inclusion; subsequently, we followed the PRISMA guideline, then systematically reviewed each study by categorizing the data sources and analytical approaches in each study, while setting up variables and defining each study's outcomes.

Topics: Aged; Bone Density; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K

Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.

Topics: Animals; Bone Development; Humans; Osteocalcin; Osteoporosis; Vitamin K

In this article we connect the dysregulation of the transsulfuration pathway to bone dysregulations and propose a novel treatment for osteoporosis. Current treatments for osteoporosis are very frequently inadequate. In osteoporosis, the risk of fractures increases with increased homocysteine (Hcy).. Here, we conduct a review on the relationship between osteoporosis and the dysregulation of the transsulfuration pathway.. we show that the transsulfuration pathway metabolizes Hcy to L-cysteine. Increased Hcy levels point to the transsulfuration pathway being dysregulated. With the transsulfuration pathway dysregulated, there will be decreased levels of L-cysteine and decreased levels of taurine, which is synthesized from L-cysteine. Taurine levels are decreased in patients with osteoporosis. Taurine regulates intracellular calcium homeostasis. Taurine, also, when conjugated with bile acids assists with absorption of fats and fat-soluble vitamins such as vitamin D and vitamin K. Dysregulated calcium homeostasis, decreased calcium absorption and decreased absorption of vitamin D and vitamin K due to low levels of taurine negatively affect bone mineral density (BMD) leading to osteoporosis and fractures.. In this article, we propose that a combination of taurine, calcium, vitamin D and vitamin K, could increase BMD reducing number of years spent in disability and reducing deaths due to fractures in patients with osteoporosis.

Topics: Calcium; Homeostasis; Humans; Osteoporosis; Taurine; Vitamin D; Vitamin K; Vitamins

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.

Topics: Fractures, Bone; Humans; Osteoporosis; Pregnane X Receptor; Vitamin K; Vitamin K Deficiency

Patients with chronic kidney disease (CKD) are at increased risk of osteoporosis and vascular calcification. Bone demineralization and vascular mineralization go often hand in hand in CKD, similar to as in the general population. This contradictory association is independent of aging and is commonly referred to as the "calcification paradox" or the bone-vascular axis. Various common risk factors and mechanisms have been identified. Alternatively, calcifying vessels may release circulating factors that affect bone metabolism, while bone disease may infer conditions that favor vascular calcification. The present review focuses on emerging concepts and major mechanisms involved in the bone-vascular axis in the setting of CKD. A better understanding of these concepts and mechanisms may identify therapeutics able to target and exert beneficial effects on bone and vasculature simultaneously.

Topics: Adaptor Proteins, Signal Transducing; Animals; Cardiovascular Diseases; Glucuronidase; Humans; Inflammation; Klotho Proteins; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; Renal Insufficiency, Chronic; Signal Transduction; Vascular Calcification; Vitamin K

Vitamin K may affect bone mineral density and fracture incidence. Since publication of a previous systematic review the integrity of some of the previous evidence has been questioned and further trials have been published. Therefore an update to the systematic review was required.. This systematic review was designed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density and reducing fractures in adults.. MEDLINE, EMBASE, CENTRAL, CINAHL, clinicaltrials.gov, and WHO-ICTRP were searched for eligible trials. Randomised controlled trials assessing oral vitamin K supplementation that assessed bone mineral density or fractures in adult populations were included. A total of 36 studies were identified. Two independent reviewers extracted data using a piloted extraction form.. For post-menopausal or osteoporotic patients, meta-analysis showed that the odds of any clinical fracture were lower for vitamin K compared to controls (OR, 0.72, 95%CI 0.55 to 0.95). Restricting the analysis to low risk of bias trials reduced the OR to 0.76 (95%CI, 0.58 to 1.01). There was no difference in vertebral fractures between the groups (OR 0.96, 95%CI 0.83 to 1.11). In the bone mineral density meta-analysis, percentage change from baseline at the lumbar spine was higher at 1 year (MD 0.93, 95%, CI - 0.02 to 1.89) and 2 years (MD 1.63%, 95%CI 0.10 to 3.16) for vitamin K compared to controls; however, removing trials at high risk of bias tended to result in smaller differences that were not statistically significant. At 6 months, it was higher in the hip (MD 0.42%, 95%CI 0.01 to 0.83) and femur (MD 0.29%, 95%CI 0.17 to 0.42). There was no significant difference at other anatomical sites.. For post-menopausal or osteoporotic patients, there is no evidence that vitamin K affects bone mineral density or vertebral fractures; it may reduce clinical fractures; however, the evidence is insufficient to confirm this. There are too few trials to draw conclusions for other patient groups.

Topics: Bone Density; Dietary Supplements; Humans; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Spinal Fractures; Vitamin K

Vitamin K is a fat-soluble vitamin that was originally found as an essential factor for blood coagulation. With the discovery of its role as a co-factor for γ-glutamyl carboxylase (GGCX), its function for blood coagulation was understood as the activation of several blood coagulation factors by their γ-carboxylation. Over the last two decades, other modes of vitamin K actions have been discovered, such as the regulation of transcription by activating the steroid and xenobiotic receptor (SXR), physical association to 17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4), covalent modification of Bcl-2 antagonist killer 1 (Bak), and the modulation of protein kinase A (PKA) activity. In addition, several epidemiological studies have revealed that vitamin K status is associated with some aging-related diseases including osteoporosis, osteoarthritis, and sarcopenia. Clinical studies on single nucleotide polymorphisms of GGCX suggested an association between higher GGCX activity and bone protective effect, while recent findings using conditional knockout mice implied that a contribution in protective effect for bone loss by GGCX in osteoblastic lineage was unclear. GGCX in other cell lineages or in other tissues might play a protective role for osteoporosis. Meanwhile, animal experiments by our groups among others revealed that SXR, a putative receptor for vitamin K, could be important in the bone metabolism. In terms of the cartilage protective effect of vitamin K, both GGCX- and SXR-dependent mechanisms have been suggested. In clinical studies on osteoarthritis, the γ-carboxylation of matrix Gla protein (MGP) and gla-rich protein (GRP) may have a protective role for the disease. It is also suggested that SXR signaling has protective role for cartilage by inducing family with sequence similarity 20a (

Topics: Aging; Animals; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Matrix Gla Protein; Musculoskeletal Diseases; Osteoporosis; Pregnane X Receptor; Proteins; Vitamin K

Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis. Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear. This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.

Topics: Aged; Bone and Bones; Female; Fractures, Bone; Humans; Male; Nutrition Assessment; Osteoporosis; Vitamin K

Topics: Bone and Bones; Cell Transdifferentiation; Humans; Osteocalcin; Osteoporosis; Vascular Calcification; Vitamin K; Vitamin K 2

The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases. This review provides an overview of the types of vitamin K and their health benefits. This is followed by a critical review of the various biotechnological approaches used in the production of menaquinone, including solid and liquid state fermentations, extraction and recovery. The currently available market information is summarized and future growth prospects are discussed. Recommendations are also given for areas of future research in order to improve the production process for menaquinone and reduce costs.

Topics: Biotechnology; Cardiovascular Diseases; Dietary Supplements; Fermentation; Humans; Osteoporosis; Vitamin K

Several drugs have been associated with an increased risk of osteoporosis when used chronically. Coumarins (warfarin, acenocoumarol, phenprocoumon, and fluindione) are oral anticoagulants widely used for the prevention and treatment of arterial and venous thromboembolic diseases. These drugs are vitamin K antagonists that interfere with γ-carboxyglutamate formation, and consequently inhibit the carboxylation of glutamate residues of proteins that are synthesized in the bone. These effects on bone turnover and dietary restrictions in patients on anticoagulation are possible mechanisms inducing osteoporosis in coumarin users. However, conflicting evidence is available concerning the risk of osteoporosis and bone fractures in patients on treatment with these drugs. This risk is likely to be clinically relevant in long-term (more than 1 year) coumarin users. Novel direct oral anticoagulants, recently introduced in clinical practice, exert reduced interference on bone metabolism; however, limited in vitro and animal data are currently available, and their long-term effects will only become apparent in time.

Topics: 1-Carboxyglutamic Acid; Administration, Oral; Animals; Anticoagulants; Humans; Osteoporosis; Protein Processing, Post-Translational; Vitamin K

Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial.. To assess whether the use of VKAs is associated with an increased prevalence and/or incidence of osteoporosis, fractures, or lower bone mineral density (BMD) values.. We conducted a systematic PubMed and EMBASE literature search until August 31, 2014, and a meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD, comparing patients treated with VKAs and healthy controls (HCs) or with patients with medical illness (medical controls, MCs). Standardized mean differences ± 95% and confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures.. Of 4597 initial hits, 21 studies were eligible, including 79 663 individuals treated with VKAs vs. 597,348 controls. Compared with HCs, VKA-treated individuals showed significantly higher fracture risk in cross-sectional (three studies; RR = 1.24; 95% CI: 1.12-1.39, P < 0.0001) and longitudinal studies (seven studies; RR = 1.09; 95% CI: 1.01-1.18, P = 0.03) and more incident hip fractures (four studies; RR = 1.17; 95% CI: 1.05-1.31, P = 0.003). Analyzing studies that matched VKA participants with HCs (four studies), both these findings in longitudinal studies became non-significant. Notably, the VKA and MC group had similar BMD values at all investigated sites. Compared with HCs, a single study showed significantly lower spine T-scores in the VKA-treated group (standardized mean difference = - 0.45; 95% CI: - 0.75, - 0.14, P = 0.004).. VKAs neither increased prospectively-assessed fracture risk compared with MCs when matching eliminated confounding factors nor reduced BMD beyond effects of medical illness. Future studies, using careful matching and/or adequate MC groups, are needed to further clarify the short- and long-term effects of VKAs on bone health.

Topics: Adult; Age Factors; Aged; Anticoagulants; Bone Density; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Female; Fractures, Spontaneous; Hip Fractures; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Observational Studies as Topic; Osteoporosis; Risk; Sex Factors; Vitamin K

Vitamin K is a fat-soluble vitamin, which is involved in blood coagulation mediated by maintaining the activity of coagulation factors in the liver. Vitamin K also has extrahepatic actions and has been shown to prevent bone fractures in clinical studies. In addition, epidemiological studies suggest that a lack of vitamin K is associated with several geriatric diseases, including osteoporosis, osteoarthritis, dementia and arteriosclerosis. It has also been shown that vitamin K contributes to the prevention and treatment of some kinds of malignancies. Recently, we discovered a novel role for vitamin K as a ligand of the nuclear receptor, steroid and xenobiotic receptor (SXR), and its murine ortholog, pregnane X receptor (PXR). In addition to its established roles as a cofactor of γ-glutamyl carboxylase (GGCX) in mediating post-transcriptional modifications, vitamin K has a different mode of action mediated by transcriptional regulation of SXR/PXR target genes. Analysis of bone tissue from PXR-deficient mice showed that the bone protective effects of vitamin K are partially mediated by SXR/PXR-dependent signaling. The discoveries of a novel mode of vitamin K action have opened up new possibilities that vitamin K might be useful for prevention or treatment of a variety of diseases that affect the geriatric population.

Topics: Animals; Blood Coagulation; Humans; Osteoporosis; Vitamin K; Vitamins

Vitamin K is one of several nutrients that have been linked with bone health. In particular, there is an emerging literature regarding the questionable efficacy of vitamin K supplementation in reducing age-related bone loss. This review aims to summarize the role of vitamin K in bone health in older adults and discuss the clinical implications from a select few human studies. The evidence for vitamin K supplementation in older adults is mixed. Although the observational studies have shown linkages between vitamin K intake and lower risk of fractures in this population, the current evidence from randomized controlled trials is not strongly supportive of vitamin K supplementation in older adults for the intent of improving bone health.

Topics: Aging; Bone and Bones; Diet; Dietary Supplements; Evidence-Based Medicine; Health Promotion; Humans; Nutrition Policy; Osteoporosis; Reproducibility of Results; Vitamin K; Vitamin K Deficiency

Recent studies have found conflicting evidence on the role of α-tocopherol (αTF) on bone health. This nonsystematic review aimed to summarize the current evidence on the effects of αTF on bone health from cell culture, animal, and human studies in order to clarify the role of αTF on bone health. Our review found that αTF exerted beneficial, harmful or null effects on bone formation cells. Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis. However, high-dose αTF was possibly detrimental to bone in normal animals. Human studies mostly demonstrated a positive relationship between αTF, as assessed using high performance liquid chromatography and/or dietary questionnaire, and bone health, as assessed using bone mineral density and/or fracture incidence. Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone, the blocking of the entry of other Vitamin E isomers beneficial to bone, and the role of αTF as a prooxidant. However, these adverse effects have not been shown in human studies. In conclusion, αTF may have a dual role in bone health, whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone.

Topics: alpha-Tocopherol; Bone and Bones; Bone Density; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Observational Studies as Topic; Osteoporosis; Vitamin E; Vitamin K

Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.

Topics: Amino Acids; Ascorbic Acid; Food; Humans; Minerals; Osteoporosis; Proteins; Vitamin B Complex; Vitamin K

To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health.. APOE has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at APOE locus, known as E2, E3, and E4, may modulate BMD through its effects on lipoproteins and vitamin K transport. The purpose of this study was to determine the association of the APOE-E4 gene polymorphism with bone-related phenotypes.. We conducted a meta-analysis that combined newly analyzed individual data from two community-based cohorts, the Framingham Offspring Study (N = 1,495) and the vitamin K clinical trial (N = 377), with 15 other eligible published reports. Bone phenotypes included BMD measurements of the hip (total hip and trochanteric and femoral neck sites) and lumbar spine (from the L2 to L4 vertebrae) and prevalence or incidence of vertebral, hip, and other fractures.. In sex-pooled analyses, APOE4 carriers had a 0.018 g/cm(2) lower weighted mean trochanteric BMD than non carriers (p = 0.0002) with no evidence for between-study heterogeneity. A significant association was also detected with lumbar spine BMD (p = 0.006); however, inter-study heterogeneity was observed. Associations with lumbar spine and trochanteric BMD were observed predominantly in women and became less significant in meta-regression (p = 0.055 and 0.01, respectively). There were no consistent associations of APOE4 genotype with BMD at other skeletal sites or with fracture risk.. Based on these findings, there is insufficient evidence to support a strong and consistent association of the APOE genotype with BMD and fracture incidence.

Topics: Aged; Aged, 80 and over; Apolipoproteins E; Bone Density; Female; Genotype; Heterozygote; Hip Joint; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Osteoporotic Fractures; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Vitamin K

The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.

Topics: 1-Carboxyglutamic Acid; Bone and Bones; Humans; Neurodegenerative Diseases; Osteoporosis; Vitamin K; Vitamin K Deficiency; Vitamins

Osteoporosis is a major public health issue in Japan, and key factors for its prevention are diet and exercise. Vitamin D and K are strongly associated with bone metabolism. The recommended daily vitamin D and K requirements are 400-800 IU and 250-300μg, respectively. In addition, exercise is effective for the improvement of bone mineral density in the elderly. Regular exercise and improvement of diet are important for the prevention of osteoporosis in the aging society.

Topics: Bone and Bones; Bone Density; Diet; Exercise; Humans; Life Style; Osteoporosis; Vitamin D; Vitamin K

Sufficient calcium intake and vitamin D adequacy are prerequisite for any pharmacological treatment for osteoporosis. The latter has been often ignored in Japan, partly because serum 25(OH)D measurement is not reimbursed by health insurance policy and perhaps because natural vitamin D cannot be prescribed by phySicians in this country. Here, some of the recent metaanalyses of calcium, vitamin D metabolites, and vitamin K on osteoporosis are reviewed. A new vitamin D metabolite, eldecalcitol, will also be discussed.

Topics: Calcium; Humans; Osteoporosis; Vitamin D; Vitamin K

Osteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and/or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures.

