vitamin-k-semiquinone-radical and deoxypyridinoline

We attempted to investigate whether vitamin K2 (menatetrenone) treatment effectively prevents the incidence of new fractures in osteoporosis. A total of 241 osteoporotic patients were enrolled in a 24-month randomized open label study. The control group (without treatment; n = 121) and the vitamin K2-treated group (n = 120), which received 45 mg/day orally vitamin K2, were followed for lumbar bone mineral density (LBMD; measured by dual-energy X-ray absorptiometry [DXA]) and occurrence of new clinical fractures. Serum level of Glu-osteocalcin (Glu-OC) and menaquinone-4 levels were measured at the end of the follow-up period. Serum level of OC and urinary excretion of deoxypyridinoline (DPD) were measured before and after the treatment. The background data of these two groups were identical. The incidence of clinical fractures during the 2 years of treatment in the control was higher than the vitamin K2-treated group (chi2 = 10.935; p = 0.0273). The percentages of change from the initial value of LBMD at 6, 12, and 24 months after the initiation of the study were -1.8 +/- 0.6%, -2.4 +/- 0.7%, and -3.3 +/- 0.8% for the control group, and 1.4 +/- 0.7%, -0.1 +/- 0.6%, and -0.5 +/- 1.0% for the vitamin K2-treated group, respectively. The changes in LBMD at each time point were significantly different between the control and the treated group (p = 0.0010 for 6 months, p = 0.0153 for 12 months, and p = 0.0339 for 24 months). The serum levels of Glu-OC at the end of the observation period in the control and the treated group were 3.0 +/- 0.3 ng/ml and 1.6 +/- 0.1 ng/ml, respectively (p < 0.0001), while the serum level of OC measured by the conventional radioimmunoassay (RIA) showed a significant rise (42.4 +/-6.9% from the basal value) in the treated group at 24 months (18.2 +/- 6.1% for the controls;p = 0.0081). There was no significant change in urinary DPD excretion in the treated group. These findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures, although the vitamin K2-treated group failed to increase in LBMD. Furthermore, vitamin K2 treatment enhances gamma-carboxylation of the OC molecule.

Topics: Absorptiometry, Photon; Amino Acids; Biomarkers; Bone Density; Bone Remodeling; Female; Fractures, Spontaneous; Humans; Incidence; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Radionuclide Imaging; Treatment Outcome; Vitamin K; Vitamin K 2

Suboptimal vitamin K nutriture is evident during rapid growth. We aimed to determine whether vitamin K(2) (menaquinone-4 [MK-4]) supplementation is beneficial to bone structure and intrinsic bone tissue properties in growing rats. Male Wistar rats (5 weeks old) were assigned to either a control diet (n = 8) or an MK-4-supplemented diet (22 mg d(-1) kg(-1) body weight, n = 8). After a 9-week feeding period, we determined the serum concentration ratio of undercarboxylated osteocalcin to γ-carboxylated osteocalcin and the urinary deoxypyridinoline level. All rats were then euthanized, and their tibiae were analyzed by micro-computed tomography for trabecular architecture and synchrotron radiation micro-computed tomography for cortical pore structure and mineralization. Fourier transform infrared microspectroscopy and a nanoindentation test were performed on the cortical midlayers of the anterior and posterior cortices to assess bone tissue properties. Neither body weight nor tibia length differed significantly between the 2 groups. Dietary MK-4 supplementation decreased the ratio of undercarboxylated osteocalcin to γ-carboxylated osteocalcin but did not affect deoxypyridinoline, indicating a positive effect on bone formation but not bone resorption. Trabecular volume fraction and thickness were increased by MK-4 (P < .05). Neither the cortical pore structure nor mineralization was affected by MK-4. On the other hand, MK-4 increased mineral crystallinity, collagen maturity, and hardness in both the anterior and posterior cortices (P < .05). These data indicate the potential benefit of MK-4 supplementation during growth in terms of enhancing bone quality.

