vitamin-k-semiquinone-radical and Osteoporosis--Postmenopausal

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

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

In postmenopausal women and elderly men, bone density decreases with age and vascular calcification is aggravated. This condition is closely associated with vitamin K2 deficiency. A total of 17 different vitamin K‑dependent proteins have been identified to date. Vitamin K‑dependent proteins are located within the bone, heart and blood vessels. For instance, carboxylated osteocalcin is beneficial for bone and aids the deposition of calcium into the bone matrix. Carboxylated matrix Gla protein effectively protects blood vessels and may prevent calcification within the vascular wall. Furthermore, carboxylated Gla‑rich protein has been reported to act as an inhibitor in the calcification of the cardiovascular system, while growth arrest‑specific protein‑6 protects endothelial cells and vascular smooth muscle cells, resists apoptosis and inhibits the calcification of blood vessels by inhibiting the apoptosis of vascular smooth muscle cells. In addition, periostin may promote the differentiation, aggregation, adhesion and proliferation of osteoblasts. Periostin also occurs in the heart and may be associated with the reconstruction of heart function. These vitamin K‑dependent proteins may exert their functions following γ‑carboxylation with vitamin K, and different vitamin K‑dependent proteins may exhibit synergistic effects or antagonistic effects on each other. In the cardiovascular system with vitamin K antagonist supplement or vitamin K deficiency, calcification occurs in the endothelium of blood vessels and vascular smooth muscle cells are transformed into osteoblast‑like cells, a phenomenon that resembles bone growth. Both the bone and cardiovascular system are closely associated during embryonic development. Thus, the present study hypothesized that embryonic developmental position and tissue calcification may have a certain association for the bone and the cardiovascular system. This review describes and briefly discusses several important vitamin K‑dependent proteins that serve an important role in bone and the cardiovascular system. The results of the review suggest that the vascular calcification and osteogenic differentiation of vascular smooth muscle cells may be associated with the location of the bone and cardiovascular system during embryonic development.

Topics: Aged; Aged, 80 and over; Aging; Bone Density; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Osteoporosis, Postmenopausal; Vitamin K

Calcium intake was negatively associated with bone resorption marker such as DPD, NTX, and P1NP in Japanese postmenopausal osteoporotic patients. Not only to suppress bone resorption but also to keep higher hip bone mineral density were observed in the patients with higher intake of calcium than 800mg/day and higher vitamin D condition (more than 50nmol/L of serum 25 (OH) D). Higher calcium intake than 800mg/day from dairy and Tofu products, higher intake of vitamin D than 10μg/day from fish, and higher intake of vitamin K from vegetables should be recommended in Japanese postmenopausal osteoporotic patients. We should also pay attention to their losing weight and excess intake of these nutrients from supplements.

Topics: Bone and Bones; Bone Density; Bone Resorption; Calcium, Dietary; Female; Glycine max; Humans; Life Style; Nutrition Therapy; Osteoporosis, Postmenopausal; Recommended Dietary Allowances; Vegetables; Vitamin D; 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

Aside from its important role in blood clotting, vitamin K is an important dietary factor in regulating bone and cartilage mineralization. The vitamin K requirements to maintain musculoskeletal health may be more than the current recommendations and subclinical vitamin K deficiency may be involved in the pathogenesis of osteoporosis and osteoarthritis. Observational studies suggest that diets low in vitamin K are associated with increased risk of fractures and osteoarthritis in older adults. However, so far randomized controlled trials of vitamin K supplementation in Caucasian populations have not shown clinically significant improvements in bone mineral density at major skeletal sites. Supplementation with vitamin K may reduce the risk of fractures, but this conclusion comes from clinical trials with methodological limitations. At this time, only one randomized controlled trial has examined the effect of vitamin K supplementation on radiographic hand osteoarthritis and found no overall effect. Large well-designed randomized controlled trials are needed to compare the efficacies of vitamin K1 and K2 on fractures and osteoarthritis among older adults. In summary, currently there is not enough evidence to recommend the use of vitamin K supplements for the prevention of bone loss, fractures, or osteoarthritis in postmenopausal women.