Topics: Animals; Ascorbic Acid; Avitaminosis; Bone and Bones; Female; Fractures, Bone; Humans; Male; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Vitamin A; Vitamin B Complex; Vitamin E; Vitamin K; Vitamins

This review summarizes recently published data on the epidemiology, pathophysiology and treatment of cystic fibrosis (CF)-related low bone mineral density (BMD).. A systematic literature review reports that the pooled prevalence of osteoporosis in adults with CF is 23.5% [95% confidence interval (CI) 16.6-31.0] and the pooled prevalences of radiologically confirmed vertebral and nonvertebral fractures are 14% (95% CI 7.8-21.7) and 19.7% (95% CI 6.0-38.8), respectively. Recent data suggest that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in bone cells and that CFTR dysfunction affects bone cell activity. The secondary effects of CFTR dysfunction also influence bone metabolism. For example, bone resorption increases during CF pulmonary exacerbations due to the stimulatory effects of proinflammatory cytokines on osteoclast activity. Bisphosphonates inhibit osteoclastic bone resorption and recent data show that both oral and intravenous bisphosphonates improve BMD in patients with CF.. CF-related low BMD is a common but treatable complication of CF.

Topics: Bone Density; Calcium; Cholecalciferol; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Diphosphonates; Humans; Osteoporosis; Vitamin K

Recent interest in vitamin K has been motivated by evidence of physiological roles beyond that of coagulation. Vitamin K and vitamin K-dependent (VKD) proteins may be involved in regulation of calcification, energy metabolism, and inflammation. However, the evidence for many of these proposed roles in the maintenance of health is equivocal. There is also an emerging viewpoint that the biochemical function of vitamin K may extend beyond that of a cofactor for the VKD carboxylation of glutamyl residues (Glus) to carboxylated Glus in VKD proteins.

Topics: Cardiovascular Diseases; Dietary Supplements; Energy Metabolism; Evidence-Based Medicine; Humans; Inflammation; Osteoporosis; Randomized Controlled Trials as Topic; Vitamin K

Diagnosis and treatment of osteoporosis are evolving from BMD (bone mineral density) dependent manner to bone quality conscious manner. However, clinical methods to evaluate bone quality of diabetic patients have not been established yet. Therefore, many potentially osteoporotic patients with diabetes are not recognized as high fracture risk patients under the current therapeutic guideline of osteoporosis. On the other hand, some drugs for osteoporosis affect pathophysiology of diabetes. In the future, it is possible that drugs for osteoporosis are chosen according to the diabetic state of each patient.

Topics: Bone Density Conservation Agents; Diabetes Complications; Diphosphonates; Fractures, Bone; Humans; Osteoporosis; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Vitamin D; Vitamin K

Soybean and various types of soy products, such as natto, tofu, miso, and soy sauce, have long been consumed in Japan. Soybean, a rich source of plant proteins, contains a relatively high amount of calcium as well as being an important source of isoflavones, a group of substances whose chemical structure is similar to that of estrogen. Natto, fermented soybeans, contains vitamin K, which is involved in the activation of osteocalcin. For bone health and osteoporosis prevention in Japanese, it is thus beneficial to consume adequate amounts of soybean and soy products on a daily basis.

Topics: Asian People; Bone and Bones; Bone Density; Calcium, Dietary; Glycine max; Humans; Isoflavones; Osteocalcin; Osteoporosis; Soy Foods; Soybean Proteins; Vitamin K

Unlike pharmacological agents that are taken for proscribed periods of time, food and nutrient intakes have the possibility of affecting bone health over the entire lifespan. While deficiencies or excesses of individual nutrients have been shown to affect bone, it is likely that individual foods or dietary patterns have important effects related to skeletal health. While biochemical mechanisms exist to relate a deficiency of vitamin K to altered bone metabolism, clinical trials related to supplementation of this nutrient have been confusing. It is likely that these disparate results are related to the fact that interactions of nutrients have not been considered or the possibility that suboptimal nutrient status is a marker of poor nutritional status. Vitamin A excess has been postulated to be related to high fracture risk; however, it is likely that retinol is not the best marker for the proposed interaction. Altering whole food patterns, such as the Dietary Approaches to Stop Hypertension diet, have demonstrated beneficial effects on bone metabolism. Individuals who select some vegetarian patterns may need to consider supplementation with nutrients such as calcium and protein. Future studies should center on whole food and dietary patterns and their relationship to bone metabolism and fracture risk.

Topics: Animals; Bone and Bones; Bone Density; Calcium; Clinical Trials as Topic; Diet; Dietary Supplements; Female; Food; Fractures, Bone; Humans; Male; Milk; Nutritional Requirements; Osteoporosis; Vitamin A; Vitamin D; Vitamin K; Women's Health

Insufficient vitamin K nutrition is one of the risks for bone fracture. Vitamin K is clinically applied to osteoporosis treatment in Japan and Asian countries, as the administration has preventive effects on bone fracture. Recent studies have revealed that vitamin K functions as a ligand for Steroid and Xenobiotic Receptor (SXR), as well as a cofactor for gamma-carboxylase. In osteoblastic cells, several SXR responsive genes have been identified, including tsukushi, matrilin-2, CD14, and Msx2. Working together with gamma-carboxylated bone proteins, these SXR targets will function in the vitamin K-mediated bone protection. It has been also suggested that vitamin K could prevent or treat the hepatocellular carcinoma (HCC) in some clinical studies. SXR may also contribute to the vitamin K-dependent reduction of HCC.

Topics: Carbon-Carbon Ligases; Carcinoma, Hepatocellular; Coenzymes; Fractures, Spontaneous; Humans; Ligands; Liver Neoplasms; Osteoblasts; Osteoporosis; Pregnane X Receptor; Receptors, Steroid; Vitamin K; Vitamin K Deficiency

Calcium is a target for Anti-aging Medicine. Risk assessment for osteoporosis would be useful for estimation of future bone health. SNPs may be applicable as genetic markers to predict the risk of osteoporosis. Hormone replacement therapy, vitamins and calcium will be important for prevention and treatment of osteoporosis.

Topics: Aging; Apolipoproteins E; Bone Density; Calcium; Estrogen Replacement Therapy; Genetic Markers; Humans; Life Style; Osteoporosis; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Receptors, Estrogen; Risk; Vitamin K

A protective role for vitamin K in bone health has been suggested based on its role as an enzymatic cofactor. In observational studies, vitamin K insufficiency is generally associated with lower bone mass and increased hip fracture risk. However, these findings are not supported in randomized controlled trials (RCT) of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the elderly. This suggests that increased vegetable and legume intakes may simultaneously improve measures of vitamin K status and skeletal health, even though the mechanisms underlying these improvements may be independent of each other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears to protect against fracture risk and bone loss at the spine. However, there are emerging data that suggest the efficacy of vitamin K supplementation on bone loss is inconclusive.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Density; Child; Child, Preschool; Dietary Supplements; Female; Humans; Male; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K 1; Vitamin K Deficiency

A significant point of dietary therapy for osteoporosis is that calcium, vitamin D and vitamin K are recommended to be actively administered on top of sufficient intake of energy and the other nutrients including protein. In Japanese guidelines for the prevention and treatment of osteoporosis 2006 edition, daily intake of calcium and vitamin D is encouraged at least 800mg and 400 to 800IU (10 to 20microg) , respectively. Calcium and vitamin D are also important for maximizing the effect of drug for osteoporosis. Calcium and vitamin D supplementation could be a supportive measure, when their necessary requirement is difficult to be consumed.

Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Calcium, Dietary; Dietary Proteins; Diphosphonates; Evidence-Based Medicine; Humans; Japan; Middle Aged; Osteoporosis; Practice Guidelines as Topic; Vitamin D; Vitamin K

Vitamin K is a nutrient originally identified as an essential factor for blood coagulation. 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 K1 and K2 have been shown to exert protective effects against osteoporosis. The new biological functions of vitamin K in bone are considered to be attributable, at least in part, to promotion of gamma-carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is shared by both vitamins K1 and K2. A recent evidence of significant correlation between polymorphism of gamma-glutamyl carboxylase gene and bone mineral density supports the role of gamma-carboxylation-dependent actions of vitamin K. In contrast, vitamin K2-specific,gamma-carboxylation-unrelated functions have recently attracted scientific attention. Recent findings of vitamin K2-specific transactivation of steroid and xenobiotic receptor (SXR/PXR) may lead to new research avenue. The impact of genotype of apoE, a major vitamin K transporter, on ostepporosis as well as Alzheimer disease and atherosclerosis, raises a question whether vitamin K is involved in the pathogenesis of these diseases. Molecular bases of coagulation-unrelated pleiotropic actions of vitamin K and its implications in bone health deserve further investigations.

Topics: Adult; Bone and Bones; Humans; Osteoporosis; Vitamin K; Vitamin K Deficiency

Vitamin K is a collective term for lipid-like naphthoquinone derivatives synthesized only in eubacteria and plants and functioning as electron carriers in energy transduction pathways and as free radical scavengers maintaining intracellular redox homeostasis. Paradoxically, vitamin K is a required micronutrient in animals for protein posttranslational modification of some glutamate side chains to gamma-carboxyglutamate. The majority of gamma-carboxylated proteins function in blood coagulation. Vitamin K shuttles reducing equivalents as electrons between two enzymes: VKORC1, which is itself reduced by an unknown ER lumenal reductant in order to reduce vitamin K epoxide (K>O) to the quinone form (KH2); and gamma-glutamyl carboxylase, which catalyzes posttranslational gamma-carboxylation and oxidizes KH2 to K>O. This article reviews vitamin K synthesis and the vitamin K cycle, outlines physiological roles of various vitamin K-dependent, gamma-carboxylated proteins, and summarizes the current understanding of clinical phenotypes caused by genetic mutations affecting both enzymes of the vitamin K cycle.

Topics: Animals; Blood Coagulation; Calcium; Carbon-Carbon Ligases; Coumarins; Homeostasis; Humans; Mixed Function Oxygenases; Osteoporosis; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Epoxide Reductases

Vitamin K is receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to gamma-carboxyglutamate (Gla). The gamma-carboxylation of the Gla proteins is essential for the proteins to attract Ca2+ and to incorporate these into hydroxyapatite crystals. The best known of the three known bone-related Gla proteins is osteocalcin (OC). Even though the exact role of OC is not known, a number of studies have shown that vitamin K insufficiency or high levels of undercarboxylated osteocalcin (ucOC) is associated with an increase in the concentration of circulating ucOC. Furthermore, several studies have demonstrated that vitamin K insufficiency is associated with low bone mineral density (BMD) and increased fractures. Vitamin K supplementation, on the other hand, has been shown to improve the bone turnover profile and decrease the level of circulating ucOC. Dietary recommendations are based on saturation of the coagulation system, and in most countries the dietary intake is sufficient to obtain the amount recommended. In relation to bone, requirements might be higher. The aim of this chapter is to give an overview of the importance of vitamin K in relation to bone health in adult humans and thereby in the prevention of osteoporosis. Furthermore, I will shortly discuss the interaction with vitamin D and the paradox in relation to warfarin treatment.

Topics: Adult; Anticoagulants; Bone and Bones; Diet; Glutamic Acid; Humans; Nutritional Status; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K 1; Vitamin K 2

Osteoporosis is a metabolic bone disease characterized by reduced bone quality and quantity. As a consequence, patients are at risk for fractures, subsequent immobility, and higher mortality especially among elder patients. Because of the high incidence of complications and the associated financial burden for the health system, new parameters for diagnostic and therapeutic purposes are urgently needed. In this regard, research focused on vitamin K as a biochemical bone marker has provided promising results. Vitamin K represents an important enzyme-cofactor for the posttranslational modification and activation of several proteins involved in bone metabolism. Vitamin K has been proven to be a valuable diagnostic as well as therapeutic parameter especially in osteoporosis. Patients with osteoporosis have been shown to have decreased levels of vitamin K. Further, regular intake of vitamin K may increase bone mineral density (BMD), thereby lowering the fracture risk. Yet vitamin K alone may not sufficiently indicate the mineral status of the bone. However, the usefulness of a combination of several biochemical bone markers as improved surrogate markers of bone metabolism has been shown recently. Therefore, this review will focus on the significance and importance of vitamin K for bone metabolism. Beyond this, aspects on the current and prospective use of vitamin K as well as other newly developed biochemical bone markers will be discussed.

Topics: Biomarkers; Bone and Bones; Bone Development; Diet; Humans; Nutritional Physiological Phenomena; Osteoporosis; Vitamin K

Throughout the life cycle the skeleton requires optimum development and maintenance of its integrity to prevent fracture. Bones break because the loads placed on them exceed the ability of the bone to absorb the energy involved. It is now estimated that one in three women and one in twelve men aged >55 years will suffer from osteoporosis in their lifetime and at a cost in the UK of > 1.7 pounds x 10(9) per year. The pathogenesis of osteoporosis is multifactorial. Both the development of peak bone mass and the rate of bone loss are determined by key endogenous and exogenous factors. Ca supplements appear to be effective in reducing bone loss in women late post menopause (>5 years post menopause), particularly in those with low habitual Ca intake (<400 mg/d). In women early post menopause (<5 years post menopause) who are not vitamin D deficient, Ca supplementation has little effect on bone mineral density. However, supplementation with vitamin D and Ca has been shown to reduce fracture rates in the institutionalised elderly, but there remains controversy as to whether supplementation is effective in reducing fracture in free-living populations. Re-defining vitamin D requirements in the UK is needed since there is evidence of extensive hypovitaminosis D in the UK. Low vitamin D status is associated with an increased risk of falling and a variety of other health outcomes and is an area that requires urgent attention. The role of other micronutrients on bone remains to be fully defined, although there are promising data in the literature for a clear link between vitamin K nutrition and skeletal integrity, including fracture reduction.

Topics: Bone Density Conservation Agents; Calcium; Calcium, Dietary; Female; Fractures, Bone; Humans; Male; Nutritional Requirements; Osteoporosis; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamin K

The prevention of osteoporotic fracture is an essential socioeconomical priority, especially in the developed countries including Japan. Estrogen, selective estrogen-receptor modulators (SERMs), and bisphosphonate are potent inhibitors of bone resorption; and they have clinical relevance to reduce osteoporotic fractures in postmenopausal women. However, we can prevent at most 50% of vertebral fractures with these agents. For the better compliance of aminobisphosphonate, the use of a daily bisphosphonate regimen is moving to a weekly or monthly bisphosphonate regimen. Both cathepsin K inhibitors and modulators of the RANK-RANKL system, which can reduce bone resorption, are the candidates for the future treatment of osteoporosis. As well as bone resorption, we need to increase bone formation to prevent osteoporotic fractures, particularly in elderly patients with low bone turnover. In the U.S., Europe, and Australia, they have already started intermittent parathyroid hormone injection and/or oral strontium ranelate to stimulate bone formation. We still need to discover new agents to reduce osteoporotic fractures for the better quality of life without fractures.

Topics: Aging; Bone and Bones; Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Diphosphonates; Fractures, Bone; Humans; Osteogenesis; Osteoporosis; Receptors, Androgen; Selective Estrogen Receptor Modulators; Treatment Outcome; Vitamin D; Vitamin K

Epidemic rates of osteoporosis in the western world have yielded intense efforts to develop management approaches to combat this potentially devastating disorder; recent research has unveiled innovative strategies which hold considerable promise for prevention of skeletal compromise and amelioration of suboptimal bone health. According to many algorithms and practice directives, the contemporary assessment and management of osteoporosis focuses heavily on determination of fracture risk and pharmaceutical intervention for those patients deemed to be at high risk. While routine recommendations for calcium and vitamin D have been incorporated into most regimens, disproportionately little attention has been given to recent research elucidating improved bone health and diminution in fracture rates experienced by patients receiving specific nutrients. In mainstream medical practice, clinical analysis and management of nutritional or dietary issues is sometimes perceived as unconventional, primitive or unsophisticated health care. Recent evidence-based research, however, supports intervention with adequate amounts of specific nutrients including vitamin D, strontium, vitamin K, and essential fatty acids in the prevention and primary management of osteoporosis.

Topics: Bone Density; Bone Density Conservation Agents; Calcium, Dietary; Diet; Evidence-Based Medicine; Fatty Acids, Essential; Humans; Osteoporosis; Risk Factors; Strontium; Vitamin D; Vitamin K

Poor vitamin K nutrition has recently been linked to several chronic diseases associated with abnormal calcification, which affect many elderly. To understand the impact of vitamin K nutrition on healthy aging it is necessary to assess both the determinants and the adequacy of vitamin K nutritional status of the elderly.. Overall, elderly persons consume more vitamin K than young adults. However, a subgroup of the elderly population does not meet the current recommended dietary intakes for this nutrient. The first meta-analysis evaluating the data on the role of vitamin K and bone health concluded that increased intakes of vitamin K are warranted to reduce bone loss and fracture risk among the elderly. Recent studies suggest that nondietary determinants of vitamin K status need to be factored into any discussion on the adequacy of nutritional status of the elderly. One promising area of research is the interrelationship between estrogen and vitamin K.. Evidence is emerging to support recommendations to increase intakes of vitamin K among the elderly to reduce bone loss and fracture risk. Much more research is required, however, to identify nondietary determinants of vitamin K status, and their impact on the elderly.

Topics: Aging; Fractures, Bone; Humans; Nutritional Requirements; Nutritional Status; Osteoporosis; Vitamin K; Vitamins

Calcium and vitamin D are the mainstays of nutritional intervention for the prevention and treatment of osteoporosis. However, conditions that alter nutritional status as well as other nutrients should be considered when diagnosing and treating osteoporosis and osteopenia. Current research supports the early diagnosis and treatment of anorexia nervosa to prevent associated bone loss and increased risk of fracture. Weight restoration in patients with anorexia nervosa is central to bone mass stabilization. Other nutritional considerations include nutrients such as vitamin B-12 and vitamin K that may reduce fracture risk by increasing bone mineral density as well as the improvement of bone microarchitecture. Diets high in fruits and vegetables contribute nutrients such as magnesium associated with bone health and may also produce an alkaline environment, reducing calcium excretion and thus improving bone density.

Topics: Anorexia Nervosa; Bone Density; Diet; Dietary Supplements; Fruit; Homocysteine; Humans; Nutritional Requirements; Osteoporosis; Randomized Controlled Trials as Topic; Vegetables; Vitamin B 12; Vitamin K

Bone health, characterized by its mass, density, and micro-architectural qualities, is maintained by a balanced system of remodeling. The lack of these qualities, caused by an uncoupling of the remodeling process, leads to bone fragility and an increased risk for fracture. The prime regulator of bone remodeling is the RANK/RANKL/OPG system. The common origin of both bone and immune stem cells is the key to understanding this system and its relationship to the transcription factor nuclear factor kappaB in bone loss and inflammation. Via this coupled osteo-immune relationship, a catabolic environment from heightened proinflammatory cytokine expression and/or a chronic antigen-induced activation of the immune system can initiate a switch-like diversion of osteoprogenitor-cell differentiation away from monocyte-macrophage and osteoblast cell formation and toward osteoclast and adipocyte formation. This disruption in bone homeostasis leads to increased fragility. Dietary and specific nutrient interventions can reduce inflammation and limit this diversion. Common laboratory biomarkers can be used to assess changes in body metabolism that affect bone health. This literature review offers practical information for applying effective strategic nutrition to fracture-risk individuals while monitoring metabolic change through serial testing of biomarkers. As examples, the clinician may recommend vitamin K and potassium to reduce hypercalciuria, _-lipoic acid and N-acetylcysteine to reduce the bone resorption marker N-telopeptide (N-Tx), and dehydroepiandrosterone (DHEA), whey, and milk basic protein (the basic protein fraction of whey) to increase insulin-like growth factor-1 (IGF-1) and create a more anabolic profile.

Topics: Absorptiometry, Photon; Acidosis; Biomarkers; Bone Density; Bone Remodeling; C-Reactive Protein; Calcium; Celiac Disease; Dehydroepiandrosterone; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Hyperhomocysteinemia; Male; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Thyroid Diseases; Vitamin D; Vitamin K

Osteoporosis is a multifactorial chronic disease that may become even more prevalent and more of a public health problem in the decades to come. Recent research has indicated that a number of macro- and micronutrients are involved in the development of bone health. In the past decade it became evident that vitamin K played a significant role in human health beyond its well-established function in blood clotting. In fact, among the proteins known or suspected to be involved in bone and vascular biology there are several members of the vitamin K dependent or gamma-carboxyglutamic acid protein family. Based on the current evidence from epidemiologic and intervention studies, there are insufficient data to recommend a routine supplementation of vitamin K for optimal bone health. New experimental and placebo-controlled studies in humans should clarify our understanding of the role vitamin K plays in improving bone health.

Topics: 1-Carboxyglutamic Acid; Biomarkers; Bone Density; Fractures, Bone; Humans; Nutritional Status; Osteoporosis; Risk Factors; Vitamin K; Vitamins

Vitamin K's effects extend beyond blood clotting to include a role in bone metabolism and potential protection against osteoporosis. Vitamin K is required for the gamma-carboxylation of osteocalcin. Likewise, this gamma-carboxylation also occurs in the liver for several coagulation proteins. This mechanism is interrupted by coumarin-based anticoagulants in both the liver and bone.. A thorough review of the literature on vitamin K, osteocalcin and their role in bone metabolism and osteoporosis, as well as the potential bone effects of anticoagulant therapy was conducted.. Epidemiological studies and clinical trials consistently indicate that vitamin K has a positive effect on bone mineral density and decreases fracture risk. Typical dietary intakes of vitamin K are below the levels associated with better BMD and reduced fracture risk; thus issues of increasing dietary intakes, supplementation, and/or fortification arise. To effectively address these issues, large-scale, intervention trials of vitamin K are needed. The effects of coumarin-based anticoagulants on bone health are more ambiguous, with retrospective studies suggesting that long-term therapy adversely affects vertebral BMD and fracture risk. Anticoagulants that do not affect vitamin K metabolism are now available and make clinical trials feasible to answer the question of whether coumarins adversely affect bone. The research suggests that at a minimum, clinicians should carefully assess anticoagulated patients for osteoporosis risk, monitor BMD, and refer them to dietitians for dietary and supplement advice on bone health. Further research is needed to make more efficacious decisions about vitamin K intake, anticoagulant therapy, and bone health.

Topics: Anticoagulants; Bone and Bones; Bone Density; Coumarins; Humans; Nutritional Requirements; Osteocalcin; Osteoporosis; Risk Factors; Time Factors; Vitamin K; Vitamin K Deficiency

Vitamin K (VK) is well known for its role in the synthesis of a number of blood coagulation factors. VK is also an important factor for bone metabolism via gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recently, it is rare that severe VK deficiency is observed. However, low dietary VK intake or low VK status has been shown to be associated with low bone mineral density and increased hip fracture risk. These studies suggest that there is potential VK insufficiency in bone, even in sufficient VK status for blood coagulation. In the present review, the studies concerning relationship between serum VK concentration and bone health, including pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and factors which affect on blood circulation of VK, are reviewed.

Topics: Adult; Aged; Biomarkers; Bone and Bones; Bone Density; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Hip Fractures; Humans; Male; Matrix Gla Protein; Middle Aged; Nutrition Assessment; Osteocalcin; Osteoporosis; Risk; Vitamin K; Vitamin K Deficiency

Topics: Asian People; Bone Density Conservation Agents; Calcium, Dietary; Diphosphonates; Humans; Nutritional Requirements; Osteoporosis; Selective Estrogen Receptor Modulators; Vitamin D; Vitamin K

Metabolic bone disease (osteodystrophy) is an important complication of patients with chronic liver disease; its etiology is complex and multifactorial. Osteodystrophy is manifested as osteopenia/osteoporosis. Osteoporosis can predispose patients to bone fractures, increasing morbidity and mortality, especially after liver transplantation. Early evaluation, screening, and treatment of bone disorders in patients with liver disease are essential to minimize fracture risk and to improve clinical outcome and quality of life.

Topics: Ascorbic Acid; Bone and Bones; Bone Diseases, Metabolic; Calcium; Chronic Disease; Humans; Liver Diseases; Nutrition Therapy; Osteoporosis; Vitamin D; Vitamin K

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

Active vitamin D has been most widely used in Japan for the treatment of osteoporosis. However, clinical evidence for its efficacy as an anti-osteoporotic drug is scarce in terms of fracture prevention. Recent reports suggest that active vitamin D may prevent fracture not only through enhancement of intestinal calcium absorption but also by improving bone quality and/or strength independently of bone mass and by improving neuromuscular function to reduce the number of fall. Low serum concentrations of vitamin K have been reported in patients with osteoporosis, and serum osteocalcin appears to be undercarboxylated in these individuals, a process dependent on vitamin K. Undercarboxylated osteocalcin is also a significant risk for hip fracture. Clinical studies in Japan suggest that menatetrenone (vitamin K2) reduces skeletal losses and, in a small randomized clinical trial, it reduced the rate of vertebral fractures. Menatetrenone is currently used in Japan, the Republic of Korea and Thailand.

Topics: Humans; Osteoporosis; Vitamin D; Vitamin K

A significant point of nutritional care and management for osteoporosis is that calcium and vitamin D are recommended to be actively administered on top of sufficient intake of energy and the other nutrients including protein. Daily intake of calcium and vitamin D is encouraged at least 800 mg and 10 to 20 microg, respectively. Calcium and vitamin D are also important for maximizing the effect of osteoporosis drug therapy. Supplement of calcium or vitamin D could be a supportive measure, when their necessary amount is difficult to be consumed.

Topics: Aged; Calcium, Dietary; Female; Humans; Male; Osteoporosis; Vitamin D; Vitamin K

Many reports have indicated the significant correlation between low vitamin K intakes and the increased prevalence of osteoporotic fractures. The role of vitamin K in bone metabolism is assumed to be mediated by carboxylation of vitamin-K-dependent proteins. In addition, recent researches suggest the novel action of vitamin K(2) via nuclear receptors. The role of vitamin K in the prevention as well as the treatment of osteoporosis should be more emphasized.

Topics: Bone and Bones; Humans; Osteoporosis; Vitamin K

Calcium intake was reported to be associated with peak bone mass. Vitamin D insufficiency, which is less severe than deficiency, is prevalent in the elderly and known to cause osteoporosis. Protein malnutrition increases the fracture risk due to decreased bone mineral density and muscle weakness. Other nutrients have also been reported to be associated with osteoporosis. Thus nutritional aspect of osteoporosis should be interpreted from the broader perspectives. Since nutritional status greatly varies from one nation to another, we must add our original evidence in Japan to the report from WHO.

Topics: Calcium; Calcium, Dietary; Dietary Proteins; Humans; Japan; Nutritional Physiological Phenomena; Nutritional Status; Osteoporosis; Protein Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; World Health Organization

Arteriosclerosis, characterized by remodeling and stiffening of large elastic arteries is the most significant manifestation of vascular aging. The increased stiffening is believed to originate from a gradual mechanical senescence of the elastic network, alterations in cross-linking of extracellular matrix components, fibrosis and calcification of elastic fibers (medial elastocalcinosis). The stiffening of large arteries reduces their capacitance and accelerates pulse wave velocity, thus contributing to a widening of pulse pressure and to the increased prevalence of isolated systolic hypertension with age. Current antihypertensive drugs were mainly designed to reduce peripheral resistance and are not adequate to alter the pathological process of vascular stiffening or even to selectively reduce systolic blood pressure in isolated systolic hypertension. This review puts forward the concept that elastocalcinosis is a valuable therapeutic target and presents evidence that this process can be prevented and reversed pharmacologically.

Topics: Aged; Aging; Antihypertensive Agents; Arteries; Arteriosclerosis; Calcinosis; Humans; Hypertension; Muscle, Smooth, Vascular; Osteoporosis; Systole; Vitamin K; Warfarin

Vitamin K is used as an anti-osteoporosis drug in Japan. Moreover, vitamin K intake has been found to decrease hip fracture risk. In the bone homeostasis, vitamin K action is mediated through two molecular mechanisms: posttranslational modification of proteins, and regulation of gene expression. The former is vitamin K-dependent carboxylation, in which vitamin K functions as an essential cofactor for modification of glutamic acid residues to gamma-carboxyglutamic acid residues. The latter is a novel mechanism that regulates the transcription of target genes by vitamin K through activation of steroid and xenobiotic receptor (SXR). The two mechanisms may coordinately contribute to vitamin K function in the bone metabolism.

Topics: Animals; Bone and Bones; Carboxylic Acids; Glutamates; Humans; Osteoporosis; Receptors, Steroid; Vitamin K

Subclinical vitamins deficiency is common in the elderly, especially in osteoporotic patients. However, most physicians in this area are just focused on drugs for the treatment of osteoporosis. It is already established that several vitamins influence bone turnover, bone mineral density, or even the risk of hip fractures. Improving these vitamins status may help to treat and prevent osteoporosis in elderly people. Recently higher vitamin D intake is recognized to be needed to keep not only bone health but also muscle strength. More sun exposure might be needed for improved bone health in the elderly. Deficiency of Vitamin K, C, or B(12) may be also important modifiable risk factors for osteoporosis and bone fracture. Excessive retinal supplementation may become associated with higher bone loss. Thus such diet rich in fruit and vegetables together with fish and meat could fulfill a balance among these vitamins and should be recommended for prevention or treatment of osteoporosis.

Topics: Aged; Ascorbic Acid; Humans; Osteoporosis; Vitamin D; Vitamin K; Vitamins

This paper reviews the interventions to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight. Weightlessness during space flight results in calcium, vitamin D, and vitamin K deficiency, increases urinary calcium excretion, decreases intestinal calcium absorption, and increases serum calcium level, with decreased levels of serum parathyroid hormone and calcitriol. Bone resorption is increased, whereas bone formation is decreased. The loss of bone mineral density (BMD) in the spine, femoral neck and trochanter, and pelvis is 1.0-1.6% per month. High calcium intake and vitamin D supplementation during space flight does not affect bone metabolism, but prevents an elevation of serum calcium level through increased calcitriol level, while vitamin K counteracts the reduction in bone formation. However, there are no data to show the efficacy of pharmaceutical agents for prevention of development of osteoporosis in astronauts during flight, although the preventative effect of bisphosphonates, testosterone, and vitamin K2 on cancellous bone loss in the tibia or BMD loss in the hindlimb was reported in tail-suspended mature rats. It still remains uncertain whether these agents can prevent cortical bone loss caused by weightlessness in tail-suspended rats. Therefore, in addition to calcium, vitamin D, and vitamin K supplementation, agents that have both potent anti-resorptive and anabolic effects on cancellous and cortical bone may be needed to stabilize calcium balance and bone metabolism and prevent bone loss in astronauts during space flight.

Topics: Aerospace Medicine; Animals; Astronauts; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Calcium; Calcium, Dietary; Dietary Supplements; Diphosphonates; Energy Intake; Humans; Osteoporosis; Rats; Sodium Chloride, Dietary; Space Flight; Testosterone; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K 2; Vitamin K Deficiency; Weightlessness; Weightlessness Countermeasures; Weightlessness Simulation

Cystic fibrosis (CF) is the most common genetic disease that causes respiratory failure within the Caucasian population. The life span of patients with CF has gradually increased from a median of 2 years of age to >30 years. Concurrent with this increased lifespan, a variety of other nutritional, endocrine and bone issues have been recognised. Decreased absorption of fat-soluble vitamins (D and K in particular) because of pancreatic insufficiency, altered sex hormone production, chronic inflammation, a lack of physical activity, glucocorticoid treatment and an intrinsic hyper-resorptive bone physiology are some of the factors that contribute to the prominence of bone disease within the CF population. In some series, three-quarters of adult patients with CF have osteopenia or osteoporosis. Lung transplantation is one viable treatment for patients with end-stage CF, which requires a lifetime of antirejection medication. Immunosuppressant therapies have a detrimental effect on bone mineral density (BMD). To combat the multifactorial nature of CF-related bone disease, advances in nutritional and vitamin supplementation, and anti-resorptive and anabolic therapies have evolved. Chronic vitamin D depletion contributes to bone disease in the CF population. The isoform of vitamin D that is the best and safest supplement, with the lowest cost, has yet to be identified. However, it is clear that many patients with CF who receive the standard of care (i.e. two daily combination vitamin A, D, E and K tablets [ADEKs]) may still be vitamin D-deficient. More aggressive supplementation needs to be individualised, with close monitoring of serum 25-hydroxyvitamin D levels. Similarly, routine calcium supplementation may be important, and evidence is accumulating that vitamin K also plays an important role in maximising and maintaining BMD. Early recognition and treatment of delayed puberty in adolescents and hypogonadism in adults with hormone replacement therapy is recommended to maintain BMD in patients with CF. Bisphosphonates, including pamidronic acid, etidronic acid and alendronic acid, reduce bone resorption by inhibiting the recruitment and function of osteoclasts. Pamidronic acid is beneficial in improving BMD in CF patients before and after transplantation. Bisphosphonate therapy and minimisation of glucocorticoid dosage have been shown to be efficacious in glucocorticoid-induced osteoporosis. Teriparatide is the first US FDA-approved anabolic growth agent for bone

Topics: Adult; Clinical Trials as Topic; Cystic Fibrosis; Diphosphonates; Human Growth Hormone; Humans; Osteoporosis; Teriparatide; Vitamin D; Vitamin K

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

Vitamin K has several biological effects and dietary intake seems to be more important than previously believed because of low bioavailability of the vitamins from the colon.. Data from the literature were identified on PubMed, and data from NORKOST II (a dietary study from 1997 based on a nation-wide sample of respondents) were used to calculate dietary intake of vitamin K.. The dietary intake of vitamin K in Norway seems to be < 50% of what is recommended. The stores of vitamin K are small and T/2 in the body is approximately 1-1.5 day. Vitamin K executes its effects by carboxylation of proteins and as ligand (vitamin K2) for a nuclear transcription factor. Biological effects beyond coagulation include bone formation, neural functioning and blood vessel calcification. Anticoagulation with warfarin inhibits vitamin K-dependent reactions and may have detrimental effects on bone formation.. It is possible that the high incidence of osteoporosis in Norway may be due to the low dietary intake of vitamin K, hence it is suggested that the intake of vitamin K should be increased and vitamin K antagonists be replaced with specific thrombin inhibitors. New technology allows measurements of plasma concentration of vitamin K in relation to malabsorption, insufficient diet, and osteoporosis.

