Spirulina abstracts draft 6

Vitamin K and Bone Health

High-dose vitamin K supplementation reduces fracture incidence in
postmenopausal women: a review of the literature.
Iwamoto J, Sato Y, Takeda T, Matsumoto H.
Institute for Integrated Sports Medicine, Keio University School of Medicine,
Shinjuku-ku, Tokyo 160-8582, Japan. [email protected]
Although systematic review and meta-analysis of randomized controlled trials
(RCTs) have concluded that vitamin K is effective in preventing fractures, the
effect of vitamin K on the skeleton remains a matter of controversy. 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 RCTs by using the search terms "vitamin K(1) or
vitamin K(2)," "bone," and "postmenopausal women" and the following inclusion
criteria: approximately 50 or more subjects per group and study period of 2 years
or longer. Seven RCTs met the inclusion criteria. The results of these RCTs
showed that vitamin K(1) and vitamin 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(1) and vitamin
K(2) supplementation improved indices of bone strength in the femoral neck and
reduced the incidence of clinical fractures. The review of the reliable literature
confirmed the effect of vitamin K(1) and vitamin K(2) supplementation on the
skeleton of postmenopausal women mediated by mechanisms other than bone
mineral density and bone turnover.
PMID: 19410972 [PubMed - in process]
Osteoporos Int. 2009 Jun;20(6):935-42. Epub 2008 Sep 30.
High prevalence of vitamin K and D deficiency and decreased BMD
in inflammatory bowel disease.
Kuwabara A, Tanaka K, Tsugawa N, Nakase H, Tsuji H, Shide K, Kamao
M, Chiba T, Inagaki N, Okano T, Kido S.
Department of Food and Nutrition, Kyoto Women's University, 35, Imakumano-
kitahiyoshicho, Higashiyama, Kyoto 605-8501, Japan.
SUMMARY: Vitamin K and D deficiency and decreased bone mineral density
(BMD) were highly prevalent in patients with inflammatory bowel disease (IBD),
especially Crohn's disease (CD). Dietary intakes of these vitamins, however, were
above the Japanese adequate intakes in IBD patients, suggesting that
malabsorption is the basis for hypovitaminosis K and D and decreased BMD.
INTRODUCTION: We have studied the possible involvement of vitamin K and
D deficiency in the pathogenesis of decreased BMD in IBD. METHODS: Seventy
patients with IBD were evaluated for their BMD; plasma levels of vitamin K;
phylloquinone (PK), menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein
induced by vitamin K absence (PIVKA-II), and undercarboxylated osteocalcin
(ucOC) levels; and their food intake. RESULTS: Compared with ulcerative colitis
(UC) patients, CD patients had significantly lower plasma vitamin K and 25OH-D
concentrations; significantly higher serum levels of PTH, PIVKA-II, and ucOC;
and significantly lower BMD scores at almost all measurement sites. More IBD
patients were vitamin K deficient in bone than in liver. Multiple regression
analyses revealed that low plasma concentrations of vitamin K and 25OH-D were
independent risk factors for low BMD and that they were associated with the
patients' fat intake, but not with their intake of these vitamins. CONCLUSION:
IBD patients have high prevalence of decreased BMD and vitamin K and D
deficiency probably caused by malabsorption of these vitamins.
Publication Types:

Importance of calcium, vitamin D and vitamin K for osteoporosis
prevention and treatment.
Lanham-New SA.