Topics: Aging; Animals; Female; Health Status; Humans; Musculoskeletal Development; Musculoskeletal Physiological Phenomena; Musculoskeletal System; Osteoarthritis; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K; Vitamin K Deficiency

The prevention of cardiovascular and osteoporotic risk is a topic of great importance in the peri- and postmenopausal periods. This paper reviews the role of resveratrol, inositol, vitamin D and K in the prevention of cardiovascular and osteoporotic risk in peri- and post-. The phytoestrogen-like activity of resveratrol has potential clinical implications in the gynecological practice. In particular transresveratrol inhibits low-density lipoprotein oxidation, which is a recognized risk factor for cardiovascular diseases. Resveratrol has also a documented antiplatelet effect and may prevent cardiovascular diseases inhibiting the cardiac fibroblasts proliferation. With regard to bone health, in in vitro studies resveratrol has shown activities in osteoblastic MC3T3-E1 cells. Resveratrol also interacts with vitamin D in promoting bone health. Resveratrol is considered a caloric restriction mimetic and potentially effects factors involved in the metabolic syndrome. Myo-inositol has documented in clinical studies its effectiveness in improving the metabolic syndrome in post menopausal women. Thus the supplementation with inositol and resveratrol may be useful in the prevention of insulin resistance and consequently metabolic syndrome and cardiovascular diseases risk. Finally vitamin K2 effects calcium metabolisms and subjects with higher levels of calcium in the bones tend to have a lower frequency of vascular calcifications and a lower cardiovascular risk. Vitamin K2 also has a key role in the bone homeostasis. A supplement including resveratrol, inositol, vitamin K and vitamin D offers a novel opportunity to the woman in peri- and postmenopause.

Topics: Animals; Cardiovascular Diseases; Cell Line; Female; Humans; Inositol; Mice; Osteoporosis, Postmenopausal; Perimenopause; Postmenopause; Resveratrol; Risk Factors; Stilbenes; Vitamin D; Vitamin K

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

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

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

Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K (VK) status. Serum ucOC concentration in perimenopausal women is significantly higher than that in premenopausal women. In addition, serum ucOC concentration is closely associated with not only FSH concentration but also estradiol concentration. Serum ucOC concentration rapidly increases in women after bilateral oophorectomy. The effect of hormone therapy (HT) on alternate days on ucOC concentration is weaker than the effect of HT daily and ucOC concentration after 12 months of HT daily may be decreased due to the conversion of ucOC to carboxylated OC by the effect of VK through increased TG induced by oral conjugated equine estrogen (CEE) . Additionally, the effect of HT with transdermal estradiol on ucOC concentration in women is weaker than the effect of HT with oral CEE.

Topics: Biomarkers; Estradiol; Estrogen Replacement Therapy; Female; Femoral Neck Fractures; Follicle Stimulating Hormone; Humans; Menopause; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Risk; Triglycerides; Vitamin K; Vitamin K Deficiency

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

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

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

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

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

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

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

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

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

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

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

Vitamin K is involved in blood coagulation and in bone metabolism via the carboxylation of glutamate residues in (hepatic) blood coagulation factors and (osteoblastic) bone proteins. The bioavailability of nutritional vitamin K depends on the type of food, the dietary fat content, the length of the aliphatic side chain in the K-vitamer and probably also the genetically determined polymorphism of apolipoprotein E. Although undercarboxylation of blood coagulation factors is very rare, undercarboxylated osteocalcin (bone Gla-protein) is frequently found in postmenopausal women. Supplementation of these women with extra vitamin K causes the markers for bone formation to increase. In parallel, a decrease of the markers for bone resorption is frequently seen. Insufficient data are available to conclude that the regular administration of vitamin K concentrates will reduce the loss of bone mass in white women at risk for developing postmenopausal osteoporosis.

