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. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. Dietary isoflavones differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol as compared with those who do not. Soymilk or progesterone
for prevention of bone loss A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Hydrolysis of isoflavone glycosides to aglycones by beta-glycosidase does not alter plasma and urine isoflavone pharmacokinetics in postmenopausal women. Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Estrogen therapy arrests bone loss in elderly women. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen.
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 OBJECTIVE The aim of this study was to evaluate the effects of isoflavone on the climacteric symptoms ( Kupperman Menopausal index ) , vaginal pH , vaginal cytology ( vaginal maturation index ) and endometrium ( evaluated by ultrasound and biopsy ) in postmenopausal women . METHODS It was a single-center , 6-month , r and omized , double-blind , estrogen-controlled trial . Seventy-nine women were r and omly assigned to one of the two treatment groups : isoflavone ( n=40 ) : 300 mg of the st and ardized soy extract with a medium dose of 120 mg isoflavones/day as glycoside and aglycone ( 60 mg twice a day ) , or estrogen ( n=39 ) : one capsule of 0.625 mg conjugated equine estrogens and other capsule with glucose 0.625 mg ( placebo ) . RESULTS After treatment , there was a decrease in the symptomatology in both estrogen and isoflavone groups . There was a significant decrease in vaginal pH , an increase in superficial vaginal cells and endometrium proliferation after 3 and 6 months of treatment in the estrogen group , but no differences were observed in the isoflavone group for these variables . CONCLUSIONS We concluded that the daily st and ardized soy extract with 120 mg isoflavones ' effect on symptoms was similar to that from estrogen . Soy isoflavone has no effect on endometrium and vaginal mucosa during the treatment CONTEXT Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes , but its use has risks . Isoflavones , estrogenlike compounds naturally occurring in plant foods , might confer positive effects with fewer adverse effects . OBJECTIVE To investigate whether soy protein with isoflavones improves cognitive function , bone mineral density , and plasma lipids in postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years , recruited from a population -based sample in the Netherl and s , conducted between April 2000 and September 2001 . INTERVENTION Participants were r and omly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones ( 52 mg genistein , 41 mg daidzein , and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months . MAIN OUTCOME MEASURES Cognitive function was assessed using the following instruments : dementia , Mini-Mental State Examination ; memory , Rey Auditory Verbal Learning Test , immediate recall , delayed recall , and recognition , the Digit Span forward and reversed , and the Doors test ; complex attention tasks , Digit Symbol Substitution and Trailmaking , A1 , A2 , and B ; and verbal skills , Verbal Fluency A and N , animals and occupations , and the Boston Naming Task . Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning . Lipid assessment included lipoprotein(a ) , total cholesterol , low-density lipoprotein , high-density lipoprotein , and triglycerides . RESULTS A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis . Adherence was good ( median plasma genistein levels , 17.2 and 615.1 nmol/L for placebo and soy group , respectively ) . Cognitive function , bone mineral density , or plasma lipids did not differ significantly between the groups after a year . CONCLUSION This double-blind r and omized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function , bone mineral density , or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later Human and animal studies suggest that dietary soy isoflavones reduce cancer risk , ameliorate postmenopausal syndrome and decrease bone resorption in postmenopausal women . The capacity to form the metabolite equol from daidzein is suggested as an important modulator of response to isoflavones ; this capacity depends on gut colonization with appropriate bacteria . We administered a dietary supplement containing high-dose purified soy isoflavones ( genistein , 558 mg/day ; daidzein , 296 mg/day ; and glycitein , 44 mg/day ) to 30 postmenopausal women for 84 days and collected peripheral lymphocytes at timed intervals . Using microarray analysis , we determined whether changes in gene expression associated with this treatment support existing hypotheses as to isoflavones ' mechanisms of action . Expression of a large number