Nutritional Sciences Division, Faculty of Health and Medical Sciences,
University of Surrey, Guildford, Surrey GU2 7XH, UK. s.lanham-
[email protected]
Throughout the life cycle the skeleton requires optimum development and
maintenance of its integrity to prevent fracture. Bones break because the loads
placed on them exceed the ability of the bone to absorb the energy involved. It is
now estimated that one in three women and one in twelve men aged >55 years
will suffer from osteoporosis in their lifetime and at a cost in the UK of > 1.7
pounds x 10(9) per year. The pathogenesis of osteoporosis is multifactorial. Both
the development of peak bone mass and the rate of bone loss are determined by
key endogenous and exogenous factors. Ca supplements appear to be effective in
reducing bone loss in women late post menopause (>5 years post menopause),
particularly in those with low habitual Ca intake (<400 mg/d). In women early
post menopause (<5 years post menopause) who are not vitamin D deficient, Ca
supplementation has little effect on bone mineral density. However,
supplementation with vitamin D and Ca has been shown to reduce fracture rates
in the institutionalised elderly, but there remains controversy as to whether
supplementation is effective in reducing fracture in free-living populations. Re-
defining vitamin D requirements in the UK is needed since there is evidence of
extensive hypovitaminosis D in the UK. Low vitamin D status is associated with
an increased risk of falling and a variety of other health outcomes and is an area
that requires urgent attention. The role of other micronutrients on bone remains to
be fully defined, although there are promising data in the literature for a clear link
between vitamin K nutrition and skeletal integrity, including fracture reduction.
Publication Types:
PMID: 18412990 [PubMed - indexed for MEDLINE] Arch Phys Med Rehabil. 2005 Mar;86(3):576-81.
Vitamin K deficiency and osteopenia in elderly women with
Alzheimer's disease.
Sato Y, Honda Y, Hayashida N, Iwamoto J, Kanoko T, Satoh K.
Department of Neurology, Mitate Hospital, Tagawa, Japan. [email protected]
OBJECTIVE: To analyze the relation between vitamin K status and bone mineral
density (BMD) in women with Alzheimer's disease (AD). DESIGN: Cross-
sectional study. SETTING: Outpatient departments of neurology and
neuropsychiatry at a hospital in Japan. Participants One hundred women with AD
(mean age, 79.8 y) and 100 age-matched community dwelling controls (mean age,
80.6 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
Patients were divided into 2 groups according to the degree of dementia: the mild
AD group was composed of patients with a score in Mini-Mental State
Examination (MMSE) of 16 and above (n=42); patients in the severe AD group
had MMSE scores below 15 (n=58). We assessed body mass index (BMI). BMD
was measured by computed x-ray densitometry. Serum concentrations of vitamin
K 1 , 25-hydroxyvitamin D (25[OH]D 3 ), intact parathyroid hormone (PTH), and
Glu osteocalcin (OC) were measured. RESULTS: BMI was significantly lower in
women with more severe AD. Metacarpal BMD ( P <.02) and serum
concentrations of vitamin K 1 ( P <.03) and 25(OH)D 3 ( P <.001) were
significantly lower in the severe AD group than in the mild AD group. Serum
levels of intact PTH and Glu OC in severely demented patients were higher than
those with mild dementia ( P <.001). Serum PTH concentration correlated
negatively with serum 25(OH)D 3 level ( r =-.241, P =.016). Serum concentration
of vitamin K 1 correlated positively with that of 25(OH)D 3 ( r =.423, P <.001)
and MMSE score ( r =.353, P <.001), and negatively with Glu OC ( r =-.580, P
<.001). CONCLUSIONS: In female AD patients, nutritional vitamin K 1
deficiency may reduce production of fully carboxylated OC, which in turn may
cause reduced BMD. Lower BMIs in more severe AD may imply the presence of
general malnutrition in such a patient group.
PMID: 15759247 [PubMed - indexed for MEDLINE]
Br J Nutr. 2009 May 19:1-8. [Epub ahead of print]
The effect of menaquinone-7 (vitamin K2) supplementation on
osteocalcin carboxylation in healthy prepubertal children.
van Summeren MJ, Braam LA, Lilien MR, Schurgers LJ, Kuis W, Vermeer
C.
