***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: BACKGROUND Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass . OBJECTIVE This study cross-sectionally examined whether higher dietary intakes , total intakes , and serum concentrations of antioxidants may be associated with higher  bone mineral density ( BMD ) . DESIGN Total hip ( and subregions ) , spine , and total-body BMDs were measured in 11,068 women aged 50 - 79 y enrolled in the Women 's Health Initiative Observational Study and Clinical Trial at 3 clinics .  Antioxidant intakes from diet ( vitamin A , retinol , beta-carotene , vitamin C , vitamin E , and selenium ) were estimated by using a self-reported food-frequency question naire . Antioxidants from supplements were estimated with an interviewer-administered question naire . A r and om subset ( n = 379 ) had serum concentrations of retinol , carotenoids , and tocopherols measured . RESULTS After adjustment for important BMD-related covariates , increasing intakes of antioxidants were not independently associated with BMD . A significant interaction effect was observed between intake of total vitamin C  ( lower three-fourths compared with highest one-fourth ) and use of  hormone therapy ( HT ) ( P < 0.01 ) . The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body ( P < 0.045 ) , spine ( P = 0.03 ) , and total-hip BMDs ( P = 0.029 ) . CONCLUSIONS Our results do not support independent associations between dietary intake , total intake , or serum concentrations of antioxidants and BMD in women participating in the Women 's Health Initiative . The extent to which HT use may interact with  vitamin C intake and BMD warrants further exploration BACKGROUND Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants .  Although a vitamin E-vitamin K interaction was proposed to underlie this effect , it has not been systematic ally investigated in adults with normal baseline coagulation status . OBJECTIVE The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants . DESIGN  Vitamin K status , which was assessed with the use of plasma phylloquinone concentrations , the degree of under-gamma-carboxylation of prothrombin ( proteins induced by vitamin K absence-factor II , PIVKA-II ) , and the percentage of undercarboxylated osteocalcin ( ucOC ) , was determined in 38 men and women with rheumatoid arthritis ( study A ) and in 32 healthy men ( study B ) participating in 2 independent , 12-wk r and omized clinical trials of vitamin E supplementation ( 1000 IU/d ) . RESULTS Mean ( + /- SD ) PIVKA-II increased from 1.7 + /- 1.7 to 11.9 + /- 16.1 ng/mL ( P < 0.001 ) in study A and from 1.8 + /- 0.6 to 5.3 + /- 3.9 ng/mL ( P < 0.001 ) in study B in response to 12 wk of vitamin E supplementation . An increase in PIVKA-II is indicative of poor vitamin K status . In contrast , the other measures of vitamin K status ( ie , plasma phylloquinone concentration and percentage of ucOC ) did not change significantly in response to the supplementation . CONCLUSIONS High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy . The clinical significance of these changes warrants further investigation , but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function , a condition associated with increased free radicals . Vitamin E , a lipid-soluble vitamin , is a potent antioxidant which can scavenge free radicals in the body . In this study , we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats . Three-month-old female Wistar rats were r and omly divided into ovariectomized control , sham-operated , and ovariectomized rats treated with either alpha-tocopherol or tocotrienol . Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis . Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume ( BV/TV ) and trabecular number ( Tb . N ) and an increase in trabecular separation ( Tb . S ) . The increase in osteoclast surface ( Oc . S ) and osteoblast surface ( Ob . S ) in ovariectomy indicates an increase in bone turnover rate . Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb . N as well as the increase in Tb . S , while reducing the Oc . S and increasing the Ob . S. In conclusion , the two forms of vitamin E were able to prevent bone loss due to ovariectomy . Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model Vitamin E absorption requires the presence of fat ; however , limited information exists on the influence of fat quantity on optimal absorption . In the present study we compared the absorption of stable-isotope-labelled vitamin E following meals of varying fat content and source . In a r and omised four-way cross-over study , eight healthy individuals consumed a capsule containing 150 mg (2)H-labelled RRR-alpha-tocopheryl acetate with a test meal of toast with butter ( 17.5 g fat ) , cereal with full-fat milk ( 17.5 g fat ) , cereal with semi-skimmed milk ( 2.7 g fat ) and water ( 0 g fat ) . Blood was taken at 0 , 0.5 , 1 , 1.5 , 2 , 3 , 6 and 9 h following ingestion , chylomicrons were isolated , and (2)H-labelled