Topics: Algorithms; Amino Acids; Animals; Biomarkers; Body Weight; Bone Development; Bone Resorption; Calcification, Physiologic; Diet; Male; Mechanical Phenomena; Organ Size; Osteocalcin; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Tibia; Tomography, X-Ray Computed; Trabecular Meshwork; Vitamin K; Vitamins

Vitamin K deficiency is a relatively common condition in neonates. However, the role of vitamin K in neonatal bone metabolism remains to be determined. Osteocalcin (OC) is the most abundant noncollagenous protein in bone, and is regulated to be gamma-carboxylated by vitamin K. In this study, we measured gamma-carboxylated osteocalcin (Gla-OC) and non- or undercarboxylated osteocalcin (Glu-OC) separately, and examined the effects of vitamin K on osteocalcin metabolism. Eighteen full-term healthy neonates were enrolled in this study. In the cord and d-5 blood samples, the OC levels were determined by three different methods to examine the intact OC by immunoradiometric assay (IRMA), Gla-OC, and Glu-OC. Serum vitamin K fractions, hepaplastin test, and type 1 procollagen carboxyl extension peptide were also determined. Urine samples were also collected from the first voiding and on d 5 to determine urinary pyridinoline, deoxypyridinoline, and gamma-carboxylated glutamic acid. Serum levels of phylloquinone (PK) and menaquinone (MK)-4 increased on d 5 following vitamin K administration and increased intake in breast milk and/or formula. The OC levels determined by IRMA did not change between cord and d-5 blood samples, but the Gla-OC level increased remarkably and Glu-OC reduced to a negligible level. OC in cord blood is mainly Glu-OC, and Glu-OC is replaced with Gla-OC within 5 d of life after vitamin K supplement. The IRMA assay fails to distinguish Gla-OC from Glu-OC and caution is needed to estimate bone turnover with this method in the perinatal period.

Topics: Adult; Amino Acids; Bone and Bones; Fetal Blood; Humans; Immunoradiometric Assay; Infant, Newborn; Osteocalcin; Protein Processing, Post-Translational; Vitamin K; Vitamin K 1; Vitamin K 2

Microgravity induces bone loss by mechanism(s) that remain largely unknown.. We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively.. During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity.. Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Astronauts; Biomarkers; Bone and Bones; Bone Resorption; Circadian Rhythm; Collagen; Collagen Type I; Humans; Male; Osteocalcin; Peptides; Procollagen; Space Flight; Time Factors; Vitamin K

Rapid bone loss is a serious health problem for astronauts during long lasting missions in space. We have recorded the changes of biochemical markers for bone metabolism in one of the astronauts during the 6-month space flight of the EUROMIR-95 mission. Immediately after launch both bone resorption markers and urinary calcium excretion increased about two fold, whereas bone formation markers remained unchanged. After 12 1/2 weeks the astronaut received vitamin K1 (10 mg/day for 6 weeks). Vitamin K is known to be involved in the formation of gamma-carboxyglutamate (Gla) in proteins, such as the calcium-binding bone Gla-proteins osteocalcin and matrix Gla-protein. Concomitant with the start of vitamin K treatment, the calcium-binding capacity of osteocalcin increased, and so did the urinary excretion of free Gla. This is suggestive for a subclinical vitamin K-deficiency in the astronaut before vitamin K-supplementation. During periods of high vitamin K status markers for bone formation (osteocalcin and bone alkaline phosphatase) had increased as compared to the first part of the flight. The mean increases were 14 and 23%, respectively. Our data suggest that increased intake of vitamin K may contribute to counteracting microgravity-induced loss of bone mass during long lasting space missions, but need confirmation in more astronauts.

Topics: 1-Carboxyglutamic Acid; Adult; Aerospace Medicine; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Development; Bone Resorption; Calcium; Humans; Osteocalcin; Osteoporosis; Parathyroid Hormone; Space Flight; Vitamin K; Vitamin K 1; Weightlessness; Weightlessness Countermeasures