~ Male Osteoporosis: The Hidden Epidemic, Part 2

Tests, Treatments, and Supplements

Because of its slow and insidious nature, osteoporosis may not be diagnosed until after a serious fracture has occurred. For this reason, all modern guidelines recommend aggressive case-finding and screening programs.33 The growing recognition that men are at much higher risk than previously believed means that men, too, should undergo regular screening. The sidebar on the previous page describes the best screening test to evaluate bone mineral density. Because prevention is much more effective than treatment, however, most experts recommend the use of nutritional supplements, even when early screening results are negative.

The main prescription medication for osteoporosis is a category of drugs called bisphosphonates—such as Fosamax®—that can prevent bone loss.34 These drugs work by inhibiting osteoclasts, thereby slowing bone resorption. They have no significant effect on new bone formation, and may have significant side effects such as gastric ulcers or gastritis.35,36 They are not currently recommended as preventive treatment.7 Even when these drugs are used, adequate supplies of calcium and vitamin D may still be crucial for promoting bone health.37,38

According to Dr. Moyad of the University of Michigan, “complementary therapies, which may also have an impact on reducing osteoporosis risk, have not received attention.” He notes, “Dietary and supplemental calcium and vitamin D have been shown, in some preliminary investigations, to maintain bone density in women and men,” and “the supplemental doses required to impact risk have been moderate, appear to be safe, are of low cost, and thus may provide an additional route for reducing risk, especially if these interventions are initiated at the start of medical treatment.” According to Dr. Moyad, “Simple, inexpensive, and potentially effective dietary and supplemental approaches to reduce the risk of osteoporosis in men exist, and they should be discussed with patients.”6

These supplemental approaches include mineral and vitamin supplements, hormone-like substances, protein supplements, and phyto-estrogens (including soy isoflavones). The mainstay of prevention and treatment for osteoporosis in men and women is to ensure adequate intake of calcium and vitamin D through dietary supplementation.

In a randomized, double-blind, placebo-controlled study published in 2000, daily supplementation with 750 mg of calcium reduced the loss of bone mineral density at the hip significantly more than placebo. Vitamin D alone had a similar, though smaller, effect.39 This study provided either calcium or vitamin D, but not the combination, and the authors point out that vitamin D is most effective in those who have insufficient calcium intake.

A 2005 randomized study found increased bone mineral density in patients who received 500 mg of calcium and 400 IU of vitamin D daily with or without the bisphosphonate drug etidronate (Didronel®). The drug-treated group had no greater improvement than the supplement-only group.40 In another study, supplementation with the vitamin D derivative calcitriol and phosphate produced a larger increase in bone mineral density than etidronate.41

Recently, new synthetic versions of vitamin D have become available that offer more specific benefits directly to bone. One such product, ED-71, was shown to increase bone mass more than regular vitamin D3, while having a similar degree of effect on increasing intestinal calcium absorption.42

Calcium: Not Just for Women

The recommendations above are general and apply to both men and women. As male osteoporosis becomes an increasingly important issue, new guidelines are appearing that specifically target men. Calcium and vitamin D supplements make up part of the so-called “bottom line” recommendations in a 2005 review of men’s health needs,43 and ensuring adequate intakes has been called the “cornerstone of any regimen aimed at treating or preventing osteoporosis in men.”2 Supplementation with calcium and vitamin D is at the top of all recent recommendations for treating osteoporosis in men,44 including guidelines issued by the American College of Rheumatology.45 An expert meeting of the Belgian Bone Club concluded, “supplemental calcium and vitamin D should be considered as the first-line therapy.”46 The same group determined that while combinations of anti-resorptive drugs should not be used, calcium and vitamin D in combination should be encouraged.

An expert panel convened by the World Health Organization Collaborating Center for Osteoporosis Prevention47 issued the following statements about the use of oral supplements of calcium and vitamin D in preventing and treating osteoporosis:
  1. When given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active, safe, and effective for the prevention and treatment of osteoporotic fractures in all patients (that is, those with and without adequate dietary calcium intake).

  2. In patients with insufficient dietary intake of calcium and vitamin D, supplements are an essential but not sufficient component of an integrated management strategy for the prevention and treatment of osteoporosis.

  3. Supplements are cost-effective in the prevention and treatment of osteoporosis.

  4. Awareness of the efficacy of calcium and vitamin D supplementation is still low and further work needs to be done to increase awareness among patients, physicians, and people at risk. This lack of knowledge was borne out in a US study, in which an extensive review of the records of male veterans at risk for osteoporosis found that only 8% received the recommended calcium and vitamin D supplementation.45
Calcium: How Much, How Often?

Calcium supplements come in various forms, as calcium carbonate, gluconate, citrate, or others.

It is important to remember that the amount of calcium used in these various studies is based only on the elemental calcium content of the supplement. Be sure to read the label of the supplement you are taking—the amount of elemental calcium should provide at least 1000 mg a day.

