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 Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures 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 Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins , notably osteocalcin . High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture . However , data are limited on the effects of dietary vitamin K. OBJECTIVE We investigated the hypothesis that high intakes of vitamin K are associated with a lower  risk of hip fracture in women . DESIGN We conducted a prospect i ve analysis within the Nurses ' Health Study cohort . Diet was assessed in 72327 women aged 38 - 63 y with a food-frequency question naire in 1984 ( baseline ) . During the subsequent 10 y of follow-up , 270 hip fractures result ing from low or moderate trauma were reported . RESULTS Women in quintiles 2 - 5 of vitamin K intake had a significantly lower age-adjusted relative risk ( RR : 0.70 ; 95 % CI : 0.53 , 0.93 ) of hip fracture than women in the lowest quintile ( < 109 microg/d ) . Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis , including calcium and vitamin D intakes , were added to the models . Risk of hip fracture was also inversely associated with lettuce consumption ( RR : 0.55 ; 95 % CI : 0.40 , 0.78 ) for one or more servings per day compared with one or fewer servings per week ) , the food that contributed the most to dietary vitamin K intakes . CONCLUSIONS Low intakes of vitamin K may increase the  risk of hip fracture in women . The data support the suggestion for a re assessment of the vitamin K requirements that are based on bone health and blood coagulation BACKGROUND Vitamin K has been suggested to have a role in bone metabolism , and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture . OBJECTIVE The objective of this study was to determine whether phylloquinone ( vitamin K(1 ) ) intake and biochemical indicators of vitamin K status are related to bone mineral content ( BMC ) and markers of bone formation and bone resorption in girls . DESIGN Vitamin K status [ plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin ( % ucOC ) ] was measured at baseline in a study of 245 healthy girls aged 3 - 16 y. Cross-linked N-telopeptide of type 1 collagen ( NTx ) breakdown , osteocalcin , and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation . BMC of the total body , lumbar spine , and hip and dietary phylloquinone intake were measured annually for 4 y. RESULTS Phylloquinone intake ( median : 45 microg/d ) was not consistently associated with bone turnover markers or BMC . Better vitamin K status ( high plasma phylloquinone and low % ucOC ) was associated with lower bone resorption and formation . Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations ( P < 0.05 ) , and % ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations ( P < 0.05 ) . Indicators of vitamin K status were not consistently associated with current BMC or gain in BMC over the 4-y study period . CONCLUSIONS Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet . R and omized phylloquinone supplementation trials are needed to further underst and the potential benefits of phylloquinone on bone acquisition in growing children 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 The effect of  maternal phylloquinone supplementation  on vitamin K in breast milk was studied to establish : ( 1 ) if phylloquinone is the source of menaquinone-4 in breast milk ; ( 2 ) the dose-effect relationship between intake and obtainable levels . Four groups of lactating mothers with a full-term healthy infant participated and took oral phylloquinone supplements of 0.0 ( n 8) , 0.8 ( n 8) , 2.0 ( n 8) , and 4.0 ( n 7 ) mg/d for 12d , starting at day 4 post-partum . Milk sample s were collected on days 4 , 8 , 16 , and 19 . Blood sample s were collected on days 4 and 16 .  Vitamin K and vitamin E concentrations , the latter for reason of comparison , were assayed . Phylloquinone and menaquinone-4 were present in all milk sample s : 5.84 ( SD 2.31 ) and 2.98 ( SD 1.51 ) nmol/l ( n 31 ) respectively , in colostrum ( day 4 sample ) . A strong correlation between the vitamers was found ( r 0.78 , P<0.001 ) . Breast-milk phylloquinone levels were raised in a dose-dependent manner : 4- , 12- , and 30-fold on day 16 for the 08 , 2.0 , and 4.0 mg group respectively . In addition , menaquinone-4 levels were higher : 2.5- ( P<0.05 ) and 7-fold ( P<0.001 ) in the 2.0 and 4.0 mg groups respectively . Plasma of supplemented subjects contained 3- , 5- , and 10-fold higher phylloquinone levels on day 16 . Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma sample s. All day 16 plasma sample s of the 4 mg supplemented group contained the vitamin . There was no correlation between the K-vitamers in plasma . Vitamin E and phylloquinone appear to differ in their distribution in breast milk , milk : plasma concentration ratios were < or = 1 and 3 - 5 for vitamin E and phylloquinone respectively . The milk : plasma concentration ratio of 
    Output:
    
agent
This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss .
In the case of the latter , there is a strong effect on incident fractures among Japanese patients
***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 Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures 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 Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins , notably osteocalcin . High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture . However , data are limited on the effects of dietary vitamin K. OBJECTIVE We investigated the hypothesis that high intakes of vitamin K are associated with a lower  risk of hip fracture in women . DESIGN We conducted a prospect i ve analysis within the Nurses ' Health Study cohort . Diet was assessed in 72327 women aged 38 - 63 y with a food-frequency question naire in 1984 ( baseline ) . During the subsequent 10 y of follow-up , 270 hip fractures result ing from low or moderate trauma were reported . RESULTS Women in quintiles 2 - 5 of vitamin K intake had a significantly lower age-adjusted relative risk ( RR : 0.70 ; 95 % CI : 0.53 , 0.93 ) of hip fracture than women in the lowest quintile ( < 109 microg/d ) . Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis , including calcium and vitamin D intakes , were added to the models . Risk of hip fracture was also inversely associated with lettuce consumption ( RR : 0.55 ; 95 % CI : 0.40 , 0.78 ) for one or more servings per day compared with one or fewer servings per week ) , the food that contributed the most to dietary vitamin K intakes . CONCLUSIONS Low intakes of vitamin K may increase the  risk of hip fracture in women . The data support the suggestion for a re assessment of the vitamin K requirements that are based on bone health and blood coagulation BACKGROUND Vitamin K has been suggested to have a role in bone metabolism , and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture . OBJECTIVE The objective of this study was to determine whether phylloquinone ( vitamin K(1 ) ) intake and biochemical indicators of vitamin K status are related to bone mineral content ( BMC ) and markers of bone formation and bone resorption in girls . DESIGN Vitamin K status [ plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin ( % ucOC ) ] was measured at baseline in a study of 245 healthy girls aged 3 - 16 y. Cross-linked N-telopeptide of type 1 collagen ( NTx ) breakdown , osteocalcin , and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation . BMC of the total body , lumbar spine , and hip and dietary phylloquinone intake were measured annually for 4 y. RESULTS Phylloquinone intake ( median : 45 microg/d ) was not consistently associated with bone turnover markers or BMC . Better vitamin K status ( high plasma phylloquinone and low % ucOC ) was associated with lower bone resorption and formation . Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations ( P < 0.05 ) , and % ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations ( P < 0.05 ) . Indicators of vitamin K status were not consistently associated with current BMC or gain in BMC over the 4-y study period . CONCLUSIONS Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet . R and omized phylloquinone supplementation trials are needed to further underst and the potential benefits of phylloquinone on bone acquisition in growing children 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 The effect of  maternal phylloquinone supplementation  on vitamin K in breast milk was studied to establish : ( 1 ) if phylloquinone is the source of menaquinone-4 in breast milk ; ( 2 ) the dose-effect relationship between intake and obtainable levels . Four groups of lactating mothers with a full-term healthy infant participated and took oral phylloquinone supplements of 0.0 ( n 8) , 0.8 ( n 8) , 2.0 ( n 8) , and 4.0 ( n 7 ) mg/d for 12d , starting at day 4 post-partum . Milk sample s were collected on days 4 , 8 , 16 , and 19 . Blood sample s were collected on days 4 and 16 .  Vitamin K and vitamin E concentrations , the latter for reason of comparison , were assayed . Phylloquinone and menaquinone-4 were present in all milk sample s : 5.84 ( SD 2.31 ) and 2.98 ( SD 1.51 ) nmol/l ( n 31 ) respectively , in colostrum ( day 4 sample ) . A strong correlation between the vitamers was found ( r 0.78 , P<0.001 ) . Breast-milk phylloquinone levels were raised in a dose-dependent manner : 4- , 12- , and 30-fold on day 16 for the 08 , 2.0 , and 4.0 mg group respectively . In addition , menaquinone-4 levels were higher : 2.5- ( P<0.05 ) and 7-fold ( P<0.001 ) in the 2.0 and 4.0 mg groups respectively . Plasma of supplemented subjects contained 3- , 5- , and 10-fold higher phylloquinone levels on day 16 . Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma sample s. All day 16 plasma sample s of the 4 mg supplemented group contained the vitamin . There was no correlation between the K-vitamers in plasma . Vitamin E and phylloquinone appear to differ in their distribution in breast milk , milk : plasma concentration ratios were < or = 1 and 3 - 5 for vitamin E and phylloquinone respectively . The milk : plasma concentration ratio of 
    Output:
    