of genes was altered by isoflavone treatment , including induction of genes associated with cyclic adenosine 3',5'-monophosphate ( cAMP ) signaling and cell differentiation and decreased expression of genes associated with cyclin-dependent kinase activity and cell division . We report that isoflavone treatment in subjects who have the capacity to produce equol differentially affects gene expression as compared with nonproducers , supporting the plausibility of the importance of equol production . In general , isoflavones had a stronger effect on some putative estrogen-responsive genes in equol producers than in nonproducers . Our study suggests that , in humans , isoflavone changes are related to increased cell differentiation , increased cAMP signaling and G-protein-coupled protein metabolism and increased steroid hormone receptor activity and have some estrogen agonist effects ; equol-production status is likely to be an important modulator of responses to isoflavones Summary Background Given concerns over the use of hormone replacement therapy ( HRT ) , women are seeking natural alternatives to cope with the symptoms and effects of menopause . The bone sparing effects of soy protein and its isoflavones is well established in animal studies , while 5 previous human studies on soy and bone have yielded variable outcomes due in part to their short duration of study . Progesterone has been suggested as a bone – trophic hormone , but the effect of long – term , low dose transdermal progesterone is unknown . Aim The aim of the study was to compare for the first time the long – term effects of soymilk , with or without isoflavones with natural transdermal progesterone , or the combination , on bone mineral density in the lumbar spine and hip . Methods Postmenopausal , Caucasian women with established osteoporosis or at least 3 risk – factors for osteoporosis , were r and omly assigned , double – blind to one of four treatment – groups : soymilk containing isoflavones  ( soy+ , n = 23 ) ,  transdermal progesterone ( TPD+ , n = 22 ) , or the combination of soy+ and TDP+,(n = 22 )  or placebo ( isoflavone – poor soymilk , soy÷ and progesterone – free – cream TDP÷ , n = 22 ) . All subjects received comparable intakes of calcium , minerals and vitamins . Bone mineral content ( BMC ) and density ( BMD ) were measured in lumbar spine and hip by using dual – energy X-ray absorptiometry ( DEXA ) at baseline and after 2 years . Findings The percentage change in lumbar spine BMD and BMC respectively , did not differ from zero in the soy+ group ( + 1.1 % , + 2.0 % ) and TDP+ group ( ÷1.1 % , + 0.4 % ) but significant bone loss occurred in the control group ( ÷4.2%,÷4.3 % ) and the combined treatment group ( ÷2.8 % , ÷2.4 % ) . No significant changes occurred for femoral neck BMD or BMC .InterpretationDaily intake of two glasses of soymilk containing 76 mg isoflavones  prevents lumbar spine bone loss in postmenopausal women . Transdermal progesterone had bone – sparing effects but when combined with soy milk a negative interaction between the two treatments occurs result ing in bone – loss to a greater extent than either treatment alone Raloxifene HCl , a selective estrogen receptor modulator , has been shown to increase bone mineral density ( BMD ) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus . However , it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level , nor how changes with raloxifene compare with estrogen . In this r and omized , double blind study , we evaluated the effects of raloxifene ( Evista , 60 mg/day ) or conjugated equine estrogens ( CEE ; Premarin , 0.625 mg/day ) on bone architecture , bone turnover , and BMD . Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for st and ard histomorphometric indexes . Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4 , 10 , 18 , and 24 weeks of treatment . Total body , lumbar spine , and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry . Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE , but not in the raloxifene , group . Bone mineralization did not change in either group . Most markers of bone resorption and formation decreased in both groups , but to a greater degree in the CEE group ( P < .05 ) . Total body and lumbar spine BMD increased from baseline in both groups , with a greater increase in the CEE group ( P < 0.05 ) . Hip BMD significantly increased from baseline in the raloxifene group , but the change was not different from that in the CEE group . These results suggest that raloxifene reduces bone turnover and increases bone density , although to a lesser extent than CEE . Thus , raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P < 0.0001 ) and 4.36 % ( + /-6.42 % ) at the spine ( P < 0.0001 ) . There were