Topics: Animals; Biological Availability; Bone and Bones; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Vitamin K

Topics: Biomarkers; Bone and Bones; Calcium; Female; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Oxidation-Reduction; Protein Precursors; Prothrombin; Vitamin K

We conducted a randomized placebo-controlled double-blinded clinical trial of MK-7 or placebo daily for 3 years in postmenopausal women with osteopenia. BMD decreased at all sites without differences between the MK-7 and placebo-treated women. Changes in bone turnover markers and microstructure were similar between the two groups.. Vitamin K is a cofactor in the carboxylation of osteocalcin (OC) and carboxylated OC promotes mineralization of bone. Clinical studies suggest that vitamin K2 prevents bone loss. The aim of the study was to investigate the effect of vitamin K2 as an add-on to calcium and vitamin D supplementation on osteocalcin, bone mass, and microarchitecture in postmenopausal women.. We conducted a randomized placebo-controlled double-blinded clinical trial, including 142 postmenopausal women with osteopenia who received vitamin K2 (375 μg MK-7) or placebo daily for 3 years. Both groups received vitamin D3 (38 μg/day) and calcium (800 mg/day). We measured bone turnover markers in serum and bone mineral density and microarchitecture by DXA and HRpQCT.. Undercarboxylated osteocalcin decreased in the MK-7-group (- 65.2 ± 23.5%) (mean ± SD) compared with the placebo group (- 0.03 ± 38.5%), p < 0.01 after 1 year. After 3 years, aBMD decreased at all sites without differences between the MK-7 and placebo-treated women (p > 0.09). aBMD decreased at the total hip by 1.5 ± 2.5% and 2.4 ± 2.7% in the MK-7 and the placebo groups, respectively, at the femoral neck by 1.5 ± 3.5% and 1.0 ± 5.0% in the MK-7 and the placebo groups, respectively, and at the lumbar spine by 1.8 ± 3.9% and 1.1 ± 3.1% in the MK-7 and the placebo groups, respectively. Changes in bone turnover markers were also similar between the two groups.We have previously reported improved microarchitecture with MK-7 after 1 year. However, changes in microstructure over 3 years were similar between the two groups, as assessed by both HRpQCT and DXA trabecular bone score.. Treatment with MK-7 375 μg daily as an add-on to calcium and vitamin D increased carboxylation of osteocalcin. However, treatment of postmenopausal women with osteopenia for 3 years did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture.. The study was registered at Clinicaltrial.gov : NCT01922804 .

Topics: Bone Density; Bone Diseases, Metabolic; Double-Blind Method; Female; Humans; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K; Vitamins

osteoporosis is a metabolic bone disease that leads to increased bone fragility and increased risk of fracture.. the aim of the present research was to determine the effectiveness of a diary intake of three different dairy products (250 ml) enriched with vitamins and calcium on decreasing bone mass. METHOS: the present study is a comparative trial of three dairy products fortified with calcium and vitamin D, parallel, randomized, double-blind andsingle-center. Bone mass content (BMC), bone mass density (BMD), T-score and Z-score were measured in different locations, besides biochemical markers along 18 months in premenopausal women. Two hundred and ten volunteers from all the three groups were submitted to the same monitoring procedures, consisting on blood extraction, urine collection and energy X-ray absorptiometry (DEXA) done in the laboratory. The monitoring was carried on three times, first at month 0 (baseline), the second at month 9 (in the middle of the treatment) and, finally, at month 18 (the end of the treatment).. the majority of anatomical locations showed both BMC and BMD decrease ranging between 0.5% and 1.5%. The T-score and the Z-scoreincreased in lumbar spine after the treatment with the dairy products. Moreover, the most noteworthy change on the biomarkers of bone resorption was showed by plasmatic tartrate-resistant acid phosphatase (TRAP), with and increase between 20.7% and 29.5% after the intake of the different products.. therefore, the intake of the three dairy products improves the bone mass in lumbar spine, leading to important changes in the concentration of biomarkers of bone resorption. Especially, tartrate-resistant acid phosphatase seems to be strongly influenced by the intake of every dairy product. However, no significant differences were found between the different dairy products used in the present study. Therefore, the intake of dairy product seems to be more determinant than micronutrients supplementation.

Topics: Absorptiometry, Photon; Adult; Bone Density; Bone Development; Bone Remodeling; Calcium, Dietary; Dairy Products; Dietary Supplements; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Premenopause; Vitamin D; Vitamin K; Vitamins; White People

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

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

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Editor in Chief because of the stated concerns listed below. This article was accepted for publication by a previous editor and editorial board, at a time when submissions and documentation were in paper form, prior to the transition of The American Journal of Medicine to a digital submission and review process. These records are no longer extant and consequently we are unable to review the comments of the reviewers and editors involved at that time. We have attempted to contact the authors regarding these concerns and received no response. We are therefore retracting this article since the evidence presented below strongly argues for scientific misconduct.\ \ The integrity of these publications is severely compromised by wide-ranging and serious concerns about governance, ethics, authorship, implausible study conduct, implausible workload, discrepant participant numbers and treatment groups, impossible data, implausible data, implausible outcome data, and discrepant methodology.

