menaquinone-6 and Osteoporosis--Postmenopausal

Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed.. To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up.. We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis.. Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation.. This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.

Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K 2

Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.. We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.. Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (. The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.

Topics: Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Vitamin K 2

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

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To identify the role of vitamin K2 for the prevention and treatment of osteoporosis in postmenopausal women, we conducted this meta-analysis of 19 randomized controlled trials. Our results showed that vitamin K2 might play a role in maintaining the bone mineral density and in reducing the incidence of fractures for postmenopausal women with osteoporosis.. Vitamin K2 has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, which was not confirmed in western countries. Thus, we conduct this meta-analysis to verify the hypothesis that vitamin K2 plays a role in the prevention and treatment of osteoporosis for postmenopausal women.. We searched the Cochrane Library, Pub Med, EMBASE, and ISI web of knowledge (until December 1, 2013) and reference lists of eligible articles. A meta-analysis of all-including randomized controlled trials was then performed.. Nineteen randomized controlled trials encompassing 6759 participants have met the inclusion criteria. Subgroup analysis of postmenopausal women with osteoporosis revealed a significant improvement of vertebral BMD for both medium-term and long-term results favoring vitamin K2 group (p < 0.00001 and p = 0.0005). However, no significant difference in BMD changes was revealed for the non-osteoporosis subgroup analysis. As for the incidence of fractures, pooled analysis of the seven related studies demonstrated no significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.63, p = 0.08). However, sensitivity analysis by rejecting the study inducing heterogeneity demonstrated a significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.50, p = 0.0005). Significant differences were found in undercarboxylated osteocalcin reduction and osteocalcin increment. The result of adverse reaction analysis showed that vitamin K2 group seemed to have a higher adverse reaction rate (RR = 1.22, p = 0.06).. This meta-analysis seemed to support the hypothesis that vitamin K2 plays kind of a role in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. The reduction of undercarboxylated osteocalcin and increment of osteocalcin may have some relation to the process of bone mineralization. However, the effect of vitamin K2 for postmenopausal women without osteoporosis had not been identified. Further high-quality RCTs with large sample size are needed to confirm the role of vitamin K2 in osteoporosis for postmenopausal women.

Topics: Aged; Aged, 80 and over; Bone Density; Female; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K 2; Vitamins

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

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

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

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

Topics: Cardiovascular Diseases; Evidence-Based Medicine; Female; Humans; Male; Neoplasms; Nutrition Policy; Osteoporosis; Osteoporosis, Postmenopausal; Parkinson Disease; Vitamin K 2; Vitamins

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

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

Vitamin K2, raloxifene, and bisphosphonates, such as etidronate, alendronate, and risedronate, are widely used in the treatment of postmenopausal osteoporosis in Japan. A meta-analysis study has demonstrated the efficacy of anti-resorptive agents: raloxifene and etidronate have been shown to reduce the incidence of vertebral fractures, and alendronate and risedronate have been shown to reduce the incidence of both vertebral and hip fractures. Furthermore, a report of the World Health Organization (WHO) has provided evidence from a randomized controlled trial suggesting that vitamin K2, which may stimulate bone formation via gamma-carboxylation of osteocalcin and/or steroid and xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Based on the weight of the currently available evidence, it is recommended that alendronate and risedronate, rather than vitamin K2, should be chosen initially for the treatment of postmenopausal osteoporosis, because these agents have been shown to be the most efficacious for reducing the incidence of both vertebral and hip fractures among the current range of commercially available agents. However, the more potent anti-fracture efficacy of combined treatment with the anti-resorptive and commercially available anabolic agents may need to be established. Some studies have shown that combined treatment with a bisphosphonate and vitamin K2 may be more effective than treatment with a bisphosphonate alone in preventing vertebral fractures. On the other hand, the results of a preclinical study do suggest the possible efficacy of combined treatment with vitamin K2 and raloxifene in the prevention of vertebral and hip fractures in postmenopausal women, although no clinical studies have reported on the effects of combined treatment with vitamin K2 and raloxifene in postmenopausal women with osteoporosis. Vitamin K deficiency, as indicated by high serum levels of undercarboxylated osteocalcin, has been shown to contribute to the occurrence of hip fractures in elderly women. Thus, we propose that the important role of vitamin K2 used in combination with bisphosphonates or raloxifene should not be underestimated in the prevention of fractures in postmenopausal women with osteoporosis with vitamin K deficiency.

