human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
Summary Vitamin K may affect  bone mineral density and fracture incidence .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    