Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. Effects of soy protein isolate on bone mineral density and physical performance indices in postmenopausal women-a 2-year randomized, double-blind, placebo-controlled trial Soy isoflavones attenuate bone loss in early postmenopausal Chinese women Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. [Relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density of Chinese postmenopausal women]. One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial. One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. Soy Isoflavones: No Effects on Bone Mineral Content and Bone Mineral Density in Healthy, Menstruating Young Adult Women after One Year Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. 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 Bone mineral density in postmenopausal Chinese women treated with calcium fortification in soymilk and cow's milk The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women. 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 Red clover isoflavones enriched with formononetin lower serum LDL cholesterol—a randomized, double-blind, placebo-controlled study The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Design and baseline characteristics of the soy phytoestrogens as replacement estrogen (SPARE) study--a clinical trial of the effects of soy isoflavones in menopausal women. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. Hormone replacement therapy and the prevention of postmenopausal osteoporosis Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial.
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 : Postmenopausal decreases in body composition , physical performance , and bone mass have been shown to be reversed by estrogen , but given the concerns regarding its use , women are looking for alternatives such as soy isoflavones . Most studies on the effects of soy on bone mineral density ( BMD ) in postmenopausal women have been short-term , that is , 3 to 6 months , and failed to provide conclusive evidence . There is no evidence of its effects on physical performance . The aim of the present study was to investigate the effects of soy plus isoflavones on BMD and physical performance in postmenopausal women . Methods : This was a 2-year r and omized controlled trial . A total of 203 healthy postmenopausal women were given either 25 g of soy protein without isoflavones , 25 g of soy protein with 90 mg of isoflavones , or 25 g of milk protein ( casein and whey ) as a control agent for 24 months . Women were followed every 6 months with BMD and physical performance measurements for 2 years . Primary analysis was intent-to-treat analysis . Analysis of variance , & khgr;2 and Fisher 's exact tests , and analysis of covariance were used . Results : There was a significant decrease in the BMD of the lumbar spine and femoral neck in those who completed the study in all groups . Soy isoflavones prevented major bone loss from baseline at the femoral trochanter with no between-group significance . Physical performance measurements decreased in all the groups . Conclusions : Twenty-five grams of soy protein with 90 mg of isoflavones has no added benefit in preventing bone loss or improving physical performance 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 Estrogen ( E ) deficiency associated with the menopause is the major cause of bone loss in aging women . However , men also lose significant amounts of bone with age , but they do not have the equivalent of menopause , and serum total testosterone ( T ) and E levels decline only marginally with age in men . Thus , it has been difficult to attribute bone loss in aging men to either T or E deficiency . Here , we show in a population -based , age-stratified sample of 346 men , aged 23 - 90 yr , that serum total T and E ( estradiol plus estrone ) levels decreased over the life span by 30 % and 12 % , respectively , but bioavailable ( or nonsex hormone-binding globulin-bound ) T and E levels decreased by 64 % and 47 % , respectively . In these men and in a parallel cohort of 304 women , aged 21 - 94 yr , serum PTH increased 84 % and 64 % over the life span , and urinary N-telopeptide of type I collagen ( NTx ) excretion , a bone resorption marker , increased 77 % and 80 % between age 50 - 85 yr in the men and women , respectively . By univariate analyses , serum bioavailable T and E levels correlated positively with bone mineral density ( BMD ) at the total body , spine , proximal femur , and distal radius and negatively with urinary NTx excretion in men and women . Urinary NTx excretion was also negatively associated with BMD in both sexes . By multivariate analyses , however , serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women . Thus , bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women . These studies suggest that in contrast to traditional belief , age-related bone loss may be the result of E deficiency not just in postmenopausal women , but also in men 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 Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women , most of these studies are of short duration ( i.e. six months ) . The objective of this study was to examine if one year consumption of soy-containing foods ( providing 25 g protein and 60 mg isoflavones ) exerts beneficial effects on bone in postmenopausal women . Methods Eighty-seven eligible postmenopausal women were r and omly assigned to consume soy or control foods daily for one year . Bone mineral density ( BMD ) and bone mineral content ( BMC ) of the whole body , lumbar ( L1-L4 ) , and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year . Blood and urine markers of bone metabolism were also assessed . Results and Discussion Sixty-two subjects completed the one-year long study . Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups . However , there were no significant changes in total hip BMD and BMC irrespective of treatment . Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase ( BSAP ) activity , insulin-like growth factor-I ( IGF-I ) , and osteocalcin ( BSAP : 27.8 and 25.8 % , IGF-I : 12.8 and 26.3 % , osteocalcin : 95.2 and 103.4 % for control and soy groups , respectively ) . Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion , a marker of bone resorption . Conclusion Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation , this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women UNLABELLED The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward 's triangle regions . INTRODUCTION The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals . In this study , we determined the effects of isoflavone intake , walking exercise , and their interaction on bone , fat mass , and lipid metabolism over 1 year in postmenopausal Japanese women . MATERIAL S AND METHODS A total of 136 postmenopausal women at < 5 years after the onset of menopause were r and omly assigned to four groups : ( 1 ) placebo , ( 2 ) walking ( 45 minutes/day , 3 days/week ) with placebo , ( 3 ) isoflavone intake ( 75 mg of isoflavone conjugates/day ) , and ( 4 ) combination of isoflavone plus walking .  BMD , fat mass , serum lipid , and serum and urinary isoflavone concentrations were assessed . RESULTS A significant main effect of isoflavone  on the reduction in trunk fat mass was obtained at 12 months . Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3 , 6 , and 12 months and that in the legs and arms at 6 and 12 months . Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention . After 12 months , a significant main effect of isoflavone on BMD was observed only at Ward 's triangle . Walking prevented bone loss at the total hip and the Ward 's triangle to significant degrees . The effect of the combined intervention on BMD at total hip and Ward 's triangle regions was greater than that of either alone . No significant interaction was observed between isoflavone and walking in any measurements recorded during the study . CONCLUSIONS Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward 's triangle regions than either alone . Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners . Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women 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 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 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 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 Summary Eighteen months of daily consumption of milk containing 250 mg calcium prevented bone mineral density ( BMD ) loss at the hip and the femoral neck in postmenopausal Chinese women aged 45 to 65 . Introduction Estrogen-related bone loss in postmenopausal women can be prevented by the consumption of milk with high doses of calcium and soymilk with high doses of isoflavones . However , high doses of calcium and isoflavones may not be necessary to attain a beneficial effect of milk and soymilk on BMD . We hypothesized that BMD will increase in postmenopausal Chinese women who consume daily 250 mg calcium in milk or soymilk . Milk prevented bone loss at the hip and the femoral neck in postmenopausal Chinese women . Methods A total of 141 eligible Chinese women without osteoporosis , aged 45–65 , and postmenopausal for more than 2 years were r and omized into groups receiving for 18 months ( A ) milk with 250 mg calcium daily , ( B ) soymilk with 250 mg calcium daily , or ( C ) neither milk nor soymilk . Dual-energy X-ray absorptiometry measured the BMD of the spine and hip at 0 , 6 , 12 , and 18 months . Results The BMD in the hip ( 2.52 % ) and the femoral neck ( 2.82 % ) of the women consuming milk was significantly higher ( hip , P = 0.01 ; femoral neck , P < 0.0000001 ) . The women in the control group experienced a reduction in BMD at all sites ; the reduction in BMD was only significant at the hip during 12 months ( P = 0.008 ) and at the femoral neck during 18 months ( P = 0.005 ) . Conclusions Daily consumption of milk containing 250 mg calcium over 18 months prevents BMD loss at the hip and the femoral neck in postmenopausal Chinese women 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 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 Background : Although postmenopausal combined hormone replacement therapy reduces the risk of hip fracture , long-term use may be associated with an increased risk of breast cancer , and in women more than 10 years after menopause it is associated with an increased risk of cardiovascular disease . Isoflavones , because of preferential binding to estrogen receptor beta , may retain the beneficial effects on bone but lessen the adverse effects on the breast . Objective : The objective of this study was to study the effects of an isoflavone obtained from red clover ( Rimostil ) on bone mineral density , and on low-density lipoprotein ( LDL ) cholesterol . Design : In a double-blind , r and omized , placebo-controlled trial , 50 mg of Rimostil was given to women who were menopausal for at least 1 year .  Bone mineral density of the spine , femoral neck and forearm and serum LDL cholesterol were measured at baseline and at 6-month intervals . The duration of follow-up was 2 years . Results : There was no beneficial effect of Rimostil  on bone density at any site . There was a 12 % fall in serum LDL cholesterol in the Rimostil-treated arm , which was significantly greater than the 2 % drop seen in the control arm ( P=0.005 ) 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 Following the results of the Women 's Health Initiative , many women now decline estrogen replacement at the time of menopause and seek natural remedies that would treat menopausal symptoms and prevent bone loss and other long-term consequences of estrogen deficiency , but without adverse effects on the breast , uterus , and cardiovascular system . The results of most soy studies in this population have had limitations because of poor design , small sample size , or short duration . This report describes the study rationale , design , and procedures of the Soy Phytoestrogens As Replacement Estrogen ( SPARE ) study , which was design ed to determine the efficacy of soy isoflavones in preventing spinal bone loss and menopausal symptoms in the initial years of menopause . Women ages 45 to 60 without osteoporosis and within 5 years from menopause were r and omized to receive soy isoflavones 200 mg daily or placebo for 2 years . Participants have yearly measurements of spine and hip bone density , urinary phytoestrogens , and serum lipids , thyroid stimulating hormone , and estradiol . Menopausal symptoms , mood changes , depression , and quality of life are assessed annually . The SPARE study recruited 283 women , 66.1 % were Hispanic white . With a large cohort , long duration , and large isoflavone dose , this trial will provide important , relevant , and currently unavailable information on the benefits of purified soy isoflavones in the prevention of bone loss and menopausal symptoms in the first 5 years of menopause . Given the high proportion of Hispanics participating in the study , the results of this trial will also be applicable to this minority group 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 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 Fracture prevention is one of the public health priorities worldwide . Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis , the most common metabolic bone disease . Different effective treatments for osteoporosis are available . Hormone replacement therapy ( HRT ) at different doses rapidly normalizes turnover , preserves bone mineral density ( BMD ) at all skeletal sites , leading to a significant , reduction in vertebral and non-vertebral fractures .  Tibolone , a selective tissue estrogenic activity regulator ( STEAR ) , is effective in the treatment of vasomotor symptoms , vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT . Selective estrogen receptor modulators ( SERMs ) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures . The combination of bazedoxifene and conjugated estrogens , defined as tissue selective estrogen complex ( TSEC ) , is able to reduce climacteric symptoms , reduce bone turnover and preserve BMD . In conclusion , osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms . The use of a st and ard dose of HRT for osteoporosis prevention is based on biology , epidemiology , animal and pre clinical data , observational studies and r and omized , clinical trials . The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover , with compelling scientific evidence 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 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 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
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 .