Topics: Adjuvants, Immunologic; Aged; Bone Density; Calcitonin; Estrogen Replacement Therapy; Etidronic Acid; Female; Humans; Hydroxycholecalciferols; Japan; Middle Aged; Osteoporosis, Postmenopausal; Spinal Fractures; Vitamin K

Apolipoprotein E (Apo E) genotypes have been associated with a number of involutional disorders. Recently some studies have examined whether the Apo E 4 allele might play a role in the pathophysiology of postmenopausal osteoporosis. However, association analysis between Apo E genotypes, BMD, bone loss or fracture risk have not brought universal findings. The aim of this study was, therefore, to determine the relationship between the presence or absence of Apo E 4 allele and BMD in postmenopausal women of Caucasian origin. We studied 113 women, age 62.5 +/- 8.9 yr, who underwent measurement of hip and spine BMD by dual-energy absorptiometry (DXA, g/cm2). Apo E genotypes were assessed by PCR amplification and by restriction typing with Cfol enzyme. The Apo E allele frequencies in the study population were as follows: E2 0.084, E3 0.845, E4 0.071. Because the Apo E 4 allele was associated with osteoporosis in previous studies, the probands were dichotomized by the presence or absence of Apo E 4 allele. After adjustment for BMI and years since menopause BMD at the lumbar spine varied significantly by Apo E 4 status. Women with Apo E 4 allele had significantly lower BMD at the lumbar spine than women with no Apo E 4 allele (p<0.003, ANCOVA). In contrast, there were no significant differences in BMD at the hip comparing women with or without the Apo E 4 allele. To conclude, these data may support the importance of Apo E 4 allele in determining postmenopausal spine bone mass.

Topics: Absorptiometry, Photon; Aged; Apolipoprotein E4; Apolipoproteins E; Bone Density; Cross-Sectional Studies; Female; Gene Frequency; Humans; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Vitamin K; White People

The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density (BMD) of the lumbar spine was examined in postmenopausal women with osteoporosis. Ninety-two osteoporotic women who were more than 5 years after menopause, aged 55-81 years, were randomly divided into four administration groups: vitamin D3 (1alpha hydroxyvitamin D3, 0.75 microg/day) (D group; n = 29), vitamin K2 (menatetrenone, 45 mg/day) (K group; n = 22), vitamin D3 plus vitamin K2 (DK group, n = 21), and calcium (calcium lactate, 2 g/day) (C group; n = 20). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at 0, 1, and 2 years after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the four groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P < 0.001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the D and K groups compared with that in the C group (P < 0.05 and P < 0.001, respectively), and a significant increase in BMD in the DK group compared with that in the C, D, and K groups (P < 0.0001, P < 0.05 and P < 0.01, respectively). These findings indicate that combined administration of vitamin D3 and vitamin K2, compared with calcium administration, appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis.

Topics: Aged; Aged, 80 and over; Bone Density; Cholecalciferol; Drug Therapy, Combination; Female; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Vitamin K

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

The effect of vitamin supplements on bone metabolism indices in patients with osteoporosis has received scant attention in the literature. Over a 2-week period, vitamin supplements of K and K+D were given to 20 post-menopausal osteoporotic women with previous Colles fractures. Osteoporosis was confirmed by bone mass measurements that demonstrated that broadband ultrasound attenuation (os calcis) was almost as discriminatory as dual energy X-ray absorptiometry (spine and hip) in Colles fracture patients compared with matched controls. Vitamin K corrected the carboxylation defect in osteocalcin and while less marked 4 weeks later, the improvement was still detectable. The result after K+D was similar. The level of carboxylation became the same as in premenopausal women. Total osteocalcin level (bound) osteocalcin. While there was vitamin K correctable undercarboxylation of osteocalcin, simultaneously there was no evidence of undercarboxylation of prothrombin.