It may turn out that not only is supplementation vital to preventing and treating osteoporosis, but that the timing of the supplementation is important. For example, in a study of healthy volunteers, two doses of 500 mg of calcium and 400 IU of vitamin D taken six hours apart produced a more prolonged decrease in serum parathyroid hormone levels (low levels of which indicate adequate calcium levels) than a single dose with the same total amounts of calcium and vitamin D.48

Calcium can be paired with other bone-promoting supplements for an even greater benefit. Bone mineral density increased and fracture rate fell in men treated early with a fluoride-calcium regimen,49 while salmon calcitonin and calcium produced significantly increased bone mineral density at multiple bone sites in men.50

Other Vitamins and Minerals

Silicon, the second most common element in the Earth’s crust, is an ultra-trace element that is vital for a large number of biological functions.53 For more than two decades, it has been recognized that silicon plays a fundamental role in bone health54 and may be protective against neurodegenerative conditions such as Alzheimer’s disease.56 The details of silicon’s importance in preventing and treating osteoporosis in men are only now beginning to emerge.55-58

During new bone formation, silicon is essential for forming the protein cross-links in the organic matrix. In a rat model, bone formation in silicon-supplemented animals increased by 30% while bone resorption decreased by 31%.59 Similar results were found more recently in rats and horses.60,61

In humans, higher silicon intake is associated with higher bone mineral density.62 This effect has been found to be especially important in men and premenopausal women.56 Because the primary dietary sources of silicon for men are beer and bananas,63 supplemental silicon is likely to be required.

The most recent and exciting data on silicon supplements in humans come from a study presented at the American Society for Bone and Mineral Research meeting in September 2005.64 The authors conducted a randomized, controlled trial of a highly bioavailable silicon supplement, choline-stabilized orthosilic acid (ch-OSA). While all the study subjects received both calcium and vitamin D3 supplements, the treatment groups also were given three different doses of ch-OSA. After 12 months, patients who took the silicon supplements at the two higher doses (6 mg and 12 mg of silicon) had significant improvements in markers of bone formation compared to controls. Bone mineral density also improved at the femoral neck in the 6-mg silicon group. The authors concluded that ch-OSA plus calcium and vitamin D3 is a safe, well-tolerated treatment with a potentially beneficial effect on bone turnover, especially bone collagen.

Oral magnesium supplementation has been shown to significantly reduce the bone turnover rate in men.65 Because increased bone turnover rate is known to be an important factor in osteoporosis, magnesium supplementation may offer a natural approach to preventing and possibly managing this condition. While supplementing with magnesium and calcium at the same time may decrease the absorption of the respective minerals, this interaction has not been shown to be clinically significant.66 Thus, consuming supplements that combine calcium and magnesium may be the most convenient way for individuals to acquire these crucial minerals. Nutrition experts recommend obtaining calcium and magnesium in ratios ranging from 1:1 to 2:1.

Vitamin K, long known to be critical in the blood-clotting system, more recently has been been found to be important in bone and mineral metabolism. Vitamin K2 is active and more powerful than vitamin K1 in both decreasing bone loss through resorption and enhancing the bone-building process. K2 was recently recommended for consideration in helping to prevent or treat osteoporosis in patients whose underlying conditions put them at risk for the disease.67 Because vitamin K contributes to blood clotting, individuals who use warfarin should consult their physicians before taking vitamin K.

Hormone Replacement Therapy

Conventional hormone replacement therapy with equine estrogens and synthetic progestins (medroxy progesterone acetate) has been used for years to prevent or mitigate osteoporosis in women, but recent reports of dangerous consequences, such as breast and uterine cancer, have cast doubts on its safety. Dehydroepiandrosterone (DHEA) may offer an alternative in people who do not have hormone-dependent cancers.

Both men and women manufacture DHEA throughout their lives as the common precursor to the sex hormones. DHEA levels, however, decline dramatically as men and women age. Restoring DHEA levels to the optimal range found in healthy young adults may enhance bone mineral density.68 Importantly, and unlike prescription bisphosphonate drugs, DHEA appears to enhance new bone formation as well as inhibit bone resorption. This effect has been reported to be greater in women than in men, but a group of Italian researchers found that supplementation with 25 mg per day of DHEA in a group of aging men with partial androgen deficiency increased serum levels of DHEA, DHEA-S, androstenedione, total and free testosterone, progesterone, 17-hydroxyprogesterone, estrone, estradiol, and growth hormone.16 These hormones all promote bone deposition and prevent bone resorption in the presence of adequate supplies of calcium, magnesium, and phosphorus. Importantly, supplementation with DHEA also lowered serum levels of the gonadotropin-releasing hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH); this is the desirable effect obtained by many drugs used in treating prostate cancers, and may also help to reduce bone turnover and limit mineral losses.

Serum DHEA-S levels correlate strongly with bone mineral density in adults; DHEA-S is believed to convert to androstenedione and then to estrone within the osteoblast cell only.69 This effect could explain how DHEA can augment bone density without producing unwanted feminizing effects on the body as a whole.

Most experts are calling for larger, placebo-controlled trials to fully define DHEA’s benefits on bone mineral density.68 Because DHEA is metabolized to estrogen and testosterone, it should not be used in people with known hormone-dependent cancers such as breast or prostate cancer.

Hormone replacement therapy may benefit more than just bone mass and density. A small, randomized, double-blind, placebo-controlled trial in 2001 demonstrated improved performance on tests of spatial and verbal memory in older men who received testosterone injections compared to those who received placebo.15 Because testosterone can be metabolized into estradiol, a female hormone, estradiol levels also rose in the treated men, and the authors raised the valid question of whether the observed improvement was due to higher estradiol levels.

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

Summary

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.

References . . .


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