The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women

Abstract

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, randomized 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 clinicaltrials.gov as NCT00043745.

FIGURE 1

Study participant CONSORT (Consolidated Standards of Reporting Trials) diagram. ¹Altogether, 8 women discontinued treatment but completed the trial (1 at Iowa State University, 7 at University of California at Davis), and 31 women were lost to follow-up (LTFU; 2 at Iowa State University, 29 at University at California at Davis). Diagram indicates the last time point [baseline (base) or 6, 12, 24 mo] for each woman who was LTFU and reasons provided for discontinuing. ²Eleven subjects at University of California at Davis had thickened endometria [(determined by transvaginal ultrasound (TVU)] and thus did not meet inclusion criterion (≤5 mm). BMD, bone mineral density.

FIGURE 2

Parallel profile plot for intent-to-treat women (n = 224) with mean (±SEM) values for lumbar spine, total proximal femur, femoral neck, and whole-body bone mineral density (BMD) at each time point (baseline and 6, 12, 24, and 36 mo) for each treatment group: control, n = 74; 80 mg/d, n = 77; 120 mg/d, n = 73. Tests for parallel profiles for lumbar spine (Wilks' = 0.981, P = 0.85), neck (Wilks' = 0.951, P = 0.21), and whole-body (Wilks' = 0.962, P = 0.38) BMD indicated no interaction between treatment and time. A test for parallel profile for proximal femur BMD (Wilks' = 0.926, P = 0.030) indicated an interaction between treatment and time.