Soy isoflavones attenuate bone loss in early postmenopausal Chinese women Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial Soy Isoflavones: No Effects on Bone Mineral Content and Bone Mineral Density in Healthy, Menstruating Young Adult Women after One Year The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. [Relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density of Chinese postmenopausal women]. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. The effects of soy isoflavone on bone density in north region of climacteric Chinese women
Background Previous studies show that daily doses of 40–99 mg soy isoflavones produce inconsistent effects on preventing estrogen-related bone loss in postmenopausal women . Aim of the study To examined the bone-sparing effect of isoflavones at a higher dose in early Chinese postmenopausal women . Methods A total of 90 eligible women aged 45–60 years were r and omly assigned to three treatment groups ( 30 subjects/group ) with daily dosages of 0 ( placebo ) , 84 and 126 mg isoflavones for 6 months . Further inclusion criteria included body mass index < 30 kg/m2 and Kuppermann Climacteric Scale > 15 . Bone mineral density ( BMD ) of the spine and hip were measured using dual- energy X-ray absorptiometry at 0 and 6 months . Serum osteocalcin , bone-specific alkaline phosphatase ( BAP ) and urinary deoxypyridinoline were examined at 0 , 3 and 6 months . Results Mean percent changes in BMD at the lumbar spine ( p = 0.114 ) and femoral neck ( p = 0.053 ) increased with the supplementations of soy isoflavones after adjusting for age , years since menopause , body weight and height , dietary intakes of isoflavones , calcium and protein , physical activities and baseline BMD at the relevant sites . We observed significantly dose-dependent linear relationship between the  supplemental isoflavones  and percent changes of BMD at the spine ( p = 0.042 ) and femoral neck ( p = 0.016 ) post-treatment , and urinary total deoxypyridinoline ( p = 0.014 ) at 12 weeks but not at 24 weeks after adjusting for the above factors . No significant difference in percent changes in serum osteocalcin ( p > 0.05 ) and BAP ( p > 0.05 ) was found among the three treatment groups at 12-week and 24-week post-treatment . Conclusion There is a significantly dose-dependent effect of soy isoflavones on attenuating bone loss at the spine and femoral neck possibly via the inhibition of bone resorption in non-obese postmenopausal Chinese women with high Kuppermann Scale INTRODUCTION Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss .  Isoflavones have been reported to protect bone from estrogen deficiency , but their modest effects on bone resorption have been difficult to measure with traditional analytical methods . METHODS In this r and omized-order , crossover , blinded trial in 11 healthy postmenopausal women , we compared four commercial sources of isoflavones from soy cotyledon , soy germ , kudzu , and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate ( Actonel ) for their antiresorptive effects on bone using novel (41)Ca methodology . RESULTS Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24 % , respectively ( P < 0.0001 ) . Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens , only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9 % ( P = 0.0002 ) and 5 % ( P = 0.03 ) , respectively . Calcium absorption and biochemical markers of bone turnover were not influenced by interventions . CONCLUSIONS Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period OBJECTIVE To investigate the effect of soy isoflavone supplementation on bone mineral density ( BMD ) and markers of bone turnover  in postmenopausal women . METHODS In this r and omized , placebo-controlled clinical trial , we used a crossover design to test the effect of soy isoflavone ( 110 mg/day ) ( 1.3:1.0:0.22 ratio of genistein/daidzein/ glycitein ) on bone formation , bone resorption , bone mineral content ( BMC ) , and BMD for 6 months . RESULTS Postmenopausal women ( n = 19 ) , mean age 70.6 + /- 6.3 years and mean time since menopause 19.1 + /- 5.5 years , were given isoflavone supplements for 6 months . There was a 37 % decrease in urinary concentrations of type 1 collagen alpha1-chain helical peptide ( HP ) , a marker of bone resorption , during the isoflavone supplementation compared with baseline ( p < 0.05 ) and a significant difference in mean ( SE ) HP excretion levels when isoflavone was compared with placebo ( 43.4 + /- 5.2 vs. 56.3 + /- 7.2 microg/mmol creatinine [ cr ] , p < 0.05 ) . With isoflavone supplementation , mean spine BMD at L2 and L3 was significantly greater when treatment was compared with control , with a difference between means of 0.03 + /- 0.04 g and 0.03 + /- 0.04 g ( p < 0.05 ) , respectively . There were nonsignificant increases from baseline for total spine BMC ( 3.5 % ) , total spine BMD ( 1 % ) , total hip BMC ( 3.6 % ) , and total hip BMD ( 1.3 % ) with the isoflavone treatment . CONCLUSIONS Soy isoflavone , in isolated form , was effective in this study to significantly decrease bone resorption  in postmenopausal women . Further investigation needs to be done to evaluate the