Topics: Absorptiometry, Photon; Adult; Aged; Biomarkers; Bone Density; Colles' Fracture; Cross-Over Studies; Female; Femur; Humans; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Premenopause; Protein Precursors; Prothrombin; ROC Curve; Single-Blind Method; Spinal Canal; Ultrasonography; Vitamin D; Vitamin K

Osteoporosis commonly affects postmenopausal women and accounts for 300,000 hip fractures in the United States each year. More women are deferring or discontinuing pharmacologic treatment because of intolerable adverse reactions or fear of long-term safety. Supplementing dietary intake of certain vitamins and minerals can have positive effects on bone parameters. Calcium is frequently recommended for osteoporotic patients but many not confer much benefit toward bone density. Certain forms of vitamins A and K have been shown to increase bone density. Isoflavones and phytates are phytochemicals found in soy foods that are comparable to bisphosphonates when consumed at certain levels. Lastly, increasing certain daily fruit and vegetable servings can improve bone health. Nutritional interventions are typically safe alternatives that should be considered for postmenopausal women who are seeking nonpharmacologic treatment options for osteoporosis.

Topics: Aged; Aged, 80 and over; Bone Density; Diet; Dietary Supplements; Female; Fruit; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytic Acid; Phytochemicals; Severity of Illness Index; Vegetables; Vitamin A; Vitamin K

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

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

Bivariate random-effects meta-analysis (BVMA) is a method of data synthesis that accounts for treatment effects measured on two outcomes. BVMA gives more precise estimates of the population mean and predicted values than two univariate random-effects meta-analyses (UVMAs). BVMA also addresses bias from incomplete reporting of outcomes. A few tutorials have covered technical details of BVMA of categorical or continuous outcomes. Limited guidance is available on how to analyze datasets that include trials with mixed continuous-binary outcomes where treatment effects on one outcome or the other are not reported. Given the advantages of Bayesian BVMA for handling missing outcomes, we present a tutorial for Bayesian BVMA of incompletely reported treatment effects on mixed bivariate outcomes. This step-by-step approach can serve as a model for our intended audience, the methodologist familiar with Bayesian meta-analysis, looking for practical advice on fitting bivariate models. To facilitate application of the proposed methods, we include our WinBUGS code. As an example, we use aggregate-level data from published trials to demonstrate the estimation of the effects of vitamin K and bisphosphonates on two correlated bone outcomes, fracture, and bone mineral density. We present datasets where reporting of the pairs of treatment effects on both outcomes was 'partially' complete (i.e., pairs completely reported in some trials), and we outline steps for modeling the incompletely reported data. To assess what is gained from the additional work required by BVMA, we compare the resulting estimates to those from separate UVMAs. We discuss methodological findings and make four recommendations. Copyright © 2015 John Wiley & Sons, Ltd.

Topics: Bayes Theorem; Bone Density; Bone Density Conservation Agents; Diphosphonates; Female; Humans; Linear Models; Meta-Analysis as Topic; Models, Statistical; Osteoporosis, Postmenopausal; Probability; Treatment Outcome; Vitamin K

