Table 3.

Randomized, Controlled Trials of Soy for Bone in postmenopausal women

Author, year	Design	Subjects	Intervention type, dose, and duration	Outcome
Potter, 1998 22	RCT with 3 groups: ISP low isoflavones, ISP high isoflavones, or casein placebo	Postmenopausal women Ages 39–83 n=66	Both ISP supplements contained 40g/day soy protein. Low isoflavone:56 mg/day. High isoflavone: 90 mg/day. Background diet NCEP Step 1 diet. Duration: 6 months	Significant increases in BMC and BMD occurred in lumbar spine for high isoflavone group compared to placebo.
Harkness, 2004 54	RCT with cross-over design placebo and soy isoflavone capsule	Postmenopausal women Mean age 70.6 N=19	Soy isoflavone capsule contained 110 mg/day isoflavones (1.3:1.0:0.2 ratio of genistein: daidzein: glycitein) Duration: 6 months	Mean spine BMD significantly greater in treatment compared to control.
Morabito, 2002 55	RCT with 3 groups: HT, genistein, and placebo	Postmenopausal women Ages 47–57 N=90	HT: 1 mg 17β-estradiol and 0.5 mg norethisterone acetate. Genistein: 54 mg/day Duration: 1 year	Both genistein and HT significantly increased BMD in the femur and lumbar spine.
Alekel, 2000 56	RCT with 3 groups: ISP with isoflavones (ISP+), ISP without isoflavones (ISP−), and control	Perimenopausal women Median age=50 N=69	ISP+ contained 80mg/day isoflavones. Both ISP+ and ISP− contained 40g/day of soy protein. Duration: 24 weeks	Regression analysis showed that ISP+ treatment had a positive effect on change in BMD.
Lydeking-Olsen,2004 57	RCT with 4 groups: soymilk, transdermal progesterone, combination, and placebo	Postmenopausal women Caucasian With established osteoporosis or 3 risk factors for the disease N=89	Soymilk contained isoflavones. Combination group consumed soymilk and used transdermal progesterone. Placebo group consumed isoflavone-free soymilk and progesterone-free cream. Duration: 2 years	In the soymilk group, BMC and BMD did not differ from baseline, but significant bone loss occurred in placebo group and combination group.
Chiechi, 2002 58	RCT with 3 groups: Soy-rich diet, HT group, control group.	Healthy postmenopausal women Ages 39–60 n=187	Soy-rich diet group added 1 soy food serving per day and exchanged 2 meals 2 times a week with soy rich meals provided by the study. Duration: 6 months	Diet not as effective as HT in reducing bone turnover. BMD significantly decreased only in the control group. Safety: endometrial thickness increased slightly in soy diet group, increased significantly in HT group.
Chen YM, 2003 59	RCT with 3 groups: placebo, mid-dose, and high-dose, in pill form	Postmenopausal women Chinese Ages 48–62 N=203	All supplements contained 500mg/d calcium and 125 IU/d vitamin D. Isoflavone amounts Placebo: 0 mg/day Mid-dose: 40mg/day High-dose: 80 mg/day Duration: 1 year	Rate of change in BMC was significantly higher in high-dose group compared to placebo and mid-dose groups. Effect was mild and only found in women with initial BMC < median.
Chen YM, 2004 60	RCT with 3 groups: placebo, mid-dose, and high-dose, in pill form	Postmenopausal women Chinese Ages 48–62 N=203	All supplements contained 500mg/d calcium and 125 IU/d vitamin D. Isoflavone amounts Placebo: 0 mg/day Mid-dose: 40mg/day High-dose: 80 mg/day Duration: 1 year	Rate of change in BMC was significantly effected by isoflavones in later postmenopausal women (years since menopause>4), lower body weight (<55.5 kg), and lower calcium intake.
Uesugi, 2002 40	RCT with 2 groups: soy isoflavone capsule and placebo	Perimenopausal women Ages 40–62 N=23	Soy isoflavone capsule contained 61.8 mg of isoflavones. Duration: 4 weeks	Excretion of bone resorption markers was reduced significantly in the isoflavone group. BMC or BMD not tested.
Kreijkamp-Kaspers, 2004 34	RCT with 2 groups: ISP or casein protein	Postmenopausal women Ages 60–75 n=202	ISP contained 25.6 g/day of soy protein and 99mg/day of isoflavones. Duration: 12 months	Bone mineral density did not differ between the groups after 1 year.
Gallagher, 2004 36	RCT with 3 groups: ISP with high, low, or no isoflavone	Postmenopausal women Mean age=55 N=65	High isoflavone 96mg/d Low isoflavone 52 mg/d No isoflavone <4mg/d Duration: 9 months	No effect of any of the ISP supplements on BMD in spine or femoral neck.
Dalais, 1998 61	RCT with crossover design and 2 arms: wheat/soy arm and wheat/linseed arm	Postmenopausal women Ages 45–65 N=52	Wheat, linseed, and soy were baked into bread which was substituted for usual bread intake. Duration: 12 weeks each diet	No changes in BMD found between the groups. BMC increased by 5.2% after the soy phase (significant). No increases in BMC after wheat or linseed phase.
Roughead, 2005 37	Controlled feeding study with crossover design. 2 groups: control diet and soy diet	Postmenopausal women Ages 52–69 N=13	In soy diet, 25g high-isoflavone soy protein was substituted for an equivalent amount of meat protein. Duration: 7 weeks each diet	Diet did not affect biomarkers of bone retention.
Dalais, 2003 20	RCT with 2 groups: ISP or casein placebo supplement	Postmenopausal women Ages 50–75 n=106	ISP contained 40 g/day of soy protein and 118 mg isoflavones. Duration: 3 months	No significant differences in markers of bone resorption between placebo and control groups.
Arjmandi, 2005 62	RCT with 2 dietary treatments: soy or control	Postmenopausal women Age <65 years old n=87	Soy diet contained 25g soy protein/day and 60mg isoflavones. Control diet contained no soy or isoflavones. Foods were provided to participants Duration: 1 year	Both soy and control groups significantly decreased whole body and lumbar BMC and BMD. Both soy and placebo treatments positively affected markers of bone formation.

^*Abbreviations: RCT=Randomized Controlled Trial, NCEP=National Cholesterol Education Program, ISP=Isolated Soy Protein, HT=hormone therapy