Department of Paediatrics, University Medical Centre Utrecht, PO Box 85090,
3508 AB Utrecht, The Netherlands.
Vitamin K contributes to bone health, probably through its role as cofactor in the
carboxylation of osteocalcin. Intervention studies in adults have demonstrated that
markedly higher osteocalcin carboxylation is obtained by intakes of vitamin K
well above the current recommended dietary intake. However, the relationship
between increased vitamin K2 intake and enhanced osteocalcin carboxylation has
never been shown in healthy children. The objective was to study the effect of 45
mug menaquinone-7 (MK-7; one of the vitamin K2 species) on the circulating
levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin
(cOC) in healthy prepubertal children. We hypothesised that MK-7
supplementation will reduce the ucOC:cOC ratio (UCR), indicating an improved
vitamin K status. The present study is a double-blind randomised placebo-
controlled trial examining the effect of 8 weeks MK-7 supplementation on the
carboxylation of osteocalcin in healthy children (n 55). Serum levels of ucOC,
cOC and MK-7 were measured at baseline and after 8 weeks, together with bone
markers and coagulation parameters. The UCR was used as an indicator of
vitamin K status. In the MK-7-supplemented group (n 28), the circulating
concentration of inactive ucOC reduced and the UCR improved whereas the
concentration of MK-7 increased. Within the placebo group, ucOC, cOC, UCR
and MK-7 did not significantly change over time. In both groups, bone markers
and coagulation parameters remained constant over time. These findings
demonstrate that in healthy, prepubertal children, modest supplementation with
MK-7 increases circulating concentrations of MK-7 and increases osteocalcin
carboxylation.
PMID: 19450370 [PubMed - as supplied by publisher]
Int J Artif Organs. 2009 Feb;32(2):67-74.
Coagulation meets calcification: the vitamin K system.
Krueger T, Westenfeld R, Schurgers L, Brandenburg V.
Department of Nephrology and Clinical Immunology, University Hospital of the
RWTH Aachen, Aachen - Germany.
Morbidity and mortality are massively increased in patients with chronic kidney
disease (CKD) and patients with end-stage renale disease (ESRD). Bone disease
(renal osteodystrophy) and vascular disease (accelerated arteriosclerosis) are two
typical entities contributing to this excess morbidity and mortality. Vitamin K and
vitamin K-dependent-proteins play pivotal roles in the physiology of
mineralization and in preventing ectopic calcification: two of these vitamin K-
dependent-proteins are osteocalcin (regulating bone mineralization) and matrix-
Gla protein (MGP, local calcification inhibitor in the vessel wall). Vitamin K
deficiency impairs the physiological function of osteocalcin and MGP and,
therefore, presumably contributes to bone demineralisation and vascular
calcification (the so-called calcification paradox). In this context, the usage of
vitamin K antagonists for long-term oral anticoagulation therapy might be risky
especially in CKD patients exhibiting a high background level of vascular
calcification. We present a summary of data describing the potential role of
vitamin K deficiency and supplementation in bone and vascular disease in
patients with CKD or ESRD.
PMID: 19363777 [PubMed - in process]

Vitamin K, circulating cytokines, and bone mineral density in older
men and women.
Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O'Donnell CJ,
Gundberg CM, Peterson JW, Booth SL.
US Department of Agriculture Human Nutrition Research Center on Aging at
Tufts University, Boston, MA, USA.
BACKGROUND: Vitamin K modulates cytokines involved in bone turnover,
including interleukin-6 (IL-6) and osteoprotegerin in vitro. OBJECTIVE: The
objective of this study was to assess 1) associations between measures of vitamin
K status [plasma phylloquinone and serum percentage of undercarboxylated
osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP)
concentrations and 2) the effect of daily 500 mug phylloquinone supplementation
for 3 y on cytokine concentrations. DESIGN: Concentrations of IL-6,
osteoprotegerin, and CRP and bone mineral density (BMD) were measured at
baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y;
58.5% women) participating in a randomized trial that studied the effect of
vitamin K supplementation on bone loss. RESULTS: Cross-sectionally, plasma
phylloquinone was inversely associated with IL-6 and CRP, whereas serum
%ucOC was inversely associated with IL-6. Osteoprotegerin was associated
positively with plasma phylloquinone and inversely with %ucOC. No differences
were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations
between participants who received phylloquinone supplementation and those who
did not. Overall, no association was observed between the 3-y changes in
circulating cytokines and BMD. CONCLUSIONS: Poor vitamin K status was
associated with high concentrations of cytokines involved in bone turnover, but
vitamin K supplementation did not confer a decrease in cytokine concentrations.
The healthy status of this cohort may explain a lack of effect of vitamin K
supplementation on cytokine concentrations. This trial was registered with
www.clinicaltrials.gov as NCT00183001.