Serum undercarboxylated osteocalcin (ucOC) is an index of vitamin K nutritional status in treatment-naive postmenopausal osteoporotic women. The purpose of the present study was to reveal the association between vitamin K nutritional status and serum ucOC concentrations in postmenopausal osteoporotic women taking bisphosphonates. Eighty-six postmenopausal women with osteoporosis (age range: 47-90 years) initiated bisphosphonate treatment. Vitamin K nutritional status was evaluated using a simple vitamin K-intake questionnaire and serum ucOC concentrations were measured after 6 months of treatment. The patients were divided into two groups according to the simple vitamin K-intake questionnaire score: a low vitamin K-intake (score <40) group (n=67) and a normal vitamin K-intake (score >=40) group (n=19). There were no significant differences between the groups in baseline parameters including age, height, body weight, body mass index, serum alkaline phosphatase (ALP), urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and changes in serum ALP and urinary NTX concentrations during the 6-month treatment period. However, the mean serum ucOC concentration after 6 months of treatment was significantly higher in the low vitamin K-intake group (2.79 ng/mL) than in the normal vitamin K-intake group (2.20 ng/mL). These results suggest that 78% of postmenopausal osteoporotic women treated with bisphosphonates may have vitamin K deficiency as indicated by low vitamin K-intake and high serum ucOC concentrations, despite having a similar reduction in bone turnover to women who have normal vitamin K-intake.. 血清未羧化的骨钙素(ucOC)是治疗初始的绝经后骨质疏松妇女的维生素K 营 养状况的指标。本研究的目的是揭示服用双磷酸盐的绝经后骨质疏松妇女维生 素K 的营养状况和血清ucOC 的浓度之间的关联。86 位绝经后骨质疏松妇女 开始双磷酸盐治疗(年龄范围47-90 岁)。采用简单的维生素K 摄入量调查问卷 评估维生素K 的营养状况，治疗6 个月后测定血清中ucOC 的浓度。根据简单 的维生素K 摄入量调查问卷评分将患者分为两组：低维生素K 摄入组(得分 <40, n=60)和正常维生素K 摄入组(得分>=40, n=19)。两组患者的基线参数包括 年龄、身高、体重、体质指数、血清碱性磷酸酶(ALP)和尿N-末端肽交联的I 型胶原蛋白(NTX)，以及6 个月治疗期间血清ALP 和尿NTX 浓度的变化之间 没有显著差异。然而治疗6 个月之后，低维生素K 摄入组的平均血清ucOC 浓 度(2.79 ng/mL)显著高于正常维生素K 摄入组(2.20 ng/mL)。这些结果表明，尽 管78%用双磷酸盐治疗的绝经后骨质疏松妇女与正常维生素K 摄入量的妇女 有相似的骨转化降低，但从低维生素K 摄入量和高血清ucOC 浓度看出他们可 能缺乏维生素K。

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Diphosphonates; Follow-Up Studies; Humans; Japan; Middle Aged; Nutritional Status; Osteocalcin; Osteoporosis, Postmenopausal; Surveys and Questionnaires; Treatment Outcome; Vitamin K; Vitamin K Deficiency

The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis.. Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure.. These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite.

Topics: Animals; Bone Density Conservation Agents; Carboxylic Acids; Cell Line; Cell Proliferation; Denervation; Disease Models, Animal; Female; Humans; Injections, Intraperitoneal; Interleukin-6; Methylation; Mice, Inbred C57BL; Molecular Structure; Naphthoquinones; Osteoblasts; Osteoporosis, Postmenopausal; Ovariectomy; Random Allocation; Sciatic Nerve; Structure-Activity Relationship; Vitamin K

Low vitamin K1 intake and low plasma vitamin K1 levels are associated with low bone mineral density (BMD) and increased osteoporotic fracture risk in postmenopausal women. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures.

Topics: Aged; Bone Density; Bulgaria; Female; Femur Neck; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Vitamin K; Vitamins

Low vitamin K intakes and high levels of undercarboxylated osteocalcin (ucOC) are risk factors for hip fractures. However, the relationship between ucOC and vitamin K intakes, bone mineral density (BMD) and bone biochemical markers is not clarified.. We enrolled 221 healthy women, and examined BMD, urinary type-I collagen cross-linked-N-telopeptide (uNTX), and nutrient intakes. BMD was measured at the lumbar spine and femoral neck.. Vitamin K intakes were significantly and negatively correlated with ucOC after adjustment for age, height, and body weight (r=-0.305, p<0.0001). ucOC was negatively associated with lumbar BMD (r=-0.147, p<0.05), but not femoral neck BMD (r=-0.099, p=0.095) after adjustment for age, height, and body weight. In multiple regression analysis, even after adjustment for age, height, body weight, and vitamin K intake, a significant and positive correlation remained between ucOC and urinary NTX (r=0.493, p<0.0001). Moreover, in postmenopausal women, ucOC levels were positively correlated with urinary NTX, but not BMD.. Dietary vitamin K intakes influence serum levels of ucOC in healthy women. Furthermore, ucOC may be linked to bone biochemical markers.