Topics: Bone Density Conservation Agents; Clinical Trials as Topic; Diphosphonates; Drug Therapy, Combination; Female; Humans; Meta-Analysis as Topic; Osteoporosis, Postmenopausal; Vitamin K 2; Vitamin K Deficiency; Vitamins

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

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

The role of vitamin K in the prevention and treatment of osteoporosis and arterial calcification is examined.. Vitamin K is essential for the activation of vitamin K-dependent proteins, which are involved not only in blood coagulation but in bone metabolism and the inhibition of arterial calcification. In humans, vitamin K is primarily a cofactor in the enzymatic reaction that converts glutamate residues into gamma-carboxyglutamate residues in vitamin K-dependent proteins. Numerous studies have demonstrated the importance of vitamin K in bone health. The results of recent studies have suggested that concurrent use of menaquinone and vitamin D may substantially reduce bone loss. Menaquinone was also found to have a synergistic effect when administered with hormone therapy. Several epidemiologic and intervention studies have found that vitamin K deficiency causes reductions in bone mineral density and increases the risk of fractures. Arterial calcification is an active, cell-controlled process that shares many similarities with bone metabolism. Concurrent arterial calcification and osteoporosis have been called the "calcification paradox" and occur frequently in postmenopausal women. The results of two dose-response studies have indicated that the amount of vitamin K needed for optimal gamma-carboxylation of osteocalcin is significantly higher than what is provided through diet alone and that current dosage recommendations should be increased to optimize bone mineralization. Few adverse effects have been reported from oral vitamin K.. Phytonadione and menaquinone may be effective for the prevention and treatment of osteoporosis and arterial calcification.

Topics: Antifibrinolytic Agents; Arteriosclerosis; Female; Humans; Osteoporosis, Postmenopausal; Treatment Outcome; Vitamin K; Vitamin K 1; Vitamin K 2

Topics: Bone Density; Cholecalciferol; Drug Therapy, Combination; Female; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Vitamin K 2

The article entitled “Effects of Vitamin K2 on Osteoporosis, published in Curr Pharm Des 2004; 10(21): 2557-76, by Iwamoto\ J, Takeda T and Sato Y.” has been retracted by the Editorial office of the journal Current Pharmaceutical Design, as the text,\ data and some figures used/referred in this review article are from sources which have been retracted or under investigation on\ the basis of data fabrication and falsification, authorship misconduct, duplicate publication, unethical research practices, text\ recycling/self-plagiarism, and unresolved concerns about data integrity and research conduct. The authors were informed of\ this complaint and were requested to give justification on the matter in their defense. However, no reply was received from\ their side in this regard. Some sources that have been retracted are as follows:. 1. Iwamoto J, Takeda T, Ichimura S. Combined treatment with vitamin K2 and bisphosphonate in postmenopausal women with osteoporosis. Yonsei Med J 2003; 44: 751-6. Available at: https://eymj.org/DOIx.php?id=10.3349/ymj.2019.60.1.115.. 2. Sato Y, Honda Y, Kuno H, Oizumi K. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Bone 1998; 23: 291-6. Available at: https://www.sciencedirect.com/science/article/pii/S8756328298001082.. 3. Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, et al. Amelioration of osteoporosis by menatetrenone in elderly female\ Parkinson's disease patients with vitamin D deficiency. Bone 2002; 31: 114-8. Available at: https://pubmed.ncbi.nlm.nih.gov/\ 12110423/.. Bentham Science apologizes to its readers for any inconvenience this may have caused. The Bentham Editorial Policy on Article. Retraction can be found at https://benthamscience.com/editorial-policies-main.php. It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Topics: Animals; Calcium; Cholecalciferol; Drug Therapy, Combination; Female; Hip Fractures; Humans; Liver Diseases; Male; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Space Flight; Vitamin K 2; Weightlessness

Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and risedronate, is widely used in the treatment with osteoporosis in Japan. Etidronate increases the lumbar bone mineral density (BMD), and prevents new vertebral fractures, in patients with osteoporosis, while alendronate and risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2, should be initially chosen for the treatment of osteoporosis, because they are more efficacious than vitamin K2. Available evidence suggest that risedronate prevents deterioration of the connectivity of the trabeculae in ovariectomized rats, whereas vitamin K2 increase the trabecular thickness, and that a combination of risedronate and vitamin K2 has a synergistic effect on preventing the deterioration of trabecular bone architecture induced by estrogen deficiency. Some studies have shown that combined treatment with etidronate and vitamin K2 appears to be more effective than etidronate alone in the prevention of new osteoporotic vertebral fractures. Based on these findings, combined treatment with vitamin K2 and bisphosphonates may be more efficacious in the prevention new vertebral fractures than a single treatment with bisphosphonate in postmenopausal women with osteoporosis. Thus, this combined treatment should be recommended for the treatment of postmenopausal osteoporosis. It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency.