Topics: Adult; Blood Coagulation; Bone Density; Calcinosis; Child; Female; Food Analysis; Humans; Male; Nerve Degeneration; Norway; Nutritional Requirements; Osteoporosis; Vitamin K

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. During recent years vitamin K-dependent proteins were discovered to be of vital importance for bone and vascular health. Recommendations for dietary vitamin K intake have been made on the basis of the hepatic requirements for the synthesis of blood coagulation factors. Accumulating evidence suggests that the requirements for other functions than blood coagulation may be higher. This paper is the result of a closed workshop (Paris, November 2002) in which a number of European vitamin K experts reviewed the available data and formulated their standpoint with respect to recommended dietary vitamin K intake and the use of vitamin K-containing supplements.

Topics: Antifibrinolytic Agents; Arteriosclerosis; Bone and Bones; Calcinosis; Dietary Supplements; Fractures, Bone; Humans; Nutritional Requirements; Osteocalcin; Osteoporosis; Safety; Vitamin K; Vitamin K Deficiency

To assess growing evidence that vitamin K (phylloquinone) plays an important role in bone health and, subsequently, in prevention of osteoporotic fractures.. We searched MEDLINE from January 1972 to December 2002 using the key words vitamin K and bone health. We reviewed 30 articles that seemed relevant or had a human focus. All evidence can be categorized as level II.. Evidence suggests that dietary phylloquinone intake of <100 microg daily might not be optimal for bone health. Low intake of vitamin K could contribute to osteoporosis and subsequent fracture due to the undercarboxylation of osteocalcin.. Family physicians need to be aware of the importance of encouraging adequate vitamin K intake, particularly among institutionalized elderly people, to prevent increased bone resorption. Further study is needed to determine the exact role of vitamin K in bone metabolism, and methods of assessing vitamin K requirements need to be standardized.

Topics: Aged; Bone Resorption; Clinical Trials as Topic; Epidemiologic Studies; Family Practice; Female; Fractures, Bone; Humans; Male; Nutrition Policy; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K Deficiency

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

Topics: Acid-Base Equilibrium; Animals; Calcium, Dietary; Dietary Proteins; Estrogens, Non-Steroidal; Humans; Isoflavones; Osteoporosis; Phytoestrogens; Plant Preparations; Vitamin D; Vitamin K

Osteoporosis is one of the most common bone-related disorders in the elderly. It is a complex disease, and largely determined genetically. Traditional gene expression studies have shown that osteoporosis has complex regulating mechanisms which are controlled by multiple inherent factors, such as hormones, cytokines, various receptors, etc. The complex nature of osteoporosis, and the large number of genes involved in its onset and development, suggest the use of the state of the art microarray technique as a powerful tool to unravel mechanisms underlying etiology of osteoporosis.

Topics: Aged; Female; Forecasting; Gallium; Gene Expression Regulation; Humans; Oligonucleotide Array Sequence Analysis; Osteoporosis; Osteoporosis, Postmenopausal; RNA; Vitamin K

Osteoporosis is a serious public health concern. Skeletal fragility, leading to spine and hip fractures, is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of life is critical for the formation and retention of a healthy skeleton. It is important to prevent bone loss from occurring, to identify potential risk factors, and to correct them. Many genetic and lifestyle factors influence the risk for osteoporosis. Among these, diet is believed to be one of the most important, especially the roles of calcium and vitamin D. Deficiency in other dietary factors--eg, protein, vitamin K, vitamin A, phytoestrogens, and other nutrients--might also contribute to the risk for osteoporosis. In this article, the roles of diet and nutritional supplementation in preventing and treating osteoporosis are reviewed.

Topics: Adolescent; Adult; Aged; Bone and Bones; Calcium, Dietary; Child; Child, Preschool; Diet; Dietary Supplements; Estrogens, Non-Steroidal; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Isoflavones; Life Style; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Quality of Life; Risk Factors; United States; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

There is a closely relationship between vitamin K and osteoporosis. As a cofactor for carboxylase activity, vitamin K can facilitate the conversion of glutamyl to gamma-carboxyglutamyl residues and influence the synthesis and excretion of gamma-carboxylation of osteocalcin to increase the formation of bone. Vitamin K can also effectively inhibit the absorption of bone mass. Besides, there are increasing evidences that vitamin K can effect the synthesis and excretion of nephrocalcin and interlukin-1,6 that can regulate calcium balance and bone metabolism. Meanwhile, there is a consistent line of evidence in human epidemiologic and intervention studies that clearly demonstrate that vitamin K can not only increase bone mineral density in osteoporotic people, but also reduce fracture rates to improve bony health. However more researches are required before vitamin K is widely applied in prevention and treatment of osteoporosis. The American Medical Association recently has increased the dietary reference intakes of vitamin K to 90 mg/d for females and 120 mg/d for males.

Topics: Animals; Bone Density; Humans; Nutritional Requirements; Osteocalcin; Osteoporosis; Vitamin K

Topics: Bone Resorption; Calcium; Dietary Proteins; Humans; Nutritional Status; Osteoporosis; Potassium; Vitamin D; Vitamin K

Low energy intake, low calcium intake, low plasma 25-hydroxy-vitamin D or low calcitriol levels, and high salt intake might support the development of space osteoporosis. Therefore, my colleagues and I monitored the daily energy and calcium intakes in eight astronauts during their respective space missions (Spacelab D2, Euromir 94, Euromir 95). In most of these astronauts, energy intake was reduced by more than 20% compared with their calculated energy expenditure. In all three missions, the average daily calcium intake of the eight astronauts was 25% lower than the German recommended daily allowances of 900 mg/d for healthy people without osteoporosis risk. In some astronauts, the calcium intake was extremely low at 53 and 74 mg/d. Sodium intake in these astronauts varied from 39 mEq/d to a very high intake of 462 mEq/d. As a consequence of these results, we examined in the 21-d Mir 97 mission a preventative dietary approach of high calcium intake of at least 1000 mg/d with vitamin D supplementation (650 IU/d of Ergocalciferol) and constant sodium intake (180 mEq/d). Total serum calcium concentration and urinary calcium excretion significantly increased during this mission. Synthesis of 25-OH-cholecalciferol synthesis was markedly reduced because of inadequate ultraviolet light, whereas total 25-OH-Vitamin D levels were unchanged. However, parathyroid hormone and calcitriol levels decreased significantly. Sodium excretion decreased significantly, resulting in positive sodium balances. Based on these results, dietary calcium and vitamin D do not stabilize bone turnover because markers of bone formation were reduced and markers of bone resorption were increased. We concluded that, in contrast to terrestrial conditions, adequate or even high calcium and vitamin D intakes during microgravity do not efficiently counteract the development of space osteoporosis. Conversely, vitamin K (Konakion) seemed to counteract microgravity-induced reduction of bone formation markers. In the 179-d Euromir 95 mission, investigators administered 10 mg of vitamin K from inflight day 86 to day 136 in one astronaut. During and after supplementation, bone formation markers increased significantly during this part of the mission. Therefore, vitamin K seems to play a significant role in bone turnover during space flight.

Topics: Aerospace Medicine; Bed Rest; Biomarkers; Bone and Bones; Bone Resorption; Calcium, Dietary; Energy Intake; Humans; Osteoporosis; Sodium Chloride, Dietary; Space Flight; Vitamin D; Vitamin K; Weightlessness; Weightlessness Countermeasures; Weightlessness Simulation

Topics: Animals; Bone and Bones; Bone Density; Bone Development; Calcium; Child; Diet; Female; Humans; Infant; Maternal Nutritional Physiological Phenomena; Milk; Minerals; Osteoporosis; Pregnancy; Sodium; Vitamin D; Vitamin K

Topics: Animals; Bone and Bones; Femoral Neck Fractures; Fractures, Stress; Humans; Osteocalcin; Osteoporosis; Spinal Fractures; Vitamin K

Topics: Calcium, Dietary; Dietary Proteins; Humans; Magnesium; Nutrition Assessment; Osteoporosis; Vitamin D; Vitamin K

Topics: Biological Availability; Bone and Bones; Cognition Disorders; Humans; Osteoporosis; Oxidative Stress; Vitamin K; Vitamins

For early prevention or inhibition of postmenopausal and age-related bone loss, nutritional interventions might be a first choice. For some vitamins and minerals an important role in bone metabolism is known or suggested. Calcium and vitamin D support bone mineral density and are basic components in most preventive strategies. Magnesium is involved in a number of activities supporting bone strength, preservation, and remodeling. Fluorine and strontium have bone-forming effects. However, high amounts of both elements may reduce bone strength. Boron is especially effective in case of vitamin D, magnesium, and potassium deficiency. Vitamin K is essential for the activation of osteocalcin. Vitamin C is an important stimulus for osteoblast-derived proteins. Increasing the recommended amounts (US RDA 1989), adequate intakes (US DRI 1997), or assumed normal intakes of mentioned food components may lead to a considerable reduction or even prevention of bone loss, especially in late postmenopausal women and the elderly.

Topics: Ascorbic Acid; Bone Density; Boron; Calcium; Female; Humans; Magnesium; Middle Aged; Minerals; Osteoporosis; Osteoporosis, Postmenopausal; Strontium; Vitamin D; Vitamin K; Vitamins

In search of vitamin K literature, interesting results were discovered. A summary is presented.. The literature was found by using Medline. The level of vitamin K1 in the Norwegian diet was estimated from tables of food consumption and vitamin K1 per 100 g.. Vitamin K is required for the carboxylation of the amino acid glutamic acid to gamma-carboxyglutamic acids on proteins, which is essential for the calcium binding capacity of Gla proteins (such as osteocalcin). These proteins are found in tissues such as bone, brain, pancreas and lungs, showing that Gla proteins have further important functions. Low intakes of the vitamin may be an important factor for osteoporosis and possibly also for atherosclerosis. The level of vitamin K1 in the Norwegian diet (purchase level) is estimated to be 60 micrograms K1/day before correction of waste. This level is lower than the recommended dietary allowance (1 microgram/kg body weight/day).. There is a discussion in the literature of whether the allowances should be considerably higher (375 micrograms K1/day). Deep green vegetables and soybean oil are the best sources of vitamin K1, while cheese gives some K2. On the basis of this knowledge about the importance of vitamin K and osteoporosis, an intervention test should be done with respect to the high incidence of osteoporosis in Norway. Analysis of Norwegian foods for vitamin K1 and K2 is needed.

Topics: Adult; Aged; Cardiovascular Diseases; Feeding Behavior; Female; Humans; Male; Middle Aged; Norway; Osteoporosis; Osteoporosis, Postmenopausal; Risk Factors; Vitamin K

In the past decade it has become evident that vitamin K has a significant role to play in human health that is beyond its well-established function in blood clotting. There is a consistent line of evidence in human epidemiologic and intervention studies that clearly demonstrates that vitamin K can improve bone health. The human intervention studies have demonstrated that vitamin K can not only increase bone mineral density in osteoporotic people but also actually reduce fracture rates. Further, there is evidence in human intervention studies that vitamins K and D, a classic in bone metabolism, works synergistically on bone density. Most of these studies employed vitamin K(2) at rather high doses, a fact that has been criticized as a shortcoming of these studies. However, there is emerging evidence in human intervention studies that vitamin K(1) at a much lower dose may also benefit bone health, in particular when coadministered with vitamin D. Several mechanisms are suggested by which vitamin K can modulate bone metabolism. Besides the gamma-carboxylation of osteocalcin, a protein believed to be involved in bone mineralization, there is increasing evidence that vitamin K also positively affects calcium balance, a key mineral in bone metabolism. The Institute of Medicine recently has increased the dietary reference intakes of vitamin K to 90 microg/d for females and 120 microg/d for males, which is an increase of approximately 50% from previous recommendations.

Topics: Bone and Bones; Bone Density; Drug Synergism; Female; Fractures, Bone; Humans; Male; Nutritional Requirements; Osteocalcin; Osteoporosis; Vitamin D; Vitamin K

The K vitamins, a group of napthoquinones, are required for the carboxylation of a limited number of proteins including the bone matrix protein osteocalcin. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones), differ regarding food source (green vegetables and fermented products, respectively), bioavailability and intermediate metabolism. Epidemiological studies provide evidence for an association between a low vitamin K intake and an enhanced osteoporotic fracture risk. Doses of vitamin K1 up to 15 times the current recommended dietary allowance have successfully been used to reduce the percentage of undercarboxylated osteocalcin in the circulation. Studies demonstrating clear beneficial effects on bone health, however, are still lacking. In contrast, therapy with very high pharmacological doses of the vitamin K2 menatetrenone has impressively been used to prevent further bone mineral loss and fracture risk in osteoporotic patients.

Topics: Biological Availability; Bone and Bones; Bone Density; Calcium; Clinical Trials as Topic; Fractures, Bone; Humans; Liver; Osteocalcin; Osteoporosis; Vitamin D; Vitamin K

To investigate the physiological roles of vitamin K analogues in bone metabolism, especially in osteoporosis, we have developed a sensitive and simple analysis system for vitamin K analogues in the serum and bone. After the separation of vitamin K analogues on a reversed-phase column, the analogues were reduced once in a platinum catalyst reduction column on-line and then monitored quantitatively by electrochemical detector (EICOM ECD-300) operated in the oxidation mode (+0.6 V vs. Ag/AgCl). The detection limits at a signal-to-noise ratio of 3 were 2-10 pg for vitamin K analogues. We also investigated the extraction procedures for the vitamin K analogues from serum and bone. Quantitative recoveries from serum and bone were obtained in the range of 80-101% for vitamin K analogues. We could determine both the circulating vitamin K levels in osteoporotic patients and the vitamin K contents in trabecular and cortical bone of osteoarthritis.

Topics: Animals; Bone and Bones; Catalysis; Chromatography, High Pressure Liquid; Electrochemistry; Humans; Osteoarthritis; Osteoporosis; Oxidation-Reduction; Platinum; Rats; Sensitivity and Specificity; Vitamin K

Among the proteins known or suspected to be involved in bone and vascular biology are several members of the vitamin K-dependent or Gla protein family. This review focuses on the role of two of these: osteocalcin and matrix Gla protein. Osteocalcin metabolism has been implicated in the pathogenesis of osteoporosis through an unknown mechanism that may be linked to suboptimal vitamin K status resulting in its undercarboxylation and presumed dysfunction. Recent studies that have investigated this hypothesis are discussed, as are recent promising clinical studies of vitamin K supplementation in osteoporosis. A recently delineated function of matrix Gla protein is as a powerful inhibitor of calcification of arteries and cartilage. In the period covered by this review there have been several landmark studies using cell systems, whole animals and genetic techniques that have consolidated and extended our knowledge of the role of matrix Gla protein in the prevention of ectopic calcification.

