title: Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG) Effect of vitamin K on vascular health and physical function in older people with vascular disease–a randomised controlled trial Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. Inhibiting the progression of arterial calcification with vitamin K in HemoDialysis patients (iPACK-HD) trial: rationale and study design for a randomized trial of vitamin K in patients with end stage kidney disease Factors Affecting Bone Loss in Female Endurance Athletes Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. Age-Related Changes in Serum Undercarboxylated Osteocalcin and its Relationships with Bone Density, Bone Quality, and Hip Fracture Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial Vitamin K Supplement Along with Vitamin D and Calcium Reduced Serum Concentration of Undercarboxylated Osteocalcin While Increasing Bone Mineral Density in Korean Postmenopausal Women over Sixty-Years-Old Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules 
  Vitamin K1 Supplementation Retards Bone Loss in Postmenopausal Women Between 50 and 60 Years of Age
   Risedronate therapy for prevention of hip fracture after stroke in elderly women [RETRACTED] Vitamin K supplementation does not significantly impact bone mineral density and biochemical markers of bone in pre- and perimenopausal women. Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. Dietary Vitamin K2 Supplement Improves Bone Status After Lung and Heart Transplantation Multidetector-row computed tomography is useful to evaluate the therapeutic effects of bisphosphonates in glucocorticoid-induced osteoporosis Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease. Effect of vitamin K supplementation on bone loss in elderly men and women.
abstract: We have recently demonstrated that glucocorticoid ( GC ) suppresses bone formation and enhances bone resorption , with result ant bone loss . This altered bone turnover is not due to the action of parathyroid hormone ( PTH ) , but appears to be related to the suppression of osteoprotegerin ( OPG ) . As vitamin K2 ( menatetrenone ) has been used for the treatment of osteoporosis , the present study was carried out to evaluate the effect of vitamin K2 on GC-induced bone loss . Twenty patients with chronic glomerulonephritis treated with GC for the first time were chosen for this study . Ten patients received GC alone  ( group A ) and the other 10 patients each received 15 mg of vitamin K2 per day in addition to GC ( group B ) . Markers of bone metabolism , including serum OPG , osteocalcin ( OC ) , bone-specific alkaline phosphatase activity ( BAP ) , PTH , tartrate-resistant acid phosphatase ( TRAP ) , and bone mineral density ( BMD ) , were measured before and during the treatment . OPG was significantly decreased in group A ( P < 0.001 ) , while no significant change was seen in group B. TRAP was markedly increased in both groups , more particularly in group A ( P < 0.01 ) . PTH was decreased in group A , but was increased in group B. OC was decreased at month 1 but subsequently increased until month 12 in both groups . BAP had decreased at month 3 in group A ( P < 0.05 ) , but not in group B. BMD of the lumbar spine was significantly reduced after 6 months ( P < 0.01 ) , and 12 months ( P < 0.001 ) of treatment in group A , whereas there was no remarkable change in group B. The present study demonstrated that the inhibition exerted by vitamin K2 of the reduction in OPG induced by GC may , at least in part , play a role in the prevention and treatment of GC-induced  bone loss Background and Aims Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures . The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease . Methods and results A double blind , r and omised , placebo-controlled trial . Participants aged ≤ 70 years with a history of vascular disease were r and omised to receive 6 months of daily oral 100mcg vitamin K2 ( MK7 subtype ) or matching placebo with outcomes measured at 0 , 3 and 6 months . The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months . Secondary outcomes included carotid-radial pulse wave velocity , augmentation index , blood pressure , carotid intima-media thickness , C-reactive protein , B-type natriuretic peptide , cholesterol and desphospho-uncarboxylated matrix Gla protein levels . H and grip strength and the Short Physical Performance Battery assessed physical function , while postural sway was measured using a 3-dimensional force platform . Results 80 participants were r and omised , mean age 77 ( SD 5 ) years ; 44/80 were male .  Vitamin K levels rose in the intervention arm compared to placebo ( + 48 pg/ml vs −6 pg/ml , p=0.03 ) at 6 months . Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months ( −130 [ SD 117 ] pmol/L vs + 13 [ SD 180 ] pmol/L , p<0.001 ) . No change was seen in endothelial function ( between group difference −0.3 % [ 95%CI −1.3 to 0.8 ] , p=0.62 ) . A modest , non-significant improvement in pulse wave velocity was seen in the vitamin K group ( −0.8 m/s [ 95%CI −1.8 to 0.3 ] , p=0.15 ) while all other vascular and physical function outcomes unchanged . Conclusions Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease It has been previously shown that the level of circulating undercarboxylated osteocalcin ( ucOC ) is elevated in elderly women in comparison with young , healthy , premenopausal ones . To underst and the mechanism of the increase in the ucOC in the elderly and to assess its potential consequences on bone fragility , we have measured  ucOC  in the sera of 195 elderly institutionalized women 70 - 101 yr of age . In 45 women ( 23 % ) serum ucOC was above the upper limit of the normal range for young women . The level of ucOC was negatively correlated with 25OHD ( r = -0.32 , P < 0.001 ) even after excluding the effect of age , parathyroid hormone ( PTH ) , and creatinine by partial correlation ( r = -0.24 , P < 0.002 ) . During an 18-mo follow-up , 15 women sustained a hip fracture and their baseline ucOC level was higher ( P < 0.01 ) in women who subsequently sustained hip fracture than in the nonfracture group contrasting with no significant differences for serum calcium , phosphate , alkaline phosphatase , creatinine , PTH , 250HD , and total and carboxylated OC . The risk of hip fracture was increased in women with elevated ucOC ( relative ratio 5.9 , 99.9 % Cl 1.5 - 22.7 , P < 0.001 ) . During 1 yr of calcium/vitamin D2 treatment , ucOC decreased ( P < 0.05 ) , especially in those with the initially increased values ( from 2.22 + /- 0.35 to 1.41 + /- 0.29 ng/ml , P < 0.005 ) contrasting with an increase in the placebo group ( P < 0.05 ) . In conclusion , the increase in ucOC in the elderly reflects not