Topics: Aged; Bone and Bones; Bone Density; Diphosphonates; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Vitamin K 2

We assessed the health state utility value (HSUV) reductions associated with vertebral fractures using data collected in the Japanese Osteoporosis Intervention Trial-03 (JOINT-03). Our analysis revealed that assessment of HSUVs after morphometric vertebral fracture is important to capture the burden of vertebral fractures.. Evaluation of the HSUV after fracture is important to calculate the quality-adjusted life years (QALYs) of osteoporosis patients, which is essential information in the context of health economic evaluation.. JOINT-03 study patients were aged ≥65 years and treated with risedronate and vitamin K. Among 2922 follow-up HSUVs, 201 HSUVs were categorized as HSUVs that were observed after incident vertebral fractures on X-ray films. The median time from the detection of an incident vertebral fracture until the EQ-5D assessment was 53 days (25th percentile, 0 day; 75th percentile, 357 days). The impact of incident vertebral fractures on HSUVs was quantified as -0.03. Among the five health profile domains on the EQ-5D, an incident vertebral fracture had significant effects on anxiety/depression, self-care, and usual activities.. The results suggest that incident morphometric vertebral fracture was associated with impairment of the HSUV for patients with osteoporosis not only immediately but also several months after the fracture.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Humans; Japan; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Pain; Pain Measurement; Patient Reported Outcome Measures; Quality-Adjusted Life Years; Risedronic Acid; Spinal Fractures; Vitamin K 2

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

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Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; 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Clinical studies suggest that vitamin K2 protects against bone loss and fractures; however, its effect on bone quality has never been investigated. We investigated the effect of vitamin MK-7 on undercarboxylated osteocalcin (ucOC), and bone mass and quality.. We conducted a randomised, placebo-controlled, double-blinded clinical trial.. We investigated the effect of MK-7 375 µg for 12 months on bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), bone microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) and biochemical bone turnover markers in 148 postmenopausal women with osteopenia. All of them were supplemented with calcium and vitamin D.. ucOC decreased in the MK-7 group (-65.6 (59.1; 71.0) %) (median (CI)) compared with the placebo group (-6.4 (-13.5; 1.2) %) after 3 months (P < 0.01). HRpQCT after 12 months demonstrated that trabecular number in tibia was unchanged in the MK-7-group (-0.1 ± 1.9%) (mean ± s.d.) and decreased in the placebo group (-3.5 ± 2.2%), trabecular spacing was unchanged in the MK-7 group (+1.2 ± 8.0%) and increased in the placebo group (+4.5 ± 9.7%), and trabecular thickness was unchanged in the MK-7 group (+0.2 ± 1.7%) and increased in the placebo group (+4.0 ± 2.2%) (between-group changes for all: P < 0.05). There were no significant differences between the groups in HRpQCT-derived parameters at the radius or in BMD at any site.. The changes in bone microarchitecture in the placebo group are consistent with the age-related deterioration of trabecular structure, with a loss of trabeculae and a greater mean thickness of the remaining trabeculae. This suggests that vitamin MK-7 preserves trabecular bone structure at the tibia.

Topics: Absorptiometry, Photon; Age Factors; Aged; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Cancellous Bone; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Tibia; Tomography, X-Ray Computed; Vitamin K 2

Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects.

Topics: Aged; Biomarkers; Bone Density; Chromatography, High Pressure Liquid; Dietary Supplements; Double-Blind Method; Female; Forearm; Humans; Japan; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Surveys and Questionnaires; Time Factors; Vitamin K 2

Risedronate decreases osteoporotic fracture incidence; however, its effects remain unclear in elderly osteoporotic patients. Vitamin K mediates carboxylation of osteocalcin (OC), and high undercarboxylated osteocalcin (ucOC) levels indicate vitamin K deficiency and increased osteoporotic fracture risk. We aimed to evaluate the effects of risedronate alone or combined with vitamin K2 on serum ucOC, OC, and incidence of vertebral fractures in elderly osteoporotic patients. A total of 101 women with postmenopausal osteoporosis aged >60 years were randomly stratified into two groups-R group (n = 51), treated with risedronate alone; and R + K group (n = 50), treated with risedronate and vitamin K2. Serum ucOC, OC and incidence of vertebral fractures were evaluated before treatment and at 6 and 12 months post-treatment. Decreased ucOC rates at 6 and 12 months were not significant between groups. However, at 6 and 12 months, decreased OC rates in the R group (p < 0.01 and 0.05, respectively) were significantly higher than in the R + K group, and ucOC/OC change rates in the R group (p < 0.05 and 0.001, respectively) were significantly lower than in the R + K group. Vertebral fracture incidence was not significantly different between the groups at 6 and 12 months. ucOC levels in patients with incident vertebral fractures were significantly higher than in patients without incident vertebral fractures in the R group at 6 months (p < 0.05). Although no significant difference was observed for ucOC decrease rate and incidence of vertebral fractures between treatments, ucOC levels in patients with incident vertebral fractures were significantly greater than in patients without when using risedronate alone.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Etidronic Acid; Female; Humans; Incidence; Osteocalcin; Osteoporosis, Postmenopausal; Prospective Studies; Risedronic Acid; Spinal Fractures; Vitamin K 2

To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women.. This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups.. A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol.. Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women.