PMID: 18689371 [PubMed - indexed for MEDLINE]



Vitamin K and Bone Health
Clin Exp Rheumatol. 2008 May-Jun;26(3):484-91.
Extremes in vitamin K status of bone are related to bone ultrasound
properties in children with juvenile idiopathic arthritis.
van Summeren MJ, Vermeer C, Engelbert RH, Schurgers LJ, Takken T,
Fischer K, Kuis W.
Department of Paediatric Immunology, University Medical Centre Utrecht, The
Netherlands. [email protected]
OBJECTIVE: Osteopenia is a common complication of juvenile idiopathic
arthritis (JIA). In adults, low bone density and increased fracture risk are
associated with low vitamin K status of bone. The vitamin K-dependent protein
osteocalcin plays an important role in bone metabolism. Its activity depends upon
post-translational carboxylation in which vitamin K is an essential co-factor.
Hence, vitamin K deficiency leads to under-carboxylated (i.e., inactive)
osteocalcin (ucOC). Little is known about the vitamin K status and bone health in
children with juvenile idiopathic arthritis (JIA). We studied the vitamin K status
of bone and its association with bone mass properties in children with JIA
compared to healthy children. METHODS: We performed a cross sectional study
in 55 children with JIA and 54 healthy controls between 6-18 years of age. Bone
markers, ultrasound bone mass properties and vitamin K status of bone were
determined. RESULTS: Overall, no differences in vitamin K status of bone were
found between the study groups. Among children with JIA, a high ratio of
ucOC/cOC indicating low vitamin K status was associated with low bone
ultrasound parameters, whereas children with a high vitamin K status had
markedly higher bone properties. This association was independent of physical
activity, age, gender and BMI. CONCLUSION: These results suggest that vitamin
K may be one of multiple risk factors for low bone mass in children with JIA, in
addition to other recognized determinants of bone mass. The question remains
whether JIA patients would benefit from increased dietary vitamin K intake.
Publication Types:
PMID: 18578975 [PubMed - indexed for MEDLINE]
Vitamin K and Bone Health

Diagnosis of osteoporosis with vitamin k as a new biochemical
marker.
Heiss C, Hoesel LM, Wehr U, Wenisch S, Drosse I, Alt V, Meyer C, Horas U,
Schieker M, Schnettler R.
Department of Trauma Surgery, University Hospital of Giessen-Marburg,
Giessen, Germany.
Osteoporosis is a metabolic bone disease characterized by reduced bone quality
and quantity. As a consequence, patients are at risk for fractures, subsequent
immobility, and higher mortality especially among elder patients. Because of the
high incidence of complications and the associated financial burden for the health
system, new parameters for diagnostic and therapeutic purposes are urgently
needed. In this regard, research focused on vitamin K as a biochemical bone
marker has provided promising results. Vitamin K represents an important
enzyme-cofactor for the posttranslational modification and activation of several
proteins involved in bone metabolism. Vitamin K has been proven to be a
valuable diagnostic as well as therapeutic parameter especially in osteoporosis.
Patients with osteoporosis have been shown to have decreased levels of vitamin
K. Further, regular intake of vitamin K may increase bone mineral density
(BMD), thereby lowering the fracture risk. Yet vitamin K alone may not
sufficiently indicate the mineral status of the bone. However, the usefulness of a
combination of several biochemical bone markers as improved surrogate markers
of bone metabolism has been shown recently. Therefore, this review will focus on
the significance and importance of vitamin K for bone metabolism. Beyond this,
aspects on the current and prospective use of vitamin K as well as other newly
developed biochemical bone markers will be discussed.
Publication Types:
PMID: 18374203 [PubMed - indexed for MEDLINE]
Vitamin K and bone health in adult humans.
Bügel S.
Department of Human Nutrition, University of Copenhagen, Rolighedsvej 30,
DK-1958 Frederiksberg C, Denmark.
Vitamin K is receiving more attention in relation to its role in bone metabolism.