only some degree of vitamin K deficiency but also their poor vitamin D status , suggesting that vitamin D may be important , either directly or indirectly through its effect on bone turnover , for achieving a normal gamma-carboxylation of OC . The ucOC , but not conventional calcium metabolism parameters , predicts the subsequent risk of hip fracture , suggesting that serum ucOC reflects some changes in bone matrix associated with increased fragility Background Cardiovascular disease , which is due in part to progressive vascular calcification , is the leading cause of death among patients with end stage kidney disease ( ESKD ) on dialysis . A role for vitamin K in the prevention of vascular calcification is plausible based on the presence of vitamin K dependent proteins in vascular tissue , including matrix gla protein ( MGP ) . Evidence from animal models and observational studies support a role for vitamin K in the prevention of vascular calcification . A large-scale study is needed to investigate the effect of vitamin K supplementation on the progression of vascular calcification in patients with ESKD , a group at risk for sub- clinical vitamin K deficiency . Methods / Design We plan a prospect i ve , r and omized , double-blind , multicenter controlled trial of incident ESKD patients on hemodialysis in centers within North America . Eligible subjects with a baseline coronary artery calcium score of greater than or equal to 30 Agatston Units , will be r and omly assigned to either the treatment group ( 10 mg of phylloquinone three times per week ) or to the control group ( placebo administration three times per week ) . The primary endpoint is the progression of coronary artery calcification defined as a greater than 15 % increase in CAC score over baseline after 12 months . Discussion Vitamin K supplementation is a simple , safe and cost-effective nutritional strategy that can easily be integrated into patient care . If vitamin K reduces the progression of coronary artery calcification it may lead to decreased morbidity and mortality in men and women with ESKD.Trial registration NCT 01528800.Abrégé Context eLa maladie cardiovasculaire , qui est partiellement attribuable à la calcification vasculaire progressive , est la cause principale de décès chez les patients atteints d’insuffisance rénale terminale ( IRT ) en hémodialyse . La vitamine K pourrait jouer un rôle dans la prévention de la calcification vasculaire , en raison de la présence de protéines dépendantes à la vitamine K dans les tissus vasculaires , do nt l’ostéocalcine . Le modèle animal , de même que des études d’observation , témoignent du rôle de la vitamine K dans la prévention de la calcification vasculaire . Une étude réalisée à gr and e échelle serait nécessaire afin d’étudier l’effet de la supplémentation de vitamine K sur la progression de la calcification vasculaire chez les patients atteints d’IRT , un groupe à risque pour les carences infracliniques en vitamine K.Méthode/type d’étudeNous prévoyons effectuer un essai clinique aléatoire , à double insu et multicentrique auprès de patients atteints d’IRT , traités en hémodialyse hospitalière en Amérique du Nord . On affectera au hasard les sujets admissibles qui présentent dans l’artère coronaire un taux de calcium supérieur ou égal à 30 unités d’Agatston , soit au groupe auquel on administre un traitement ( 10 mg de phylloquinone trois fois par semaine ) , soit au groupe témoin ( administration du placebo trois fois par semaine ) . Le critère d’évaluation principal est la progression de la calcification de l’artère coronaire , définie comme une augmentation supérieure à 15 % ( résultat CAC ) par rapport au point de référence , au bout de douze mois . Discussion La supplémentation de vitamine K est une stratégie nutritionnelle à la fois simple , sécuritaire et rentable , qui peut être aisément intégrée aux soins aux patients . S’il s’avère que la vitamine K réduit la progression de la calcification de l’artère coronaire , il pourrait y avoir une diminution de la morbidité et de la mortalité chez les hommes et les femmes atteints d’IRT Background : Low bone mass leading to stress fractures is a well-known and yet unsolved problem among female athletes . Purpose : To quantify the rate of bone loss in healthy female athletes and investigate the effects of estrogen and vitamin K supplementation on bone loss . Study Design : Prospect i ve cohort study . Methods : We classified 115 female endurance athletes into amenorrheic , eumenorrheic , or estrogen-supplemented groups and r and omized them to receive either placebo or vitamin K1 . The bone mineral densities of the subjects ' femoral neck and lumbar spine were measured at baseline and after 2 years . Results : Bone mineral density in the lumbar spine remained constant , but bone density in the femoral neck had decreased significantly after 2 years in all three subgroups . The decrease was higher in amenorrheic ( —6.5 % ± 4.0 % ) than in eumenorrheic ( —3.2 % ± 4.1 % ) and estrogen-supplemented athletes ( —3.9 % ± 3.1 % ) . Supplementation with vitamin K did not affect the rate of bone loss . Conclusions : The rate of bone loss in all three subgroups of female athletes was unexpectedly high ; neither estrogen nor vitamin K supplementation prevented bone loss . Clinical Relevance : High-intensity training maintained over several years must be regarded in women as a risk factor for osteoporosis , and protocol s for optimal treatment should be developed Low vitamin K status is associated with low BMD and increased fracture risk . Additionally , a specific menaquinone , menatetrenone ( MK4 ) , may reduce fracture risk . However , whether vitamin K plays a role in the skeletal health of North American women remains unclear . Moreover , various K vitamers ( e.g. , phylloquinone and MK4 ) may have differing skeletal effects . The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic , postmenopausal , North American women . In this double-blind , placebo-controlled study , 381 postmenopausal women received phylloquinone  ( 1 mg daily ) , MK4 ( 45 mg daily ) , or placebo for 12 mo . All participants received daily calcium and vitamin D(3 ) supplementation . Serum bone-specific alkaline phosphatase ( BSALP ) and n-telopeptide of type 1 collagen ( NTX ) were measured at baseline and 1 , 3 , 6 , and 12 mo . Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo . At baseline , the three treatment groups did not differ in demographics or study endpoints . Compliance with calcium , phylloquinone , and MK4  treatment was 93 % , 93 % , and 87 % , respectively . Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX . No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed . This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy , postmenopausal , North American women receiving calcium and vitamin D supplementation Summary Vitamin K mediates the synthesis of proteins regulating bone metabolism . We have tested whether high vitamin K2 intake promotes bone mineral density and bone strength . Results showed that K2 improved BMC and femoral neck width , but not DXA-BMD . Hence high vitamin K2 intake may contribute to preventing postmenopausal bone loss . Introduction Vitamin K is involved in the synthesis of several proteins in bone . The importance of K vitamins for optimal bone health has been suggested by population -based studies , but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results . Unlike BMC , DXA-BMD does not take into account the geometry ( size , thickness ) of bone , which has an independent contribution to bone strength and fracture risk . Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake . Methods A r and omized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K2 ( MK-4 , menatetrenone ) during three years .  BMC and hip geometry were assessed by DXA . Bone strength indices were calculated from DXA-BMD , femoral neck width ( FNW ) and hip axis length ( HAL ) . Results K2 did not affect the DXA-BMD , but BMC and the FNW had increased relative to placebo . In the K2-treated group hip bone strength remained unchanged during the 3-year intervention period , whereas in the placebo group bone strength decreased significantly . Conclusions Vitamin K2 helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW , whereas it has little effect on DXA-BMD Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women . Method This multicenter , r and omized , double-blinded , double-dummy , noninferiority , positive drug-controlled clinical trial was conducted in five Chinese sites . Eligible Chinese women with postmenopausal osteoporosis ( N=236 ) were r and omized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day , respectively , for 1 year . Additionally , all patients received calcium 500 mg/day . Posttreatment bone mineral density ( BMD ) , new fracture onsets , and serum osteocalcin ( OC ) and undercarboxylated OC ( ucOC ) levels were compared with the baseline value in patients of both groups . Results A total of 213 patients ( 90.3 % ) completed the study . After 1 year of treatment , BMD among patients in Group M significantly increased from baseline by 1.2 % and 2.7 % at the lumbar spine and trochanter , respectively ( P<0.001 ) ; and the percentage increase of BMD in Group A was 2.2 % and 1.8 % , respectively ( P<0.001 ) . No difference was observed between groups . There were no changes in femoral neck BMD in both groups . Two patients ( 1.9 % , 2/108 ) in Group M and four patients ( 3.8 % , 4/105 ) in Group A had new fracture onsets ( P>0.05 ) . In Group M , OC and ucOC decreased from baseline by 38.7 % and 82.3 % , respectively ( P<0.001 ) . In Group A , OC and ucOC decreased by 25.8 % and 34.8 % , respectively ( P<0.001 ) . Decreases in serum OC and ucOC were more obvious in Group M than in Group A ( P<0.001 ) . The safety profile of menatetrenone was similar to alfacalcidol . Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2 ) and D(3 ) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis . SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density < 0.98 g/cm(2 ) ( osteopenia and osteoporosis ) as measured by dual-energy X-ray absorptiometry . In this study , we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996 . Subjects were r and omized into four groups ( each having 43 subjects in vitamin K(2 ) therapy group , vitamin D(3 ) therapy group , vitamin K(2 ) and D(3 ) combined therapy group , or a control group receiving dietary therapy alone ) and treated with respective agents for 2 years , with bone mineral density was measured prior to therapy and after 6 , 12 , 18 , and 24 months of treatment . The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide ( P1CP ) , serum intact osteocalcin , and urinary pyridinoline . Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time ( APTT ) and analysis of concentrations of antithrombin III ( AT III ) , fibrinogen , and plasminogen . RESULTS Combined therapy with vitamin K(2 ) and D(3 ) for 24 months markedly increased bone mineral density ( 4.92 + /- 7.89 % ) , while vitamin K(2 ) alone increased it only 0.135 + /- 5.44 % . The bone markers measured , revealed stimulation of both bone formation and resorption activity . We observed an increase in coagulation and fibrinolytic activity that was within the normal range , suggesting that balance was maintained in the fibrinolysis-coagulation system . CONCLUSIONS Continuous combination therapy with vitamin K(2 ) and D(3 ) may be useful for increasing vertebral bone mass in postmenopausal women . Furthermore , the increase in coagulation function observed during this therapy was within the physiological range , and no adverse reactions were observed PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) .  Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin We previously showed that circulating undercarboxylated osteocalcin  ( ucOC ) is elevated in elderly women and is a powerful marker of the subsequent risk of hip fracture in elderly institutionalized women ( J Clin Invest 1993 ; 91:1769 ) . To investigate the relationship between bone mass and ucOC , we measured bone mineral density ( BMD ) of the hip with dual-energy x-ray absorptiometry in 98 elderly institutionalized women , 81.4 + /- 6.0 years old .  ucOC was negatively correlated with BMD at all sites ( r = -0.26 to -0.38 , p < 0.001 to p < 0.0001 ) , even after exclusion of the effect of age by partial correlation ( for the femoral neck , r = -0.26 , p < 0.01 ) and after controlling for serum parathyroid hormone . BMD was significantly lower at all sites of measurement in women with elevated ucOC ( > 1.65 ng/ml , upper limit of the normal range in young women ) than in those with normal ucOC ( for the neck , 0.58 + /- 0.13 versus 0.43 + /- 0.13 g/cm2 , p < 0.001 ) . Similar results were obtained for ucOC expressed as the fraction of total OC ( ucOC% ) . Multiple regression showed that ucOC has the highest predictive value for BMD when including age and body weight in the equation . In summary , our data indicate that serum ucOC is an independent determinant of BMD of the hip in elderly women . The mechanism by which serum ucOC is related to bone mass is unclear and should be addressed in further studies . However , our data suggest that ucOC level may be an interesting marker in the investigation of bone status in the elderly AIM To investigate the effect of vitamin K2 ( menatetrenone ) treatment on bone mineral density ( BMD ) and a bone metabolic marker ( osteocalcin ) in postmenopausal women with osteoporosis living in Indonesia . METHODS A double-blind r and omized placebo-controlled study of 63 postmenopausal women with osteoporosis . The vitamin K2 group ( n = 33 ) received 45 mg menatetrenone and 1500 mg calcium carbonate per day and the control group ( n = 30 ) received placebo and 1500 mg calcium carbonate per day for 48 weeks . BMD of lumbal spine ( L2-L4 ) , osteocalcin ( OC ) and undercarboxylated OC were measured before , 24 and 48 weeks after initiation of the treatment . RESULTS After 48 weeks of treatment , the mean percentage change of lumbar BMD in the vitamin K2 group was significantly higher ( P < 0.05 ) than that of the control group . The undercarboxylated OC level decreased by 55.9 % in the menatetrenone group and 9.3 % in the control group compared with the baseline level . The difference between the two groups was significant ( P < 0.01 ) . The adverse events were three minor gastrointestinal cases , which subsided after temporary cessation of therapy . CONCLUSIONS Treatment with 45 mg vitamin K2 with 1500 mg calcium per day for postmenopausal women with osteoporosis for 48 weeks result ed in a significant increase in lumbar BMD and a significant decrease in undercarboxylated OC levels Abstract . The effect of the degree of carboxylation of osteocalcin ( OC ) on the properties of bone is unclear . The aim of this study was to relate serum concentrations of total OC ( tOC ) and undercarboxylated OC ( ucOC )  , measured with a two-site immunoassay , to bone mineral density ( BMD ) at the femoral neck and ultrasonic transmitted velocity ( UTV ) at the os calcis in 257 women aged 60–99 years , 22 of whom had sustained a hip fracture . There was an increase in tOC ( r = 0.19 , P= 0.003 ) and ucOC ( r = 0.20 , P= 0.002 ) with age . No significant difference in tOC or ucOC between subjects with and without hip fracture was found . Serum tOC was negatively correlated with femoral neck BMD ( r = −0.23 , P= 0.0001 ) and os calcis UTV ( r = −0.29 , P= 0.0001 ) and partial correlations indicated that these relationships were independent of age . Serum ucOC also correlated negatively with os calcis UTV ( r = −0.21 , P= 0.001 ) and less strongly with femoral neck BMD ( r = −0.13 , P= 0.052 ) . After adjusting for age , only the relationship between ucOC and os calcis UTV remained significant ( r = −0.16 , P= 0.017 ) . It is concluded that in women over 60 years , the increase in tOC reflects an age-related rise in bone remodeling , whereas the increase in ucOC reflects an age-related fall in vitamin K status . The stronger relationship of ucOC with UTV than BMD suggests that the rise in ucOC may perhaps relate more to changes in bone quality than mineral content . Higher serum ucOC concentrations in subjects with a history of hip fracture could not be confirmed Background 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 . Methods and Findings This single-center study was design ed as a 2-y r and omized , 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 r and omized 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 . Conclusions 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 . Trial registration : Clinical Trials.gov ( # NCT00150969 ) and Current Controlled Trials ( # IS RCT N61708241 There are inconsistent findings on the effects of vitamin K on bone mineral density ( BMD ) and undercarboxylated osteocalcin ( UcOC ) . The present intervention study evaluated the effect in subjects over 60-yr-old . The vitamin K group ( vitamin K + vitamin D + calcium supplement ; 15 mg of vitamin K2 [ menatetrenone ] three times daily , 400 IU of vitamin D once a day , and 315 mg of calcium twice daily ) and the control group ( vitamin D + calcium supplement ) were r and omly assigned . During the six months of treatment , seventy eight women participated ( 38 in the vitamin K group and 40 in the control group ) and 45 women completed the study . The baseline characteristics of study participants did not differ between the vitamin K and the control groups . In a per protocol analysis after 6 months , L3 bone mineral density has increased statistically significantly in the vitamin K group compared to the control group ( 0.01 ± 0.03 g/cm2 vs -0.008 ± 0.04 g/cm2 , P = 0.049 ) . UcOC concentration was also significantly decreased in the vitamin K group ( -1.6 ± 1.6 ng/dL vs -0.4 ± 1.1 ng/dL , P = 0.008 ) . In conclusion , addition of vitamin K to vitamin D and calcium supplements in the postmenopausal Korean women increase the L3 BMD and reduce the UcOC concentration Alendronate decreases the risk of femoral neck fracture by suppressing bone turnover , and also decreases the serum total osteocalcin level . A low serum carboxylated osteocalcin level or high undercarboxylated osteocalcin level could be risk factors for femoral neck fracture . Vitamin K mediates the carboxylation of osteocalcin , but the effect of alendronate therapy with or without vitamin K2 supplementation remains unknown . Forty-eight postmenopausal women were enrolled in a 1-year prospect i ve r and omized trial and assigned to alendronate monotherapy ( 5 mg/day ) ( group A , n = 26 ) or vitamin K2 ( 45 mg/day ) plus alendronate ( 5 mg/day ) ( group AK , n = 22 ) . Bone mineral density was measured by dual-energy X-ray absorptiometry at 0 and 12 months ; bone turnover parameters were measured at 0 , 3 , and 12 months . Four patients discontinued alendronate therapy , and we analyzed the remaining 44 patients ( 23 in group A and 21 in group AK ) who completed 1 year of treatment . Alendronate decreased undercarboxylated osteocalcin ; carboxylated osteocalcin was not affected . Addition of vitamin K2 enhanced the decrease of undercarboxylated osteocalcin levels and led to a greater increase of femoral neck bone mineral density .  Alendronate monotherapy does not decrease carboxylation of osteocalcin , and combination of vitamin K2 and alendronate brings further benefits on both osteocalcin carboxylation and BMD of femoral neck in postmenopausal women with osteoporosis UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p < 0.001 ) , the percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p < 0.001 ) , serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p < 0.001 ) , and PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation Risedronate decreases osteoporotic fracture incidence ; however , its effects remain unclear in elderly osteoporotic patients . Vitamin K mediates carboxylation of osteocalcin ( OC ) , and high undercarboxylated osteocalcin ( ucOC ) levels indicate vitamin K deficiency and increased osteoporotic fracture risk . We aim ed to evaluate the effects of risedronate alone or combined with vitamin K2 on serum ucOC , OC , and incidence of vertebral fractures in elderly osteoporotic patients . A total of 101 women with postmenopausal osteoporosis aged > 60 years were r and omly stratified into two groups — R group ( n = 51 ) , treated with risedronate alone ; and R + K group ( n = 50 ) , treated with risedronate and vitamin K2 .  