vitamin-k-semiquinone-radical and Spinal-Fractures

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

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

Anticoagulant therapy in patients with atrial fibrillation requires careful evaluation because its benefits i.e. prevention of thromboembolism, must be greater than the risk of bleeding. Patients at higher risk of thrombosis are evaluated through specific scores, such as the CHA(2)DS(2)VASc, coupled with scoring systems for assessing bleeding risks, such as the HAS-BLED score. In addition to bleeding, other risks have been associated with the use of warfarin, including an increased susceptibility to vascular calcifications and fractures caused by a reduction in the levels of vitamin K dependent carboxylated enzymes, matrix Gla-protein (MGP) and bone Gla-protein or osteocalcin (BGP). In fact, while on one side warfarin is used to prevent embolism, on the other hand acting as a vitamin K antagonist it blocks the inhibitory effect of MGP on vascular calcification. Similarly, patients treated with warfarin carry a greater risk of developing osteoporosis and fractures, due to reduced BGP activity. Recently, a new generation of anticoagulant drugs has been developed, such as dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor-Xa inhibitor. They offer an interesting alternative to warfarin, because they do not require frequent blood tests for monitoring while offering similar results in terms of efficacy. Lacking the inhibitory effect on the vitamin K cycle, the consequent side effects can be avoided. If, compared to warfarin treated patients, a lower incidence of vascular calcifications and fractures will be demonstrated, the advantages over warfarin may be even greater, leading to further benefits in terms of morbidity and mortality.

Topics: Animals; Anticoagulants; Atrial Fibrillation; Drug Design; Drug Monitoring; Hemorrhage; Humans; Spinal Fractures; Thromboembolism; Vascular Calcification; Vitamin K; Warfarin

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

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

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

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

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p = 0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363-0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).

Topics: Calcitriol; Calcium; Cross-Sectional Studies; Fibroblast Growth Factor-23; Humans; Parathyroid Hormone; Renal Dialysis; Spinal Fractures; Vitamin D; Vitamin K

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ-carboxy-glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≥1 year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≥20%) and aortic and iliac calcifications were also investigated in a spine (D(5) -L(4)) radiograph. Three-year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14-7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification.

Topics: Adult; Aged; Case-Control Studies; Cohort Studies; Female; Humans; Italy; Logistic Models; Male; Middle Aged; Renal Dialysis; Spinal Fractures; Survival Analysis; Vascular Calcification; 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

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

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

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