menatetrenone and Body-Weight

The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans incorporating components of (1) improved nutrition, (2) increased health literacy, and (3) increased physical activity.. To conduct a Comparative Effectiveness Research (CER) study comparing changes in bone mineral density in healthy women over-40 with above-average compliance when following one of three bone health Plans incorporating the SG's three components.. Using an open-label sequential design, 414 females over 40 years of age were tested, 176 of whom agreed to participate and follow one of three different bone-health programs. One Plan contained a bone-health supplement with 1,000 IUs of vitamin D(3 )and 750 mg of a plant-sourced form of calcium for one year. The other two Plans contained the same plant form of calcium, but with differing amounts of vitamin D(3) and other added bone health ingredients along with components designed to increase physical activity and health literacy. Each group completed the same baseline and ending DXA bone density scans, 43-chemistry blood test panels, and 84-item Quality of Life Inventory (QOL). Changes for all subjects were annualized as percent change in BMD from baseline. Using self-reports of adherence, subjects were rank-ordered and dichotomized as "compliant" or "partially compliant" based on the median rating. Comparisons were also made between the treatment groups and two theoretical age-adjusted expected groups: a non-intervention group and a group derived from a review of previously published studies on non-plant sources of calcium.. There were no significant differences in baseline BMD between those who volunteered versus those who did not and between those who completed per protocol (PP) and those who were lost to attrition. Among subjects completing per protocol, there were no significant differences between the three groups on baseline measurements of BMD, weight, age, body fat and fat-free mass suggesting that the treatment groups were statistically similar at baseline. In all three treatment groups subjects with above average compliance had significantly greater increases in BMD as compared to the two expected-change reference groups. The group following the most nutritionally comprehensive Plan outperformed the other two groups. For all three groups, there were no statistically significant differences between baseline and ending blood chemistry tests or the QOL self-reports.. The increases in BMD found in all three treatment groups in this CER stand in marked contrast to previous studies reporting that interventions with calcium and vitamin D(3) reduce age-related losses of BMD, but do not increase BMD. Increased compliance resulted in increased BMD levels. No adverse effects were found in the blood chemistry tests, self-reported quality of life and daily tracking reports. The Plans tested suggest a significant improvement over the traditional calcium and vitamin D(3) standard of care.

Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Blood Glucose; Body Weight; Bone Density; Boron; C-Reactive Protein; Calcium; Cholecalciferol; Comparative Effectiveness Research; Dietary Supplements; Female; Humans; Lipids; Magnesium; Middle Aged; Minerals; Motor Activity; Patient Education as Topic; Plant Extracts; Quality of Life; Strontium; Treatment Outcome; Vitamin K 2

Menaquinone-4 is a type of vitamin K that has a physiological function in maintaining bone quality via γ-carboxylation of osteocalcin. However, little is known about the beneficial effect of intake of dosages below1500 μg/day.. Fifteen healthy males aged 25.0 years (median) participated in a non-placebo-controlled dose-examination study. They received menaquinone-4 daily for 5 weeks at 0, 300, 600, 900, and 1500 μg/day in weeks 1, 2, 3, 4, and 5, respectively. Compared with baseline, serum γ-carboxylated osteocalcin levels were significantly greater at an intake of 900 μg/day or more; serum undercarboxylated osteocalcin levels and the ratio of serum undercarboxylated osteocalcin to γ-carboxylated osteocalcin were significantly lower than baseline at doses of 600 μg/day or more.. This preliminary graded-dose study suggested that menaquinone-4 supplementation at 600 μg/day or more is likely to be important in terms of vitamin K requirements for bone health.

