Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

Abstract

Background: Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial.

Objective: Our aim was to test the effect of soy isoflavone supplementation on bone health.

Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed.

Results: After study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism.

Conclusion: Daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

FIGURE 1

Flowchart of the study design and subject participation throughout the current study. GI, gastrointestinal; HRT, hormone replacement therapy.

FIGURE 2

Mean (±SEM) whole-body (WB) bone mineral density (BMD) values by supplementation group, with 1- and 2-y outcomes as the dependent variable, according to a general linear model with adjustment for study site, soy protein intake, and pretreatment values. Letters above the columns at 1 y (placebo: n = 128; 80 mg soy isoflavones/d: n = 122; 120 mg soy isoflavones/d: n = 123) and at 2 y (placebo: n = 126; 80 mg soy isoflavones/d: n = 119; 120 mg soy isoflavones/d: n = 117) denote differences between the treatment groups where a and c = placebo compared with 80 mg/d (P > 0.05) and b and d = placebo compared with 120 mg/d (P < 0.05).

FIGURE 3

Mean (±SEM) changes in whole-body (WB) bone mineral density (BMD) T scores by supplementation group, with 1- and 2-y outcomes as the dependent variable, according to a general linear model with adjustment for study site, soy protein intake, and pretreatment values. Letters below the columns at 1 y (placebo: n = 128; 80 mg soy isoflavones/d: n = 122; 120 mg soy isoflavones/d: n = 123) and at 2 y (placebo: n = 126; 80 mg soy isoflavones/d: n = 119; 120 mg soy isoflavones/d: n = 117) denote differences between the treatment groups where a and c = placebo compared with 80 mg/d (P > 0.05), b = placebo compared with 120 mg/d (P < 0.05), and d = placebo compared with 120 mg/d (P > 0.05).