long-term effects of soy isoflavone on bone mass and fracture risk It is believed that soy isoflavone has much potential effectiveness on the postmenopausal status ; however , the optimal dose for preventing postmenopausal bone loss still remains unclear . This open-labeled , self-controlled pilot study was undertaken to determine the effect of 1-year supplementation of different high dosages of soy isoflavone in postmenopausal Taiwanese women . Forty-three women aged 45 - 67 years were enrolled and r and omly assigned into a control ( C ) , 100 mg/day isoflavone ( IF100 ) and 200 mg/day isoflavone ( IF200 ) groups for 1 year . Dual-energy X-ray absorptiometry and other related biochemical markers of bone metabolism were measured . Results indicated that the decrease in bone mineral density ( BMD ) was significant for lumbar vertebrae L1 - 3 , L1 - 4 and the femur neck in the C group ; surprisingly , the BMD of L1 - 3 was significantly elevated in the IF100 group ; however , there were no consistent responses in the IF200 group . No significant change except loss of the bone mineral content of Ward 's triangle ( P=.003 ) was found in the IF200 group after treatment . The percentage change at L1 - 3 was less ( P=.04 ) in the IF200 group when compared to the IF100 group . A relatively uniform direction of bone formation in exp and ing the weight and area with different rates of change result ed in different BMD changes . Both indicated a change of bone formation patterns with the higher-dose supplement . A protective effect of IF100 on estrogen-related bone loss was observed . A lack of a benefit such as high safety in the IF200 group for 1-year administration was ensured and lacked undesirable side effects Summary The treatment of 300-mg/day isoflavones ( aglycone equivalents ) ( 172.5 mg genistein + 127.5 mg daidzein ) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density ( BMD ) from declining as compared with the placebo group in a r and omized , double-blind , two-arm design ed study enrolling 431 postmenopausal women 45–65 years old . Introduction This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women . Methods Four hundred and thirty-one women , aged 45–65 years , orally consumed 300-mg/day isoflavones ( aglycone equivalents ) or a placebo for 2 years in a parallel group , r and omized , double-blind , two-arm study . Each participant also ingested 600 mg of calcium and 125 IU of vitamin D3 per day . The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter . Serum bone-specific alkaline phosphatase , urinary N-telopeptide of type 1 collagen/creatinine , and other safety assessment s were examined regularly . Results Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment . Serum concentrations of isoflavone metabolites , genistein and daidzein , of the intervention group were remarkably elevated following intake of isoflavones ( p < 0.001 ) . However , differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant ( lumbar spine , p = 0.42 ; total femur , p = 0.39 ) between the isoflavone and placebo groups , according to the generalized estimating equation ( GEE ) method . A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD ( p < 0.001 ) . Differences in bone marker levels were not significant between the two treatment groups . Conclusion Treatment with 300-mg/day isoflavones ( aglycone equivalents ) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group Objective : Many studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss , but no data reported whether such an effect could be influenced by other important factors affecting bone loss . This study examines whether the associations between isoflavone supplementation and rates of change in bone mineral content ( BMC ) could be modified by years since menopause ( YSM ) , body weight ( BW ) , and dietary calcium intake in postmenopausal Chinese women aged 48 to 62 years . Design : A group of 203 eligible women were r and omly assigned to three treatment groups : placebo ( daily dose of 0 mg isoflavones + 500 mg calcium , n = 67 ) , mid-dose ( 40 mg isoflavones + 500 mg calcium , n = 68 ) ; and high-dose ( 80 mg isoflavones + 500 mg calcium , n = 68 ) . Bone mineral density ( BMD ) and BMC at the whole body , spine , and hip were measured by dual-energy x-ray absorptiometry at baseline and posttreatment after 1 year . YSM , BW , and dietary calcium intake stratified analyses were performed to evaluate whether the associations between isoflavones  supplementation and BMC change rates were varied with these factors . Results : Both univariate and multivariate analyses observed significant favorable effect of isoflavone supplementation on rates of change in BMC at the total hip and trochanter among later postmenopausal women ( > 4 y ) , in women with lower BW ( ≤median , 55.5 kg ) , or among women with lower level of calcium intake ( ≤median , 1095 mg/d ) . Conclusions : The independent effect of soy on the maintenance of hip BMC is more marked in women in later menopause or those with lower BW or calcium intake Background : The effects of isoflavone-enriched soy protein on human bone mineral content ( mass ) and density in healthy , menstruating