parallel increases in total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P < 0.0124 ) . The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol  increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P < 0.001 ) , 4.91 % ( + /-6.0 % ) at the spine ( P < 0.0001 ) , and parallel changes at the total hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone 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 Objectives : To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink , and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes . The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones . Methods : A r and omized , double-blind , placebo-controlled , parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period . The women were r and omized to receive a dietary beverage containing isoflavones or an isoflavone-free , isocaloric placebo preparation . Results : Although there was a high compliance rate among individual patients , there was a 25 % withdrawal rate from the study in the active group . The incidence of complaints of bad taste tended to be higher in the active group ( p = 0.07 ) , and the total number of adverse events was significantly higher in this group ( p < 0.001 ) . There was no statistically significant difference in the incidence of flushes between the groups . There was no difference between the groups in Greene Menopause Symptom Scores , vaginal maturation value , levels of follicle stimulating hormone ( FSH ) or sex hormone-binding globulin ( SHBG ) , or bone turnover markers . Conclusions : Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study . The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture , in future trials . At the dose used no benefit was seen in relief from menopausal symptoms , although for the sample size , the study could only have been expected to detect major differences between the groups Animal studies demonstrated that phytoestrogen had a protective effect against  bone loss after ovariectomy . However , data on dietary phytoestrogen intake as well as its relationship with bone mineral density ( BMD ) in human are not available . Six hundred fifty southern Chinese women , aged 19 to 86 yr , were recruited to determine their dietary phytoestrogen intake by a food frequency question naire . BMDs at the lumbar spine and hip region were measured using dual energy x-ray absorptiometry . The subjects were analyzed according to various tertiles of phytoestrogen intake . Among the postmenopausal women ( n = 357 ) , significant differences in the lumbar spine ( L2 - 4 ) BMD ( 0.820 + /- 0.145 vs. 0.771 + /- 0.131 g/cm2 , P < 0.05 ) and Ward 's triangle BMD ( 0.450 + /- 0.151 vs. 0.415 + /- 0.142 g/cm2 ; P < 0.05 ) were found between the highest and lowest intake of isoflavone after adjusting for age , height , weight , years since menopause , smoking , alcohol consumption , HRT usage , and daily calcium intake . Women with the highest intake of isoflavone had significantly lower levels of serum PTH ( 19.38 + /- 14.61 vs. 26.56 + /- 11.19 pg/ml ; P < 0.05 ) , osteocalcin ( 4.95 + /- 3.61 vs. 6.69 + /- 5.05 mg/liter ; P = 0.05 ) , and urinary N-telopeptide ( 34.18 + /- 25.31 vs. 49.66 + /- 41.00 nmol bone collagen equivalents/mmol creatinine ; P < 0.05 ) when compared with those with the lowest intake of isoflavone . No association between dietary phytoestrogen intake and BMDs was seen in the premenopausal women with high endogenous E ( n = 293 ) . In conclusion , postmenopausal women with habitually high intake of dietary isoflavone are associated with higher BMD values at both the spine and hip region . Customarily high isoflavone intake may help to reverse the state of secondary hyperparathyroidism associated with E withdrawal and hence lower the rate of bone turnover in postmenopausal women There is evidence to suggest accelerated bone loss following estrogen cessation . The effect of cessation of raloxifene therapy on bone turnover is unknown . Our aim was to determine the effect of cessation of raloxifene treatment on bone turnover and bone mineral density ( BMD ) in postmenopausal , osteopenic women . Women aged 50 to 80 years received raloxifene for 96 weeks and were then r and omized to continue raloxifene  ( group 1 , n=20 ) or placebo  ( group 2 , n=20 ) for a further 96 weeks . A third group ( group 3 , n=14 ) received no treatment .  