Serum ucOC , OC and incidence of vertebral fractures were evaluated before treatment and at 6 and 12 months post-treatment . Decreased ucOC rates at 6 and 12 months were not significant between groups . However , at 6 and 12 months , decreased OC rates in the R group ( p < 0.01 and 0.05 , respectively ) were significantly higher than in the R + K group , and ucOC/OC change rates in the R group ( p < 0.05 and 0.001 , respectively ) were significantly lower than in the R + K group . Vertebral fracture incidence was not significantly different between the groups at 6 and 12 months . ucOC levels in patients with incident vertebral fractures were significantly higher than in patients without incident vertebral fractures in the R group at 6 months ( p < 0.05 ) . Although no significant difference was observed for ucOC decrease rate and incidence of vertebral fractures between treatments , ucOC levels in patients with incident vertebral fractures were significantly greater than in patients without when using risedronate alone An open-label study with blinded evaluation was performed to compare the preventive effect of a calcium supplement alone ( monotherapy ) or calcium supplement plus menatetrenone ( combined therapy ) on fracture in osteoporotic postmenopausal women aged 50 years or older . Patients were r and omized to receive monotherapy ( n = 2,193 ) or combined therapy ( n = 2,185 ) . Before r and omization , the subjects were stratified into a subgroup without vertebral fractures ( n = 2,986 ; no-fracture subgroup ) and a subgroup with at least one vertebral fracture ( n = 1,392 ; fracture subgroup ) . The incidence rate of new vertebral fractures during 36 months of treatment ( primary endpoint ) did not differ significantly between either subgroup of the two treatment groups . Although the cumulative 48-month incidence rate of new clinical fractures ( secondary endpoint ) was lower in the combined therapy group , the difference was not significant . There was a lower risk of new vertebral fractures in patients with at least five baseline fractures who received combined therapy . Also , the loss of height was less with combined therapy than with monotherapy  among patients 75 years of age or older at enrollment , those whose last menstrual period occurred 30 years or more before enrollment , and those with at least five vertebral fractures at enrollment .  Adverse events and adverse reactions were more frequent in the combined therapy group . In conclusion , menatetrenone therapy was not effective for preventing vertebral fractures in the full analysis set of this study , but the results suggested that it may prevent vertebral fractures in patients with more advanced osteoporosis Although several observational studies have demonstrated an association between vitamin K status and bone mineral density ( BMD ) in postmenopausal women , no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far . In the trial presented here we have investigated the potential complementary effect of vitamin K1 ( 1 mg/day ) and a mineral + vitamin D supplement ( 8 µg/day ) on postmenopausal bone loss . The design of our study was a r and omized , double-blind , placebo-controlled intervention study ; 181 healthy postmenopausal women between 50 and 60 years old were recruited , 155 of whom completed the study . During the 3-year treatment period , participants received a daily supplement containing either placebo , or calcium , magnesium , zinc , and vitamin D ( MD group ) , or the same formulation with additional vitamin K1 ( MDK group ) . The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years , as measured by DXA . The group receiving the supplement containing additional vitamin K1  showed reduced bone loss of the femoral neck : after 3 years the difference between the MDK and the placebo group was 1.7 % ( 95 % Cl : 0.35–3.44 ) and that between the MDK and MD group was 1.3 % ( 95 % Cl : 0.10–3.41 ) . No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine . If co-administered with minerals and vitamin D , vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck BACKGROUND There is a high incidence of hip fractures in patients with hemiplegic stroke .  Bone mineral density ( BMD ) is decreased in the hemiplegic side in patients after stroke , correlating with the degree of paralysis and of hypovitaminosis D. OBJECTIVE To evaluate the efficacy of risedronate in reducing the severity of osteoporosis and in decreasing the risk of hip fractures in elderly women following an acute stroke . METHODS This was a 12-month , r and omized , double blind , placebo-controlled trial . In a prospect i ve study of stroke patients , 187 patients received a daily dose of 2.5 mg risedronate for 12 months , and the remaining 187 received placebo .  Incidence of hip fracture was compared between the two groups at the endpoint of the study . RESULTS Seven patients sustained hip fractures on the hemiplegic side in the placebo group , and one hip fracture occurred in the risedronate group ( p = 0.0360 ; OR = 7.0 ) . BMD increased by 1.5 % and decreased by 4.9 % in the risedronate group and placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 53.4 % in the risedronate group and increased by 35.8 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density in elderly women following an acute stroke and prevents hip fractures Because of its role in osteoblastic metabolism , vitamin K has been studied with respect to bone . However , there has been limited research examining the influence of long-term vitamin K supplementation on bone mineral density ( BMD ) . Therefore , the purpose of this study was to assess the impact of 6 months of vitamin K supplementation on BMD and biomarkers of bone in pre- and perimenopausal women . Based on previous work , we hypothesized that vitamin K would improve BMD and biochemical markers of bone formation . A double-blind , placebo-controlled , r and omized trial is an effective way to study the impact of long-term supplementation . Thus , 14 pre- and perimenopausal women , 25 to 50 years of age , were r and omly assigned to an experimental group ( E ) that received 600 microg/d of vitamin K in the form of phylloquinone ( K(1 ) ) or a control group ( C ) that received identical-looking placebo tablets .  