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

We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.. Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health.. Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment.. MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.. MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.

Topics: Aged; Aging; Bone Density; Bone Density Conservation Agents; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Female; Femur Neck; Hip Joint; Humans; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Spinal Fractures; Vitamin K 2

Vitamin K2 may preserve bone strength and reduce fracture risk. In this randomised double-blind placebo-controlled trial among healthy postmenopausal Norwegian women, 1 year supplementation of vitamin K2 in the form of Natto capsules had no effect on bone loss rates.. Japanese studies indicate that vitamin K2 (menaquinone-7 (MK-7)) intake may preserve bone strength, but this has not been documented in Europeans. The aim of this study was to assess the effect of MK-7 on bone mineral density (BMD) changes in postmenopausal Norwegian women.. Three hundred thirty-four healthy women between 50 and 60 years, 1-5 years after menopause, were recruited to a randomised double-blind placebo-controlled trial. The participants were randomly assigned into two groups, one receiving 360 microg MK-7 in the form of Natto capsules and the other the same amount of identical-looking placebo capsules containing olive oil. BMD was measured at total hip, femoral neck, lumbar spine and total body at baseline and 12 months together with serum levels of bone-specific alkaline phosphatase, Crosslaps, total osteocalcin (N-mid OC), carboxylated (cOC) and under-carboxylated osteocalcin (ucOC).. After 12 months, there were no statistical differences in bone loss rates between the groups at the total hip or any other measurement site. Serum levels of cOC increased and ucOC decreased in the treatment versus the placebo group (p < 0.001).. MK-7 taken as Natto over 1 year reduced serum levels of ucOC but did not influence bone loss rates in early menopausal women.

Topics: Biomarkers; Bone Density; Dietary Supplements; Double-Blind Method; Female; Femur Neck; Follow-Up Studies; Hip Joint; Humans; Lumbar Vertebrae; Medication Adherence; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Vitamin K 2

An open-label study with blinded evaluation was performed to compare the preventive effect of a calcium supplement alone (monotherapy) or calcium supplement plus menatetrenone (combined therapy) on fracture in osteoporotic postmenopausal women aged 50 years or older. Patients were randomized to receive monotherapy (n = 2,193) or combined therapy (n = 2,185). Before randomization, the subjects were stratified into a subgroup without vertebral fractures (n = 2,986; no-fracture subgroup) and a subgroup with at least one vertebral fracture (n = 1,392; fracture subgroup). The incidence rate of new vertebral fractures during 36 months of treatment (primary endpoint) did not differ significantly between either subgroup of the two treatment groups. Although the cumulative 48-month incidence rate of new clinical fractures (secondary endpoint) was lower in the combined therapy group, the difference was not significant. There was a lower risk of new vertebral fractures in patients with at least five baseline fractures who received combined therapy. Also, the loss of height was less with combined therapy than with monotherapy among patients 75 years of age or older at enrollment, those whose last menstrual period occurred 30 years or more before enrollment, and those with at least five vertebral fractures at enrollment. Adverse events and adverse reactions were more frequent in the combined therapy group. In conclusion, menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set of this study, but the results suggested that it may prevent vertebral fractures in patients with more advanced osteoporosis.

Topics: Aged; Aged, 80 and over; Calcium, Dietary; Dietary Supplements; Drug Therapy, Combination; Female; Hemostatics; Humans; Middle Aged; Osteoporosis, Postmenopausal; Spinal Fractures; Vitamin K 2

The effect of vitamin K(2) (menatetrenone) on bone turnover was investigated in postmenopausal patients with osteoporosis. A 6-month open-label, randomized prospective study was conducted in 109 patients. The control group (n = 53) received calcium aspartate (133.8 mg of elemental calcium daily), while the menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months. Serum and urinary levels of bone turnover markers were monitored. The serum level of undercarboxylated osteocalcin (uc-OC) was significantly lower (P < 0.001) in the menatetrenone group than in the control group (at 1 month), while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC) in the menatetrenone group than the control group (P = 0.018). Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward. In addition, a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months (P = 0.006). Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen (NTX) excretion compared with the control group after 6 months, while there was no significant difference of urinary deoxypyridinoline excretion between the two groups. In conclusion, one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased after 6 months of treatment. Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention.