Vitamin K is a coenzyme for glutamate carboxylase, which mediates the
conversion of glutamate to gamma-carboxyglutamate (Gla). The gamma-
carboxylation of the Gla proteins is essential for the proteins to attract Ca2+ and
to incorporate these into hydroxyapatite crystals. The best known of the three
known bone-related Gla proteins is osteocalcin (OC). Even though the exact role
of OC is not known, a number of studies have shown that vitamin K insufficiency
or high levels of undercarboxylated osteocalcin (ucOC) is associated with an
increase in the concentration of circulating ucOC. Furthermore, several studies
have demonstrated that vitamin K insufficiency is associated with low bone
mineral density (BMD) and increased fractures. Vitamin K supplementation, on
the other hand, has been shown to improve the bone turnover profile and decrease
the level of circulating ucOC. Dietary recommendations are based on saturation of
the coagulation system, and in most countries the dietary intake is sufficient to
obtain the amount recommended. In relation to bone, requirements might be
higher. The aim of this chapter is to give an overview of the importance of
vitamin K in relation to bone health in adult humans and thereby in the prevention
of osteoporosis. Furthermore, I will shortly discuss the interaction with vitamin D
and the paradox in relation to warfarin treatment.
Publication Types:
PMID: 18374202 [PubMed - indexed for MEDLINE] Br J Nutr. 2008 Oct;100(4):852-8. Epub 2008 Feb 18.
Vitamin K status is associated with childhood bone mineral content.
van Summeren MJ, van Coeverden SC, Schurgers LJ, Braam LA, Noirt F,
Uiterwaal CS, Kuis W, Vermeer C.
Department of Paediatric Immunology, University Medical Centre Utrecht, PO
Box 85090, Utrecht, The Netherlands. [email protected]
In adult bone, vitamin K contributes to bone health, probably through its role as
co-factor in the carboxylation of osteocalcin. In children, the significance of
vitamin K in bone-mass acquisition is less well known. The objective of this
longitudinal study was to determine whether biochemical indicators of vitamin K
status are related to (gains in) bone mineral content (BMC) and markers of bone
metabolism in peripubertal children. In 307 healthy children (mean age 11.2
years), BMC of the total body, lumbar spine and femoral neck was determined at
baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to
carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both
time points. Markers of bone metabolism, sex steroids, vitamin D status and
growth hormones were measured at baseline only. Large variations in the levels
of the UCR were found at both time-points, indicating a substantial
interindividual difference in vitamin K status. Improvement of vitamin K status
over 2 years (n 281 children) was associated with a marked increase in total body
BMC (r -49.1, P<0.001). The UCR was associated with pubertal stage, markers of
bone metabolism, sex hormones and vitamin D status. A better vitamin K status
was associated with more pronounced increase in bone mass in healthy
peripubertal children. In order to determine the significance of these findings for
childhood bone health, additional paediatric studies are needed.
Publication Types:
PMID: 18279558 [PubMed - indexed for MEDLINE] Mayo Clin Health Lett. 2007 Nov;25(11):4.
Vitamin K linked to bone strength.
[No authors listed]
Publication Types:
PMID: 18232068 [PubMed - indexed for MEDLINE] J Endocrinol Invest. 2007;30(6 Suppl):24-8.
Role of vitamin K on biochemical markers, bone mineral density,
and fracture risk.
Francucci CM, Rilli S, Fiscaletti P, Boscaro M.
Division of Endocrinology, Department of Internal Medicine, Polytechnic
University of Marche, Ancona, Italy. [email protected]
Osteoporosis is a multifactorial chronic disease that may become even more
prevalent and more of a public health problem in the decades to come. Recent
research has indicated that a number of macro- and micronutrients are involved in
the development of bone health. In the past decade it became evident that vitamin
K played a significant role in human health beyond its well-established function
in blood clotting. In fact, among the proteins known or suspected to be involved
in bone and vascular biology there are several members of the vitamin K
dependent or gamma-carboxyglutamic acid protein family. Based on the current
evidence from epidemiologic and intervention studies, there are insufficient data
to recommend a routine supplementation of vitamin K for optimal bone health.
New experimental and placebo-controlled studies in humans should clarify our
understanding of the role vitamin K plays in improving bone health.