Regional BMD and percent body fat , measured by dual-energy x-ray absorptiometry , and serum osteocalcin and urinary N-telopeptide levels were all assessed at 0 , 3 , and 6 months . When BMD was measured across time , C had a significant increase ( P = .011 ) in greater trochanter BMD compared to E. The E group had a nonsignificant increase ( P = .067 ) in shaft BMD compared to the C group . There was no significant difference between E and C in serum osteocalcin concentrations over time . Urinary N-telopeptide levels increased significantly over time in E compared to C ( P = .008 ) . Six months of 600 microg/d vitamin K(1 ) supplementation did not improve regional BMD in this group of pre- and perimenopausal women The effect of vitamin K2 ( menatetrenone ) on bone turnover was investigated in postmenopausal patients with osteoporosis . A 6-month open-label , r and omized prospect i ve study was conducted in 109 patients . The control group ( n = 53 ) received calcium aspartate ( 133.8 mg of elemental calcium daily ) , while the menatetrenone group ( n = 56 ) received 45 mg of menatetrenone daily for 6 months . Serum and urinary levels of bone turnover markers were monitored . The serum level of undercarboxylated osteocalcin ( uc-OC ) was significantly lower ( P < 0.001 ) in the menatetrenone group than in the control group ( at 1 month ) , while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid ( Gla-OC ) in the menatetrenone group than the control group ( P = 0.018 ) . Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward . In addition , a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months ( P = 0.006 ) . Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen ( NTX ) excretion compared with the control group after 6 months , while there was no significant difference of urinary deoxypyridinoline excretion between the two groups . In conclusion , one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin , while urinary NTX excretion was increased after 6 months of treatment . Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention The purpose of this study is to evaluate the efficacy of vitamin K2 and 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2D3 ] in preventing bone loss induced by estrogen deficiency during therapy with the GnRH agonist ( GnRH-a ) leuprolide .  One hundred ten women ( mean age , 46.2+/-0.5 yr ) , receiving leuprolide therapy for estrogen-dependent diseases ( such as endometriosis and uterine leiomyomas ) , were r and omly allocated into four groups ( group A , leuprolide only ; group B , leuprolide with vitamin K2 ; group C , leuprolide with 1,25-(OH)2D3 ; and group D , leuprolide with vitamin K2 and 1,25-(OH)2D3 ) .  Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after 6 months of treatment . Bone formation and resorption markers were also measured before and after 6 months of treatment . There were no significant differences in the background parameters among the four groups . Bone mineral density was reduced in all four groups , but the percent changes varied slightly , at - 5.25 % ( group A ) , -3.72 % ( P < 0.05 vs. group A ) ( group B ) , -4.13 % ( group C ) , and -3.59 % ( P < 0.01 vs. group A ) ( group D ) , respectively . Bone formation markers were significantly increased in all four groups , and the percent changes of bone formation markers were highest in group B. Bone resorption markers also increased significantly in all four groups after treatment of 6 months . Group B tended to have the highest percent changes of bone resorption markers among the four groups , but these increases were not significantly different between any of the groups . Vitamin K2 , especially when combined with 1,25-(OH)2D3 , can partially prevent bone loss caused by estrogen deficiency . However , because this effect is attributable mainly to the activation of bone formation , it is not sufficient to eliminate bone loss induced by GnRH-a therapy Background . Osteoporosis is a problem after transplantation . Studies since the last year indicate that vitamin K plays a role in optimal bone health . The aim of this r and omized , double blind , prospect i ve longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 ( 180 μg menakinon-7 ) on bone mass , the first year after lung and heart transplantation . Methods . After preoperative baseline investigation of bone mass and bone-related biochemistry , 35 lung and 59 heart recipients were postoperatively r and omized to vitamin K2 or placebo and reinvestigated the following year . Results . In all recipients , 1 year after solid organ transplantation , the difference between vitamin K2 and placebo for the lumbar spine ( L2–L4 ) bone mineral density ( BMD ) was 0.028 ( SE 0.014 ) g/cm2 , P=0.055 and for L2 to L4 bone mineral content was 1.33 ( SE 1.91 ) g/cm2 ( P=0.5 ) . In lung recipients separately , the difference for bone mineral content was 3.39 g ( SE 1.65 ) , P=0.048 and in heart recipients 0.45 ( SE 0.02 ) g , P=0.9 after controlling for baseline measures . In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD , controlled for possible confounding variables ( including use of bisphosphonate ) , and the only significant predictors were organ ( B=−0.065 g/cm2 , P<0.001 ) and vitamin K2 ( B=0.034 g/cm2 , P=0.019 ) . Insufficient vitamin D status was common , and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. Conclusions . One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients . Vitamin D status should receive more attention Osteoporosis is one of the major complications of glucocorticoid therapy . Osteoporosis is usually defined by the levels of bone mineral density ( BMD ) assessed by dual energy X-ray absorptiometry ( DEXA ) ; however , glucocorticoids often induce fractures in patients with normal BMD . Thus , novel diagnostic approaches are required . In this study , we examined whether multidetector-row computed tomography ( MDCT ) is useful to assess the bone status in glucocorticoid-induced osteoporosis ( GIO ) . Because bisphosphonates have been proven to prevent bone fracture in GIO , we tried to detect the therapeutic effects of bisphosphonates in GIO by MDCT . Fifteen Japanese patients with immunoglobulin A nephropathy who had normal renal function were enrolled in this open-label r and omized trial . Patients were r and omly divided into three groups — calcitriol ( VD ) , menatetrenone ( VK ) , or bisphosphonate ( Bis ) . Bone conditions were analyzed twice by three different methods —bone turnover markers , DEXA , and MDCT — at the start and 6 months after the start of therapy . Both bone markers and DEXA could not detect significant differences among the therapeutic groups ; however , MDCT-based analyses detected the preventive effects of bisphosphonates in GIO . Compared to VD , Bis improved