alpha-tocopherol was analysed in the chylomicron and plasma sample s. There was a significant time ( P<0.001 ) and treatment effect ( P<0.001 ) in (2)H-labelled alpha-tocopherol concentration in both chylomicrons and plasma between the test meals . (2)H-labelled alpha-tocopherol concentration was significantly greater with the higher-fat toast and butter meal compared with the low-fat cereal meal or water ( P<0.001 ) , and a trend towards greater concentration compared with the high-fat cereal meal ( P=0.065 ) . There was significantly greater (2)H-labelled alpha-tocopherol concentration with the high-fat cereal meal compared with the low-fat cereal meal ( P<0.05 ) . The (2)H-labelled alpha-tocopherol concentration following either the low-fat cereal meal or water was low . These results demonstrate that both the amount of fat and the food matrix influence  vitamin E absorption . These factors should be considered by consumers and for future vitamin E intervention studies 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 Smoking increases the concentrations of free radicals , which have been suggested to be involved in bone resorption . We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking . We prospect ively studied 66,651 women who were 40 - 76 years of age . Forty-four of the cohort members who sustained a first hip fracture within 2 - 64 months of follow-up ( n = 247 ) and 93 out of 873 age-matched controls were current smokers . Information on diet was obtained by a vali date d food-frequency question naire . The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories ( low/high ) , where median intakes among the controls were used as cut-off points . After adjustment for major osteoporosis risk factors , the odds ratio ( OR ) for hip fracture among current smokers with a low intake of vitamin E was 3.0 ( 95 % confidence interval 1.6 - 5.4 ) and of vitamin C 3.0 ( 1.6 - 5.6 ) . In contrast , the OR decreased to 1.1 ( 0.5 - 2.4 ) and 1.4 ( 0.7 - 3.0 ) with high intakes of vitamin E and C , respectively . This effect was not seen for beta-carotene , selenium , calcium , or vitamin B6 . In current smokers with a low intake of both vitamins E and C , the OR increased to 4.9 ( 2.2 - 11.0 ) . The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers . Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking , and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers , whereas a more adequate intake seems to be protective Recent studies have shown that estrogen ( E ) likely plays a dominant role in inhibiting bone resorption in normal elderly men . Because both E and T inhibit osteoclast development and activity , stimulate osteoclast apoptosis , and inhibit osteoblast production of IL-6 , it is unclear why T is less potent than E in inhibiting bone resorption in vivo . Osteoprotegerin ( OPG ) binds to and inactivates RANKL , the final mediator of osteoclastogenesis . In vitro , OPG production is stimulated by E , and preliminary data suggest that T has the opposite effect . Thus , we analyzed serum for OPG levels from a study in which 59 elderly men ( mean age , 68 yr ) were made acutely hypogonadal using a GnRH agonist  and were also placed on an aromatase inhibitor to block conversion of and rogens to estrogens . They were studied first under conditions of physiologic E and T replacement , and then r and omized to no replacement , replacement with E alone , T alone , or both E and T. E alone result ed in an 18.6 + /- 7.9 % ( mean + /- SEM ) increase in serum OPG levels ( P < 0.05 ) , whereas T alone tended to decrease OPG levels ( by 10.0 + /- 8.5 % ; P < 0.05 compared with E alone ) . Using a two-factor ANOVA model , there was a highly significant T effect ( P = 0.006 ) on decreasing serum OPG levels . Serum TNF-alpha , IL-6 , and IL-6 soluble receptor levels increased significantly in the men who had both E and T withdrawn , and the increases in TNF-alpha and IL-6sR were absent in the men treated with either E or T. However , due to the variability in these cytokine measurements , the ANOVA models were not significant for E or T effects . Taken together , these data suggest that in vivo , T decreases OPG levels , whereas E tends to have the opposite effect . These differential effects of E vs. T on OPG production may explain , at least in part , why T has weaker effects than E on inhibiting bone resorption in vivo in humans 
    Output:
    
Our review found that αTF exerted beneficial , harmful or null effects on bone formation cells .
Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis .
However , high-dose αTF was possibly detrimental to  bone in normal animals .
Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone , the blocking of the entry of other Vitamin E isomers beneficial to bone , and the role of αTF as a prooxidant .
However , these adverse effects have not been shown in human studies .
In conclusion , αTF may have a dual role in bone health , whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone