***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 Concerns regarding the risk of estrogen replacement have result ed in a significant increase in the use of soy products by menopausal women who , despite the lack of evidence of the efficacy of such products , seek alternatives to menopausal hormone therapy . Our goal was to determine the efficacy of soy isoflavone tablets in preventing bone loss and menopausal symptoms . METHODS The study design was a single-center , r and omized , placebo-controlled , double-blind clinical trial conducted from July 1 , 2004 , through March 31 , 2009 . Women aged 45 to 60 years within 5 years of menopause and with a bone mineral density T score of -2.0 or higher in the lumbar spine or total hip were r and omly assigned , in equal proportions , to receive daily soy isoflavone tablets , 200 mg , or placebo . The primary outcome was changes in bone mineral density in the lumbar spine , total hip , and femoral neck at the 2-year follow-up . Secondary outcomes included changes in menopausal symptoms , vaginal cytologic characteristics , N -telopeptide of type I bone collagen , lipids , and thyroid function . RESULTS After 2 years , no significant differences were found between the participants receiving soy tablets ( n = 122 ) and those receiving placebo ( n = 126 ) regarding changes in bone mineral density in the spine ( -2.0 % and -2.3 % , respectively ) , the total hip ( -1.2 % and -1.4 % , respectively ) , or the femoral neck ( -2.2 % and -2.1 % , respectively ) . A significantly larger proportion of participants in the soy group experienced hot flashes and constipation compared with the control group . No significant differences were found between groups in other outcomes . CONCLUSIONS In this population , the daily administration of tablets containing 200 mg of soy isoflavones for 2 years did not prevent bone loss or menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00076050 Objective : Equol is more biologically active than its precursor daidzein , which is the principal isoflavone found in soybean . There are interindividual differences in the ability to produce equol ; these may lead to differences in the effects of isoflavone intervention on human health . This study aim ed to investigate whether the effects of soy isoflavones on bone and fat mass are related to an individual 's equol status . Design : We performed a 1-year double-blind , r and omized trial to compare the effects of isoflavone ( 75 mg of isoflavone conjugates/day ) with those of placebo on bone mineral density , fat mass , and serum isoflavone concentrations in early postmenopausal Japanese women who were classified based on their equol-producer phenotype . Results : After 1 year , the isoflavone intervention significantly increased the serum equol concentration in the equol producers but not in the nonproducers . In the isoflavone group , the annualized changes in the bone mineral density of the total hip and intertrochanteric regions were −0.46 % and −0.04 % , respectively , in the equol producers and −2.28 % and −2.61 % , respectively , in the nonproducers ; these values were significantly different ( P < 0.05 for both the regions ) . Significant differences were observed between the equol producers and nonproducers in the isoflavone group with regard to the annualized changes in the fat mass . No significant difference in the annualized changes in bone mineral density and fat mass was observed between the equol producers and nonproducers in the placebo group . Conclusions : Our data suggest that the preventive effects of isoflavones on bone loss and fat accumulation in early postmenopausal women depend on an individual 's equol-producing capacity BACKGROUND No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover  in perimenopausal women . OBJECTIVE Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones ( 80.4 mg/d ) in attenuating bone loss during the menopausal transition . DESIGN Perimenopausal subjects were r and omly assigned , double blind , to treatment : isoflavone-rich soy ( SPI+ ; n = 24 ) , isoflavone-poor soy ( SPI- ; n = 24 ) , or whey ( control ; n = 21 ) protein . At baseline and posttreatment , lumbar spine bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured by using dual-energy X-ray absorptiometry . At baseline , midtreatment , and posttreatment , urinary N:-telopeptides and serum bone-specific alkaline phosphatase ( BAP ) were measured . RESULTS The percentage change in lumbar spine BMD and BMC , respectively , did not differ from zero in the SPI+ or SPI- groups , but loss occurred in the control group ( -1.28 % , P : = 0.0041 ; -1.73 % , P : = 0.0037 ) . By regression analysis , SPI+ treatment had a positive effect on change in BMD ( 5.6 % ; P : = 0.023 ) and BMC ( 10.1 % ; P : = 0.0032 ) . Baseline BMD and BMC ( P : < or = 0.0001 ) negatively affected the percentage change in their respective models ; baseline body weight ( P : = 0.0036 ) and bone-free lean weight ( P : = 0.016 ) contributed positively to percentage change in BMD and BMC , respectively . Serum BAP posttreatment was negatively related to percentage change in BMD ( P : = 0.0016 ) and BMC ( P : = 0.019 ) . Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones , not soy protein , exerted the effect . CONCLUSION Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women We assessed the dose-dependent effects of daily soybean isoflavone ( IF ) consumption in reversing bone loss in adult ovariectomized rats . On d 0 , female Wistar rats ( 7 mo old ; n = 55 ) were either sham-operated ( SH ; n = 14 ) or ovariectomized ( n = 41 ) . On d 80 , intermediate rats ( SH : n = 5 ; ovariectomized : n = 5 ) were killed to confirm the ovariectomy-induced bone loss . The remaining ovariectomized rats were r and omly assigned to one of four groups of nine rats each and fed soybean IF ( mixed with a soy protein-free semipurified diet ) at 0 ( OVX ) , 20 ( IF20 ) , 40 ( IF40 ) or 80 ( IF80 ) mg/(kg body . d ) for 84 d. Simultaneously , SH rats were fed the semipurified diet without any additional compound and killed on d 164 , as were the other rats . As expected , both bone mineral density in the total femur and in its diaphyseal and metaphyseal subregions and cancellous bone area/measured surface in the distal femur metaphysis were lower in OVX than in SH rats ( P : < 0.05 ) . OVX rats had higher plasma osteocalcin concentration and urinary deoxypyridinoline excretion than SH rats ( P : < 0.05 ) . On d 164 , osteocalcin and deoxypyridinoline concentrations were lower in IF40 or IF80 rats than in OVX rats ( P : < 0.05 ) . Nevertheless , neither bone mineral density nor cancellous bone area was greater in IF-fed rats than in OVX rats . Therefore , in adult ovariectomized rats , daily soybean IF consumption decreased bone turnover but did not reverse established osteopenia BACKGROUND Soy consumption is associated with a lower incidence of hip fracture in Asian than in Western women , an effect often attributed to estrogen-like compounds ( isoflavones ) in soy . It is not known whether premenopausal soy exposure initiated in adulthood can increase bone mass and thereby reduce fracture risk . OBJECTIVE We aim ed to determine whether a high-isoflavone soy diet influences bone mass in soy-naïve , premenopausal cynomolgus monkeys ( Macaca fascicularis ) . DESIGN Ninety-four skeletally mature females were r and omly assigned to consume diets whose protein content came from either high-isoflavone soy or casein and lactalbumin . Animals were socially housed . Bone mass and circulating isoflavone concentrations were measured at baseline and 19 and 31 mo after the start of treatment ; bone biomarkers were measured at baseline and 31 mo . RESULTS There were no significant differences at any timepoint in whole-body bone mineral content between casein-fed ( 112.5 + /- 2.1 , 119.2 + /- 1.9 , and 120.7 + /- 2.1 g ) and soy-fed ( 117.2 + /- 2.1 , 122.4 + /- 2.0 , and 125.4 + /- 2.3 g ; P=0.12 ) monkeys . Similar results were seen for spinal bone mineral density ( casein-fed : 0.46 + /- 0.01 , 0.50 + /- 0.01 , and 0.52 + /- 0.01 g/cm(2 ) ; soy-fed : 0.47 + /- 0.01 , 0.51 + /- 0.01 , and 0.52 + /- 0.01 g/cm(2 ) ; P=0.30 ) and bone biomarker measurements -bone-specific alkaline phosphatase ( soy-fed : 82.3 + /- 4.1 and 63.2 + /- 3.4 ng/mL ; casein-fed : 94.1 + /- 4.5 and 61.7 + /- 4.3 ng/mL ; P=0.22 ) and C-terminal crosslink of type 1 collagen ( soy-fed : 0.944 + /- 0.06 and 0.89 + /- 0.08 nmol/L ; casein-fed : 0.97 + /- 0.07 and 0.78 + /- 0.06 nmol/L ; P=0.20 ) . CONCLUSION A soy diet high in isoflavones does not significantly affect bone characteristics in initially soy-naïve premenopausal monkeys BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P < 0.05 ) . CONCLUSIONS Because soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447 Our previous study on bone health among premenopausal women showed that bone mass consolidation is attained by the early 30s , and small loss of spinal bone mineral density ( SBMD ) occurs soon after peak bone mass attainment . Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health . However , data are lacking , particularly in Asian women . This study aims to investigate the effect of soy isoflavones intake on the maintenance of peak bone mass in a cohort of 132 women aged 30 - 40 years who were followed up for 3 years . Baseline measurements of SBMD ( L2-L4 ) were obtained using dual-energy X-ray densitometry , and dietary intake of soy foods and other key nutrients , including dietary calcium , were obtained through a quantitative food frequency method . Information on body measurements ; physical activity ( 
    Output:
    
RESULTS In vitro and animal studies show a positive effect of isoflavones on bone which has not been clearly confirmed by long-term human trials .
Equol producers seem to present a more positive response to isoflavone intervention .
Isoflavone rich diets could help maintain peak bone mass in premenopausal women .
The effect of isoflavones in perimenopausal women is insufficiently studied but it seems to attenuate bone loss in the menopausal transition .
In postmenopause , isoflavones may present a modest benefit but its clinical relevance in preventing osteoporotic fractures remains to be determined .
The present review suggests that isoflavone increase bone mineral density and decrease the bone turnover resorption markers .
The effect of soy isoflavones on BMD is mediated by equol production , reproductive status , supplement type , isoflavone dose and intervention duration