Publication Types:
PMID: 17721070 [PubMed - indexed for MEDLINE]
[Serum vitamin K concentration and nutrition]
[Article in Japanese]
Tsugawa N, Okano T.
Kobe Pharmaceutical University, Department of Hygienic Sciences.
Vitamin K (VK) is well known for its role in the synthesis of a number of blood
coagulation factors. VK is also an important factor for bone metabolism via
gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla
protein, and protein S. Recently, it is rare that severe VK deficiency is observed.
However, low dietary VK intake or low VK status has been shown to be
associated with low bone mineral density and increased hip fracture risk. These
studies suggest that there is potential VK insufficiency in bone, even in sufficient
VK status for blood coagulation. In the present review, the studies concerning
relationship between serum VK concentration and bone health, including
pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and
factors which affect on blood circulation of VK, are reviewed.
Publication Types:
PMID: 17982192 [PubMed - indexed for MEDLINE] [Vitamin K and bone quality]
[Article in Japanese]
Hara K, Akiyama Y.
Eisai Co., Ltd., Clinical Research Center, Applied Drug Research Department,
Pharmacological Evaluation Section.
Meta-analysis involving previous clinical studies showed that VK(2) decreased
the incidence of fracture. In particular, the results based on the data on bone
mineral density and fracture suggested that VK(2) improves bone quality.
Preclinical studies regarding bone quality reported that VK(2) improved the
trabecular microarchitecture (connectivity and width) in an ovariectomized
model, and that VK(2) increased the bone strength without influencing the bone
mineral content in a model fed a low-Mg diet and a vitamin C deficiency model,
increasing the collagen level and proline hydroxylation. Thus, improvement in
bone quality via actions on the bone geometry and collagen level/quality may be
involved in a VK(2)-related decrease in the incidence of new fracture in clinical
studies.
Publication Types:
PMID: 17982187 [PubMed - indexed for MEDLINE] Int J Vitam Nutr Res. 2006 Nov;76(6):385-90.
A preliminary assessment of vitamin K1 intakes and serum
undercarboxylated osteocalcin levels in 11-13 year old Irish girls.
Collins A, Cashman KD, Kiely M.
Department of Food and Nutritional Sciences, University College, Cork, Ireland.
[email protected]
Low vitamin K1 intakes have been associated with low bone mineral density in
women and reduced bone turnover in girls. No European data exist on the
relationship between vitamin K1 and serum undercarboxylated osteocalcin
(ucOC), an indicator of K1 status in adolescents. The aim of the current study was
to assess intakes of vitamin K1 in relation to serum ucOC status in Irish girls. A
detailed dietary history method, which measured habitual intakes from a typical
14-day period, was used to estimate vitamin K1 intakes in 18 girls aged 11-13
years. Recently compiled and validated food composition data for vitamin K1
were used to determine vitamin K1 intakes. An enzyme immunoassay was used to
measure ucOC in fasting serum samples. The mean (+/- SD) intake of vitamin K1
in the girls was 72.4 microg/day (SD 34.4). Vegetables (particularly broccoli,
composite dishes, and lettuce) contributed 53% of total vitamin K1 intakes.
Thirty-Seven percent of the girls failed to meet the current U.S. adequate intake
for adolescents of 60 microg/day vitamin K1. Serum ucOC levels were inversely
related to body weight-adjusted vitamin K1 intakes, controlling for energy intake
(partial correlation r = -0.538; p = 0.026). The data indicate that large-scale
studies to examine relationships between vitamin K1 (and green vegetable)
intakes and bone growth and development in adolescents are warranted.
PMID: 17607958 [PubMed - indexed for MEDLINE]
Med Monatsschr Pharm. 2007 Jan;30(1):35-6.
[Vitamin K for prevention of fracture]
[Article in German]
Ecker-Schlipf B.
PMID: 17262902 [PubMed - indexed for MEDLINE]

[Active vitamin D and vitamin K as therapeutic agents for
osteoporosis]
[Article in Japanese]
Katagiri H.
Department of Orthopaedic Surgery, Medicine of Sensory and Motor Organs,
Faculty of Medicine, Tottori University.
Active vitamin D has been most widely used in Japan for the treatment of
osteoporosis. However, clinical evidence for its efficacy as an anti-osteoporotic
drug is scarce in terms of fracture prevention. Recent reports suggest that active
vitamin D may prevent fracture not only through enhancement of intestinal
calcium absorption but also by improving bone quality and/or strength
independently of bone mass and by improving neuromuscular function to reduce
the number of fall. Low serum concentrations of vitamin K have been reported in
patients with osteoporosis, and serum osteocalcin appears to be undercarboxylated
in these individuals, a process dependent on vitamin K. Undercarboxylated
osteocalcin is also a significant risk for hip fracture. Clinical studies in Japan
suggest that menatetrenone (vitamin K2) reduces skeletal losses and, in a small
randomized clinical trial, it reduced the rate of vertebral fractures. Menatetrenone
is currently used in Japan, the Republic of Korea and Thailand.
Publication Types:
PMID: 16972672 [PubMed - indexed for MEDLINE]
[Protective effects of vitamin K against osteoporosis and its
pleiotropic actions]
[Article in Japanese]
Kaneki M.
Harvard Medical School, Massachusetts General Hospital, Department of
Anesthesia & Critical Care.
Vitamin K is a nutrient originally identified as an essential factor for blood
coagulation. Recently, vitamin K has emerged as a potential protector against
osteoporosis and hepatocarcinoma. Accumulated evidence indicates that
subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues,
particularly in bone, exists widely in the otherwise healthy adult population. Both
vitamin K(1) and K(2) have been shown to exert protective effects against
osteoporosis. Moreover, therapeutic potential of vitamin K(2) as an anti-hepatoma
drug has been recently highlighted. Most of the new biological functions of
vitamin K in bone and hepatoma cells are considered to be attributable to
promotion of gamma-carboxylation of glutamic acid residues in vitamin K-
dependent proteins, which is shared by both vitamins K(1) and K(2). In contrast,
vitamin K(2)-specific, gamma-carboxylation-unrelated functions have also been
demonstrated. These functions include stimulation of steroid and xenobiotic
receptor (SXR)-mediated transcription and anti-oxidant property. Thus, biological
differences between vitamins K(1) and K(2), and a potential involvement of
gamma-carboxylation-independent actions in the new roles of vitamin K remain
open issues. Molecular bases of coagulation-unrelated pleiotropic actions of
vitamin K and its implications in human health deserve further investigations.
Publication Types:
PMID: 16951479 [PubMed - indexed for MEDLINE] Arch Intern Med. 2006 Jun 26;166(12):1256-61.
Vitamin K and the prevention of fractures: systematic review and
meta-analysis of randomized controlled trials.
Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson
DJ.
York Trials Unit, Department of Health Sciences, University of York, York YO10
5DD, England. [email protected]
BACKGROUND: Observational and some experimental data suggest that low
intake of vitamin K may be associated with an increased risk of fracture.
OBJECTIVE: To assess whether oral vitamin K (phytonadione and menaquinone)
supplementation can reduce bone loss and prevent fractures. DATA SOURCES:
The search included the following electronic databases: MEDLINE (1966 to June
2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the
ISI Web of Science (1945 to June 2005), the National Research Register
(inception to the present), Current Controlled Trials, and the Medical Research
Council Research Register. STUDY SELECTION: Randomized controlled trials
that gave adult participants oral phytonadione and menaquinone supplements for
longer than 6 months were included in this review. DATA EXTRACTION: Four
authors extracted data on changes in bone density and type of fracture. All articles
were double screened and double data extracted. DATA SYNTHESIS: Thirteen
trials were identified with data on bone loss, and 7 reported fracture data. All
studies but 1 showed an advantage of phytonadione and menaquinone in reducing
bone loss. All 7 trials that reported fracture effects were Japanese and used
menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found
an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI],
0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip
fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.
CONCLUSIONS: This systematic review suggests that supplementation with
phytonadione and menaquinone-4 reduces bone loss. In the case of the latter,
there is a strong effect on incident fractures among Japanese patients.
Publication Types:
PMID: 16801507 [PubMed - indexed for MEDLINE]

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