Bone turnover markers and bone density ( BMD ) were measured throughout the study . Raloxifene treatment for 96 weeks result ed in a decrease in bone turnover ( PINP by 31 % ) and an increase in spine BMD ( by 2 % ) but no change in hip BMD for groups 1 and 2 . Continuation of raloxifene ( group 1 ) maintained these changes . Following cessation of raloxifene ( group 2 ) , bone markers returned to baseline levels ( by 120 weeks ) . Hip BMD was decreased by 2 % at 192 weeks compared to baseline . Bone markers in the controls ( group 3 ) remained at the upper limit of the reference range throughout , with decreases in BMD of 2.3 % ( spine ) and 2.8 % ( hip ) . Bone loss following cessation of raloxifene therapy at 96 weeks was greater than in the control group , suggesting accelerated bone loss . The beneficial effect on bone turnover of 96 weeks of raloxifene was lost 6 months after cessation of treatment Probiotics are live microorganisms that exert beneficial effects on the host , when administered in adequate amounts . Mostly , probiotics affect the gastrointestinal ( GI ) tract of the host and alter the composition of gut microbiota . Nowadays , the incidence of hip fractures due to osteoporosis is increasing worldwide . Ovariectomized ( OVX ) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women . Therefore , this study aim ed to examine the effects of Bifidobacterium longum ( B. longum ) on bone mass density ( BMD ) , bone mineral content ( BMC ) , bone remodeling , bone structure , and gene expression in OVX rats . The rats were r and omly assigned into 3 groups ( sham , OVX , and the OVX group supplemented with 1 mL of B. longum 108–109 colony forming units (CFU)/mL ) . B. longum was given once daily for 16 weeks , starting from 2 weeks after the surgery . The B. longum supplementation increased ( p < 0.05 ) serum osteocalcin ( OC ) and osteoblasts , bone formation parameters , and decreased serum C-terminal telopeptide ( CTX ) and osteoclasts , bone resorption parameters . It also altered the microstructure of the femur . Consequently , it increased BMD by increasing ( p < 0.05 ) the expression of Sparc and Bmp-2 genes .  B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation BACKGROUND Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption , but the balance between its long-term risks and benefits remains unclear . Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear . METHODS We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age . An additional 435 women who were prepared to receive a combination of estrogen and progestin  were r and omly assigned to one of the above treatments or open-label estrogen-progestin . The main outcome measure was the change in bone mineral density of the lumbar spine , hip , distal forearm , and total body measured annually for two years by dual-energy x-ray absorptiometry . RESULTS The women who received placebo lost bone mineral density at all measured sites , whereas the women treated with 5 mg of alendronate daily had a mean ( + /-SE ) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine , 1.9+/-0.1 percent at the hip , and 0.7+/-0.1 percent for the total body ( all P<0.001 ) . Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density .  Alendronate did not increase bone mineral density of the forearm , but it slowed the loss . The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate . Alendronate was well tolerated , with a safety profile similar to that of placebo or estrogen-progestin . CONCLUSIONS Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin The effects of soy protein ( 40 g/d ) containing moderate and higher concentrations of isoflavones on blood lipid profiles , mononuclear cell LDL receptor messenger RNA , and bone mineral density and content were investigated in 66 free-living , hypercholesterolemic , postmenopausal women during a 6-mo , parallel-group , double-blind trial with 3 interventions . After a control period of 14 d , during which subjects followed a National Cholesterol Education Program Step I low-fat , low-cholesterol diet , all subjects were r and omly assigned to 1 of 3 dietary groups : Step I diet with 40 g protein/d obtained from casein and nonfat dry milk ( CNFDM ) , Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein ( ISP56 ) , or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein ( ISP90 ) . Total and regional bone mineral content and density were assessed . Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group ( P < 0.05 ) . HDL cholesterol increased in both ISP56 and ISP90 groups ( P < 0.05 ) . Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM ( P < 0.05 ) . Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group ( P < 0.05 ) . Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women . However , only the higher isoflavone-containing product protected against spinal bone loss We investigated whether the bioavailability of isoflavones  could be enhanced by enzymatic hydrolysis of glycosides to aglycones before consumption of a nonfermented soy food . Two drinks were formulated with an enriched isoflavone extract from soy germ ( Fujiflavone P10 ) , one of which was hydrolyzed enzymatically with beta-glucosidase to produce aglycones . In a r and omized , double-blinded , cross-over study , six European , postmenopausal women consumed each soy drink at a 1-wk interval at a concentration of 1 mg total isoflavones/kg body . The plasma and urinary pharmacokinetics of daidzein , genistein and glycitein  did not differ after consumption of the two beverages . Plasma total isoflavone concentrations reached 4 - 5 micro mol/L. The pharmacokinetics of glycitein  were similar to those of daidzein . The isoflavone secondary metabolites detected were dihydrodaidzein in plasma and O-desmethylangolensin , equol , and dihydrogenistein in urine . The ratios of individual isoflavones to one another were not conserved from food to plasma to urine , indicating that the individual isoflavones do not have the same absorptions and body retentions . In conclusion , previous hydrolysis of glycosides to aglycones does not enhance the bioavailability of isoflavones in humans The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis . Acting by different mechanisms , these two agents decrease bone resorption and thereby increase or preserve bone mineral density ( BMD ) . The comparative and combined effects of these medications have not been rigorously studied . This prospect i ve , double blind , placebo-controlled , r and omized clinical trial examined the effects of oral alendronate and conjugated estrogen , in combination and separately , on BMD , biochemical markers of bone turnover , safety , and tolerability in 425 hysterectomized postmenopausal women with low bone mass . In addition , bone biopsy with histomorphometry was performed in a subset of subjects . Treatment included placebo , alendronate ( 10 mg daily ) , conjugated equine estrogen ( CEE ; 0.625 mg daily ) , or alendronate ( 10 mg daily ) plus CEE ( 0.625 mg daily ) for 2 yr . All of the women received a supplement of 500 mg calcium daily . At 2 yr , placebo-treated patients showed a mean 0.6 % loss in lumbar spine BMD , compared with mean increases in women receiving alendronate , CEE , and alendronate plus CEE of 6.0 % ( P < 0.001 vs. placebo ) , 6.0 % ( P < 0.001 vs. placebo ) , and 8.3 % ( P < 0.001 vs. placebo and CEE ; P = 0.022 vs. alendronate ) , respectively . The corresponding changes in total proximal femur bone mineral density were + 4.0 % , + 3.4 % , + 4.7 % , and + 0.3 % for the alendronate , estrogen , alendronate plus estrogen , and placebo groups , respectively . Both alendronate and CEE significantly decreased biochemical markers of bone turnover , specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase . The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone , but the mean absolute values remained within the normal premenopausal range . Alendronate , alone or in combination with CEE , was well tolerated . In the subset of patients who underwent bone biopsies , histomorphometry showed normal bone histology with the expected decrease in bone turnover , which was somewhat more pronounced in the combination group . Thus , alendronate and estrogen produced favorable effects on BMD . Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated 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 Although osteoporosis is an age-related disorder , the accelerated bone loss observed in postmenopausal women may be preventable with early diagnosis and adequate estrogen replacement . In a prospect i ve study , we investigated the effect of oral estrogen replacement using conjugated estrogens ( Premarin , 0.625 mg ) or micronized 17 beta-estradiol ( Estrace , 1 mg ) versus no estrogen in sequential single-photon bone density measurements over 3-year intervals in 397 postmenopausal women .  Estradiol , 1 mg , and conjugated estrogens , 0.625 mg , were equally effective in regarding bone loss . The rate of bone loss was about the same for  estrogen users regardless of age ( 51 to 80 years ) and was approximately one third that of nonusers . Among nonusers a uniform accelerated rate of bone loss of 2.5 % per year was noted between 56 and 70 years old , whereas between the ages of 51 and 55 years and after age 70 years , the rate of bone loss was significantly less . Ever users over age 65 years showed continued protection from bone loss as long as estrogen therapy was continued . Previous estrogen users who stopped estrogen after age 65 years lost bone more rapidly than women of similar age who had never taken estrogen . Thus to prevent accelerated bone loss in postmenopausal women , we recommend early and continued hormone replacement for life . Estrogen nonusers should be monitored at regular intervals to minimize accelerated bone loss BACKGROUND Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects . Despite numerous clinical trials of short-term isoflavone supplementation , there is a paucity of data regarding longer-term outcomes and safety . OBJECTIVE Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health . DESIGN A multicenter , r and omized , double-blind , placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women . At baseline and after 1 and 2 y , clinical blood chemistry values were measured and a well-woman examination was conducted , which included a mammogram and a Papanicolaou test . A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids . RESULTS The baseline characteristics of the groups were similar . After 2 y of daily isoflavone exposure , all clinical chemistry values remained within the normal range . The only variable that changed significantly was blood urea nitrogen , which increased significantly after 2 y ( P = 0.048 ) but not after 1 y ( P = 0.343 ) in the supplementation groups . Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations . No significant differences in endometrial thickness or fibroids were observed between the groups . Two serious adverse events were detected ( one case of breast cancer and one case of estrogen receptor-negative endometrial cancer ) , which was less than the expected population rate for these cancers . CONCLUSION Daily supplementation for 2 y with 80 - 120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women . This trial was registered at clinical trials.gov as NCT00665860 The purpose of this study is to evaluate the efficacy of vitamin K2 and 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2D3 ] in preventing bone loss induced by estrogen deficiency during therapy with the GnRH agonist ( GnRH-a ) leuprolide .  One hundred ten women ( mean age , 46.2+/-0.5 yr ) , receiving leuprolide therapy for estrogen-dependent diseases ( such as endometriosis and uterine leiomyomas ) , were r and omly allocated into four groups ( group A , leuprolide only ; group B , leuprolide with vitamin K2 ; group C , leuprolide with 1,25-(OH)2D3 ; and group D , leuprolide with vitamin K2 and 1,25-(OH)2D3 ) .  Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after 6 months of treatment . Bone formation and resorption markers were also measured before and after 6 months of treatment . There were no significant differences in the background parameters among the four groups . Bone mineral density was reduced in all four groups , but the percent changes varied slightly , at - 5.25 % ( group A ) , -3.72 % ( P < 0.05 vs. group A ) ( group B ) , -4.13 % ( group C ) , and -3.59 % ( P < 0.01 vs. group A ) ( group D ) , respectively . Bone formation markers were significantly increased in all four groups , and the percent changes of bone formation markers were highest in group B. Bone resorption markers also increased significantly in all four groups after treatment of 6 months . Group B tended to have the highest percent changes of bone resorption markers among the four groups , but these increases were not significantly different between any of the groups . Vitamin K2 , especially when combined with 1,25-(OH)2D3 , can partially prevent bone loss caused by estrogen deficiency . However , because this effect is attributable mainly to the activation of bone formation , it is not sufficient to eliminate bone loss induced by GnRH-a therapy OBJECTIVES Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss . Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear . In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of  postmenopausal bone loss in Thais . METHODS The subjects consisted of 146 Thai women no more than 6 years postmenopausal . The subjects were r and omly allocated to receive 750 mg supplemental calcium alone , calcium and conjugated equine estrogen ( CEE ) at 0.3 or 0.625 mg , calcium and calcitriol at 0.25 or 0.5 microg daily . Those receiving CEE also took 5 mg medrogestone for 12 days each month . BMD at L2 - 4 and femoral neck were measured at baseline 1 year and 2 years after treatments . Data were expressed as mean + /- S.E. RESULTS Subjects on supplemental calcium alone had approximately 2.5 % decreases in L2 - 4 ( P < 0.05 ) and femoral BMD ( P < 0.01 ) at 2 years . CEE ( 0.3 mg ) result ed in 3.20 + /- 1.2 % increase in vertebral BMD ( P < 0.05 ) while no significant change in BMD was demonstrated at the femoral neck . Likewise , 0.625 mg of CEE induced 5.4 + /- 1.4 % increase in vertebral BMD at 2 years ( P < 0.001 ) without change in the femoral BMD . In regard to calcitriol , no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol . CONCLUSION We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais . It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement
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 .