vitamin-k-semiquinone-radical and Fractures--Bone

We describe the mechanism of action of vitamin K, and its implication in cardiovascular disease, bone fractures, and inflammation to underline its protective role, especially in chronic kidney disease (CKD).. Vitamin K acts as a coenzyme of y-glutamyl carboxylase, transforming undercarboxylated in carboxylated vitamin K-dependent proteins. Furthermore, through the binding of the nuclear steroid and xenobiotic receptor, it activates the expression of genes that encode proteins involved in the maintenance of bone quality and bone remodeling. There are three main types of K vitamers: phylloquinone, menaquinones, and menadione. CKD patients, for several conditions typical of the disease, are characterized by lower levels of vitamin K than the general populations, with a resulting higher prevalence of bone fractures, vascular calcifications, and mortality. Therefore, the definition of vitamin K dosage is an important issue, potentially leading to reduced bone fractures and improved vascular calcifications in the general population and CKD patients.

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Female; Fractures, Bone; Humans; Male; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin K

Vitamin K is principally known because it is involved in blood coagulation. Furthermore, epidemiological studies showed that its deficit was associated with increased fragility fractures, vascular calcification and mortality. There are two main types of vitamin K vitamers: Phylloquinone (or PK) and Menaquinones (MKn). Vitamin K acts both as coenzyme of y-glutamyl carboxylase (GGCX) transforming undercarboxylated in carboxylated vitamin K-dependent proteins (e.g., Osteocalcin and Matrix Gla Protein) and as a ligand of the nuclear steroid and xenobiotic receptor (SXR) (in murine species Pregnane X Receptor: PXR), expressed in osteoblasts. It has been highlighted that the uremic state is a condition of greater vitamin K deficiency than the general population with resulting higher prevalence of bone fractures, vascular calcifications and mortality. The purpose of this literature review is to evaluate the protective role of Vitamin K in bone health in CKD patients.

Topics: Animals; Bone and Bones; Fractures, Bone; Humans; Mice; Osteocalcin; Renal Insufficiency, Chronic; Vitamin K

Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review.. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use).. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019.. Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis.. Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria.. Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups.. There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.

Topics: Adolescent; Adult; Biomarkers; Blood Coagulation; Bone Density; Child; Cystic Fibrosis; Dietary Supplements; Fractures, Bone; Humans; Middle Aged; Osteocalcin; Osteogenesis; Protein Precursors; Prothrombin; Quality of Life; Randomized Controlled Trials as Topic; Vitamin K; Vitamin K Deficiency; Vitamins

Vitamin K is essential for blood coagulation and plays an important role in extrahepatic metabolism, such as in bone and blood vessels, and in energy metabolism. This review discusses the assessment of vitamin K sufficiency and the role of vitamin K in bone health. To elucidate the exact role of vitamin K in other organs, accurate tools for assessing vitamin K deficiency or insufficiency are crucial. Undercarboxylated vitamin K-dependent protein levels can be measured to evaluate tissue-specific vitamin K deficiency/insufficiency. Vitamin K has genomic action through steroid and xenobiotic receptor (SXR); however, the importance of this action requires further study. Recent studies have revealed that the bone-specific, vitamin K-dependent protein osteocalcin has a close relationship with energy metabolism through insulin sensitivity. Among the organs that produce vitamin K-dependent proteins, bone has attracted the most attention, as vitamin K deficiency has been consistently associated with bone fractures. Although vitamin K treatment addresses vitamin K deficiency and is believed to promote bone health, the corresponding findings on fracture risk reduction are conflicting. We also discuss the similarity of other vitamin supplementations on fracture risk. Future clinical studies are needed to further elucidate the effect of vitamin K on fracture risk.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Bone Density; Female; Fractures, Bone; Humans; Male; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

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

Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture.. We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models.. We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14).. We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.

Topics: Administration, Oral; Anticoagulants; Fractures, Bone; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; 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

The association between dietary vitamin K intake and the risk of fractures is controversial. Therefore we perform a meta-analysis of cohort or nested case-control studies to investigate the relationship between dietary vitamin K intake and the risk of fractures. A comprehensive search of PubMed and EMBASE (to July 11, 2016) was performed to identify cohort or nested case-control studies providing quantitative estimates between dietary vitamin K intake and the risk of fractures. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were pooled by using a random-effects model. Four cohort studies and one nested case-control study, with a total of 1114 fractures cases and 80,982 participants, were included in our meta-analysis. Vitamin K intake in all included studies refers exclusively to the intake of phylloquinone (vitamin K1), which is the predominant form of vitamin K in foods. We observed a statistically significant inverse association between dietary vitamin K intake and risk of fractures (highest vs. the lowest intake, RR = 0.78, 95% CI: 0.56-0.99; I = 59.2%, P for heterogeneity = .04). Dose-response analysis indicated that the pooled RR of fracture for an increase of 50 μg dietary vitamin K intake per day was 0.97 (95% CI: 0.95-0.99) without heterogeneity among studies (I = 25.9%, P for heterogeneity = .25). When stratified by follow-up duration, the RR of fracture for dietary vitamin K intake was 0.76 (95% CI: 0.58-0.93) in studies with more than 10 years of follow-up. Our study suggests that higher dietary vitamin K intake may moderately decrease the risk of fractures.

Topics: Diet; Fractures, Bone; Humans; Observational Studies as Topic; Risk; Vitamin K

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

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

Morbidity and decreased function related to osteoporosis, fracture, cardiovascular disease, stroke, and peripheral vascular disease are encountered by clinicians daily. Although we have seen vast advancement in treatment and management of these conditions, preventative practice has unfortunately served a lesser role in patient care. Increasing the dietary intake of vitamin K may have substantial utility in the prevention of these disease states. Since the discovery of vitamin K in 1935, its primary role was thought to be involved in the synthesis of clotting factors II, VII, IX, and X. Recently, its function in other metabolic pathways has emerged, leading to exploration of its significance beyond coagulation. Vitamin K is essential to bone physiology and prevention of atherosclerosis. It is involved in bone remodeling, cell signaling, apoptosis, arterial calcification, and chemotaxis, and it has anti-inflammatory effects. Conversely, warfarin, a potent vitamin K inhibitor, has demonstrated adverse effects on bone remodeling and atherosclerosis. Natural forms of vitamin K are available in multiple dietary sources, and some structural forms are more readily available for use in metabolic pathways than are others. With regard to supplementation, the specific form of vitamin K is often not disclosed, and the recommended daily value is potentially less than what is physiologically required. On the basis of a review of the literature, it appears advantageous to encourage patients to eat a diet rich in vitamin K; however, the benefit of vitamin K supplementation alone is yet to be thoroughly conveyed.

Topics: Dietary Supplements; Dose-Response Relationship, Drug; Fractures, Bone; Humans; Prognosis; 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

Vitamin K is well known for its role in the synthesis of a number of blood coagulation factors. Vitamin K is also an important factor for bone metabolism via gamma-carboxylation of vitamin K-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recent studies suggest that there is potential vitamin K insufficiency in bone, even in sufficient vitamin K status for blood coagulation. In the present review, the studies concerning relationship between vitamin K status and fracture are reviewed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Fractures, Bone; Humans; Male; Matrix Gla Protein; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency; Young Adult

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

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

Although systematic review and meta-analysis of randomized controlled trials (RCTs) have concluded that vitamin K is effective in preventing fractures, the effect of vitamin K on the skeleton remains a matter of controversy. The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for RCTs by using the search terms "vitamin K(1) or vitamin K(2)," "bone," and "postmenopausal women" and the following inclusion criteria: approximately 50 or more subjects per group and study period of 2 years or longer. Seven RCTs met the inclusion criteria. The results of these RCTs showed that vitamin K(1) and vitamin K(2) supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) and vitamin K(2) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K(1) and vitamin K(2) supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.

Topics: Bone and Bones; Bone Density; Bone Density Conservation Agents; Dietary Supplements; Dose-Response Relationship, Drug; Female; Femur Neck; Fractures, Bone; Humans; Osteocalcin; Postmenopause; 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

Vitamin D and K are nutrients necessary for bone health. Vitamin D insufficiency, which is milder than vitamin D deficiency to cause rickets and osteomalacia, is associated with increased fracture risk. Serum 25 (OH) D concentration, a good marker for vitamin D status, must be higher than the traditional held consensus of 20 ng/mL for bone health. Daily dose of 800 IU or higher is considered to be necessary for fracture prevention. Recently, much attention has been paid on extra-hepatic actions of vitamin K including bone. Elevated serum concentration of undercarboxylated osteocalcin, a sensitive marker for vitamin K inadequacy in the bone, is a risk factor for fracture independent of bone mineral density.

Topics: Biomarkers; Fats; Fractures, Bone; Humans; Osteocalcin; Osteomalacia; Rickets; Risk; Solubility; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

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

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

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

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

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

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

Those who have already suffered from bone fractures have been found to have lower serum vitamin K (VK) concentrations than age-matched controls. Also in dialysis patients, serum VK(1) concentration are reported to be significantly lower in patients with previous fractures compared to those without. In most studies, there are no significant changes in the serum Ca, P, and intact PTH levels during the VK administration in dialysis patients. Investigation of the changes in metabolic bone markers, such as bone specific alkaline phosphatase (BAP) , during the VK therapy has yielded various results. Although the reason for these discrepancy is not well understood, it may be attributed to the differences in clinical features, including parathyroid function of the patients and to the differences in VK administered.

Topics: Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Dialysis; Fractures, Bone; Humans; Vitamin D Deficiency; Vitamin K

Topics: Arthritis, Rheumatoid; Cohort Studies; Fractures, Bone; Glucocorticoids; Glycine max; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Prospective Studies; Risk; Risk Factors; 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

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

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

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

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

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

Two recent studies examined the association between chronic use of warfarin, a vitamin K antagonist, and fracture rate among older women. Whereas one study reported no association, the other reported a significantly higher risk for vertebral and rib fractures among warfarin users compared with nonusers. The effect of vitamin K antagonists on age-related bone loss continues to be controversial.

Topics: Animals; Anticoagulants; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Vitamin K; Warfarin; Women's Health

Topics: Bone Density; Calcium; Dietary Supplements; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Vitamin D; Vitamin K

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

The connective tissues are a complex organisation of tissues, cells and intercellular materials spread throughout the body and are subject to a large number of diseases. Such complexity makes the study of the metabolism of the connective tissues in health and more particularly in disease states difficult if one uses conventional biochemical methodology. Fortunately the techniques of quantitative cytochemistry, as developed in recent years, have made it possible to study the metabolism of even such complex and refractory connective tissues as bone. Using properly validated assays of enzyme activity in unfixed sections from various tissues a number of the diseases of the connective tissues have been studied. For example the synovia from patients with rheumatoid arthritis and related conditions have been studied using these techniques and marked alterations in the metabolism of the synovial lining cell population of this tissue have been demonstrated. These alterations in metabolism are believed to be related to the destruction of cartilage and bone found in such diseases. Investigations of the metabolism of the chondrocytes of articular cartilage in a strain of mice which spontaneously develops osteoarthritis has revealed a lack of certain key enzymes of carbohydrate metabolism in precisely those areas where degradation of the matrix of articular cartilage begins suggesting a causal relationship between these events. These same techniques have been used to study the cellular kinetics and metabolism of the dermis and epidermis in the disfiguring disease, psoriasis. The metabolism of healing bone fractures, the diagnosis and treatment of the mucopolysaccharidoses and the metabolic effects of currently used anti-inflammatory and anti-rheumatic drugs have also been examined. Perhaps the most exciting aspect of these studies has been the development and use of the technique of the cytochemical bioassay (CBA) to study hormonally mediated diseases of the connective tissues. Such studies have recently shed new light on the molecular lesion in pseudohypoparathyroidism. Though still in their relative infancy the studies described in this review show the potential inherent in the use of quantitative cytochemistry for the study of diseases of the connective tissues.

Topics: Animals; Arthritis, Rheumatoid; Cartilage, Articular; Cell Division; Connective Tissue Diseases; Disease Models, Animal; Epidermal Cells; Fractures, Bone; Glucosephosphate Dehydrogenase; Glycolysis; Hexosephosphates; Histocytochemistry; Humans; Lysosomes; Mitochondria; Mucopolysaccharidoses; NADP; Osteoarthritis; Pseudohypoparathyroidism; Psoriasis; Synovial Membrane; Vitamin K; Wound Healing; Zinc

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

Chronic kidney disease and osteoporosis are major public health problems associated with an aging population. Vitamin K insufficiency is prevalent among patients with end-stage renal disease (ESRD). Preliminary data indicate that poor vitamin K status may compromise bone health and that increased inflammation may be in the causal pathway. We performed an ancillary analysis of data collected in the frame of prospective observational cohort studies exploring various aspects of bone health in de novo renal transplant recipients to investigate the association between vitamin K status, inflammation, bone mineral density, and incident clinical fractures. Parameters of mineral metabolism (including biointact PTH and FGF23, sclerostin, calcidiol, calcitriol) and inflammation (CRP and IL-6), osteoprotegerin, bone turnover markers (P1NP, BsAP, and TRAP5B), and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) were assessed on blood samples collected immediately prior to kidney transplantation in 468 patients. Areal bone mineral density (aBMD) was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry within 14 days posttransplant. Poor vitamin K status, defined by dp-ucMGP >500 nmol/L, was highly prevalent (90%). High dp-ucMGP levels independently associated with elevated inflammatory markers and low aBMD. No associations were observed between vitamin K status and bone turnover markers. During a median follow-up of 5.1 years, 33 patients sustained a fragility fracture. In Cox-proportional hazards analysis, a dp-ucMGP above median associated with incident fractures, independent of classical determinants, including age, gender, history of fracture, and aBMD (HR 2.21; 95% CI, 1.00 to 4.91; p < 0.05). In conclusion, poor vitamin K status associates with inflammation and low aBMD in patients with ESRD and confers an increased risk of incident fractures in de novo renal transplant recipients. © 2018 American Society for Bone and Mineral Research.

Topics: Adult; Aged; Biomarkers; Bone Density; Female; Femur Neck; Fibroblast Growth Factor-23; Fractures, Bone; Humans; Kidney Failure, Chronic; Lumbar Vertebrae; Male; Middle Aged; Risk Factors; Vitamin K

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

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

Topics: Anticoagulants; Fractures, Bone; Humans; Vitamin K

Topics: Bone Diseases, Metabolic; Fractures, Bone; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Vitamin K

Topics: Fractures, Bone; Humans; Randomized Controlled Trials as Topic; Vitamin K; Vitamins

In the past decades, an increased interest in the roles of vitamin D and K has become evident, in particular in relation to bone health and prevention of bone fractures. The aim of the current study was to evaluate vitamin D and K status in children with low-energy fractures and in children without fractures.. The study group of 20 children (14 boys, 6 girls) aged 5 to 15 years old, with radiologically confirmed low-energy fractures was compared with the control group of 19 healthy children (9 boys, 10 girls), aged 7 to 17 years old, without fractures. Total vitamin D (25(OH)D3 plus 25(OH)D2), calcium, BALP (bone alkaline phosphatase), NTx (N-terminal telopeptide), and uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) serum concentrations were evaluated. Ratio of serum uncarboxylated osteocalcin to serum carboxylated osteocalcin ucOC:cOC (UCR) was used as an indicator of bone vitamin K status. Logistic regression models were created to establish UCR influence for odds ratio of low-energy fractures in both groups.. There were no statistically significant differences in the serum calcium, NTx, BALP, or total vitamin D levels between the two groups. There was, however, a statistically significant difference in the UCR ratio. The median UCR in the fracture group was 0.471 compared with the control group value of 0.245 (. In this pilot study, better vitamin K status expressed as the ratio of ucOC:cOC-UCR—is positively and statistically significantly correlated with lower rate of low-energy fracture incidence.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Age Factors; Biomarkers; Calcifediol; Carboxylic Acids; Case-Control Studies; Child; Down-Regulation; Female; Fractures, Bone; Humans; Logistic Models; Male; Odds Ratio; Osteocalcin; Pilot Projects; Vitamin K

Topics: Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Vitamin K

Topics: Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Vitamin K

The research on skeletal system health in children and young adults, while recognizing the important role of calcium and vitamin D, goes beyond these nutritional standards. This review focuses on the role of vitamin K in combination with vitamin D and other factors in bone health. The current understanding is that maintaining bone health and prevention of low-energy fractures in any pediatric population includes nutritional factors combined with an active lifestyle. Calcium, vitamin D, and vitamin K supplementation contribute independently and collectively to bone health. The beneficial role of vitamin K, particularly vitamin K2 as menaquinone-7 (MK-7), in bone and cardiovascular health is reasonably well supported scientifically, with several preclinical, epidemiological, and clinical studies published over the last decade. Osteocalcin and matrix-Gla (glutamate-containing) protein (MGP) exemplify vitamin K-dependent proteins involved in building bone matrix and keeping calcium from accumulating in the arterial walls, respectively. An important part of the mechanism of vitamin K involves carboxylation and posttranslational activation of the family of vitamin K-dependent proteins, which prevent expression of pro-inflammatory factors and support improvement in bone mineral concentration, bone mineral density, and the quality of bone matrix. Understanding the combined approach to a healthy skeletal system in children and young adults, including the roles of vitamins D and K, calcium, healthy diet, and exercise, is particularly important in view of reports of subclinical insufficiency of vitamins D and K in otherwise healthy pediatric populations with low-energy bone fractures.

Topics: Bone Density; Child, Preschool; Fractures, Bone; Humans; Life Style; Nutritional Status; Vitamin D; Vitamin K; Young Adult

Successful vitamin K antagonist (eg, warfarin) reversal with 4-factor prothrombin complex concentrate (4F-PCC) without vitamin K (phytonadione) for emergent surgery in a patient at moderate-to-high risk for thromboembolism is reported. This approach may decrease the risk for development of thrombus, as it limits the amount of time the patient's anticoagulation is subtherapeutic. It also may increase the risk of bleeding, so patient selection is essential if this strategy is employed. Caution must be exercised to complete the procedure or surgery in the window of peak 4F-PCC effect (∼1-6 hours postinfusion).

Topics: Accidents, Traffic; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation Factors; Compartment Syndromes; Crush Injuries; Drug Hypersensitivity; Fibula; Fractures, Bone; Humans; International Normalized Ratio; Leg Injuries; Male; Preoperative Care; Stroke; Vitamin K; Warfarin

Data on the association between dietary vitamin K intake and fracture risk are limited among Chinese. This study examined such an association in community-dwelling elderly in Hong Kong. We present data from 2,944 subjects (1,605 men, 1,339 women) who participated in a prospective cohort study. Baseline dietary intakes of energy, protein, calcium, vitamin D, and vitamin K were assessed using a food-frequency questionnaire. Data on incident hip fracture and nonvertebral fracture during a median of 6.9 follow-up years were collected from a hospital database. Cox regression analyses were performed with adjustments for age, education attainment, smoking status, alcohol use, body mass index, hip bone mineral density, physical activity, use of calcium supplement, and energy-adjusted nutrient intakes. There were 29 (1.8 %) men and 19 (1.4 %) women with incident hip fractures and 97 (6.0 %) men and 88 (6.6 %) women with nonvertebral fractures. The median (interquartile range) of dietary vitamin K intake was 241.8 (157.5-360.8) and 238.9 (162.4-343.6) μg/day in men and women, respectively. Similar dietary vitamin K intakes were observed between subjects with hip or nonvertebral fractures and subjects without hip or nonvertebral fractures. In both men and women, dietary vitamin K intake was not associated with fracture risks at all measured sites in either crude or adjusted models. In Chinese community-dwelling elderly, hip or nonvertebral fracture risk was not associated with dietary vitamin K intake. The high dietary vitamin K intake of the studied group may have limited the ability to detect the association between vitamin K intake and fracture risk.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Asian People; Dietary Supplements; Female; Fractures, Bone; Humans; Independent Living; Male; Prospective Studies; Risk Factors; Vitamin K; Vitamins

Topics: Calcium, Dietary; Dietary Supplements; Fatty Liver; Fractures, Bone; Humans; Inflammation; Inflammatory Bowel Diseases; Iron; Micronutrients; Non-alcoholic Fatty Liver Disease; Nutritional Physiological Phenomena; Trace Elements; Vitamin D; Vitamin E; Vitamin K

In Japan, γ-carboxylation of blood coagulation factors is the basis for determining adequate intake (AI) for vitamin K in Dietary Reference Intakes (DRIs) issued in 2010. Recently, vitamin K is also known to be essential for preventing fracture. In this study, relative susceptibility of liver and bone to vitamin K deficiency was studied. Thirty-seven elderly institutionalized subjects were evaluated for vitamin K status by measuring serum PIVKA (protein induced by vitamin K absence) -II and ucOC (undercarboxylated osteocalcin) levels, as sensitive markers for hepatic and skeletal vitamin K deficiency, respectively. Serum PIVKA-II and ucOC levels, with their cut-off values in the parentheses, were 20.2±8.9 mAUmL (28 mAU/mL) and 4.7±3.0 ng/mL (4.5 ng/mL), respectively. Median vitamin K intake was approximately 200 μg/day, which is more than 3 times higher than the current Japanese AI. Vitamin K intake was significantly correlated with serum PIVKA-II and ucOC/OC levels, but not with serum ucOC level. Although serum ucOC level is generally a good indicator for vitamin K status, multiple regression analysis revealed that elevated bone turnover marker significantly contributed to serum ucOC level. All subjects had vitamin K intake exceeding AI for vitamin K. Nevertheless, serum PIVKA-II and ucOC concentrations exceeded the cut-off value in 14% and 43% of subjects, respectively. The present findings suggest that vitamin K intake greater than the current AI is required for the skeletal health in the institutionalized elderly.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Diet; Elder Nutritional Physiological Phenomena; Energy Intake; Female; Fractures, Bone; Homes for the Aged; Humans; Liver; Liver Diseases; Male; Nursing Homes; Osteocalcin; Protein Precursors; Prothrombin; Vitamin K; Vitamin K Deficiency