Topics: Adult; Biomarkers; Body Mass Index; Body Weight; Bone and Bones; Dietary Supplements; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Male; Osteocalcin; Vitamin K 1; Vitamin K 2; Young Adult

Prior 8-week treatment with menatetrenone, MK-4, followed by 8-week risedronate prevented the shortcomings of individual drugs and significantly increased the strength of ovariectomized ICR mouse femur compared to the ovariectomized (OVX) controls. Neither MK-4 following risedronate nor the concomitant administration may be recommended because they brought the least beneficial effect.. The objective of this study was to determine the best combinatory administration of risedronate at 0.25 mg/kg/day (R) with vitamin K(2) at approximately 100 microg MK-4/kg/day (K) to improve strength of osteoporotic mouse bone.. Thirteen-week-old ICR mice, ovariectomized at 9-week, were treated for 8 weeks with R, K, or R plus K (R/K), and then, either the treatment was withdrawn (WO) or switched to K or R in the case of R and K. After another 8 weeks, the mice were killed, and mechanical tests and analyses of femur properties by peripheral quantitative computed tomography, microfocus X-ray tube computed tomography, and confocal laser Raman microspectroscopy were carried out.. The K to R femur turned out superior in parameters tested such as material properties, bone mineral density, BMC, trabecular structure, and geometry of the cortex. The increased cross-sectional moment of inertia, which occurred after K withdrawal, was prevented by risedronate in K to R. In addition to K to R, some properties of R to WO diaphysis and K to WO epiphysis were significantly better than OVX controls.. Prior treatment with MK-4 followed by risedronate significantly increased femur strength in comparison to the OVX controls.

Topics: Animals; Body Weight; Bone Density Conservation Agents; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Etidronic Acid; Female; Femur; Mice; Mice, Inbred ICR; Osteoporosis; Ovariectomy; Risedronic Acid; Vitamin K 2

In this study, we focused on collagen metabolism as a factor involved in menatetrenone (MK-4)-related improvement in bone quality. Using rats with a congenital ascorbic acid (AA) deficiency, osteogenic disorder Shionogi (ODS) rats, we established a model in which abnormal collagen metabolism reduced bone mechanical properties, and investigated the effects of MK-4. We divided 13-week-old ODS rats into four groups: Pre, AA sufficiency (AA(+)), AA deficiency-control (AA(-)control), and AA deficiency+ MK-4-treated (AA(-)MK-4). MK-4 was given as a dietary supplement (30 mg/kg). At the beginning (pre) and after two, three, and four weeks, seven rats in each group were killed to measure plasma bone metabolism and femoral bone mass data and bone mechanical properties. In the rats killed after four weeks, histomorphometric data of the tibiae, the total amino acid level in bone collagen, and rates of proline and lysine hydroxylation were determined. In the AA(+)group, both the cortical bone mass data and bone mechanical properties were serially increased. However, in the AA(-)control group, the cortical bone mass data were similar for four weeks and the bone mechanical properties decreased after three to four weeks. After four weeks, the total level of amino acids in bone collagen and rates of proline and lysine hydroxylation were significantly lower in the AA(-)control group than in the AA(+)group. MK-4 increased bone mechanical properties after four weeks without influencing cortical bone mass. Simultaneously, it inhibited decreases in the total level of amino acids in collagen (P = 0.017). The rates of proline and lysine hydroxylation were higher in the AA(-)MK-4 group than in the AA(-)control group, but not significantly. These results suggest the level of collagen and abnormalities of hydroxylation are involved in the AA deficiency-related reduction in bone mechanical properties, and that MK-4 improves bone mechanical properties by restoring collagen metabolism.

Topics: Amino Acids; Animals; Ascorbic Acid Deficiency; Biomechanical Phenomena; Body Weight; Bone and Bones; Chromatography, High Pressure Liquid; Collagen; Collagen Type I; Femur; Organ Size; Osteocalcin; Osteogenesis; Peptides; Rats; Regression Analysis; Vitamin K 2