Topics: Aged; Biomarkers; Bone Density; Bone Remodeling; Calcium; Female; Hemostatics; Hormones; Humans; Lumbar Vertebrae; Osteocalcin; Osteoporosis, Postmenopausal; Protein Processing, Post-Translational; Time Factors; Treatment Outcome; Vitamin K 2

It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Topics: Biomarkers; Blood Pressure; Bone and Bones; Dietary Supplements; Double-Blind Method; Estradiol; Female; Humans; Japan; Lipids; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Vitamin D; Vitamin K 1; Vitamin K 2; Vitamins

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

Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K(2) intake promotes bone mineral density and bone strength. Results showed that K(2) improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K(2) intake may contribute to preventing postmenopausal bone loss.. Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake.. A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K(2) (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).. K(2) did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K(2)-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly.. Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.

Topics: Absorptiometry, Photon; Aged; Bone Density; Female; Femur Neck; Follow-Up Studies; Hip Fractures; Humans; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Risk Factors; Vitamin K 2; Vitamins

To investigate the effect of vitamin K2 (menatetrenone) treatment on bone mineral density (BMD) and a bone metabolic marker (osteocalcin) in postmenopausal women with osteoporosis living in Indonesia.. A double-blind randomized placebo-controlled study of 63 postmenopausal women with osteoporosis. The vitamin K2 group (n = 33) received 45 mg menatetrenone and 1500 mg calcium carbonate per day and the control group (n = 30) received placebo and 1500 mg calcium carbonate per day for 48 weeks. BMD of lumbal spine (L2-L4), osteocalcin (OC) and undercarboxylated OC were measured before, 24 and 48 weeks after initiation of the treatment.. After 48 weeks of treatment, the mean percentage change of lumbar BMD in the vitamin K2 group was significantly higher (P < 0.05) than that of the control group. The undercarboxylated OC level decreased by 55.9% in the menatetrenone group and 9.3% in the control group compared with the baseline level. The difference between the two groups was significant (P < 0.01). The adverse events were three minor gastrointestinal cases, which subsided after temporary cessation of therapy.. Treatment with 45 mg vitamin K2 with 1500 mg calcium per day for postmenopausal women with osteoporosis for 48 weeks resulted in a significant increase in lumbar BMD and a significant decrease in undercarboxylated OC levels.

Topics: Aged; Bone Density; Double-Blind Method; Female; Humans; Indonesia; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Placebos; Vitamin K 2

We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3.. Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment.. Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1).. Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.

Topics: Alkaline Phosphatase; Amino Acids; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Cholecalciferol; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K 2

To investigate the therapeutic effect of combined use of vitamin K(2) and D(3) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis.. We enrolled 172 women with vertebral bone mineral density <0.98 g/cm(2) (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K(2) therapy group, vitamin D(3) therapy group, vitamin K(2) and D(3) combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen.. Combined therapy with vitamin K(2) and D(3) for 24 months markedly increased bone mineral density (4.92 +/- 7.89%), while vitamin K(2) alone increased it only 0.135 +/- 5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis-coagulation system.. Continuous combination therapy with vitamin K(2) and D(3) may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.

Topics: Absorptiometry, Photon; Amino Acids; Antithrombin III; Blood Coagulation Tests; Bone Density; Cholecalciferol; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrinogen; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Peptide Fragments; Plasminogen; Procollagen; Treatment Outcome; Vitamin K 2

The purpose of the present study was to compare the effects of etidronate and menatetrenone on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Seventy-two osteoporotic women, more than 5 years after menopause, 53-78 years of age, were randomly divided into three administration groups: E group; intermittent cyclical etidronate (200 mg/day, 14 days per 3 months; n = 25); M group; menatetrenone (45 mg/day, daily; n = 23); and C group (control); calcium lactate (2 g/day, daily; n = 24). Forearm BMD was measured by dual-energy X-ray absorptiometry at 0, 6, 12, 18, and 24 months after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the three groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P < 0.0001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the M group compared with that in the C group (P < 0.0001), and a significant increase in BMD in the E group compared with that in the C and M groups (P < 0.0001 and P < 0.01, respectively). The indices of new vertebral fractures/1000 patient-years in the E and M groups were significantly higher than that in the C group (chi(2) = 47.7; P < 0.0001 and chi(2) = 42.4; P < 0.0001, respectively), and did not differ significantly between the E and M groups. The present preliminary study provides evidence to suggest that, despite the lower increase in BMD produced by menatetrenone, this agent, as well as etidronate, may have the potential to reduce osteoporotic vertebral fractures in postmenopausal women with osteoporosis.