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

Excessive intakes of vitamin A have been shown to have adverse skeletal effects in animals. High vitamin A intake may lead to an increased risk of fracture in humans.. The objective was to evaluate the relation between total vitamin A and retinol intakes and the risk of incident total and hip fracture in postmenopausal women.. A total of 75,747 women from the Women's Health Initiative Observational Study participated. The risk of hip and total fractures was determined using Cox proportional hazards models according to different intakes of vitamin A and retinol.. In the analysis adjusted for some covariates (age; protein, vitamin D, vitamin K, calcium, caffeine, and alcohol intakes; body mass index; hormone therapy use; smoking; metabolic equivalents hours per week; ethnicity; and region of clinical center), the association between vitamin A intake and the risk of fracture was not statistically significant. Analyses for retinol showed similar trends. When the interaction term was analyzed as categorical, the highest intake of retinol with vitamin D was significant (P = 0.033). Women with lower vitamin D intake (< or =11 microg/d) in the highest quintile of intake of both vitamin A (hazard ratio: 1.19; 95% CI: 1.04, 1.37; P for trend: 0.022) and retinol (hazard ratio: 1.15; 95% CI: 1.03, 1.29; P for trend: 0.056) had a modest increased risk of total fracture.. No association between vitamin A or retinol intake and the risk of hip or total fractures was observed in postmenopausal women. Only a modest increase in total fracture risk with high vitamin A and retinol intakes was observed in the low vitamin D-intake group.

Topics: Aged; Alcohol Drinking; Body Mass Index; Caffeine; Calcium, Dietary; Cohort Studies; Dietary Proteins; Estrogen Replacement Therapy; Female; Fractures, Bone; Hip Fractures; Humans; Longitudinal Studies; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Proportional Hazards Models; Risk Factors; Smoking; Vitamin A; Vitamin D; Vitamin K

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

Topics: Aged; Fractures, Bone; Humans; Incidence; Japan; Vitamin K; Vitamins

Topics: Fractures, Bone; Humans; Vitamin K

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

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

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

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

Vitamin K is essential for the carboxylation of glutamic acid residues, such as osteocalcin. Recent studies have reported that vitamin K reduces vertebral and hip fractures without increasing bone mass in patients with osteoporosis, suggesting that vitamin K could affect bone quality. However, the mechanism is unknown. To investigate the involvement of the carboxylation of osteocalcin in bone quality, the present preliminary study examined serum bone markers and ultrasound velocity, a possible indicator of bone quality, in 14 healthy prepubertal children (eight boys and six girls) aged between 7 and 12 years. Venous blood was collected between 0800 and 0900 h after an overnight fast, and serum levels of intact, carboxylated and undercarboxylated osteocalcin, bone-specific alkaline phosphatase and type I procollagen carboxyl extension peptide were measured. Speed of sound in the right tibia was measured using a SoundScan 2000 Compact (Myriad Ultrasound System, Rehovot, Israel). As a result, there was no significant correlation between the serum bone markers and the Z score for the speed of sound. In contrast, the ratio of serum carboxylated osteocalcin to serum intact osteocalcin was positively correlated with the Z score for the speed of sound (r = 0.621, P = 0.016). These findings suggest, for the first time, that carboxylation of osteocalcin is related to bone quality. Further studies are needed to clarify the role of carboxylation of osteocalcin in bone, and this will provide a new insight into the mechanism of vitamin K treatment in osteoporosis.

Topics: Alkaline Phosphatase; Biomarkers; Bone and Bones; Carbon Dioxide; Child; Female; Fractures, Bone; Humans; Male; Osteocalcin; Peptide Fragments; Procollagen; Tibia; Ultrasonography; 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: Adolescent; Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Fractures, Bone; Humans; Male; Mathematics; Middle Aged; Osteocalcin; Vitamin K; Vitamin K Deficiency

This investigation of 219 hemodialysis patients relates the history and prospective risk of bone fractures to apolipoprotein E (apoE) genotype. A greater percentage of the 41 patients with the E3/4 and E4/4 genotypes than of the 38 patients with the E2/3 and E2/2 genotypes had a history of bone fractures at the time of recruitment (44% versus 16%, P < 0.005). During the 4 years following recruitment, more of the patients with apoE genotypes E3/4 and E4/4 than with apoE genotypes E2/3 and E2/2 suffered bone fractures, but this difference was not statistically significant (17.1 versus 5.3%, P < 0.1). ApoE genotype appears to be an important genetic risk factor for bone fracture, possibly due to its previously reported influence on vitamin K concentrations in blood.

Topics: Adult; Aged; Aged, 80 and over; Apolipoproteins E; Bone and Bones; Female; Fractures, Bone; Genotype; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors; Vitamin K

Topics: Animals; Biomarkers; Bone and Bones; Fractures, Bone; Humans; Pyridoxine; Vitamin B 6 Deficiency; Vitamin K

This investigation of 68 hemodialysis patients (ages 33 to 91) analyzed the association of biochemical indicators of vitamin K nutriture and bone metabolism, and related both to past bone fracture history and prospective bone fracture risk. Phylloquinone concentrations were significantly lower in the 23 patients with previous fractures compared to those without (0.93 vs. 1.50 nmol/liter, P < 0.003) and a smaller percentage of their serum osteocalcin was carboxylated (48.8 vs. 53.6%, P < 0.03). The 41 patients who never had fractures had nearly three times higher phylloquinone concentrations than the nine patients with fractures during a four-year follow-up period (1.59 vs. 0.55 nmol/liter, P < 0.002) and more carboxylated serum osteocalcin (55.2 vs. 42.0%, P < 0.01). None of the patients with phylloquinone concentrations over 2.2 nmol/liter had elevated intact parathyroid hormone (iPTH) concentrations, and only patients with less than 1 nmol/liter phylloquinone had severe hyperparathyroidism (iPTH > 300 ng/liter). Our data thus indicate that suboptimal vitamin K nutriture in hemodialysis patients is associated both with increased bone fracture risk and with a high prevalence of hyperparathyroidism.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Fractures, Bone; Humans; Hyperparathyroidism, Secondary; Middle Aged; Nutritional Status; Osteocalcin; Parathyroid Hormone; Prospective Studies; Renal Dialysis; Risk Factors; Vitamin K; Vitamin K 1

It is now clear that vitamin K1 is part of a biochemical cycle that is essential for the conversion of specific bone peptides into a form that can bind calcium. We have used a recently described procedure for assaying vitamin K1 in plasma to test the involvement of this vitamin in fracture healing. Markedly depressed circulating levels were found in patients with fractures and the time taken for this level to return to normal appeared to be influenced by the severity of the fracture.

Topics: Adolescent; Adult; Aged; Female; Fractures, Bone; Humans; Male; Middle Aged; Vitamin K

The anticoagulant, dicumarol, inhibits the vitamin K cycle by blocking the conversion of the vitamin K epoxide. The effects of dicumarol on ossification have been tested by feeding it to rats in which a closed fracture of the metatarsals had been induced; the effects were studied up to 12 days postfracture. At 12 days, treatment with dicumarol caused a highly significant decrease in the amount of bone produced, without affecting the total size of the callus. Quantitative cytochemistry of unfixed, undemineralized sections showed that dicumarol also markedly affected the periosteal activities of glucose 6-phosphate dehydrogenase and of alkaline phosphatase in the first 2 mm from the fracture measured at 3 and 5 days postfracture when normally, new bone is first formed. In contrast, dicumarol had little effect on these activities in the fully formed callus.

Topics: Alkaline Phosphatase; Animals; Cicatrix; Dicumarol; Fractures, Bone; Glucosephosphate Dehydrogenase; Male; Osteogenesis; Periosteum; Rats; Rats, Inbred Strains; Vitamin K; Wound Healing

Topics: Adult; Anticoagulants; Aspirin; Drug Evaluation; Female; Fractures, Bone; Hemorrhage; Humans; Male; Middle Aged; Thromboembolism; Vitamin K

Topics: Fracture Healing; Fractures, Bone; Humans; Vitamin K