structural indices , such as bone volume fraction , trabecular separation , marrow star volume , and structure model index whereas the difference between VD and VK was not significant . Finite element analysis revealed that simulated fracture load in the Bis group was significantly improved . These findings suggested that MDCT-based assessment is superior to bone markers and /or DEXA in assessing the therapeutic effect of bisphosphonates on GIO Summary Vitamin K2 may preserve bone strength and reduce fracture risk . In this r and omised double-blind placebo-controlled trial among healthy postmenopausal Norwegian women , 1 year supplementation of vitamin K2 in the form of Natto capsules had no effect on bone loss rates . Introduction Japanese studies indicate that vitamin K2 ( menaquinone-7 ( MK-7 ) ) intake may preserve bone strength , but this has not been documented in Europeans . The aim of this study was to assess the effect of MK-7 on bone mineral density ( BMD ) changes in postmenopausal Norwegian women . Methods Three hundred thirty-four healthy women between 50 and 60 years , 1–5 years after menopause , were recruited to a r and omised double-blind placebo-controlled trial . The participants were r and omly assigned into two groups , one receiving 360 µg MK-7 in the form of Natto capsules and the other the same amount of identical-looking placebo capsules containing olive oil . BMD was measured at total hip , femoral neck , lumbar spine and total body at baseline and 12 months together with serum levels of bone-specific alkaline phosphatase , Crosslaps , total osteocalcin ( N-mid OC ) , carboxylated ( cOC ) and under-carboxylated osteocalcin ( ucOC ) . Results After 12 months , there were no statistical differences in bone loss rates between the groups at the total hip or any other measurement site . Serum levels of cOC increased and ucOC decreased in the treatment versus the placebo group ( p < 0.001 ) . Conclusion MK-7 taken as Natto over 1 year reduced serum levels of ucOC but did not influence bone loss rates in early menopausal women OBJECTIVE Clinical studies suggest that vitamin K2 protects against bone loss and fractures ; however , its effect on bone quality has never been investigated . We investigated the effect of vitamin MK-7 on undercarboxylated osteocalcin ( ucOC ) , and bone mass and quality . DESIGN We conducted a r and omised , placebo-controlled , double-blinded clinical trial . METHODS We investigated the effect of MK-7 375 µg for 12 months on bone mineral density ( BMD ) measured by dual X-ray absorptiometry ( DXA ) , bone microarchitecture measured by high-resolution peripheral quantitative computed tomography ( HRpQCT ) and biochemical bone turnover markers in 148 postmenopausal women with osteopenia . All of them were supplemented with calcium and vitamin D.  RESULTS ucOC decreased in the MK-7 group ( -65.6 ( 59.1 ; 71.0 ) % ) ( median ( CI ) ) compared with the placebo group ( -6.4 ( -13.5 ; 1.2 ) % ) after 3 months ( P < 0.01 ) . HRpQCT after 12 months demonstrated that trabecular number in tibia was unchanged in the MK-7-group ( -0.1 ± 1.9 % ) ( mean ± s.d . ) and decreased in the placebo group ( -3.5 ± 2.2 % ) , trabecular spacing was unchanged in the MK-7 group ( + 1.2 ± 8.0 % ) and increased in the placebo group ( + 4.5 ± 9.7 % ) , and trabecular thickness was unchanged in the MK-7 group ( + 0.2 ± 1.7 % ) and increased in the placebo group ( + 4.0 ± 2.2 % ) ( between-group changes for all : P < 0.05 ) . There were no significant differences between the groups in HRpQCT-derived parameters at the radius or in BMD at any site . CONCLUSION The changes in bone microarchitecture in the placebo group are consistent with the age-related deterioration of trabecular structure , with a loss of trabeculae and a greater mean thickness of the remaining trabeculae . This suggests that vitamin MK-7 preserves trabecular bone structure at the tibia OBJECTIVES 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 . SUBJECTS AND METHODS Seventy-two postmenopausal women were r and omized 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 . RESULTS 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 ) . CONCLUSIONS 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 The aim of the present study was to examine whether a holistic approach combining nutrition and lifestyle counselling with the consumption of milk and yoghurt enriched with calcium , vitamin D3 and phylloquinone ( vitamin K1 ) or menaquinone ( vitamin K2 ) would have any additional benefit on bone mineral density ( BMD ) indices measured at various skeletal sites using two different techniques , dual energy X-ray absorptiometry and quantitative ultrasonography ( QUS ) . A sample of 115 postmenopausal women were r and omized to three intervention groups , receiving daily via fortified milk and yoghurt and for 12 months , 800 mg calcium and 10 μg vitamin D3 ( CaD group , n = 26 ) ; 800 mg calcium , 10 μg vitamin D3 and 100 μg vitamin K1 ( CaDK1 group , n = 26 ) ; 800 mg calcium , 10 μg vitamin D3 and 100 μg vitamin K2 ( CaDK2 group , n = 24 ) ; and a control group ( CO group , n = 39 ) following their usual diet . All three intervention groups attended biweekly nutrition and lifestyle counselling sessions . Total BMD significantly increased in all three intervention groups and these changes were significantly higher compared to the CO ( P < 0.001 ) . Furthermore , the significant increases observed for L2–L4 BMD in the CaDK1 and CaDK2 groups were found to be significantly higher compared to the decrease observed in the CO ( P = 0.001 ) . No significant differences were observed for QUS parameters . The combined approach used in the current study led to favourable changes for all three intervention groups in total body BMD , while an additional benefit was observed for L2–L4 BMD in CaDK1 and CaDK2 groups . No significant differences were observed among groups in any of the QUS parameters Increased levels of circulating undercarboxylated osteocalcin ( ucOC ) , measured indirectly with the hydroxyapatite ( HAP ) binding assay , have been shown to predict hip fracture risk in a small group of elderly institutionalized women . The aim of this study was to confirm these findings in a prospect i ve cohort study ( EPIDOS prospect i ve study ) of 7598 healthy , independently living women over 75 yr of age . One hundred and four women who sustained a hip fracture during a 22-month follow-up period were age matched with 255 controls who did not fracture . Baseline sample s were collected before hip fracture for measurement of total OC and ucOC , assessed either with the HAP binding assay or directly with a new enzyme-linked immunosorbent assay ( ELISA ) . This direct