Topics: Absorptiometry, Photon; Aged; Bone Density; Etidronic Acid; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Prospective Studies; Spinal Fractures; Vitamin K 2

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.

Topics: Aged; Aged, 80 and over; Blood Coagulation Factors; Cyanoacrylates; Female; Hemostasis; Hemostatics; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density (BMD) in postmenopausal women, comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy.. Seventy-two postmenopausal women were randomized into four groups and treated with respective agents. Before the therapy, 6 and 12 months after the treatment, their lumbar spine BMD were measured by dual energy X-ray absorptiometry. The rates of change in BMD (delta BMD) were calculated. Correlations of BMD with age, year since menopause and the initial BMD were determined.. Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group. BMD in women treated with vitamin K2 was inversely correlated with their age (r = -0.54; P < 0.05).. Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss. In addition, the therapy should be started early in postmenopausal period.

Topics: Bone Density; Cholecalciferol; Estrogen Replacement Therapy; Female; Humans; Longitudinal Studies; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Vitamin K; Vitamin K 2

We aimed to evaluate the clinical efficacy of monotherapy with alendronate and combined therapy with alendronate and menatetrenone (vitamin K2 [VitK2]) in postmenopausal rheumatoid arthritis (RA) patients with osteoporosis or osteopenia.. Sixty-two postmenopausal RA patients with untreated osteoporosis or osteopenia (lumbar spine bone density ≤80 % of young adult mean [YAM]) were enrolled: 39 had abnormal serum undercarboxylated osteocalcin (ucOC) levels (>4.5 ng/mL) and received combined therapy with alendronate (35 mg/week) and VitK2 (45 mg/day) (ALN + K group); 23 had normal ucOC levels (≤4.5 ng/mL) and received alendronate monotherapy (35 mg/week) (ALN group). The clinical results for the 57 patients in both groups were evaluated after 1-year treatment.. The mean baseline/follow-up (FU) lumbar spine bone density (%YAM) values were 73.0/76.8 % (P < 0.01) in the ALN + K group and 77.0/80.3 % (P < 0.01) in the ALN group; a significant increase was shown in both groups. Mean proximal femoral bone density values at baseline/FU were 71.4/73.8 (P < 0.01) in the ALN + K group and 71.4/71.6 % (not significant; NS) in the ALN group; a significant increase was shown in the ALN + K group only. Serum ucOC levels were normalized in the ALN + K group at FU. At FU, bone metabolism markers [bone-specific alkaline phosphatase (BAP) and N-terminal cross-linked telopeptides of type I collagen] were decreased in both groups. One patient in the ALN + K group and three in the ALN group suffered new fractures.. Combined therapy with alendronate and VitK2 decreases bone metabolism marker levels and serum ucOC levels, and increases lumbar spine and femoral neck bone density in postmenopausal RA patients with abnormal ucOC levels and osteoporosis or osteopenia.

Topics: Aged; Alendronate; Arthritis, Rheumatoid; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Prospective Studies; Treatment Outcome; Vitamin K 2

The objective of the present study was to examine the effect of dairy products enriched with calcium, vitamin D(3), and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K(2)) on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Postmenopausal women were divided into three intervention groups and a control group (CG). All three intervention groups attended biweekly sessions and received fortified dairy products providing daily 800 mg of calcium and 10 μg of vitamin D(3) (CaD). Furthermore, in two of the three intervention groups the dairy products were also enriched with vitamin K, providing daily 100 μg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). The increase observed for serum 25(OH)D levels in all intervention groups and the increase observed for serum IGF-I levels in the CaDK2 group differed significantly compared to the changes observed in CG (P = 0.010 and P = 0.028, respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P = 0.001 and P = 0.047, respectively). Significant increases in total-body BMD were observed in all intervention groups compared to CG (P < 0.05), while significant increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary calcium intake. In conclusion, the present study revealed more favorable changes in bone metabolism and bone mass indices for the two vitamin K-supplemented groups, mainly reflected in the suppression of serum levels of bone remodeling indices and in the more positive changes in lumbar spine BMD for these two study groups.

