The potential for soy protein or soy isoflavones to alter bone metabolism and bone resorption is currently contradictory and inconclusive. The lack of agreement in the literature is thought to be related to variations in study design. These variations in study design include differences in the dosage and form of soy products studied, (i.e. soy protein isolate, whole soy foods, or extracted soy isoflavones), differences in the menopausal status of the women studied, (i.e. perimenopausal, early menopausal or late postmenopausal) differences in the duration of the various trials, and differences in the tests used to assess bone density and bone metabolism. All of these different approaches and study designs make it very difficult to determine the effectiveness of soy for bone health, and make the decision to include soy in a protocol for supporting bone health more difficult for the practitioner.
Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17- beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone, which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.
Bone mineral density (BMD) is the gold standard for determining fracture risk due to non-traumatic events. Bone turnover is an independent predictor of fracture risk. While research on the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and increasing bone density in women. Soy appears to have an estrogenic effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in a study in which soy replaced casein in the diet and compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen, genistein in maintaining bone. These authors also reported that genistein suppresses osteoclasts, the cells responsible for bone resorption, both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, and controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.
Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of soy isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the isoflavone diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip. Soy isoflavones seem to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great of ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.
An analysis of the relationship of soy isoflavone intake and bone mineral density was conducted from the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, median intakes of genistein were too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Premenopausal, but not perimenopausal Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. The mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.
Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.
A recent meta-analysis further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated in this meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline), a marker of bone turnover, demonstrated that those who consumed isoflavones had a decrease in these biomarkers of -2.08nmol/mmol, when compared to those who did not consume isoflavones. In five of the studies where isolated soy protein was used there was no significant effect on urinary deoxypyridinoline. In the current analysis, a significant reduction in urinary deoxypyridinoline was not observed in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90 mg of isoflavones per day is required to achieve benefits on bone health.
In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.
I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the meta-analysis mentioned above which analyzed nine studies the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of daidzein into its active metabolite equol by intestinal flora, and by the fact that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.
Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.
A nutritional influence of soy foods that may be overlooked is the amount of calcium in some of these foods or in diets that contain soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much, or more, calcium than a serving of dairy products.
CALCIUM CONTENT OF SELECTED SOY FOODS
| Soy Product | Serving Size | Mg of Calcium |
| Tofu, firm | ¼ block | 553 mg |
| Tofu, regular | ¼ block | 406 |
| Soy milk, Calcium fortified | 1 cup | 80-300 |
| Soy milk | 1 cup | 7 |
| Soybeans, Roasted | ¼ cup | 119 |
| Soybeans, Boiled | ¼ cup | 88 mg |
| Tempeh | ¼ cup | 77 |
With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. For these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk in addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), and dietary and exercise advice.
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