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LE Magazine January 2006

Strategies for Preventing Osteoporosis in Men

By Julius G. Goepp, MD

Protein Supplements

Until recently, it was thought that high-protein diets may cause increased resorption of calcium from bone, because elevated calcium levels were found in the urine of those with a high intake of protein. More recent studies have demonstrated just the opposite: that the increased urine calcium levels seem to be the result of increased intestinal absorption of calcium, which of course means that there is more, not less, calcium available for bone mineralization. Lower-protein diets were found to decrease calcium absorption.30 This may explain why people who habitually consume low-protein diets are known to have decreased bone density and increased bone loss.

Soy protein supplementation has been known to be protective of bone in women. In 2002, this finding was extended to men. A study of healthy older men (with an average age of 60) showed that those who supplemented daily with 40 grams of soy protein for three months significantly increased their levels of insulin-like growth factor 1 (IGF-1) compared to men who supplemented with milk protein. IGF-1 is associated with higher rates of bone formation. While markers of bone formation and resorption were not different between the two groups, the authors concluded that soy protein supplements may positively influence bone in men. They went on to suggest that a longer-duration study is warranted to demonstrate this effect.70

Phytoestrogens and Isoflavones

There has been growing interest in how another soy component—the isoflavones—may help prevent and manage heart disease, osteoporosis, and cancer. Soy isoflavones are phytoestrogens, or plant-based compounds that resemble estrogen at the molecular level. Studies of traditional diets in large populations demonstrate that foods containing phytoestrogens may offer protection against many hormone-related cancers, and that adding phytoestrogen-rich foods to the diet helps maintain bone density in people with osteoporosis.71 Particularly since the publication of the Women’s Health Initiative warning against estrogen’s use in hormone replacement therapy,14 the importance of isoflavone phytoestrogens has grown.

Direct scientific evidence for isoflavones in osteoporosis is abundant. In 2001, a review of 74 major articles concluded that evidence for the health benefits of phytoestrogens was increasing.72 A randomized, placebo-controlled clinical trial published in 2004 demonstrated a significant increase in lumbar-spine bone mineral density and a 37% reduction in urinary markers of bone turnover in patients with postmenopausal osteoporosis who supplemented with isoflavones.73

The beneficial effects of isoflavones on skeletal health have been attributed to their unique organic structures.74 Isoflavones may act differently in different tissues, to the benefit of people who consume them. For example, in bone tissue, isoflavones act as weak estrogen-like hormones in the bone-building osteoblast cells, promoting new bone formation. The estrogen-like effect in bone also causes an increase in cell-signaling proteins that may inhibit the bone-absorbing activity of the osteoclast cells. In reproductive tissues, however, isoflavones function as weak estrogen antagonists, so they do not produce the feminizing effects of estrogen itself. Many of these molecular mechanisms closely resemble the actions attributed to DHEA.69

No trial of isoflavones in men with osteoporosis has yet appeared in the literature, but there is every reason to believe that they will be at least as effective as in women. Given differences in the ways that bone loss occurs in men and women, it is possible that the osteoblast-stimulating effect of isoflavones will result in even more gain in bone density in men.

Ipriflavone, a synthetic isoflavone, has attracted much attention and research, especially in Europe, where it is now used as a drug in treating osteoporosis.75 It has been shown to effectively inhibit bone resorption and enhance bone formation in both women and men.76 A double-blind, placebo-controlled study of ipriflavone in 255 postmenopausal women found that forearm bone mineral density remained constant for two years in the treatment group while diminishing significantly in the placebo group. Markers of bone turnover were higher in the placebo group than in the treated group.77

The same investigators discovered virtually identical results in a larger trial of 453 postmenopausal women. In the ipriflavone-treated group, bone sparing of between 1.6% and 3.5% occurred, and bone turnover was reduced.78 Similar results have been reported in many other studies.79-82 Ipriflavone’s safety has also been well established, with primary side effects being mild gastrointestinal upset; these effects seemed to occur with equal frequency in both ipriflavone and placebo groups in all the trials.83

Like natural isoflavones, ipriflavone enhances estrogen’s effect on bone without acting as a female sex hormone,76 so that it may have many fewer of the undesirable feminizing effects of estrogen and related drugs. These weak estrogenic effects of isoflavones and ipriflavone are thought to account not only for their demonstrated ability to enhance bone mineral density and prevent osteoporosis, but also to explain the encouraging data on their effect in reducing prostate cancer risk. These data come from both rodent studies and limited human experience.84 Rodent models so far provide the only direct interventional data about the roles of these substances in males.

The data from animal models of ipriflavone in males is very encouraging. Two studies of ipriflavone’s effects on male rats found that the bones of animals in the treated group had an average 23% greater capacity to withstand stress, and required almost 50% more energy to cause a fracture, compared to animals in the untreated groups.85 The proportions of calcium, phosphorus, and magnesium in the bones did not differ between the groups, suggesting that there were no abnormalities in the overall mineral composition or crystalline structure of the hydroxyapatite in the stronger bones.86


For men, maintaining good bone health starts with regular doctor visits to screen for bone mineral density and prostate cancer. Other essentials are regular, weight-bearing exercise, healthy, moderate-protein diets, and supplements including vitamin D, calcium, magnesium, and isoflavones to help prevent bone mineral losses. Men at risk for hormone-dependent cancers should always discuss supplementation plans with their physicians to ensure that the supplements and medications are working together for best effect.


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