Topics: Aged; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcium, Dietary; Dairy Products; Dietary Supplements; Female; Follow-Up Studies; Humans; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Vitamin D; Vitamin K 1; Vitamin K 2; Vitamins

Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted.. Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist.. We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day).. Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses.. Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Topics: Bone Density Conservation Agents; Calcium; Canada; Cholecalciferol; Cost-Benefit Analysis; Dietary Supplements; Drug Costs; Drug Therapy, Combination; Female; Health Care Costs; Humans; Middle Aged; Models, Econometric; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Quality of Life; Quality-Adjusted Life Years; Treatment Outcome; Vitamin K 1; Vitamin K 2

Although alendronate treatment for the prevention of osteoporotic fracture has been considered to be first line treatment, there is little knowledge whether very old osteoporosis should be treated with alendronate or not. To elucidate this question, we investigated the effectiveness of osteoporotic drugs in terms of effects of treatment on bone mineral density (BMD), bone resorption markers and fracture prevention in osteoporosis aged over 75 years old or less. A total of 1,041 postmenopausal osteoporosis cases were classified into 4 categories, Young controls (n = 165) and Old controls (n = 95) (Control group), Young (n = 309) and Old osteoporosis (n = 110) treated with alendronate (ALN group), and Young (n = 238) and Old osteoporosis (n = 124) treated with vitamins D3 or K2 (VDK group). We followed their lumbar BMD, urinary excretion of NTX and incident vertebral fracture rate for three years. The effects of the ALN treatment on lumbar BMD and on urinary NTX were not different between the two age-categorized osteoporosis groups, namely, the lumbar BMD increased by around 6-7% after ALN treatment in both Old and Young groups. The urinary excretion of NTX was decreased by 50% from baseline in both Old and Young ALN treated groups. Those effects of ALN were significantly superior to those in the controls and VDK-treated groups of both age categories. Therefore, ALN biological effects on bone were not age-dependent and the effects of ALN were strongest than the other treatments. The effects on fracture prevention in the Old ALN-treated group showed a 66.7% risk reduction rate (RRR) (p< 0.05) when the fracture incidence rate in the control group (50%) was taken as 100%, while it was 18.8% RRR (ns) in VDK-treated Old group. The Young group treated with ALN showed a 35.6% RRR from the Young control group (25% as 100%) (p<0.05). The VDK treated group did not show a significant RRR of incident fracture (24.4%). Thus, alendronate was the only effective modality to prevent fractures in both young and old osteoporosis. These results clearly indicated that very old osteoporotics should be treated with alendronate at this moment.

Topics: Age Factors; Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Bone Resorption; Cholecalciferol; Cohort Studies; Female; Follow-Up Studies; Humans; Osteoporosis, Postmenopausal; Retrospective Studies; Spinal Fractures; Vitamin K 2

We have been using hormone replacement therapy (HRT) as the treatment of choice for menopausal symptoms and osteoporosis. Estrogen increases bone mineral density (BMD) for 2 or 3 years, and only maintains BMD thereafter. In the present study, we investigated whether BMD improved with HRT in combination with vitamin K(2). Ninety-four patients with postmenopausal osteoporosis were studied. All patients were placed on HRT for more than 1 year. Ten patients whose BMD had increased up to a plateau and showed a decreasing trend thereafter while they were receiving HRT were placed on HRT in combination with vitamin K(2). The long-term BMD (L(2)-L(4)) profiles of those receiving HRT alone, and the effects of HRT in combination with vitamin K(2) on the BMD profiles were examined. The rate of change in BMD (mean +/- SE) of all patients who underwent HRT alone was 2.9 +/- 1.2% 1 year after the initiation of HRT, 4.6 +/- 1.2% 2 years later, and 5.4 +/- 1.2% 3 years later. The BMD in these patients, which reached a peak increase after 3 years, no longer increased from the following year. When vitamin K(2) was administered concomitantly to 10 patients for 12 months because of the decrease in BMD, their BMD (mean +/- SE) increased significantly, from 0.734 +/- 0.021 g/cm(2) to 0.783 +/- 0.026 g/cm(2) ( P < 0.03; paired- t test). We conclude that HRT in combination with vitamin K(2) significantly improved BMD that was on the decrease after HRT alone. Therefore, as a supplementary drug for postmenopausal osteoporosis, vitamin K(2) is a good therapeutic option for patients who are placed on HRT.

Topics: Bone Density; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Treatment Outcome; Vitamin K 2

Increasing evidence indicates a significant role for vitamin K in bone metabolism and osteoporosis. In this study, we found a large geographic difference in serum vitamin K2 (menaquinone-7; MK-7) levels in postmenopausal women. Serum MK-7 concentrations were 5.26 +/- 6.13 ng/mL (mean +/- SD) in Japanese women in Tokyo, 1.22 +/- 1.85 in Japanese women in Hiroshima, and 0.37 +/- 0.20 in British women. We investigated the effect of Japanese fermented soybean food, natto, on serum vitamin K levels. Natto contains a large amount of MK-7 and is eaten frequently in eastern (Tokyo) but seldom in western (Hiroshima) Japan. Serum concentrations of MK-7 were significantly higher in frequent natto eaters, and natto intake resulted in a marked, sustained increase in serum MK-7 concentration. We analyzed the relation between the regional difference in natto intake and fracture incidence. A statistically significant inverse correlation was found between incidence of hip fractures in women and natto consumption in each prefecture throughout Japan. These findings indicate that the large geographic difference in MK-7 levels may be ascribed, at least in part, to natto intake and suggest the possibility that higher MK-7 level resulting from natto consumption may contribute to the relatively lower fracture risk in Japanese women.

