Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. Vitamin K, bone turnover, and bone mass in girls. Vitamin K intake and hip fractures in women: a prospective study. Effect of vitamin K supplementation on bone loss in elderly men and women. Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. Vitamin K, circulating cytokines, and bone mineral density in older men and women. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. Increased Incidence of Fractures in Middle-aged and Elderly Men with Low Intakes of Phosphorus and Zinc 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 Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women’s Health Study Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial
It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis . However , there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density ( BMD ) or fractures in Japan . The objectives were to evaluate the association between plasma phylloquinone ( K1 ) or menaquinone ( MK-4 and MK-7 ) concentration and BMD or fracture in Japanese women prospect ively . A total of 379 healthy women aged 30–88 years ( mean age , 63.0 years ) were consecutively enrolled .  Plasma K1 , MK-4 , MK-7 , and serum undercarboxylated osteocalcin ( ucOC ) concentrations , BMD , and incidence of vertebral fractures were evaluated . In stepwise multiple linear regression analyses , L2–4 BMD and a bone turnover marker , log K1 , concentrations were independently correlated with vertebral fracture incidence . When subjects were divided into low and high K1 groups by plasma K1 concentration , the incidence of vertebral fracture in the low K1 group ( 14.4 % ) was significantly higher than that in the high K1 group ( 4.2 % ) , and its age-adjusted RR was 3.58 ( 95 % CI , 3.26–3.93 ) . L2–4 BMD was not different between the two groups . These results suggest that subjects with  vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD 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 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 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 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 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 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 BACKGROUND Vitamin K modulates cytokines involved in bone turnover , including interleukin-6 ( IL-6 ) and osteoprotegerin in vitro . OBJECTIVE The objective of this study was to assess 1 ) associations between measures of vitamin K status [ plasma phylloquinone and serum percentage of undercarboxylated osteocalcin ( % ucOC ) ] and IL-6 , osteoprotegerin , and C-reactive protein ( CRP ) concentrations and 2 ) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations . DESIGN Concentrations of IL-6 , osteoprotegerin , and CRP and bone mineral density ( BMD ) were measured at baseline and after 3 y of follow-up in 379 healthy men and women ( 60 - 81 y ; 58.5 % women ) participating in a r and omized trial that studied the effect of vitamin K supplementation on bone loss . RESULTS Cross-sectionally , plasma phylloquinone was inversely associated with IL-6 and CRP , whereas serum % ucOC was inversely associated with IL-6 . Osteoprotegerin was associated positively with plasma phylloquinone and inversely with % ucOC . No differences were observed in the 3-y change in IL-6 , osteoprotegerin , and CRP concentrations between participants who received phylloquinone supplementation and those who did not . Overall , no association was observed between the 3-y changes in circulating cytokines and BMD . CONCLUSIONS Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover , but vitamin K supplementation did not confer a decrease in cytokine concentrations . The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations . This trial was registered with www . clinical trials.gov as NCT00183001 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 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 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 Abstract : The aim of the study was to determine dietary risk factors for fracture in men aged 46–68 years . Six thous and five hundred and seventy-six men were r and omly invited using the Municipal Registry to a diet and health study . The diet was assessed using a combined 7-day menu book for hot meals , beverages and dietary supplements and a quantitative food frequency question naire for other foods . The fracture incidence was 103/10000 person-years during a mean follow-up of 2.4 years . Zinc and phosphorus intake were associated with fracture risk and showed a threshold effect . The zinc intake in the lowest decentile , 10 mg daily , was associated with almost a doubled risk of fracture compared with the fourth and fifth quintiles ( RR = 0.47 ; 95 % confidence interval , 27–82 ) of zinc intake adjusted for energy , previous fractures , lifestyle factors and co-morbidity . Energy-adjusted phosporus intake in the lowest quintile , mean level 1357 mg , was associated with an increased fracture risk compared with subjects in the second quintile . Smoking , martial status and physical activity were independently associated with fracture risk . Calcium , retinol and vitamin D showed no associations with fracture risk . We conclude that inadequate intakes of zinc and phosporus are important risk factors for fracture 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 BACKGROUND Anticarcinogenic activities of vitamin K have been observed in various cancer cell lines , including prostate cancer cells . Epidemiologic studies linking dietary intake of vitamin K with the development of prostate cancer have not yet been conducted . OBJECTIVE We evaluated the association between dietary intake of phylloquinone ( vitamin K1 ) and menaquinones ( vitamin K2 ) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospect i ve Investigation into Cancer and Nutrition . DESIGN At baseline , habitual dietary intake was assessed by means of a food-frequency question naire .  Dietary intake of phylloquinone and menaquinones ( MK-4 - 14 ) was estimated by using previously published HPLC-based food-content data . Multivariate-adjusted relative risks of total and advanced prostate cancer in relation to intakes of phylloquinone and menaquinones were calculated in 11 319 men by means of Cox proportional hazards regression . RESULTS During a mean follow-up time of 8.6 y , 268 incident cases of prostate cancer , including 113 advanced cases , were identified . We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [ multivariate relative risk ( highest compared with lowest quartile ) : 0.65 ; 95 % CI : 0.39 , 1.06 ] . The association was stronger for advanced prostate cancer ( 0.37 ; 0.16 , 0.88 ; P for trend = 0.03 ) . Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat . Phylloquinone intake was unrelated to prostate cancer incidence ( 1.02 ; 0.70 , 1.48 ) . CONCLUSIONS Our results suggest an inverse association between the intake of menaquinones , but not that of phylloquinone , and prostate cancer . Further studies of dietary vitamin K and prostate cancer are warranted 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 Excessive intake of vitamin A is postulated to have a detrimental effect on bone by inducing osteoporosis . This may lead to an increased risk of fracture , particularly in persons who are already at risk of osteoporosis . However , few studies have specifically examined the association of vitamin A intake through diet and supplement use , with fractures in a cohort of older , community-dwelling women . We prospect ively followed a cohort of 34,703 postmenopausal women from the Iowa Women ’s Health Study to determine if high levels of vitamin A and retinol intake through food and supplement use were associated with an increased risk of hip or all fractures . A semiquantitative food frequency question naire was used to obtain the participants ’ baseline vitamin A and retinol intake . Participants were followed for a mean duration of 9.5 years for incident self-reported hip and nonhip fractures . After multivariate adjustment , it was revealed that users of supplements containing vitamin A had a 1.18-fold increased risk of incident hip fracture ( n=525 ) compared with nonusers ( 95 % CI , 0.99 to 1.41 ) , but there was no evidence of an increased risk of all fractures ( n=6,502 ) among supplement users . There was also no evidence of a dose-response relationship in hip fracture risk with increasing amounts of vitamin A or retinol from supplements . Furthermore , our results showed no association between vitamin A or retinol intake from food and supplements , or food only , and the risk of hip or all fractures . In conclusion , we found little evidence of an increased risk of hip or all fractures with higher intakes of vitamin A or retinol among a cohort of older , postmenopausal women Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33
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
BACKGROUND Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture .
OBJECTIVE To assess whether oral vitamin K ( phytonadione and menaquinone ) supplementation can reduce  bone loss  and prevent fractures .