Topics: Bone and Bones; Calcinosis; Humans; Osteocalcin; Osteoporosis; Vascular Diseases; Vitamin K

This papers summarizes the main role vitamins are believed to play in the prevention of osteoporosis, a common disease which is anticipated to rapidly increase because of the aging of the population. Vitamin D, the classical vitamin related to bone health, improves bone strength mainly by increasing intestinal calcium absorption and reabsorption of calcium by the kidney. Several intervention studies demonstrated in humans that vitamin D can improve bone status as measured by bone density. Vitamin C is considered an essential cofactor of collagen formation. Epidemiological studies report a positive association between vitamin C intake and bone density. Intervention studies on the effect of vitamin C on bone status are missing. Vitamin B6 could function as a cofactor to build up cross-links. In humans, however, there is little evidence to support this. Vitamin K is required for the biological activity of several coagulation factors; the classical function of vitamin K. Recent research also points to a role of vitamin K in bone metabolism. Vitamin K mediates the <--carboxylation of glutamyl residues on several bone proteins, notably osteocalcin. Epidemiological studies and results from first intervention trials are consistently suggesting that vitamin K may improve bone health.

Topics: Adult; Aged; Ascorbic Acid; Humans; Middle Aged; Osteoporosis; Pyridoxine; Vitamin D; Vitamin K; Vitamins

Aging of Japanese population in recent years is advancing at unexpected speed. The incidence of osteoporosis and fracture increase rapidly with aging of the population. Since 1970, at opening of our department, I have expected that a society would be composed largely of elderly people. To prevent elderly people from being beg-ridden and demented, I have made efforts to prevention and treatment of osteoporosis. Purpose of this paper is to show concerning the screening of osteoporosis in this area of Hakodate city and southern part of Hokkaido, and to report our treatment for osteoporosis. There are many ways of measuring bone mineral density (BMD), and dual energy X-ray absorptiometry (DEXA) is the simplest and the most accurate. Concerning of diagnosis of osteoporosis, we investigated the change of the BMD after hip surgery. On the other hand, we also reported the effectiveness of Vitamin-K for osteoporosis. No studies have ever been tried to clarify about this treatment. We are making efforts to enlighten the people on prevention, early diagnosis and treatment of osteoporosis.

Topics: Absorptiometry, Photon; Adolescent; Adult; Age Factors; Aged; Bone Density; Female; Humans; Japan; Male; Middle Aged; Orthopedics; Osteoporosis; Sex Factors; Vitamin K

Vitamin K2 is a known vitamin to promote post-translational modification of vitamin K-dependent protein such as osteocalcin and blood coagulation factors. The effects of vitamin K2 on cortical bone mineral density in osteoporosis has been shown in the phase III DBT trial which had been reported several years ago. However, until now there is no available data regarding to the effect of vitamin K2 on vertebral bone mineral density (LBMD) and on fracture prevention. Thus, a two years randomized open trial to examine the effects of vitamin K2 on LBMD and the fracture prevention in a total of 167 osteoporotic patients had been carried out. The LBMD in vitamin K2 treated group was maintained for 2 years while, that in the control group was deceased to -3% during 2 years observation. The vertebral fracture incidence in the control group was 0.212 +/- 0.038 events/year and that in the treated group was 0.098 +/- 0.029 (p = 0.0186). Vitamin K2 treated group showed significantly lower Glu-osteocalcin level suggesting that vitamin K2 contributed to increase in post-translational modification of osteocalcin. When the treated group was divided into two groups: Group 1 showed low serum Glu-osteocalcin level and Group 2 maintained high Glu-osteocalcin level despite vitamin K2 administration. The LBMD in group 1 significantly higher than that in the Group 2. This may indicate that sufficient tissue supply of vitamin K2 is the limiting factor to increase in LBMD. Furthermore, patients with Apo E4 phenotype showed less response in LBMD comparing to that in the patients without Apo E4. In conclusion, vitamin K2 is effective to maintain trabecular BMD in osteoporosis and effectively prevent future fracture. However, some part of the patients didn't respond to vitamin K2 treatment. Therefore, we have to develop the more practical way(s) to predict the effectiveness of vitamin K2 treatment in osteoporosis.

Topics: Bone Density; Humans; Osteoporosis; Spinal Fractures; Vitamin K

The paper concerns the nontraditional treatment of osteoporosis using endogenous substances regulating bone metabolism, and also new drugs. NO in high concentrations decreases the activity of osteoclasts, scavenges superoxides which destroy connective tissue, and activates 1 alpha-hydroxylase in kidneys. Bone metabolism is effectively influenced by donors of NO or by modulators of NO synthase. Osteoclastic function is also inhibited by vitamin K. The administration of the vitamin is indicated in osteoporotic patients with proven vitamin K deficiency. Antiestrogens (tamoxifen), ipriflavon and analogues of wortmannin have antiresorptive activity. Under certain conditions parathyroid hormone (PTH) is anabolic for bone. The positive effect on bone was confirmed with the subcutaneous administration of small doses of PTH simulating physiologic pulsatile secretion, as well as the intact somatotropin-IGF-I (insulin like growth factor-I) axis. PTH is extremely useful, especially in osteoporosis induced by hypoestrinism. Somatotropin (GH) also has an anabolic effect on bone. The hormone stimulates bone metabolism with a prevalence of formation due to direct action on bone, as well as by means of IGF-I. Further growth factors with positive osteoprotic effect are TGF-beta (transforming growth factor-beta), FGF (fibroblast growth factor) and calcium conserving dihomogammalinoleic acid. Magnesium influences bone in different ways. It activates osteoblasts, increases bone mineralization, and enhances the sensitivity of target tissues (incl. bone) to PTH and 1,25(OH)2 vitamin D3, Under certain conditions however, magnesium can stimulate bone resorption. A more potent factor than magnesium is stroncium, which not only activates osteoblats but decreases the number of osteoclasts, thus abolishing bone resorption and enhancing formation. Bicarbonates are also favourable for bone. NaHCO3 together with potassium citrate stimulates osteoblasts and enhances bone mineralisation. In the review other prospective substances are also discussed. The osteoprotic effects of most of these factors were confirmed in vitro and in studies in animals, but their use in clinical practice is still a matter for investigation. Mutual interactions with classical osteoprotic drugs remain to be established.

Topics: Animals; Bone and Bones; Growth Hormone; Humans; Insulin-Like Growth Factor I; Magnesium; Nitric Oxide; Osteoporosis; Parathyroid Hormone; Stimulation, Chemical; Strontium; Vitamin K

Vitamin K is required for the biological activity of several coagulation factors, which is considered as the classical function of vitamin K. Recent research, however, suggests a role of vitamin K in bone metabolism. The metabolic role of vitamin K is to facilitate the carboxylation of glutamyl to gamma-carboxyglutamyl residues. Besides the hepatic tissue, in which the clotting factors are produced gamma-carboxyglutamyl-containing proteins are also abundantly available in bone tissue. Osteocalcin accounts for up to 80% of the total gamma-carboxyglutamyl content of mature bone. Human carboxylated osteocalcin contains 3 gamma-carboxyglutamyl residues which confer a highly specific affinity to the calcium ion of the hydroxyapatite molecule. Besides the gamma-carboxylation of osteocalcin vitamin K may also affect other parameters of bone metabolism, such as calcium hemostasis, and prostaglandin E2 and interleukin 6 production. Evidence from observational studies and first intervention trials indicate that vitamin K intakes much higher than the current recommendations improved biochemical markers of bone formation as well as bone density. In conclusion, the mechanistic data as well as the observational data and the results of the first controlled clinical trials in humans point to a beneficial effect of additional intakes of vitamin K in bone health.

Topics: Bone Density; Female; Humans; Male; Osteoporosis; Vitamin K

Topics: Calcitonin; Calcium, Dietary; Estrogens; Female; Humans; Hydroxycholecalciferols; Male; Osteoporosis; Osteoporosis, Postmenopausal; Risk Factors; Vitamin D Deficiency; Vitamin K

Topics: Aging; Bone and Bones; Diet; Humans; Nutritional Status; Osteoporosis; Vitamin D; Vitamin K

Although the abundance of vitamin K-dependent proteins in bone suggests an important function, the precise role of vitamin K in skeletal health remains to be determined. Serum concentrations of vitamin K are reportedly reduced in older individuals and persons with osteoporotic fracture. Whether this is causally related to vitamin K insufficiency or simply reflects inadequate nutritional status is unclear. Circulating levels of undercarboxylated osteocalcin may be a sensitive marker of vitamin K inadequacy and have been reported to be increased in both postmenopausal women and individuals who sustained hip fracture. It is also possible that vitamin K indirectly affects the skeleton via control of renal calcium excretion. The effect of vitamin K antagonists (oral anticoagulants) on both renal calcium excretion and bone density is controversial. Thus, many of the reports implicating a role for vitamin K insufficiency in the development of osteoporosis are conflicting. This review summarizes current knowledge regarding a possible role of vitamin K insufficiency in the pathogenesis of osteoporosis.

Topics: Aged; Amino Acid Sequence; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Humans; Matrix Gla Protein; Middle Aged; Molecular Sequence Data; Nutritional Physiological Phenomena; Osteocalcin; Osteoporosis; Vitamin K; Vitamin K Deficiency

Since the proceedings of the last Consensus Conference on Osteoporosis were published as a supplement to The American Journal of Medicine in November 1991, there has been a plethora of well-documented studies reported in the literature. This article will address some of the issues concerning the relation between bone mass and nutrition raised in those studies.

Topics: Adolescent; Adult; Aged; Bone Density; Calcium, Dietary; Child; Female; Fractures, Bone; Humans; Life Style; Middle Aged; Nutritional Physiological Phenomena; Osteoporosis; Risk Factors; Vitamin D; Vitamin K

Topics: Blood Coagulation; Calcium; Carbon-Carbon Ligases; Female; Humans; Ligases; Liver; Menopause; Organ Specificity; Osteoporosis; Vitamin K

Topics: Administration, Oral; Adult; Animals; Anticoagulants; Coumarins; Drug Eruptions; Drug Hypersensitivity; Female; Fibrinolytic Agents; Hemorrhagic Disorders; Heparin; Humans; Male; Osteoporosis; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Vitamin K

This article provides an in-depth summary of standard and recently developed biochemical assays that are useful for the evaluation of the patient with metabolic bone disease. In addition, each of the common metabolic bone diseases is discussed in the context of the associated chemical abnormalities.

Topics: Alkaline Phosphatase; Bone Diseases, Metabolic; Calcitonin; Calcium; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Cyclic AMP; Female; Humans; Menopause; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteocalcin; Osteogenesis Imperfecta; Osteomalacia; Osteopetrosis; Osteoporosis; Parathyroid Hormone; Phosphorus; Serum Albumin; Vitamin D; Vitamin K

Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking.

Topics: Acne Vulgaris; Ascorbic Acid; Asthma; Cardiovascular Diseases; Common Cold; Fibrocystic Breast Disease; Humans; Neoplasms; Osteoporosis; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Adrenal Glands; Ascorbic Acid; Breast Neoplasms; Calciphylaxis; Calcium; Growth Hormone; Humans; Osteogenesis; Osteomalacia; Osteoporosis; Parathyroid Glands; Phosphates; Retinoids; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Young Indian women may be at risk of poor bone health due to malnutrition. The aim of this study was to examine the effects on bone metabolism of a nutritional supplement in women aged 25 to 44. The nutritional supplement was a protein-rich beverage powder fortified with multi-micronutrients including calcium (600 mg), vitamin D (400 IU), and vitamin K (55 mcg) per daily serving, while a placebo supplement was low-protein non-fortified isocaloric beverage powder. This 6-month randomised, controlled trial showed favorable changes in bone turnover markers (decreased) and calcium homeostasis; such changes in older adults have been associated with slowing of bone loss and reduced fracture risk. For example, serum CTX decreased by about 30% and PINP by about 20% as a result of the increase in calcium intake. There were also changes in the ratio of carboxylated to undercarboxylated osteocalcin and such changes have been linked to a slowing of bone loss in older subjects. For example, the ratio increased by about 60% after 3 months as a result in the improvement in vitamin K status. Finally, there were improvements in the status of B vitamins, and such changes have been associated with reductions in homocysteine, but it is uncertain whether this would affect fracture risk. The product was generally well tolerated. This study shows the nutritional supplement holds promise for improved bone health among young Indian women.

Topics: Adult; Bone Diseases, Metabolic; Bone Remodeling; Calcium; Calcium, Dietary; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Fractures, Bone; Homeostasis; Humans; India; Osteocalcin; Osteoporosis; Premenopause; Vitamin B 12; Vitamin D; 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 have reported that alfacalcidol plus menatetrenone, a vitamin K2 with four isoprene units (menaquinone-4), treatment is useful for improving bone problems in children with skeletal unloading. The aim of this study was to evaluate the effect of menatetrenone on bone metabolism in long-term glucocorticoid-treated children with alfacalcidol treatment. Twenty children who had been treated with fixed dosages of prednisolone and alfacalcidol (0.03 microg/kg/day) for 24 weeks were enrolled in a prospective pilot study, and assigned to receive alfacalcidol (0.03 microg/kg/day) or alfacalcidol (0.03 microg/kg/day) plus menatetrenone (approximately 2 mg/kg/day). Bone biochemical markers and bone mineral density (BMD) were measured at baseline and after the 12-week treatment. In the group receiving alfacalcidol plus menatetrenone, serum carboxylated osteocalcin (OC) (p =0.0022) and lumbar BMD (p=0.0029) increased and serum undercarboxylated OC (p=0.0004) decreased significantly in comparison to the group receiving alfacalcidol; further, the change of lumbar BMD showed an inverse correlation to the change of serum undercarboxylated OC (r=-0.744, p=0.0134) and positive correlations to the baseline values of bone turnover markers such as serum levels of intact OC, bone-specific alkaline phosphatase and type I procollagen carboxyl extension peptide and urinary levels of deoxypyridinoline and N-telopeptide of type I collagen. No adverse effect was observed. This is a small short-term study, but its results suggest that menatetrenone effectively and safely increases lumbar BMD probably through carboxylation of OC in long-term prednisolone-treated children with alfacalcidol treatment who have a high bone turnover. Randomized double-blind controlled trials are needed to confirm our findings.

Topics: Adolescent; Bone Density; Child; Child, Preschool; Female; Glucocorticoids; Humans; Hydroxycholecalciferols; Lumbar Vertebrae; Male; Osteocalcin; Osteoporosis; Prednisolone; Prospective Studies; Vitamin K; Vitamin K 2

Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation. To clarify whether administration of vitamin K, which enhances bone formation, prevents prednisolone-induced loss of bone mineral density (BMD), a randomized, prospective, controlled study was conducted on 20 patients with chronic glomerulonephritis scheduled for treatment with prednisolone. All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone (maximum of 40 mg) for 4 weeks, tapering to 20 mg/day over approximately 6 weeks. Ten patients received prednisolone alone (Group 1), and the other 10 patients received prednisolone plus 15 mg of menatetrenone, vitamin K, three times per day (Group 2). BMD of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and biochemical markers of bone metabolism in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone. In Group 1, treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 +/- 0.12 to 1.10 +/- 0.11 g/cm2 (P = 0.0029). Serum intact osteocalcin and procollagen type I C-peptide (PICP) concentrations, biochemical markers of bone formation, were markedly reduced. A biochemical marker of bone resorption, urinary excretion of deoxypyridinoline, was significantly reduced. In Group 2, prednisolone-induced reduction of BMD was prevented by menatetrenone administration (1.09 +/- 0.09 to 1.07 +/- 0.07 g/cm2, P = 0.153). Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration and urinary excretion of deoxypyridinoline. Thus, treatment with prednisolone resulted in loss of BMD of the lumbar spine associated with suppression of both bone formation and bone resorption. Menatetrenone is a useful agent in preventing prednisolone-induced loss of BMD.