In this study, we examined changes in bone parameters and bone strength in rats fed low-Mg diets (experiment 1) and the effects of vitamin K2 (MK-4, experiment 3) and alendronate (ALN, experiment 2) in this model. In experiment 1, 5-week-old male Wistar rats were fed three low-Mg diets (Mg 9, 6, 3 mg/100 g diet) for 4 weeks. Although the cortical bone mineral content (CtBMC) and cortical thickness (CtTh) of the femoral diaphysis in all low-Mg-diet groups were the same as or greater than those in the intact group (Mg: 90 mg/100 g diet), the maximum load and elastic modulus were significantly reduced in the 3-mg-Mg group. In experiment 2, 4-week-old Wistar rats were fed a 6-mg-Mg diet for 8 weeks, and the effect of ALN (2, 20, and 200 microg/kg twice a week) was evaluated. The administration of ALN at 200 microg/kg increased the cortical bone mineral content (CtBMC), CtTh, and maximum load, but had no effect on the elastic modulus, as compared with the low-Mg-control group. In experiment 3, the effect of MK-4 was evaluated under the same conditions as in experiment 2. The administration of MK-4 had no effect on CtBMC, CtTh, or bone components of the femoral diaphysis. However, MK-4 inhibited the decreases in maximum load and elastic modulus due to the low-Mg diet. Since there is no other experimental model in which there is a decrease in bone mechanical properties without a decrease in bone mineral content, the low-Mg diet model is considered to be an excellent model for examining bone quality. Our results from this model suggest that MK-4 and ALN affect bone mechanical properties by different mechanisms.

Topics: Alendronate; Alkaline Phosphatase; Animals; Body Weight; Bone and Bones; Bone Density; Calcitriol; Calcium; Elasticity; Femur; Hydroxyproline; Magnesium; Magnesium Deficiency; Male; Osteocalcin; Parathyroid Hormone; Rats; Rats, Wistar; Stress, Mechanical; Urine; Vitamin K 2

Vitamin K2 (menatetrenone) has been used for the treatment of osteoporosis in Japan. We investigated the effects of ovariectomy (OVX) and vitamin K2 on the calcium (Ca) balance in 20-week-old female Fischer rats. Vitamin K2 (31 mg/kg per day) was given to animals as a dietary supplement. At weeks 4 and 8 after OVX, a Ca balance study was performed for 5 days. The intestinal Ca transport was determined using the everted gut-sac technique at week 9. The Ca balance was poorer in the OVX-control group than in the sham-control group at weeks 4 and 8 after OVX. The Ca balance improved significantly in the vitamin K2 groups as compared with the sham- and OVX-control groups. The intestinal Ca transport decreased due to OVX and was higher in the vitamin K2 administration groups than in the sham- and OVX-control groups, but not to a significant extent. The bone mineral density in the femoral metaphysis as well as the cortical area and cortical thickness in the femoral diaphysis in the OVX-control group were lower than in the sham-control group. The administration of vitamin K2 significantly inhibited an OVX-induced decrease in cortical area and cortical thickness in the femur. These findings suggest that the poor Ca balance observed in ovariectomized rats may be improved by vitamin K2; vitamin K2 may be involved in preventing bone loss in vivo.

Topics: Animals; Biological Transport; Body Weight; Bone Density; Calcium; Feces; Female; Femur; Homeostasis; Intestinal Mucosa; Intestines; Organ Size; Osteoporosis; Ovariectomy; Rats; Rats, Inbred F344; Uterus; 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

Two experiments were carried out in 4-week-old rats. First, the effect of dietary calcium (Ca) content (0.05, 0.1, 0.2, 0.5 and 1.16%) on bone loss was assessed for 3 weeks. Dry weight of the femur showed a Ca-content-dependent decrease. Significant decrease in body weight and plasma Ca level was observed in the 0.05 and 0.1% Ca diet groups, but not in other groups. Second, the curative effect of V.K2 on bone strength was examined. After being fed a 0.2%-Ca diet for 3 weeks, rats were fed 0.2%- or 0.5%-Ca diets for the next 6 weeks with or without V.K2 treatment. At the beginning and after 3 and 6 weeks of treatment, femurs and lumbar vertebra (L3) were collected. In the 0.2%-Ca group, bone mineral density (BMD) and bone strength in the femur gradually increased, but were much lower than those in the intact group. In the 0.5%-Ca group, both parameters in the femur and L3 were rapidly increased. V.K2 treatment did not affect the BMD or bone strength in the femur at either point. However, the bone strength in L3 in the V.K2 group was higher than that in the 0.5%-Ca group at 3 weeks and in the 0.2%-Ca group at 6 weeks than that in the respective control group. These findings suggest that V.K2 has curative effect on bone strength in the vertebra.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Calcium; Femur; Lumbar Vertebrae; Male; Rats; Rats, Sprague-Dawley; Vitamin K; Vitamin K 2