young adult females have not been examined in a comparative prospect i ve investigation . Peri- and post-menopausal women have been reported to show beneficial effects of isoflavones on bone measurements . Therefore , young women may also be able to improve their accrual of peak bone mineral content ( BMC ) and bone mineral density ( BMD ) during the early adult years of bone consolidation with an isoflavone-enriched diet . Objectives : In this controlled , double-blind intervention , we tested the hypothesis that an isoflavone-rich soy protein diet increases BMC and BMD in young adult females over a period of one year in comparison to a control group receiving soy protein that has isoflavones removed . Design : Young healthy women of any ethnic background , 21 to 25 years of age , were divided into two groups , placebo ( n = 13 ) and supplement ( n = 15 ) . The soy protein supplement was enriched with isoflavones ( ∼90 mg of total isoflavones/day ) , whereas the control protein diet was isoflavone-deficient , even though it contained the same amount of soy protein and other ingredients as the isoflavone-rich diet . Dual-energy x-ray absorptiometric ( DXA ) measurements of BMC and BMD were made at baseline and at 6 and 12 months . DXA estimates of body composition , including fat mass and lean body mass , were generated from whole-body BMC measurements . BMI was calculated as weight ( kg ) over height ( m ) squared . Physical activity was assessed , and three-day dietary records were taken at entry ( baseline ) and at 6 and 12 months . Results : No changes in BMD after 12 months were found in either the isoflavone-treated ( treatment ) group or the isoflavone-deficient ( control ) group . Other variables also remained essentially constant over the 12-month period , including normal menstrual patterns in both the treatment and control groups . Conclusions : The isoflavone-rich soy preparation had no effects on BMC and BMD over a 12-month period in young healthy adult females with normal menses . An isoflavone-rich supplement appears to have little or no effect on bone in young adult women with normal ovarian function , at least over this 12-month study period Soy isoflavones exert inconsistent bone density-preserving effects , but the bone strength-preserving effects in humans are unknown . Our double-blind r and omized controlled trial examined 2 soy isoflavone doses ( 80 or 120mg/d ) vs placebo tablets on volumetric bone mineral density ( vBMD ) and strength ( by means of peripheral quantitative computed tomography ) in healthy postmenopausal women ( 46 - 63yr ) . We measured 3-yr changes in cortical BMD ( CtBMD ) , cortical thickness ( CtThk ) , periosteal circumference ( PC ) , endosteal circumference ( EC ) , and strength-strain index ( SSI ) at 1/3 midshaft femur ( N=171 ) , and trabecular BMD ( TbBMD ) , PC , and SSI at 4 % distal tibia ( N=162 ) . We found no treatment effect on femur CtThk , PC , or EC , or tibia TbBMD or PC . The strongest predictors ( negative ) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption ; whole-body fat mass was protective of SSI . As time since last menstrual period ( TLMP ) increased ( p=0.012 ) , 120-mg/d dose was protective of CtBMD . The strongest predictors of femur SSI were timepoint , bone resorption , and TLMP ( protective ) . Isoflavone tablets were negative predictors of SSI , but 80-mg/d dose became protective as bone turnover increased ( p=0.011 ) . Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased BACKGROUND Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy ( HRT ) . HRT has a beneficial effect on bone , but few trials in humans have investigated the effects of isoflavones on bone . OBJECTIVE The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A , 16 mg formononetin , 1 mg genistein , and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied . DESIGN Women aged 49 - 65 y ( n = 205 ) were enrolled in a double-blind , r and omized , placebo-controlled trial ; 177 completed the trial .  Bone density , body composition , bone turnover markers , and diet were measured at baseline and after 12 mo . RESULTS Loss of lumbar spine bone mineral content and bone mineral density was significantly ( P = 0.04 and P = 0.03 , respectively ) lower in the women taking the isoflavone supplement  than in those taking the placebo . There were no significant treatment effects on hip bone mineral content or bone mineral density , markers of bone resorption , or body composition , but bone formation markers were significantly increased ( P = 0.04 and P = 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I , respectively ) in the intervention group compared with placebo in postmenopausal women . Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant . CONCLUSION These data suggest that , through attenuation of bone loss , isoflavones have a potentially protective effect on the lumbar spine in women Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss , but few data are available in humans , especially in the Asian population s. This double-blind , placebo-controlled , r and omized trial examines the effects of soy isoflavones on  bone loss in postmenopausal Chinese women , aged 48 - 62 yr . Two hundred and three eligible subjects were r and omly assigned to three treatment groups with daily doses of placebo ( 1 g starch ; n = 67 ) , mid-dose ( 0.5 g starch , 0.5 g soy extracts , and approximately 40 mg isoflavones ; n = 68 ) , and high dose ( 1.0 g soy extracts and approximately 80 mg isoflavones ; n = 68 ) . All were given 12.5 mmol ( 500 mg ) calcium and 125 IU vitamin D(3 ) . Bone mineral density ( BMD ) and bone mineral content ( BMC ) of the whole body , spine , and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment . Both univariate and multivariate analyses showed that women in the high dose group had mild , but statistically significantly , higher favorable change rate in BMC at the total hip and trochanter ( P < 0.05 ) compared with the placebo and mid-dose groups , even after further adjustments for the potential confounding factors . Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC ( median or less ) . In conclusion , soy isoflavones have a mild , but significant , independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass 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 BACKGROUND Postmenopausal estrogen depletion is a major contributing factor to bone loss .  Soy isoflavones have variable effects on the prevention of postmenopausal bone loss , which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals . OBJECTIVE We aim ed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention . DESIGN The study was a blinded , r and omized , crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol . Women were equilibrated with (41)Ca before the intervention . Interventions were 5 soy isoflavone oral supplements ( 2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions ) and a bisphosphonate ( risedronate ) . Each intervention was given sequentially for 50 d followed by a 50-d washout period . The percentage of bone calcium retention was determined from the change in urinary (41)Ca : calcium . RESULTS Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4 % and 7.6 % ( P < 0.05 ) , which was a moderate effect compared with that of risedronate at 15.3 % ( 95 % CI : 7.1 % , 22.7 % ; P = 0.0014 ) . The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein , daidzein , and glycitein in their natural ratios and increased bone calcium retention by 7.6 % ( 95 % CI : 4.9 % , 10.2 % ; P < 0.0001 ) . Genistein , at 52.85 mg/d , increased bone calcium retention by 3.4 % ( 95 % CI : 0.5 % , 6.2 % ; P = 0.029 ) ; but there was no benefit at higher amounts ( 113.52 mg/d ) . There was no difference ( P = 0.5 ) in bone calcium retention between equol producers and nonproducers . CONCLUSION Soy isoflavones , although not as potent as risedronate , are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status , and mixed isoflavones in their natural ratios are more effective than enriched genistein . This trial was registered at clinical trials.gov as NCT00244907 OBJECTIVE To investigate the relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density ( BMD ) of Chinese postmenopausal women . METHODS It was a r and omly controlling test for 12 months . The Pvu II and Xba I polymorphisms of ER-alpha gene were detected by using restriction fragment length polymorphisms ( RFLP ) in 691 Chinese postmenopausal women , aged 45 - 65 years . In 497 carriers of definitive Pvu II-Xba I haplotype , 93 subjects were chosen r and omly . BMD was measured by dual energy X-ray absorptiometry ( DXEA ) . According to BMD T score in any skeleton site of 81 subjects at baseline , 29 subjects with T > or = -1.5 were grouped into observation group , and 52 subjects with T < -1.5 were r and omly assigned into two intervention groups and received either a 100 mg soy isoflavone and 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) or 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) . BMD of the whole body , lumber ( L2-L4 ) , and hip were measured at baseline and after 12 months . RESULTS After one year fellow-up , the BMD at L2-L4 , femur neck site and whole body were significantly decreased as compared with those of baseline ( P < 0.05 , change percent of BMD as follows : -3.31 % , -3.09 % , -1.88 % ) in observation group , and the whole body BMD was significantly lower at 12 month than that at baseline in subjects with Px haplotype ( percent change was -2.44 % , P < 0.05 ) , but no difference was found in subjects without Px haplotype . Whole body and femur neck BMD were significantly decreased in both Ca group and Ca + soy isoflavone group , but no significant difference of change percent between two groups . There were no significant changes in L2-L4 and trochanter BMD irrespective of treatment . ER-alpha Px haplotype had no effect on the changes in BMD in both Ca group and Ca + soy isoflavone group . CONCLUSION The rate of bone loss in Chinese postmenopausal women seems to haverelation to ER Px haplotype . Calcium supplementation for 1 year might lower the bone loss rate , but soy isoflavone supplementation for 1 year had notshowu no effects . The effect of supplementation had no relationship with ER Px haplotype BACKGROUND Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss  in midlife women . OBJECTIVE We examined the efficacy of isoflavones ( extracted from soy protein ) on bone mineral density ( BMD ) in nonosteoporotic postmenopausal women . We hypothesized that isoflavone tablets would spare BMD , with biological ( age , body weight , serum 25-hydroxyvitamin D ) and lifestyle ( physical activity , dietary intake ) factors modulating BMD loss . DESIGN Our double-blind , r and omized controlled trial ( 36 mo ) included healthy postmenopausal women ( aged 45.8 - 65.0 y ) with intent-to-treat ( n = 224 ) and compliant ( n = 208 ) analyses . Treatment groups consisted of a placebo control group and 2 soy isoflavone groups ( 80 compared with 120 mg/d ) ; women received 500 mg calcium and 600 IU vitamin D(3 ) . Outcomes included lumbar spine , total proximal femur , femoral neck , and whole-body BMD . RESULTS Analysis of variance for intent-to-treat and compliant ( > or = 80 % ) models , respectively , showed no treatment effect for spine ( P = 0.46 , P = 0.21 ) , femur ( P = 0.86 , P = 0.46 ) , neck ( P = 0.17 , P = 0.14 ) , or whole-body ( P = 0.86 , P = 0.78 ) BMD . From baseline to 36 mo , BMD declined regardless of treatment . In intent-to-treat and compliant models , respectively , BMD decreases were as follows : spine ( -2.08 % , -1.99 % ) , femur ( -1.43 % , -1.38 % ) , neck ( -2.56 % , -2.51 % ) , and whole body ( -1.66 % , -1.62 % ) . Regression analysis ( compliant model ) indicated that age , whole-body fat mass , and bone resorption were common predictors of BMD change . After adjustment for these factors , 120 mg ( compared with placebo ) was protective ( P = 0.024 ) for neck BMD . We observed no treatment effect on adverse events , endometrial thickness , or bone markers . CONCLUSION Our results do not show a bone-sparing effect of extracted soy isoflavones , except for a modest effect at the femoral neck . This trial was registered at clinical trials.gov as NCT00043745 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 Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life . In 2 r and omized , cross-over studies , 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [ control , 0.13 ; low isoflavone ( low-iso ) , 1.00 ; and high-iso , 2.01 mg/kg body wt/day , averaging 8 , 65 , and 130 mg/day , respectively ] , for over 3 months each . Food records , blood sample s , and 24-h urine collection s were obtained throughout the studies . The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase , osteocalcin , insulin-like growth factor-I ( IGFI ) , IGF binding protein-3 ( IGFBP3 ) , and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen . In premenopausal women , IGFI and IGFBP3 concentrations were increased by the low-iso diet , and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle . In postmenopausal women , bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets , and there were trends toward decreased osteocalcin , IGFI , and IGFBP3 concentrations with increasing isoflavone consumption . Although soy isoflavones do affect markers of bone turnover , the changes observed were of small magnitude and not likely to be clinical ly relevant . These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women Only a few investigations were based on limb bone density . This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders , limb bone density and the role of pathway . The research protocol involved the r and om subdivision of the enrolled sample into two groups of 40 women , who were to receive treatment for 6 months with isoflavone ( 90 mg/day ) and with placebo .  All of the patients were asked to fill in a question naire concerning their complaints . BMD of the radius and tibia were measured using quantitative ultrasound . Bone metabolism indexes calcium , phosphorus and alkaline phosphatase ( ALP ) were examined regularly . Serum cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) examined by ELISA . The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders . Compared with placebo , the tibia bone density in isoflavone group increased obviously against the base value before trail . Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo . For climacteric women  , soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density , which maybe had the relationship with the levels of IL-6 , TNF-α and ALP in serum
Conclusions : Isoflavone treatments exert a moderately beneficial effect against  estrogen-deficient bone loss in women .
The effect appears dependent on whether isoflavone treatments are in aglycone form ; we conclude that beneficial effects against bone loss may be enhanced for isoflavone aglycones
Background : Age-related estrogen deficiency leads to accelerated bone resorption .
There is evidence that , through selective estrogen receptor modulation , isoflavones may exert beneficial effects against  estrogen-deficient bone loss .
Isoflavone aglycones show higher bioavailability than their glycosidic counterparts and thus may have greater potency .
Objective : To summarize evidence , we executed a systematic review and meta- analysis examining isoflavone therapies and bone mineral density ( BMD ) loss in peri- and postmenopausal women .