Topics: Absorptiometry, Photon; Adolescent; Adult; Anti-Inflammatory Agents; Bone Density; Calcium; Chronic Disease; Drug Therapy, Combination; Female; Glomerulonephritis; Hemostatics; Humans; Male; Middle Aged; Osteoporosis; Phosphates; Prednisolone; Vitamin K; Vitamin K 2

We attempted to investigate whether vitamin K2 (menatetrenone) treatment effectively prevents the incidence of new fractures in osteoporosis. A total of 241 osteoporotic patients were enrolled in a 24-month randomized open label study. The control group (without treatment; n = 121) and the vitamin K2-treated group (n = 120), which received 45 mg/day orally vitamin K2, were followed for lumbar bone mineral density (LBMD; measured by dual-energy X-ray absorptiometry [DXA]) and occurrence of new clinical fractures. Serum level of Glu-osteocalcin (Glu-OC) and menaquinone-4 levels were measured at the end of the follow-up period. Serum level of OC and urinary excretion of deoxypyridinoline (DPD) were measured before and after the treatment. The background data of these two groups were identical. The incidence of clinical fractures during the 2 years of treatment in the control was higher than the vitamin K2-treated group (chi2 = 10.935; p = 0.0273). The percentages of change from the initial value of LBMD at 6, 12, and 24 months after the initiation of the study were -1.8 +/- 0.6%, -2.4 +/- 0.7%, and -3.3 +/- 0.8% for the control group, and 1.4 +/- 0.7%, -0.1 +/- 0.6%, and -0.5 +/- 1.0% for the vitamin K2-treated group, respectively. The changes in LBMD at each time point were significantly different between the control and the treated group (p = 0.0010 for 6 months, p = 0.0153 for 12 months, and p = 0.0339 for 24 months). The serum levels of Glu-OC at the end of the observation period in the control and the treated group were 3.0 +/- 0.3 ng/ml and 1.6 +/- 0.1 ng/ml, respectively (p < 0.0001), while the serum level of OC measured by the conventional radioimmunoassay (RIA) showed a significant rise (42.4 +/-6.9% from the basal value) in the treated group at 24 months (18.2 +/- 6.1% for the controls;p = 0.0081). There was no significant change in urinary DPD excretion in the treated group. These findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures, although the vitamin K2-treated group failed to increase in LBMD. Furthermore, vitamin K2 treatment enhances gamma-carboxylation of the OC molecule.

Topics: Absorptiometry, Photon; Amino Acids; Biomarkers; Bone Density; Bone Remodeling; Female; Fractures, Spontaneous; Humans; Incidence; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Radionuclide Imaging; Treatment Outcome; Vitamin K; Vitamin K 2

Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated osteocalcin concentrations in normal individuals with the intake of fermented soybeans (natto) were investigated. Eight male volunteers were given sequentially fermented soybeans (natto) containing three different contents of MK-7 at an interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7 x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765 micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and gamma-carboxylated osteocalcin concentrations were significantly elevated following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g). Serum undercarboxylated osteocalcin concentrations were significantly decreased by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in serum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. The present study suggests that intake of fermented soybean (natto) increases serum levels of MK-7 and gamma-carboxylated osteocalcin in normal individuals.

Topics: Adult; Alkaline Phosphatase; Calcium; Diet; Dose-Response Relationship, Drug; Female; Fermentation; Glycine max; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Phytotherapy; Sex Characteristics; Vitamin K; Vitamin K 2

The efficacy and side effects of oral vitamin K2 therapy were examined in 20 children and adults with probable secondary osteoporosis who had been hospitalized for a long period, due to severe mental and/or physical handicaps. Vitamin K2 was given for 12 months. Bone mineral density significantly increased 4 months after starting oral vitamin K2 therapy (p = 0.0038) and it retained the elevated level after 12 months of treatment. This therapy was particularly effective in patients with severe locomotor dysfunction. Serum total protein levels significantly decreased following the start of this therapy (p = 0.0012). The reasons of this decrease and its causal relationship to the administration of vitamin K2 are unknown, and should be investigated further.

Topics: Adolescent; Adult; Bone Density; Disabled Persons; Female; Humans; Male; Motor Activity; Osteoporosis; Vitamin K; Vitamin K 2

Gammacarboxyglutamate (Gla) is an uncommon amino acid formed by vitamin K action. Increasing evidence indicates that Gla-proteins are involved in the regulation of calcification processes in both bone tissue and atherosclerotic vessel wall. In a population-based study we have previously shown that in a group of 113 postmenopausal women the presence of abdominal aortic calcifications is associated with a reduced vitamin K status. In the present study we investigated whether this reduced vitamin K status was also associated with differences in bone mass or circulating calciotropic hormone levels. Serum immunoreactive osteocalcin with low affinity for hydroxyapatite (irOCfree) was used as a marker for vitamin K status. After correction for age it was found that women with atherosclerotic calcifications had a 7% lower bone mass as measured by metacarpal radiogrammetry (mean difference: 3.2 mm2, 95% CI: -0. 2-6.5, P = 0.06). No differences between both groups of women were observed for serum intact parathyroid hormone (PTH) and serum 25-hydroxyvitamin D levels. In the atherosclerotic women (n = 34), markers for vitamin K status were inversely associated with bone mass (r = -0.47, P = 0.013), whereas no such association was found in the nonatherosclerotic women (n = 79). It is concluded that the atherosclerotic women in this study may be at higher risk for osteoporotic fractures as evidenced by their lower bone mass and higher serum irOCfree levels. The finding that in atherosclerotic women vitamin K status is associated with bone mass supports our hypothesis that vitamin K status affects the mineralization processes in both bone and in atherosclerotic plaques.

Topics: Aged; Aorta; Arteriosclerosis; Bone Density; Cohort Studies; Female; Humans; Middle Aged; Osteocalcin; Osteoporosis; Postmenopause; Risk Factors; Vitamin K

Topics: Administration, Oral; Adult; Animals; Anticoagulants; Coumarins; Drug Eruptions; Drug Hypersensitivity; Female; Fibrinolytic Agents; Hemorrhagic Disorders; Heparin; Humans; Male; Osteoporosis; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Thrombocytopenia; Thrombolytic Therapy; Vitamin K

This study aims to compare the effects of teriparatide, zoledronic acid, and their combination therapy with vitamin K on osteoporotic rats.. We divided a total of 50 female Sprague-Dawley rats into five groups: A (the control group), B and D (the teriparatide group), and C and E (the zoledronic acid group). Following ovariectomy and subcutaneous heparin administration at a dose of 2 IU/kg for four weeks, osteoporosis was created. Groups A, B, and C were fed with standard feed, while Groups D and E were fed with vitamin K-rich feed. After four weeks of treatment, sacrification was performed. The right and left femurs were separated for histopathological and biomechanical evaluation, respectively. For histopathological evaluation, the femurs were decalcified, and the sections were stained with hematoxylin-eosin and evaluated under a light microscope. Fracture healing was evaluated using the classification system as described previously. For biomechanical evaluation, the 3-point stress test and torsion stress test were applied to 10 femurs from each group.. Groups B-E were histopathologically and biomechanically superior to Group A in fracture healing of osteoporotic rats; however, it was not statistically significant (p>0.05). The group that received additional vitamin K was histopathologically and biomechanically superior to the group which was fed with standard feed, although it was not statistically significant (p>0.05).. Our study results indicated that both teriparatide and zoledronic acid had beneficial effects on osteoporotic fractures with comparable histological and biochemical results. Vitamin K promoted teriparatide and zoledronic acid treatment on osteoporotic fracture healing. Based on these findings, combination therapies may yield the most optimal results in biomechanical and histological examinations.

Topics: Animals; Bone Density Conservation Agents; Female; Fracture Healing; Osteoporosis; Osteoporotic Fractures; Rats; Rats, Sprague-Dawley; Teriparatide; Vitamin K; Zoledronic Acid

Osteoporosis (OP) is an important risk factor for rotator cuff tears (RCTs). However, the relationship and mechanism between rotator cuff injury and osteoporosis are unclear. Therefore, to investigate association between rotator cuff injury and osteoporosis, and find clinical characteristics, bone mineral density, bone metabolism markers, and nutrient levels in rotator cuff injury patients with or without osteoporosis.. One hundred and four cases of patients (RCTs, n=32; RCTs-OP, n=72) who underwent rotator cuff injury and need arthroscopic rotator cuff repair between June 2021 and February 2022, along with the diagnosis of osteoporosis were identified from the dual-energy X-ray bone density screening(DXA). The outcome measure includes clinical characteristics, bone mineral density, bone metabolism markers, vitamins, and amino acids. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation.. OP with RCTs has a lower level of in 25-vitD, osteocalcin (OCN), serum Ca2+, ornithine, diaminocaproic_acid but the high level of Vitamin_B12, PTH, Vitamin_D3,γ_aminobutyric_acid, Vitamin_C and Vitamin_E than RCTs patients without OP. Predictors contained in the prediction nomogram included lumber T score, femur T score, Niacin_B3, and vitamin D, reflecting the combined effect of vitamins on RCTs-related OP progression. The model has good discriminative ability with a C-index of 0.938(95% CI:-1.83-1.39) and good scaling ability. The high C-index value of 0.95 is still achievable with range validation. Analysis of decision curves showed that non-adherence is clinically useful when intervention decisions are at the 14% probability limit of non-adherence.. This study supports the hypothesis that lumber T score, femur T score, Niacin_B3, and Vitamin D are valuable prognostic biomarkers on RCTs related OP progression.. It is found that vitamin D are valuable prognostic biomarkers, reflecting the combined effect of vitamins on RCTs related OP progression.. These findings also highlight that nutrients condition such as vitamins and amino acids of patients provide a new understanding of the development of RCTs.

Topics: Amino Acids; Biomarkers; Humans; Niacin; Osteoporosis; Rotator Cuff Injuries; Vitamin A; Vitamin D; Vitamin K; Vitamins

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

We aimed to determine serum 25-hydroxyvitamin D (25(OH)D) and undercarboxylated osteocalcin (ucOC) levels in severe motor and intellectual disabilities (SMID) patients and their association with bone turnover biomarkers.. We assessed vitamin D and K levels as indicators of osteoporosis in institutionalized adults with SMID. From December 2019 to February 2020, 93 institutionalized patients (48 men, 45 women; median age, 49 years) underwent annual routine examinations. Serum ucOC, 25(OH)D, bone-specific alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase A 5b (TRACP-5b) levels as bone formation and resorption markers and calcium and phosphorous levels were measured. Vitamin K deficiency was indirectly assessed based on ucOC levels.. Mean ucOC levels were higher than normal (i.e., vitamin K deficiency). Serum 25(OH)D levels were markedly diminished. Overall, 86% of patients had deficient 25(OH)D levels. These 25(OH)D-deficient patients had higher ucOC levels. Multiple linear regression analysis revealed an inverse correlation between 25(OH)D and ucOC levels. ucOC levels were significantly higher and 25(OH)D levels were significantly lower in tube feeding. TRACP-5b levels were significantly higher in elderly than in young women. BAP and TRACP-5b levels were normal in adults. No relationship existed between vitamin D and antiepileptic drug use.. Vitamin K and D co-deficiency was common in SMID patients. Vitamin K and D deficiencies were worse in tube-fed patients than in oral intake patients. SMID patients should undergo regular monitoring of vitamin D and K levels and supplementation of these vitamins.

Topics: Adult; Aged; Biomarkers; Bone Density; Female; Humans; Institutionalization; Intellectual Disability; Male; Middle Aged; Motor Activity; Motor Skills Disorders; Osteocalcin; Osteoporosis; Persons with Mental Disabilities; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Calcitonin; Etidronic Acid; Female; Hormone Replacement Therapy; Humans; Hydroxycholecalciferols; Osteoporosis; Postmenopause; Vitamin K

Topics: Calcitonin; Etidronic Acid; Female; Hormone Replacement Therapy; Humans; Hydroxycholecalciferols; Osteoporosis; Postmenopause; Vitamin K

Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice.. To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model.. VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX.. VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Calbindins; Creatinine; Dietary Supplements; Disease Models, Animal; Female; Lipid Metabolism; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Osteocalcin; Osteoporosis; Ovariectomy; Parathyroid Hormone; Spine; Vitamin K; X-Ray Microtomography

Topics: Anticoagulants; Female; Fractures, Spontaneous; Humans; Male; Osteoporosis; Vitamin K

Topics: Anticoagulants; Female; Fractures, Spontaneous; Humans; Male; Osteoporosis; Vitamin K

Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX.. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX.. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX.. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

Topics: Adult; Anthropometry; Biomarkers; Bone Density; Cystic Fibrosis; Female; Humans; Lumbar Vertebrae; Lung Diseases; Lung Transplantation; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Pilot Projects; Protein Precursors; Prothrombin; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins; Young Adult

Osteoporosis is a chief complication in patients with anorexia nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone vitamin K deficiency. We investigated vitamin K status in patients with anorexia nervosa to help establish prevention and treatment recommendations for osteoporosis.. Fifty-four female amenorrheic patients with anorexia nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7-31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were included in this study. We measured serum levels of undercarboxylated osteocalcin, biochemical and nutritional markers, and bone metabolic markers. Dietary vitamin K intake was evaluated by a questionnaire.. Lumbar bone mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721-0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa were significantly higher than those of controls. The 17% of restricting type and 40% of binge eating/purging type anorexia nervosa patients, serum levels of undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated significantly and negatively with vitamin K intake in patients with anorexia nervosa.. Patients with anorexia nervosa had vitamin K deficiency. Since a supplement of vitamin K might be effective for maintaining bone quality, we provide recommendations regarding vitamin K intake for prevention and treatment of osteoporosis in patients with AN.

Topics: Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bulimia Nervosa; Case-Control Studies; Female; Humans; Nutritional Status; Osteocalcin; Osteoporosis; Surveys and Questionnaires; Vitamin K; Vitamin K Deficiency

Topics: Absorptiometry, Photon; Ascorbic Acid; Bone Density Conservation Agents; Calcium, Dietary; Denosumab; Female; Humans; Life Style; Magnesium; Male; Osteoporosis; Phosphorus; Phytoestrogens; Risk Factors; Teriparatide; Vitamin A; Vitamin D; Vitamin K

Bone loss has been established as a major extra-intestinal complication of short bowel syndrome (SBS). The purpose of this study was to correlate bone mineral density (BMD) with body mass index (BMI), serum vitamin and mineral levels in patients with SBS.. The study was conducted on 13 patients (8 male and 5 female, 54.7 ± 11.4 years) with SBS (residual small bowel length of 10 to 100 cm). We determined the food ingestion, anthropometry, serum levels of vitamins C, A, D, E and K, as well as serum and urinary levels of phosphorus and calcium. BMD was measured by dual-energy x-ray absorptiometry (DXA).. Osteopenia and osteoporosis was diagnosed in all but one SBS patient. Serum levels of vitamin D were low in all volunteers. Sixty-one percent of patients had vitamin E deficiency; hypovitaminosis A and C occurred in one subject. BMI and C, E and K vitamin serum levels correlated with T-score of BMD.. Osteopenia and osteoporosis were common in SBS patients. There was a correlation between BMD and the serum levels of vitamins C, E and K, an indicative that such vitamins may influence bone health.

Topics: Absorptiometry, Photon; Adult; Aged; Ascorbic Acid; Avitaminosis; Body Mass Index; Bone Density; Bone Diseases, Metabolic; Calcium; Cross-Sectional Studies; Energy Intake; Female; Hospitalization; Humans; Male; Middle Aged; Osteoporosis; Phosphorus; Reference Values; Short Bowel Syndrome; Time Factors; Vitamin E; Vitamin K

Topics: Humans; Osteoporosis; Renal Insufficiency, Chronic; Vascular System Injuries; Vitamin K; Vitamin K 2

The aim of this study was to measure the level of Vitamin K2 (Vit K2) in osteoporotic patients and individuals with normal bone density as controls.. This case-control study was done in Outpatient Department of Rheumatology at Qazvin Boo-ali Sina Hospital in 2013. Participants were 50 patients with osteoporotic densitometry measured by DEXA (T score? -2.5) who were matched with 48 persons in control group with normal bone density (T score> -1). The level of Vit K2 in samples was measured using enzyme linked immunosorbent assay (ELISA). Data were analyzed by Mann-Whitney U test and Chi-square test.. The level of Vit K2 in patients with osteoporosis was not significantly different from the control group (Median: 75.95 vs. 71.35 nmol/L, respectively; P-value: 0.709). The authors determined cut-offs 75 percentile of vitamin K2 in all participants that was 85 nmol/L and percentages of persons in two groups were similar.. Although Vit K2 level in patients with osteoporosis was not significantly different from the control group, further studies are necessary to confirm the association of osteoporosis and Vit K2.