Topics: Age Factors; Aged; Biomarkers; Bone and Bones; Bone Density; Collagen Type I; Cross-Sectional Studies; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Nutrition Assessment; Osteocalcin; Osteoporosis, Postmenopausal; Peptides; Risk Factors; Surveys and Questionnaires; 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 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 randomized controlled trials (RCTs) by using the inclusion criteria: >or= approximately 50 subjects per group and study period of >or= 2 years. The results of 7 RCTs that met the inclusion criteria showed that vitamin K (K(1) and 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 supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. Furthermore, a post hoc analysis in a large RCT in Japan showed that high-dose vitamin K(2) supplementation decreased the subsequent incidence of vertebral fractures in osteoporotic postmenopausal women with a history of at least 5 vertebral fractures. The review of the reliable literature showed the effect of high-dose vitamin K supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.

Topics: Bone Density; Female; Fractures, Spontaneous; Humans; Meta-Analysis as Topic; Osteocalcin; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Spinal Fractures; Vitamin K

Topics: Aged; Aged, 80 and over; Algorithms; Bone Density; Bone Density Conservation Agents; Densitometry; Diphosphonates; Female; Heel; Humans; Middle Aged; Motor Activity; Osteoporosis, Postmenopausal; Practice Guidelines as Topic; Risk Factors; Ultrasonography; Vitamin D; Vitamin K; Women's Health; World Health Organization

Topics: Alendronate; Bone Remodeling; Drug Therapy, Combination; Female; Humans; Osteoporosis, Postmenopausal; Parathyroid Hormone; Vitamin K

To examine serum undercarboxylated osteocalcin (OC) with application of an ELISA in normal women and in osteoporotic patients with vertebral fractures or hip fractures, and to investigate the effects of vitamin K and/or D treatment on undercarboxylated OC and intact OC in vertebral fractures.. They were 43 premenopausal (PRE) and 48 postmenopausal healthy females (POST), 89 osteoporotic patients with vertebral fractures (VX) and, 24 patients with hip fracture (HX).. Intact OC was measured by an IRMA and undercarboxylated OC was measured by an ELISA.. Intact osteocalcin was significantly higher in POST and VX than in PRE, and was significantly lower in HX than in POST and VX. Undercarboxylated OC tended to be higher in POST, VX and HX than in PRE, but not significantly. The ratio of undercarboxylated OC to intact OC was significantly higher in HX than in POST and in VX. After 4 weeks treatment with K, D, and K + D to 56 VX, undercarboxylated OC decreased significantly in the groups with K and K + D. Intact OC tended to increase slightly in the groups given K, D, K + D, but not significantly so. Vitamin K and vitamin K + D markedly decreased the ratio of undercarboxylated/intact OC to approximately 80%. On the other hand, vitamin D did not decrease that ratio.. There was a disproportion of undercarboxylated osteocalcin to intact osteocalcin between postmenopausal women and osteoporotic patients with vertebral fractures or hip fractures. Vitamin K did decrease undercarboxylated osteocalcin, vitamin D did not change undercarboxylated osteocalcin, and vitamin D did not enhance the effect of vitamin K on undercarboxylated osteocalcin.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Hip Fractures; Humans; Immunoradiometric Assay; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Postmenopause; Premenopause; Spinal Fractures; Statistics, Nonparametric; Vitamin D; 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

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

Serum alkaline phosphatase (ALP), a gross marker of bone turnover, has been reported to be elevated after menopause, a period characterized by hallmark increases in follicle-stimulating hormone (FSH). Whether the ALP rise coincides with the perimenopausal transition when changes in FSH, estrogen levels, and menstrual cycles are first apparent is not known. The purpose of this cross-sectional study was twofold: (1) to characterize the influence of the perimenopausal transition on ALP activity and (2) to correlate ALP activity with more precise markers for bone, osteocalcin (OC), and vitamin K status assessed with undercarboxylated osteocalcin (ucOC). Thirty-eight studies of hourly FSH were conducted on cycle day 6 of the follicular phase in perimenopausal women volunteers, aged 40-54 years (mean body mass index [BMI] = 24.2 +/- 0.5). Mean FSH was used to define the perimenopausal stage (early perimenopausal, mean FSH 15 IU/L, n = 11). As expected, late perimenopausal women had irregular and longer menstrual cycles, lower estradiol (E(2)) and estrone (E(1)) levels, and a lower frequency of ovulations vs. the early group. ALP was higher (76.5 +/- 8.3 vs. 58.3 +/- 2.7 IU/L, p = 0.045) compared with the early perimenopausal group. In a subsample (n = 10), OC was associated with ALP (r = 0.69, p < 0.03), FSH was positively related to ucOC concentrations (r = 0.7, p < 0.03), and women with E(1) concentrations <40 pg/ml had double the percentage of ucOC compared with those where E(1) was >40 pg/ml (46.3% +/- 6.6% vs. 22.0% +/- 3. 1%, p < 0.006). Clinical markers of the perimenopause are associated with a nonspecific but inexpensive marker of enhanced bone turnover (i.e., higher ALP) and correlate well with more precise markers of bone activity. These findings suggest that health-promotion strategies for preserving bone should be instituted well before the last menstrual period.