Topics: Aged; Aged, 80 and over; Bacillus; Feces; Female; Femoral Neck Fractures; Fermentation; Glycine max; Humans; Incidence; Japan; Middle Aged; Osteoporosis, Postmenopausal; Risk Factors; Triglycerides; United Kingdom; Vitamin K 1; Vitamin K 2

The effect of the prolonged intake of dietary vitamin K2 (menaquinone-7, MK-7) on bone loss in ovariectomized (OVX) rats was investigated. OVX rats were freely given experimental diets containing the fermented soybean (natto; including 9.4 micrograms MK-7/100 g diet) without or with supplemental MK-7 (containing 14.1 or 18.8 micrograms of MK-7 as total per 100 g diet) for 150 days. Feeding produced a significant elevation of MK-7 concentration in the serum of OVX rats. In this case, the femoral MK-4 content was significantly increased, but MK-7 was not detected in the femoral tissues, indicating degradation of MK-7. Serum gamma-carboxylated osteocalcin concentration was significantly decreased by OVX. This decrease was significantly prevented by the feeding of the natto diets with supplemental MK-7 (18.8 micrograms/100 g diets). OVX caused a significant decrease in femoral dry weight, femoral calcium content, and mineral density. These decreases were significantly prevented by feeding with diets containing natto with MK-7 (total, 18.8 micrograms/100 g diets). This study demonstrates that the prolonged intake of natto dietary including MK-7 has a preventive effect on bone loss induced by OVX. Dietary MK-7 may be useful in the prevention of osteoporosis.

Topics: Animal Feed; Animals; Bone Density; Calcium; Diet; Female; Femur; Fermentation; Glycine max; Humans; Organ Size; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Wistar; Vitamin K; Vitamin K 2

Menatetrenone, a vitamin K2 with four isoprene units, has been reported to improve osteoporotic bone loss. The purpose of this investigation was to clarify the effect of menatetrenone on the three-dimensional (3D) trabecular microarchitecture in ovariectomized (OVX) rats by using microcomputed tomography (MCT). Forty-two 13-week-old female rats were used and divided into four groups: the OVX (OVX + MK-4) group treated with menatetrenone, the (OVX untreated) group, the sham-operated (Sham + MK-4) group treated with menatetrenone, and the sham-operated group not treated with menatetrenone (Sham untreated) group. OVX rats were fed a calcium-deficient diet. Menatetrenone treatment was begun just after the ovariectomy, and the mean menatetrenone oral intake over the 8-week period was adjusted to 30 mg/kg BW per day. The proximal metaphyseal region of the right tibia was evaluated by dual X-ray absorptiometry (DXA) and MCT. A parametric analysis of the reconstructed trabecular volume was carried out using bone volume fractions, the fractal dimension calculated by the 3D box-counting method, and the connectivity density as determined by topological analysis. Menatetrenone significantly increased the trabecular bone volume, fractal dimension, and connectivity in the OVX + MK-4 group compared with the OVX-untreated group (p < 0.01). Our results suggest that an 8-week administration of menatetrenone protects against the loss of trabecular bone volume and its connectivity when treatment is begun just after the ovariectomy. Despite this apparent protection, it remains unknown whether it is possible to reestablish trabecular connectivity if therapeutic intervention occurs after the trabecular connectivity has been lost.

Topics: Alkaline Phosphatase; Animals; Anthropometry; Body Weight; Bone Density; Calcium; Computer Simulation; Disease Models, Animal; Female; Humans; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Inbred F344; Reproducibility of Results; Tibia; Tomography, X-Ray Computed; Vitamin K; Vitamin K 2

Although vitamin K2 is an inducer of the in vitro differentiation of myeloid leukemic cell lines, its clinical efficacy in the treatment of myelodysplastic syndrome (MDS) is unclear. We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to an 80-year-old woman with MDS (refractory anemia) heavily dependent on red-cell transfusions. The patient's pancytopenia gradually improved, and she became transfusion-independent after 14 months. Pancytopenia recurred when menatetrenone was discontinued but recovered again with readministration. Administration of menatetrenone at a dose effective in improving osteoporosis may also be useful in restoring hematopoiesis in MDS patients, possibly by way of inducing differentiation.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Apoptosis; Calcifediol; Cell Differentiation; Drug Therapy, Combination; Female; Humans; Osteoporosis, Postmenopausal; Vitamin K; Vitamin K 2