Topics: Absorptiometry, Photon; Adult; Age Factors; Aged; Body Mass Index; Bone Density; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Osteoporosis; Vitamin K

Topics: Adult; Aged; Aged, 80 and over; Aging; Bone and Bones; Humans; Life Style; Middle Aged; Osteoporosis; Research; Vitamin D; Vitamin K

Osteocalcin plays a role in bone homeostasis. The vitamin K cycle is essential for the gamma-carboxylation of glutamic acid residues in osteocalcin. Some evidence suggests that long-term warfarin therapy, which inhibits the vitamin K cycle and prevents gamma-carboxylation, is associated with increased bone-fracture risk. The aim of this study was to determine the effects of warfarin and edoxaban, a direct factor Xa inhibitor, on the serum concentration of total, gamma-carboxylated (Gla-osteocalcin) and undercarboxylated osteocalcin (uc-osteocalcin) in rats.. Rats received orally administered warfarin or edoxaban, and 24h later serum and plasma were prepared. Osteocalcin level in serum was measured with ELISA. A Gla-osteocalcin was precipitated by the addition of hydroxyapatite, and the resulting supernatant was used for measuring uc-osteocalcin. Prothrombin time (PT) of plasma was also measured.. Warfarin at 1mg/kg (a dose which prolonged PT 2.62-fold) markedly increased the serum level of uc-osteocalcin and slightly increased the total osteocalcin level compared with control in rats. Serum Gla-osteocalcin significantly decreased by warfarin. Edoxaban at 1mg/kg (an antithrombotic dose) and 54mg/kg (a dose which prolonged PT 2.25-fold) had no effects on total, uc-, and Gla-osteocalcin levels.. This study demonstrates that warfarin impaired the carboxylation of osteocalcin in rats. In contrast, edoxaban at or higher doses than needed for an antithrombotic effect sustained the circulating Gla-osteocalcin level. These findings suggest that edoxaban has no effects on the production of Gla-osteocalcin and thus, may have a lower risk of adverse effects on bone health.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Carboxylic Acids; Enzyme-Linked Immunosorbent Assay; Factor Xa; Factor Xa Inhibitors; Male; Osteocalcin; Osteoporosis; Protein Processing, Post-Translational; Prothrombin Time; Pyridines; Rats; Rats, Wistar; Risk Factors; Thiazoles; Time Factors; Vitamin K; Warfarin

A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto-bone association to be primarily mediated by vitamin K.. Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 μg/pack) and K2 (380 μg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association.. Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD.. The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score < -1 SD) at the total hip and femoral neck. This association became insignificant after further adjustment for ucOC level.. Habitual intake of natto was associated with a beneficial effect on bone health in elderly men, and this association is primarily due to vitamin K content of natto, although the lack of information on dietary nutrient intake, including vitamin K1 and K2, prevented us from further examining the association.

Topics: Absorptiometry, Photon; Aged; Bone Density; Cross-Sectional Studies; Diet; Hip Joint; Humans; Lumbar Vertebrae; Male; Osteocalcin; Osteoporosis; Soy Foods; Vitamin K

Topics: Bone Density; Humans; Male; Osteoporosis; Soy Foods; Vitamin K

Osteoporotic drugs are classified to 3 categories ; anti-resorptives, supplemental and anabolic drugs. A lot of evidence has been made about each osteoporotic drug. Although concomitant drug subscriptions are often used by many physicians, little evidence has been ever made about the concomitant drug treatment. Theoretically different categorized drugs should be combined in concomitant treatment. Fragility fracture risks have been tested compared alendronate (Aln) mono-therapy and Aln + alfacalcidol (VD(3)) for 2 year in JOINT02 of ATOP study. Aln + alfacalcidol (VD(3)) concomitant treatment has significantly reduced vertebral fracture risk compared with Aln mono-therapy in patients with advanced osteoporosis with multiple and high SQ grade vertebral fracture and also reduced weight bearing bone fracture risk.

Topics: Alendronate; Bone Density Conservation Agents; Drug Therapy, Combination; Humans; Osteoporosis; Vitamin D; Vitamin K

Vitamin K is a fat-soluble vitamin involved in blood coagulation and bone metabolism. The detection and monitoring of vitamin K homologues in rheumatoid arthritis (RA) patients is a challenging problem due to the smaller concentrations of vitamin K and the presence of several interfering medications. Therefore, this study aimed to develop a new highly sensitive and selective chemiluminescence (CL) method designated to quantify vitamin K homologues in plasma of RA patients including phylloquinone (PK, vitamin K(1)), menaquinone-4 (MK-4, vitamin K(2)) and menaquinone-7 (MK-7, vitamin K(2)). The method was based on the unique photochemical properties of vitamin K homologues that were exploited for selective luminol CL reaction. The correlation coefficients of 0.998 or more were obtained in the concentration ranges of 0.1-100 ng mL(-1) vitamin K homologues. The detection limits were 0.03-0.1 ng mL(-1) in human plasma for vitamin K homologues. The developed HPLC-CL system was successfully applied for selective determination of vitamin K homologues in plasma of RA patients. The developed method may provide a useful tool for monitoring vitamin K homologues in different clinical studies such as RA, osteoporosis and hepatocellular carcinoma in which vitamin K is intervented.

Topics: Arthritis, Rheumatoid; Carcinoma, Hepatocellular; Drug Interactions; Humans; Limit of Detection; Liver Neoplasms; Luminescent Measurements; Luminol; Methods; Osteoporosis; Vitamin K

Complex regional pain syndrome (CRPS) is the complication of some injuries, such as a fracture, which affects the distal end of the injured extremity characterized by pain, allodynia, hyperalgesia, edema, abnormal vasomotor and sudomotor activity, movement disorders, joint stiffness, regional osteoporosis, and dystrophic changes in soft tissue. Exact pathogenic mechanism of CRPS is still unclear. Suggested pathogenic mechanisms of CRPS are evaluated in four major groups consist of classic inflammation, hypoxic changes and chronic ischemia, neurogenic inflammation and sympathetic dysregulation. All of these suggested pathogenic mechanisms produced by inflammatory cytokines mediated by nuclear factor kappaB. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-1,4-naphthoquinones. Vitamin K exerts a powerful influence on bone formation, especially in osteoporosis. Fat in bone stores some vitamin K. Gamma-carboxylation of the glutamic acid in osteocalcin is vitamin K dependent. Osteocalcin plays a role in calcium uptake and bone mineralization. Osteocalcin, the most abundant non-collagenous protein in bone, is produced by osteoblasts during bone matrix formation. Because osteocalcin is not carboxylated in case of vitamin K deficiency at the distal site of fracture or injury, it cannot bind to hydroxyapatite causing osteoporosis. Fracture starts a local inflammatory process in the fracture site and adjacent tissues as seen in CRPS. Vitamin K was shown to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury (which have key role in both initiation and progression of CRPS) to oligodendrocytes and neurons. We hypothesized that vitamin K has a key role and modulatory effect in CRPS pathogenesis. Vitamin K deficiency at the distal site of fracture occurs because of diminished and slowed circulation, local immobilization after extremity fracture or injury and use of vitamin K store at the distal site of the injured extremity and in the circulation for fracture healing and bone remodelling. In case of vitamin K deficiency at the distal site of fracture, classic inflammation starts with fracture at the distal tissues could not be restricted and classic inflammation, hypoxic changes, chronic ischemia, neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. Br

Topics: Ascorbic Acid; Blood Coagulation; Complex Regional Pain Syndromes; Cytokines; Fracture Healing; Fractures, Bone; Humans; Intestinal Absorption; NF-kappa B; Osteocalcin; Osteogenesis; Osteoporosis; Vitamin K

Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long-term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD.. We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease 'mechanical valve replacement' on long-term warfarin compared with 103 randomly selected matched controls.. There was a marked reduction in BMD (g/cm(2)) and T-score of lumbar spine between patients and controls (P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T-score (P < 0.03).. Screening of patients on long-term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium-vitamin D supplements for these patients.

Topics: Absorptiometry, Photon; Adult; Anticoagulants; Bone Density; Case-Control Studies; Female; Femur; Health Surveys; Heart Valve Prosthesis; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Rheumatic Heart Disease; Vitamin K; Warfarin

The UK Food Standards Agency convened an international group of expert scientists to review the Agency-funded projects on diet and bone health in the context of developments in the field as a whole. The potential benefits of fruit and vegetables, vitamin K, early-life nutrition and vitamin D on bone health were presented and reviewed. The workshop reached two conclusions which have public health implications. First, that promoting a diet rich in fruit and vegetable intakes might be beneficial to bone health and would be very unlikely to produce adverse consequences on bone health. The mechanism(s) for any effect of fruit and vegetables remains unknown, but the results from these projects did not support the postulated acid-base balance hypothesis. Secondly, increased dietary consumption of vitamin K may contribute to bone health, possibly through its ability to increase the gamma-carboxylation status of bone proteins such as osteocalcin. A supplementation trial comparing vitamin K supplementation with Ca and vitamin D showed an additional effect of vitamin K against baseline levels of bone mineral density, but the benefit was only seen at one bone site. The major research gap identified was the need to investigate vitamin D status to define deficiency, insufficiency and depletion across age and ethnic groups in relation to bone health.

Topics: Bone Density; Diet; Fractures, Bone; Fruit; Government Agencies; Health Status; Humans; Nutrition Policy; Nutritional Sciences; Osteoporosis; Research; United Kingdom; Vegetables; Vitamin D; Vitamin K

There have been no simple methods to estimate dietary nutrient intakes for the prevention and management of osteoporosis. The aim of this study was to develop and validate a new, simple food frequency questionnaire (FFQ) for dietary intake of calcium and other nutrients relevant to the bone health of adult Japanese women. We developed a 28-item FFQ. To validate this, 208 and 72 adult women aged between 18 and 69 y were recruited for testing reliability and reproducibility, respectively. In the 208 women, moderate-to-high Spearman's correlation coefficients between our FFQ and the conventional diet record method were found in intakes of calcium (r=0.668), sodium chloride (NaCl) (r=0.475), vitamin A (r=0.501), vitamin D (r=0.413), vitamin K (r=0.649), and energy (r=0.471). In the 72 women, coefficients of variance of the four repeated measurements of intakes throughout a year were 14.1% for calcium, 7.3% for NaCl, 21.2% for vitamin A, 13.6% for vitamin D, 36.8% for vitamin K, and 9.6% for energy. In conclusion, the FFQ we developed is a useful tool to evaluate the intake of dietary calcium of adult Japanese women. Although it can also measure intakes of dietary vitamin A, vitamin D, vitamin K, NaCl, and energy, further improvement is needed to measure intakes of these nutrients and energy.

Topics: Adolescent; Adult; Aged; Calcium Compounds; Diet Records; Diet Surveys; Energy Intake; Female; Food Preferences; Humans; Japan; Middle Aged; Osteoporosis; Reproducibility of Results; Sodium Chloride, Dietary; Surveys and Questionnaires; Vitamin A; Vitamin D; Vitamin K

Topics: Bone Density; Female; Humans; Osteoporosis; Treatment Outcome; Vitamin K; Vitamins

Glucocorticoids continue to be used for many inflammatory diseases, and glucocorticoid-induced osteoporosis (GIOP) remains the most common secondary form of metabolic bone disease. Recent meta-analyses suggest that both active and native vitamin D can help maintain lumbar spine bone mineral density (BMD), particularly in patients receiving lower-dose glucocorticoid therapy. Recent randomized, controlled clinical trials have shown that oral bisphosphonates are superior to vitamin D in maintaining BMD and should be continued for as long as a person receives glucocorticoid treatment. Similar to the oral bisphosphonates, intravenous ibandronate has been shown to preserve BMD and also to significantly reduce vertebral fracture risk. Increasing evidence supports a role for parathyroid hormone to prevent or treat GIOP as well. Despite effective therapies, many at-risk patients fail to receive treatment for GIOP, and even among those who initiate treatment, half discontinue within 1 to 2 years. New approaches to evidence implementation are being tested to improve the quality of osteoporosis care and decrease fracture risk among long-term glucocorticoid users.

Topics: Alendronate; Bone Density Conservation Agents; Calcium; Cost-Benefit Analysis; Diphosphonates; Etidronic Acid; Female; Glucocorticoids; Humans; Ibandronic Acid; Male; Osteoporosis; Parathyroid Hormone; Patient Compliance; Practice Guidelines as Topic; Quality of Health Care; Rheumatic Diseases; Time Factors; Vitamin D; Vitamin K

Decreased bone mass in early childhood is an increasingly recognized problem in classical galactosaemia as in many other chronic diseases. Peak bone mass is reached in late adolescence; thus, increasing peak bone mass in childhood can prevent osteoporosis. Regular bone mass measurements and preventive treatment should begin in childhood. In the absence of evidence-based guidelines for identification and treatment of decreased bone mass in children, we provide a proposal based on our experience and the available literature. Dual-energy x-ray absorptiometry (DXA) should be used for bone mass assessment. Because cooperation is required, measurements can usually be performed from the age of 4 years. Interpretation of bone mass measurements is crucial for the diagnosis of osteopenia or osteoporosis. In children and adolescents, total body bone mineral content (BMC) as well as lean tissue mass (LTM) should be measured. Comparison of BMC corrected for LTM of the patient with the BMC corrected for LTM of healthy controls allows correction for the confounding effect of bone size. DXA should be repeated every two years in case of normal BMC, as this is the time window in which abnormalities become measurable. If BMC is between 0 and -1 SD, lifestyle factors such as physical activity, intake of calcium and vitamins K and D and oestrogen supplementation (in girls) should be optimized. If BMC is below -1 SD, we advise to start with supplementation of calcium, vitamin K(1) and vitamin D(3). DXA should be repeated yearly in case of BMC below 0 SD in order to identify deteriorations and improvements early.

Topics: Absorptiometry, Photon; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcium; Child, Preschool; Estrogens; Female; Galactosemias; Humans; Male; Osteoporosis; Vitamin K

Topics: Animals; Humans; Osteocalcin; Osteoporosis; Vitamin K

Topics: Anticoagulants; Antifibrinolytic Agents; Humans; Osteoporosis; Risk Factors; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Fractures, Bone; Humans; Male; Osteoporosis; Vitamin K; Warfarin

Topics: Calcium, Dietary; Colorectal Neoplasms; Dietary Supplements; Female; Humans; Hypercholesterolemia; Hypertension; Magnesium; Osteoporosis; Premenstrual Syndrome; Vitamin D; Vitamin K; Weight Gain

A HPLC fluorescence determination method for Vitamin K derivatives (Vitamin K(1), phylloquinone, PK and K(2), menaquinones, MK-4 and MK-7) using post-column reduction and internal standards was developed. Selectivity and reproducibility were increased by optimized chromatography conditions and satisfactory precision and accuracy were attained by using synthetic internal standards. After addition of internal standards to plasma samples, lipids were extracted with ethanol and hexane. Chromatography was performed by isocratic reverse phase separation on a C18 column. Vitamin K derivatives were detected at 430 nm with excitation at 320 nm for MK-4 and 240 nm for PK and MK-7. The detection limits for MK-4, PK and MK-7 were 4, 2 and 4 pg, respectively. The recoveries of MK-4, PK and MK-7 were greater than 92% and the inter- and intra-assay R.S.D. values were 5.7-9.2% for MK-4, 4.9-9.6% for PK and 6.3-19.3% for MK-7. The data showed good correlation between proposed method and LC-APCI/MS method for MK-4 (R(2)=0.988), PK (R(2)=0.979) and MK-7 (R(2)=0.986). The method allows the determination of Vitamin K for evaluating their clinical and nutritional status.

Topics: Chromatography, High Pressure Liquid; Fluorescence; Humans; Osteoporosis; Reference Standards; Spectrometry, Mass, Electrospray Ionization; Vitamin K; Vitamin K 2

We report here the development of a precise and sensitive method for the determination of vitamin K homologues including phylloquinone (PK), menaquinone-4 (MK-4), and menaquinone-7 (MK-7) in human plasma using HPLC-tandem mass-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS/MS). The method involves the use of stable isotope (18)O-labeled internal standard compounds, which were synthesized in our laboratory, and the selection of a precursor and product ion with a MS/MS multiple reaction monitoring method. The average intraassay and interassay variation values for PK, MK-4, and MK-7 were <10%. Average spiked recoveries from authentic compounds added to normal human plasma samples for PK, MK-4, and MK-7 were 98-102%. Mean plasma concentrations of PK, MK-4, and MK-7 from healthy subjects (n = 20) were 1.22 +/-0.57, 0.39 +/- 0.46, and 6.37 +/- 7.45 ng/mL, respectively. We conclude that this novel LC-APCI-MS/MS method should be useful for the evaluation of vitamin K status in postmenopausal women and elderly subjects and provides useful information for the treatment and prevention of osteoporosis with vitamin K.

Topics: Calibration; Chromatography, High Pressure Liquid; Humans; Mass Spectrometry; Osteoporosis; Oxygen Isotopes; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Fluorescence; Vitamin K; Vitamin K 1; Vitamin K 2

Topics: Bone Density; Calcium; Fractures, Bone; Humans; Osteoporosis; Randomized Controlled Trials as Topic; Vitamin D; Vitamin K

The UK Food Standards Agency (FSA) convened a group of expert scientists to discuss and review UK FSA- and Department of Health-funded research on diet and bone health. This research focused on the lifestyle factors that are amenable to change and may significantly affect bone health and the risk of osteoporotic fracture. The potential benefits of fruits and vegetables, meat, Ca, vitamins D and K and phyto-oestrogens were presented and discussed. Other lifestyle factors were also discussed, particularly the effect of physical activity and possible gene-nutrient interactions affecting bone health.

Topics: Bone and Bones; Calcium; Consensus; Diet; Estrogens; Female; Fractures, Bone; Fruit; Humans; Male; Meat; Nutritional Physiological Phenomena; Nutritional Status; Osteoporosis; Phytotherapy; Plant Extracts; Silicon; Smoking; Sodium Chloride; Ultrasonography; United Kingdom; Vegetables; Vitamin D; Vitamin K

Topics: Dietary Supplements; Eating; Humans; Liver Cirrhosis; Osteoporosis; Vegetables; Vitamin K

Topics: Biomarkers; Bone Density; Bone Resorption; Child; Humans; Hypogravity; Insulin-Like Growth Factor I; Osteocalcin; Osteoporosis; Protein Processing, Post-Translational; Space Flight; Vitamin K

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Topics: Administration, Oral; Adult; Anticoagulants; Bone and Bones; Bone Density; Clinical Trials as Topic; Coumarins; Double-Blind Method; Female; Fractures, Bone; Heparin; Heparin, Low-Molecular-Weight; Humans; Immobilization; Meta-Analysis as Topic; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Pregnancy; Pregnancy Complications; Prospective Studies; Renal Dialysis; Retrospective Studies; Risk Factors; Time Factors; Vitamin K

Topics: Aged; Apolipoprotein E4; Apolipoproteins E; Bone Density; Cohort Studies; Female; Hip Fractures; Humans; Male; Osteoporosis; Vitamin K; Vitamin K Deficiency

The effect of dietary vitamin K2 (menaquinone-7) on bone loss in ovariectomized (OVX) rats was investigated. OVX rats were freely given experimental diets containing menaquinone-4 (MK-4; 12mg/100g diet) or menaquinone-7 (MK-7; 18.1mg/100g diet) for 24 days; MK-4 and MK-7 were equal in molar concentrations. This feeding caused a remarkable increase of MK-4 and MK-7 concentrations in the serum and femur of OVX rats. OVX-induced decrease in the femoral dry weight and femoral calcium content was prevented by the feeding of dietary MK-4 or NK-7. In separate experiments, OVX rats were freely given experimental diets containing the fermented soybean (natto; including 9.4 microg MK-7/100g diet) without or with added MK-7 (37.6 microg/100g diet) for 77 days. Feeding produced a significant elevation of MK-4 and MK-7 concentrations in the serum of OVX rats. In this case, a significant increase in the femoral MK-4 content was observed but MK-7 was not detected in the femoral tissues. OVX-induced decreases in the femoral dry weight and femoral calcium content were significantly prevented by the feeding of diets containing natto with MK-7 added (37.6 microg/100g diets). This study demonstrates that the intake of dietary MK-7 has a preventive effect on bone loss caused by OVX. This effect may be partly caused by MK-4, which is formed by degradation of MK-7.

Topics: Animals; Bone and Bones; Bone Density; Calcium; Disease Models, Animal; Female; Fermentation; Glycine max; Osteocalcin; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Vitamin K; Vitamin K 2

This study was designed to assess the effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Female Sprague-Dawley rats aged 8-9 months were ovariectomized (OVX) or sham operated and divided into five experimental groups: (1) ovariectomy (OVX), (2) OVX plus vitamin K supplementation, (3) OVX plus vitamin D supplementation, (4) OVX plus vitamin K and vitamin D supplementation, and (5) sham operation. The trabecular bone area was estimated by bone histomorphometry by microradiography and histological examination. Bone loss in OVX plus vitamin K and vitamin D group was significantly reduced at both 7 and 14 weeks compared with the OVX group. No significant bone loss in OVX plus vitamin K or OVX plus vitamin D groups was found. A similar effect of vitamin K and D supplementation on ovariectomy-induced bone loss was recognized in histological examination. Our findings indicate that vitamins K and D may have a synergistic effect on reducing bone loss. This is valuable information for the treatment of bone loss in postmenopausal women with osteoporosis.

Topics: Animals; Dietary Supplements; Female; Hydroxycholecalciferols; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tibia; Vitamin K

This paper presents a design for randomized clinical trials in which incomplete data are collected on the occurrence of potentially recurrent events through periodic monitoring. In particular, events are assumed to arise according to a point process, but information is available at the times of monitoring only if one or more events has occurred since the preceding monitoring point. The event process is modelled via a piecewise Poisson process, and a proportional rates model is introduced to represent the difference in event rates between treatment groups. The design was developed on the basis of a Wald-type test derived from the generalized estimating equations of Liang and Zeger (Biometrika 73, 13-22 (1986)). Robustification of the variance of the estimator of the treatment effect was considered under a random effects model with a semi-parametric mixture distribution. The design was adopted to address issues which arose in an osteoporosis trial conducted in Japan.

Topics: Calcium; Computer Simulation; Hemostatics; Humans; Osteoporosis; Poisson Distribution; Proportional Hazards Models; Radiography; Randomized Controlled Trials as Topic; Research Design; Spinal Injuries; Spine; Vitamin K; Vitamin K 2

Rapid bone loss is a serious health problem for astronauts during long lasting missions in space. We have recorded the changes of biochemical markers for bone metabolism in one of the astronauts during the 6-month space flight of the EUROMIR-95 mission. Immediately after launch both bone resorption markers and urinary calcium excretion increased about two fold, whereas bone formation markers remained unchanged. After 12 1/2 weeks the astronaut received vitamin K1 (10 mg/day for 6 weeks). Vitamin K is known to be involved in the formation of gamma-carboxyglutamate (Gla) in proteins, such as the calcium-binding bone Gla-proteins osteocalcin and matrix Gla-protein. Concomitant with the start of vitamin K treatment, the calcium-binding capacity of osteocalcin increased, and so did the urinary excretion of free Gla. This is suggestive for a subclinical vitamin K-deficiency in the astronaut before vitamin K-supplementation. During periods of high vitamin K status markers for bone formation (osteocalcin and bone alkaline phosphatase) had increased as compared to the first part of the flight. The mean increases were 14 and 23%, respectively. Our data suggest that increased intake of vitamin K may contribute to counteracting microgravity-induced loss of bone mass during long lasting space missions, but need confirmation in more astronauts.

Topics: 1-Carboxyglutamic Acid; Adult; Aerospace Medicine; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Development; Bone Resorption; Calcium; Humans; Osteocalcin; Osteoporosis; Parathyroid Hormone; Space Flight; Vitamin K; Vitamin K 1; Weightlessness; Weightlessness Countermeasures

1. A modern hybrid strain of laying hen (Hisex) was fed from point of lay to 68 weeks on a control diet and diets containing oystershell, fluoride, 1,25-dihydroxycholecalciferol, ascorbic acid, a lower concentration of phosphorus and a combination of a lower concentration of crude protein and higher concentration of vitamin K. Hens from a much older strain (Brown Leghorn J-line) were fed on the control diet. 2. Plasma variables were measured during lay. End-of-lay trabecular and medullary bone volumes in the proximal tarsometatarsus and free thoracic vertebra were measured by histomorphometry. 3. The majority of Hisex hens were considered to be osteoporotic by the end of lay. In contrast, none of the J-line were osteoporotic. 4. None of the nutritional treatments affected trabecular bone volumes. Medullary bone volumes were increased significantly by feeding oystershell or fluoride. 5. There was no phenotypic correlation between egg production and trabecular bone volume in the Hisex hens. 6. The experiment provided evidence that osteoporosis in laying hens, as assessed by trabecular bone volumes, is not caused by calcium deficiency and could not be prevented by any of the nutritional treatments studied.

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Bone Density; Calcitriol; Chickens; Dietary Proteins; Dietary Supplements; Female; Fluorides; Osteoporosis; Ostreidae; Oviposition; Phosphorus; Poultry Diseases; Species Specificity; Vitamin K

[14C]Menaquinone-4 was administered orally once daily at a dose of 4 mg/kg for ten days to female rats of different ages to determine its blood and tissue distribution with particular attention to its distribution in bone. Animals aged 10 and 30 months were either ovariectomized or sham-operated as a control, and young rats aged 7 weeks were used as untreated controls. Blood concentrations of radioactivity at 24h after each dose during repeated administration increased daily and approached a steady rate by the seventh dose. Higher concentrations of radioactivity in blood (plasma) were observed in older animals than in the younger ones, but there was little difference between ovariectomized rats (OVX rats) and sham-operated rats (Sham rats). In tissue samples collected at 1.5 h after administration, the liver, adipose tissue, spleen and adrenals showed higher concentrations of radioactivity than the other organs and the plasma. IN bone tissues, the bone marrow (BM) and cancellous tissue (CT) of the femur showed radioactivity concentrations which were higher than that in the plasma, and these increased during repeated administration. Finally, at 24 h after the last dose, the concentrations of radioactivity in bone tissues of older animals (BM, 5,807.2 ng eq/g; CT, 5,264.8 ng eq/g in OVX rats aged 10 months and BM, 11,479.3 ng eq/g; CT, 4,023.0 ng eq/g in OVX rats aged 30 months) were several times higher than those in younger animals (BM, 2,771.6 ng eq/g; CT, 890.2 ng eq/g in 7-week-old untreated rats). The values in OVX rats were also higher than those in Sham rats. Furthermore, micro autoradiography studies of femur sections from OVX rats indicated that [14C] Menaquinone-4 localized in cancellous tissue where bone is known to be actively remodelled. The concentrations of radioactivity in cancellous tissue and bone marrow of OVX rats aged 10 and 30 months were comparable to the pharmacologically effective concentrations of Menaquinone-4 (10(-6)-10(-5) M) in in vitro studies on bone formation. These findings suggest that orally administered Menaquinone-4 distributes specifically into the bone tissues of ovariectomized rats and this is consistent with its effect as a therapeutic agent for osteoporosis.

Topics: Aging; Animals; Autoradiography; Bone and Bones; Bone Marrow; Carbon Radioisotopes; Drug Stability; Female; Kinetics; Osteoporosis; Ovariectomy; Rats; Rats, Inbred F344; Tissue Distribution; Vitamin K; Vitamin K 2

The effects of menatetrenone, a vitamin K2 homologue, on bone loss induced by ovariectomy in rats were studied in 3 experiments. Menatetrenone was given as a dietary supplement. In experiment 1, at 2 weeks postovariectomy, menatetrenone (10 mg/kg/day given for 2 weeks) inhibited the decrease in bone density of the femoral metaphysis induced by the ovariectomy. In experiment 2, menatetrenone (3 or 30 mg/kg/day given for 6 months) inhibited the decrease in bone strength of the femur and the decrease in calcium and hydroxyproline content of the femoral diaphysis at 6 months postovariectomy. In experiment 3, menatetrenone treatment, at 30 or 100 mg/kg/day for 6 months, protected against the decrease in bone strength and calcium and hydroxyproline content in the bone loss model induced by ovariectomy and calcium-deficient diet. These findings suggest that menatetrenone protects against the bone loss induced by ovariectomy.

Topics: Animals; Bone Density; Calcium, Dietary; Female; Femur; Osteoporosis; Ovariectomy; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Vitamin K; Vitamin K 2

Vitamin K1 functions in the conversion of glutamate residues, present in certain bone peptides, into the putatively active gamma-carboxyglutamate form. We have shown previously that the circulating levels of vitamin K1 are depressed in osteoporotic patients. However, it is known that menaquinones (vitamin K2:MK) may be more effective than vitamin K1 in this conversion of the inactive to active form of glutamate residues. A procedure for measuring such menaquinones has now demonstrated a marked deficiency of MK-7 and MK-8 in patients with osteoporotic fractures. It is suggested that estimates of circulating levels of K1, MK-7, and MK-8 might provide a biochemical risk marker of osteoporotic fractures.

Topics: Aged; Aged, 80 and over; Female; Femoral Neck Fractures; Humans; Male; Middle Aged; Osteoporosis; Spinal Fractures; Vitamin K; Vitamin K 2

The authors evaluated bone mineralization by single photon absorptiometry and mineral homeostasis in 7 patients with anorexia nervosa. The patients with anorexia nervosa showed a reduction of bone mineralization in respect to age-sex matched normal values. Serum levels of calcium, ionized calcium, phosphate, magnesium, alkaline phosphatase, calcitonin and 25-hydroxyvitamin D were normal as well as phosphate and hydroxyproline urinary excretion. Osteocalcin levels were significantly low as compared to normal values (5.0 +/- 3.0 ng/ml vs 14.3 +/- 5.2 ng/ml, p less than 0.01) as well as urinary calcium excretion (0.02 +/- 1.01 vs 0.08 +/- 0.06, p less than 0.05); 1,25-dihydroxyvitamin D values were low only in 4 patients. Parathyroid hormone means levels were increased in respect to normal values (74.1 +/- 12.7 pg/ml vs 38.0 +/- 12.0, p less than 0.02). We confirm that adolescents with anorexia nervosa showed a reduced bone mineral content and alterations of mineral homeostasis that may contribute to the development of bone mineral loss.

Topics: 1-Carboxyglutamic Acid; Adolescent; Adult; Anorexia Nervosa; Bone and Bones; Calcitonin; Calcium; Calcium-Binding Proteins; Child; Female; Homeostasis; Humans; Hydroxycholecalciferols; Male; Minerals; Osteocalcin; Osteoporosis; Parathyroid Hormone; Vitamin K

The rapid loss of bone mass is one of the serious problems which have to be solved before long-lasting manned spaceflights may be considered. In this paper we describe investigations in which we have checked whether the bone loss in astronauts as well as in osteoporotic patients may be related to abnormalities in a recently discovered calcium-binding protein, named osteocalcin. It was observed that in all subjects of a limited number of osteoporotic patients, the amount of calcium-binding groups (Gla-residues) in the circulating osteocalcin was substantially reduced. The Gla-content could be normalized, however, by the oral administration of vitamin K (1 mg/day). We also analyzed the Gla-content of plasma-osteocalcin from 4 astronauts before and after the D-1 mission. The amount of Gla-residues was reduced by more than 50% in the post-flight samples. It seems probable, that an increased vitamin K-intake by the astronauts will correct the observed abnormality, but whether this will lead to a decrease of the microgravity-induced bone-loss remains to be seen.

Topics: 1-Carboxyglutamic Acid; Adult; Aerospace Medicine; Aged; Bone and Bones; Humans; Middle Aged; Osteocalcin; Osteoporosis; Space Flight; Vitamin K; Vitamin K 1; Weightlessness; Weightlessness Countermeasures

Topics: Aged; Biological Availability; Calcium; Calcium, Dietary; Estrogens; Female; Humans; Life Style; Menopause; Middle Aged; Nutritional Physiological Phenomena; Osteogenesis; Osteoporosis; Physical Exertion; Progestins; Vitamin D; Vitamin K

Topics: Bone and Bones; Calcium-Binding Proteins; Humans; Osteocalcin; Osteoporosis; Vitamin K

Topics: Adult; Aged; Aging; Ascorbic Acid; Calcium; Child; Diet; Dietary Proteins; Energy Metabolism; Female; Humans; Male; Nutritional Requirements; Osteoporosis; Vitamin K

Topics: Aged; Calcium; Calcium Chloride; Calcium Isotopes; Female; Humans; Injections, Intravenous; Kinetics; Menopause; Middle Aged; Nitrogen; Osteoporosis; Phosphorus; Vitamin K

Topics: Back Pain; Chondroitin; Glucuronates; Humans; Low Back Pain; Osteoarthritis; Osteoporosis; Prednisolone; Spinal Diseases; Spinal Dysraphism; Tuberculosis; Tuberculosis, Spinal; Vitamin K