Bone Response to Soy Isoflavones in Women (SIRBL)

Iowa State University

Status and phase: Completed; Phase 2

Conditions: Osteoporosis; Osteopenia

Treatments: Dietary Supplement: Soy isoflavones; Dietary Supplement: Extract tablets

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00043745

R01AR046922 (U.S. NIH Grant/Contract)

NIAMS-073

Details and patient eligibility

About

This study will provide valuable data on whether soy isoflavones impact bone loss in postmenopausal women. The study will help clarify potential mechanisms and contribute to our understanding of isoflavones as an alternative to traditional hormone therapy.

Full description

Soy protein, rich in isoflavones (estrogen-like compounds), has been shown to prevent bone loss in ovariectomized rats. Short-term preliminary study results in perimenopausal women suggest a bone-sparing effect. Great interest in isoflavones as an alternative to hormone replacement therapy has emerged, yet the long-term efficacy of isoflavones on bone in humans is unknown. Our objective is to determine the three-year efficacy of isoflavone-rich soy extract in attenuating bone loss in postmenopausal women. The central hypothesis is that soy isoflavones will attenuate bone loss in these women by maintaining bone formation, which is modulated by growth factors and isoflavone metabolism. The rationale for this research is that current hormone therapy is fraught with adverse side effects, resulting in non-compliance. This randomized, double-blind, placebo-controlled clinical trial will examine the effects of two doses (80 or 120 mg daily) of isoflavone-rich soy extract on bone in non-osteoporotic postmenopausal women (N=234). The specific aims of this study are: 1) to determine the bone-preserving effects of isoflavones on lumbar spine bone mineral density (BMD); 2) to relate treatment-induced changes in BMD to changes in biochemical markers of bone turnover; 3) to identify potential mechanisms by which isoflavones prevent or modulate bone loss by measuring endogenous estrogens, sex hormone-binding globulin, insulin-like growth factor-I (IGF-I), urinary minerals, serum 25(OH)vitamin D, plasma isoflavones and their metabolites, and customary intake of isoflavone-containing soy; and, 4) to ascertain the safety of isoflavone-rich soy extract. Postmenopausal women will be recruited at two sites (117 at Iowa, 117 at California). Random effects repeated measures analyses will be used to characterize change in BMD as the primary outcome, estimate treatment-induced effects, and depict change in markers of bone turnover in relation to BMD change. We will use intent-to-treat for the primary test, but also account for potential modulators (reproductive hormones, IGF-I, plasma isoflavones) that affect bone, as indicated in specific aim 3.

Enrollment: 224 patients

Sex: Female

Ages: 45 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Early postmenopausal (i.e., no menses during past 12 months) women, with an upper limit of 10 years since their last cycle
• Natural menopause (i.e., no hysterectomies or oophorectomies)
• Body mass index (BMI) > 20 and < 30

Exclusion criteria

• Current or previous (within 12 months) use of hormone replacement therapy, hormonal contraceptives, estrogens, or progestogens
• Current use of pharmacologic agents, such as selective estrogen-receptor modulators (SERMs) (e.g., raloxifene or tamoxifen) or anti-resorptive agents (e.g., alendronate or calcitonin), herbal therapies that may have estrogenic effects (e.g., herbimycin, tryphostins), or cigarettes
• Strict vegans (but will include lacto-ovo-, lacto-, and ovo-vegetarians)
• Metabolic bone disease, renal disease, history of urolithiasis, cancer, cardiovascular disease, diabetes mellitus, respiratory disease, gastrointestinal disease, liver disease, or other chronic diseases
• First-degree relative with breast cancer
• Lumbar spine BMD >= -1.5 standard deviations (SD) below mean (high-risk for osteoporosis) and BMD >= +1.0 SD above mean

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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224 participants in 3 patient groups, including a placebo group

1

Experimental group

Description:

Participants will receive moderate dose soy isoflavone (80 mg/day) tablets, extracted from soy protein

Treatment:

Dietary Supplement: Soy isoflavones

2

Experimental group

Description:

Participants will receive high dose soy isoflavone (120 mg/day) tablets, extracted from soy protein

Treatment:

Dietary Supplement: Soy isoflavones

3

Placebo Comparator group

Description:

Participants will receive soy extract devoid of isoflavones to serve as placebo

Treatment:

Dietary Supplement: Extract tablets