title: Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. Vitamin K intake and hip fractures in women: a prospective study. Vitamin K, bone turnover, and bone mass in girls. Factors Affecting Bone Loss in Female Endurance Athletes Menaquinone-4 in breast milk is derived from dietary phylloquinone. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. 
  Vitamin K1 Supplementation Retards Bone Loss in Postmenopausal Women Between 50 and 60 Years of Age
   Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis Calcium plus vitamin D supplementation and the risk of fractures. Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. 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. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate
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 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 menaquinone-4 was > 10 . In conclusion , dietary phylloquinone is a source of menaquinone-4 in breast milk . Phylloquinone supplementation to lactating mothers may be of benefit to the newborn infant , since both phylloquinone and menaquinone-4 are raised by supplementation BACKGROUND Previous studies have shown that alendronate can increase bone mineral density ( BMD ) and prevent radiographically defined ( morphometric ) vertebral fractures . The Fracture Intervention Trial aim ed to investigate the effect of alendronate on the risk of morphometric as well as clinical ly evident fractures in postmenopausal women with low bone mass . METHODS Women aged 55 - 81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture . Results for women with at least one vertebral fracture at baseline are reported here . 2027 women were r and omly assigned placebo ( 1005 ) or alendronate ( 1022 ) and followed up for 36 months . The dose of alendronate ( initially 5 mg daily ) was increased ( to 10 mg daily ) at 24 months , with maintenance of the double blind . Lateral spine radiography was done at baseline and at 24 and 36 months . New vertebral fractures , the primary endpoint , were defined by morphometry as a decrease of 20 % ( and at least 4 mm ) in at least one vertebral height between the baseline and latest follow-up radiograph . Non-spine clinical fractures were confirmed by radiographic reports . New symptomatic vertebral fractures were based on self-report and confirmed by radiography . FINDINGS Follow-up radiographs were obtained for 1946 women ( 98 % of surviving participants ) . 78 ( 8.0 % ) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 ( 15.0 % ) in the placebo group ( relative risk 0.53 [ 95 % Cl 0.41 - 0.68 ] ) . For clinical ly apparent vertebral fractures , the corresponding numbers were 23 ( 2.3 % ) alendronate and 50 ( 5.0 % ) placebo ( relative hazard 0.45 [ 0.27 - 0.72 ] ) . The risk of any clinical fracture , the main secondary endpoint , was lower in the alendronate than in the placebo group ( 139 [ 13.6 % ] vs 183 [ 18.2 % ] ; relative hazard 0.72 [ 0.58 - 0.90 ] ) . The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 ( 0.23 - 0.99 ) and 0.52 ( 0.31 - 0.87 ) . There was no significant difference between the groups in numbers of adverse experiences , including upper-gastrointestinal disorders . INTERPRETATION We conclude that among women with low bone mass and existing vertebral  fractures , alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures , as well as other clinical fractures 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 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 Significant reduction in bone mineral density ( BMD ) occurs in patients with Parkinson 's disease ( PD ) , correlating with immobilization and with vitamin D deficiency , and increasing the risk of hip fracture , especially in elderly women . As a biological indicator of compromised vitamin K status , an increased serum concentration of undercarboxylated osteocalcin ( Oc ) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women . We evaluated treatment with vitamin K(2 ) ( menatetrenone ; MK-4 ) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD . In a r and om and prospect i ve study of PD patients , 60 received 45 mg of MK-4 daily for 12 months , and the remaining 60 ( untreated group ) did not . At baseline , patients of both groups showed vitamin D and K(1 ) deficiencies , high serum levels of ionized calcium , and glutaminic residue ( Glu ) Oc , and low levels of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25-(OH)(2)D ] , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion . BMD in the second metacarpals increased by 0.9 % in the treated group and decreased by 4.3 % in the untreated group ( p < 0.0001 ) .  Vitamin K(2 ) level increased by 259.8 % in the treated group . Correspondingly , significant decreases in Glu Oc and calcium were observed in the treated group , in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures ( eight at the hip and two at other sites ) in the untreated group , and one hip fracture occurred among treated patients ( p = 0.0082 ; odds ratio = 11.5 ) . The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration , and it can also decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1,25-(OH)(2)D concentration Abstract The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density ( BMD ) of the lumbar spine was examined in postmenopausal women with osteoporosis . Ninety-two osteoporotic women who were more than 5 years after menopause , aged 55–81 years , were r and omly divided into four administration groups : vitamin D3 ( 1α hydroxyvitamin D3 , 0.75 μg/day ) ( D group ; n = 29 ) , vitamin K2 ( menatetrenone , 45 mg/day ) ( K group ; n = 22 ) , vitamin D3 plus vitamin K2 ( DK group , n = 21 ) , and calcium ( calcium lactate , 2 g/day ) ( C group ; n = 20 ) . BMD of the lumbar spine ( L2–L4 ) was measured by dual energy X-ray absorptiometry at 0 , 1 , and 2 years after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the four groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P < 0.001 ) . Two-way ANOVA with repeated measurements showed a significant increase in BMD in the D and K groups compared with that in the C group ( P < 0.05 and P < 0.001 , respectively ) , and a significant increase in BMD in the DK group compared with that in the C , D , and K groups ( P < 0.0001 , P < 0.05 and P < 0.01 , respectively ) . These findings indicate that combined administration of vitamin D3 and vitamin K2 , compared with calcium administration , appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) 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 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 BACKGROUND Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia , but their effects on fractures are unknown . METHODS We r and omly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone ( 1 - 34 ) or placebo  , administered subcutaneously by the women daily . We obtained vertebral radiographs at base line and at the end of the study ( median duration of observation , 21 months ) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry . RESULTS New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent , respectively , of the women in the 20-microg and 40-microg parathyroid hormone groups ; the respective relative risks of fracture in the 20-microg and 40-microg groups , as compared with the placebo group , were 0.35 and 0.31 ( 95 percent confidence intervals , 0.22 to 0.55 and 0.19 to 0.50 ) . New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group ( relative risk , 0.47 and 0.46 , respectively [ 95 percent confidence intervals , 0.25 to 0.88 and 0.25 to 0.861 ) . As compared with placebo , the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck ; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points . Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo . Parathyroid hormone had only minor side effects ( occasional nausea and headache ) . CONCLUSIONS Treatment of postmenopausal osteoporosis with parathyroid hormone ( 1 - 34 ) decreases the risk of vertebral and nonvertebral fractures ; increases vertebral , femoral , and total-body bone mineral density ; and is well tolerated . The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects 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 BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo .  Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people Significant reduction in bone mineral density ( BMD ) occurs in stroke patients on the hemiplegic and contralateral sides , correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition , and increasing the risk of hip fracture . We evaluated the efficacy of vitamin K2 ( menatetrenone : menaquinone-4 ; MK-4 ) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients . In a r and om and prospect i ve study , of 108 hemiplegic patients following stroke , 54 received 45 mg menatetrenone daily ( MK-4 group , n = 54 ) for 12 months , and the remaining 54 ( untreatment group ) did not . Nine patients excluded from the study . The BMD in the second metacarpals and serum indices of bone metabolism were determined . BMD on the hemiplegic side increased by 4.3 % in the MK-4 group and decreased by 4.7 % in the untreated group ( p < 0.0001 ) , while BMD on the intact side decreased by 0.9 % in the MK-4 group and by 2.7 % in the untreated group ( p < 0.0001 ) . At baseline , patients of both groups showed vitamin D and K1 deficiencies , high serum levels of ionized calcium , pyridinoline cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) , and low levels of parathyroid hormones ( PTH ) and bone Gla proteins ( BGP ) , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) and compensatory PTH secretion . Both vitamins K1 and K2 increased by 97.6 % and 666.9 % , respectively , in the MK-4 group . Correspondingly , a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group , in association with a simultaneous increase in both PTH and 1 , 25-[OH]2D . One patient in the untreated group suffered from a hip fracture , compared with none in the MK-4 group . The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration , and it also can decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1 , 25-[OH]2D concentration Abstract . The purpose of the present study was to compare the effects of etidronate and menatetrenone on bone mineral density ( BMD ) and the incidence of vertebral fractures in postmenopausal women with osteoporosis . Seventy-two osteoporotic women , more than 5 years after menopause , 53–78 years of age , were r and omly divided into three administration groups : E group ; intermittent cyclical etidronate ( 200 mg/day , 14 days per 3 months ; n = 25 ) ; M group ; menatetrenone ( 45 mg/day , daily ; n = 23 ) ; and C group ( control ) ; calcium lactate ( 2 g/day , daily ; n = 24 ) . Forearm BMD was measured by dual-energy X-ray absorptiometry at 0 , 6 , 12 , 18 , and 24 months after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the three groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P < 0.0001 ) . Two-way ANOVA with repeated measurements showed a significant increase in BMD in the M group compared with that in the C group ( P < 0.0001 ) , and a significant increase in BMD in the E group compared with that in the C and M groups ( P < 0.0001 and P < 0.01 , respectively ) . The indices of new vertebral fractures/1000 patient-years in the E and M groups were significantly higher than that in the C group ( χ2 = 47.7 ; P < 0.0001 and χ2 = 42.4 ; P < 0.0001 , respectively ) , and did not differ significantly between the E and M groups . The present preliminary study provides evidence to suggest that , despite the lower increase in BMD produced by me-natetrenone , this agent , as well as etidronate , may have the potential to reduce osteoporotic vertebral fractures in postmenopausal women with osteoporosis
target: 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: 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 .