ELISA uses human recombinant noncarboxylated OC as a st and ard and two monoclonal antibodies , one of which was raised against the 14 - 30 Glu synthetic peptide . We found that the intra- and interassay variations are less than 11 % , and this assay exhibits a 5 % cross-reactivity with purified human bone OC , used as a source of carboxylated OC . ucOC levels measured with this ELISA correlated well with the HAP binding assay in the population of 359 elderly women ( r = 0.82 ; P < 0.0001 ) . We estimated the risk of hip fracture for women with levels of ucOC in the highest quartile of values for the 255 controls . We found that increased levels of ucOC measured by ELISA were associated with increased hip fracture risk with an odds ratio ( OR ) of 1.9 ( 95 % confidence interval , 1.2 - 3.0 ) , and the ELISA had a greater sensitivity than the HAP assay . In contrast , total OC was not associated with hip fracture risk . After adjustment for femoral neck bone mineral density ( BMD ) and mobility status assessed by gait speed , ucOC still predicted hip fracture with an OR of 1.8 ( 1.0 - 3.0 ) . Women with both femoral neck BMD in the lowest quartile and ucOC in the highest quartile were at higher risk of hip fracture , with an OR of 5.5 ( 2.7 - 11.2 ) , than those with only low BMD or high ucOC levels . In conclusion , we have developed a new specific ELISA for serum ucOC , with low cross-reactivity with carboxylated OC and increased specificity and sensitivity over the HAP assay . Using this new ELISA , we found that ucOC , but not total OC , predicts hip fracture risk independently of femoral neck BMD in elderly women drawn from the general population . Thus , ucOC measurement could be combined with bone mass determination to improve the assessment of hip fracture risk in elderly women OBJECTIVE : Bone loss frequently appears in the natural history of liver disease . The effects of therapy for osteoporosis associated with cirrhosis of the liver are still controversial . We evaluated the effects of vitamin K2 on osteopenia in women with cirrhosis . METHODS : The subjects were 50 women with cirrhosis who had underlying hepatitis viral infections . Half of the patients were r and omly assigned to receive vitamin K2 ( menatetrenone ) .  The bone mineral density ( BMD ) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at entry and at 1-yr intervals for 2 yr . RESULTS : The percentages of change from the initial BMD at 1 and 2 yr after initiation of the study were , respectively , + 0.1 ± 2.6 % and −0.5 ± 3.5 % for the vitamin K2-treated group and −2.2 ± 2.4 % and −4.6 ± 3.9 % for the control group . The changes in BMD at each timepoint differed significantly between the control and treated groups ( p = 0.008 for 1 yr and p = 0.002 for 2 yr ) . In the vitamin K2-treated group , the ratio of osteocalcin to undercarboxylated osteocalcin in those patients with increases in BMD after 1 yr of treatment was significantly lower than that in patients showing decreases in BMD ( p = 0.017 ) . No adverse effects of vitamin K2 were noted . CONCLUSIONS : Vitamin K2 can prevent bone loss and may therefore be useful in the management of bone disease in women with cirrhosis of the liver 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 r and omized 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 Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn 's disease ( CD ) , this needs to be confirmed in double-blind , r and omised controlled trials ( RCT ) with phylloquinone ( vitamin K1 ) . By conducting two RCT , the present study aim ed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum ( % ucOC ; marker of vitamin K status ) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass . The initial dose-ranging RCT was conducted in adult patients with CD ( n 10 per group ) using 0 ( placebo ) , 1000 or 2000 μg of phylloquinone daily for 2 weeks . In the main RCT , the effect of placebo v. 1000 μg vitamin K/d ( both co-administered with Ca ( 500 mg/d ) and vitamin D3 ( 10 μg/d ) ) for 12 months ( n 43 per group ) on the biochemical indices of bone turnover ( determined by enzyme immunoassay ) and bone mass ( determined by dual-energy X-ray absorptiometry ) were investigated . At baseline , the mean % ucOC was 47 % , and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 % ; P < 0·01 ) and not suppressed further by 2000 μg of phylloquinone daily . Compared with the placebo , supplementation with 1000 μg of phylloquinone daily for 12 months had no significant effect ( P>0·1 ) on bone turnover markers or on the bone mass of the lumbar spine or femur , but modestly increased ( P < 0·05 ) the bone mass of the total radius . Despite near maximal suppression of serum % ucOC , supplementation with 1000 μg of phylloquinone daily ( with Ca and vitamin D3 ) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency CONTEXT Vitamin K has been implicated in bone health , primarily in observational studies . However , little is known about the role of phylloquinone supplementation on prevention of bone loss in men and women . OBJECTIVE The objective of this study was to determine the effect of 3-yr phylloquinone supplementation on change in bone mineral density ( BMD ) of the femoral neck bone in older men and women who were calcium and vitamin D replete . DESIGN , PARTICIPANTS , AND INTERVENTION In this 3-yr , double-blind , controlled trial , 452 men and women ( 60 - 80 yr ) were r and omized equally to receive a multivitamin that contained either 500 mug/d or no phylloquinone plus a daily calcium ( 600 mg elemental calcium ) and vitamin D ( 400 IU ) supplement . MAIN OUTCOME MEASURES Measurements of the femoral neck , spine ( L2-L4 ) , and total-body BMD , bone turnover , and vitamins K and D status were measured every 6 - 12 months . Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial . RESULTS There were no differences in changes in BMD measurements at any of the anatomical sites measured between the two groups . The group that received the phylloquinone supplement had significantly higher phylloquinone and significantly lower percent undercarboxylated osteocalcin concentrations compared with the group that did not receive phylloquinone . No other biochemical measures differed between the two groups . CONCLUSIONS Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin
target: Summary Vitamin K may affect  bone mineral density and fracture incidence .
background: Since publication of a previous systematic review the integrity of some of the previous evidence has been question ed and further trials have been published .
  Introduction This systematic review was design ed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density  and reducing fractures in adults .