Topics: Adult; Alkaline Phosphatase; Biomarkers; Female; Follicle Stimulating Hormone; Humans; Middle Aged; Osteoporosis, Postmenopausal; Ovulation; Premenopause; Sensitivity and Specificity; Vitamin K

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

Topics: Animals; Female; Humans; Microradiography; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Sprague-Dawley; Vitamin D; Vitamin K

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

Ovariectomized female Wistar rats[(170 +/- 15) g] were treated with vitamin K1 or/and calcium for 6 months, in order to study the effect of vitamin K or/and calcium supplementation on the prevention of osteoporosis. Vitamin K1(90 mg/kg) or/and calcium(5 g/kg) were added to a semisynthetic basal diet (VK 50 micrograms/kg, Ca5 g/kg). The findings of the study were as follows: Vitamin K1 treatment led to a significant increase of bone mineral density of the femoral diaphysis and lumbar spine, and bone ash content of the proximal one third of the femur shaft. The results suggested that vitamin K1 could, to some extent, prevent the fast bone loss and the femoral fragility induced by ovariectomy. Regarding the parameters of bone metrology and biomechanics, the effect of vitamin K1 combined with calcium on the prevention of osteoporosis is better than that of vitamin K1 or calcium alone, and the treatments with VK and Ca had better effects on femur than lumbar spine. The present study indicates that for postmenopausal women, as a risk population of osteoporosis, to increase their dietary intake of vitamin K and calcium might be helpful.

Topics: Animals; Bone Density; Calcium; Female; Humans; Osteoporosis, Postmenopausal; Ovariectomy; Random Allocation; Rats; Rats, Wistar; Vitamin K

Topics: Adult; Aged; Bone and Bones; Bone Diseases, Metabolic; Female; Hemostatics; Hip Fractures; Humans; Infant, Newborn; Male; Middle Aged; Nutritional Status; Osteocalcin; Osteoporosis, Postmenopausal; Vitamin K

Oral administration of vitamin K was reported to increase bone mineral density. However, the possible role of vitamin K in the pathogenesis of osteoporosis still remains unclear. Therefore, we measured the serum concentration of vitamin K1 and K2 (menaquinone-4, 7, 8) in 24 elderly women with osteoporotic vertebral compression fracture and in 36 elderly women without fracture. Major forms of vitamin K present in sera in this study were vitamin K1 and menaquinone-7. On the other hand, serum menaquinone-4 and -8 were undetectable in most women. Serum concentration of menaquinone-7 was significantly lower in women with fracture than in those without fracture (3.29 +/- 3.63 ng/ml vs 6.26 +/- 5.62, mean +/- SD, respectively), while no difference was found in serum vitamin K1 concentration (0.837 +/- 0.620 ng/ml vs 0.820 +/- 0.686, respectively). There was no difference between both groups in background data such as age, body height, body weight, and body mass index, as well as serum level of calcium, inorganic phosphate, creatinine, albumin, and alkaline phosphatase. These results suggest the possibility that deficiency of vitamin K, particularly that of menaquinone-7, is one of the risk factors for developing osteoporosis.

Topics: Aged; Female; Fractures, Stress; Humans; Osteoporosis, Postmenopausal; Vitamin K; Vitamin K Deficiency

Topics: Aged; Female; Humans; Nutritional Status; Osteoporosis, Postmenopausal; Vitamin K