Soy and Its Isoflavones:
A Review of Their Effects on Bone Density

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 2002 (Aug); 7 (4): 317–327 ~ FULL TEXT

Brynin R

Southern California University of Health Sciences,
16200 East Amber Valley Drive,
Whittier, CA 90609, USA

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Menopausal hormone decline contributes significantly to the risk of osteoporosis. Therapies for treating osteoporosis, such as hormone replacement therapy (estrogen or combination estrogen-progestins), inhibit bone resorption. Both animal and human studies demonstrate phytoestrogenic soy isoflavones favorably impact bone health. The exact mechanism is still unclear. Additional research is needed to determine if isoflavones are an effective alternative to hormone replacement therapy for the prevention and treatment of osteoporosis. This paper reviews in vitro, animal, and human studies involving isoflavones and bone health.

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Osteoporosis – General Overview and Statistics

The menopausal transition is characterized by a rapid decline in ovarian function and a subsequent decline in circulating hormones, including estradiol. This hormone-deficient state contributes to significant risk for developing osteoporosis in postmenopausal women. [1] Osteoporosis poses a major health threat to more than 28 million Americans, 80 percent of whom are women. Currently, in the United States, 10 million people have osteoporosis, and 18 million more have low bone mass, placing them at an increased risk for osteoporosis. [2] One in two women and one in eight men over age 50 will experience an osteoporosis- related fracture in their lifetime. [2] Osteoporosis is responsible for more than 1.5 million fractures per year, including 300,000 hip fractures, 700,000 vertebral fractures, 250,000 wrist fractures, and 300,000 fractures at other sites. [2]

Risk factors for developing osteoporosis include the following: female gender, thin and /or small frame, advanced age, family history of osteoporosis, postmenopausal (including early or surgically-induced menopause), amenorrhea, anorexia nervosa or bulimia, a diet low in calcium, long-term use of medications such as corticosteroids and anticonvulsants, low testosterone levels in men, an inactive lifestyle, cigarette smoking, excessive use of alcohol, and Caucasian or Asian heritage (although African Americans and Hispanic Americans are at significant risk as well). [2]

Bone loss occurs most rapidly during the years immediately prior to and after menopause. [3] In the 5-7 years following menopause, women can lose up to 20 percent of their bone mass. [2] Several bone protective actions exerted by estrogen include increased synthesis of 1,25(OH)2 vitamin D, control of bone-resorbing cytokine production, and decreased bone sensitivity to parathyroid hormone. [4] Conventional therapies for treating osteoporosis in women have emphasized agents that inhibit bone resorption [5] and include hormone replacement therapies, either estrogen alone (ERT) or combination estrogen and progestogens (HRT), calcitonin, raloxifene, and bisphosphonates. [6] Despite its potential benefits, hormone replacement therapy has significant risks, including increased occurrence of thromboembolic events, endometrial cancer (with unopposed estrogen), gall bladder and liver disease, and breast and ovarian cancers. Long-term compliance is poor due to side effects and patient concern about risks. [1] It has also been noted that the protective effect of estrogen on vertebral and hip fractures in women is diminished with prolonged use. [7] Therefore, there is a need for alternative treatments to HRT that provide benefits to bone without adverse effects. Data from animal studies suggest that soy isoflavones, possibly due to their structural similarity to estrogen, may protect against bone loss occurring as a result of estrogen deficiency.

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Isoflavones – General Overview

Isoflavones are a subclass of flavonoids with a chemical structure similar to 17ß-estradiol, the most potent, naturally occurring estrogen. [8, 9] Isoflavones bind to estrogen receptors, affecting estrogen-regulated processes, and are therefore referred to as phytoestrogens (plant estrogens). [3, 10] Many of their effects, however, may not involve the estrogen receptor. [9] Isoflavones are extremely limited in nature, found in nutritionally significant amounts only in soy. [1, 3, 11, 12] The main isoflavones in soybeans are genistein and daidzein (Figure 1). [14] A third isoflavone, glycitein, is also present, although in much smaller amounts. [10]

Cells vary in their distribution of the classic estrogen receptor alpha (ERa) and the newly discovered ERß, depending on the tissue. [11] For instance, reproductive cells, especially those of the uterus and breast, are abundant in ERa, [1, 11, 13] whereas, bone tissue has greater amounts of ERß. [13] Genistein binds with a much greater affinity to ERß than to ERa1, [10, 11, 13] The different tissue distribution of a- and ß-receptors points to the possibility of tissue-selective effects of the isoflavones, [1] as they appear to have different effects in different tissues. [10] Isoflavones, therefore, could influence several biological processes controlled by estrogen, including bone metabolism. [14] The occupancy time and affinity of isoflavones for the ERa receptor is much less than that of estradiol. [15]

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