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Strategies for Preventing Osteoporosis in Men

January 2006

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.


1. Gennari L, Merlotti D, Martini G,et al. Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Ciin Endocrinol Metab. 2003 Nov;88(11):5327-33.

2. Kamel HK. Male osteoporosis: new trends in diagnosis and therapy. Drugs Aging. 2005;22(9):741-8.

3. Levy P, Levy E, Audran M, et al. The cost of osteoporosis in men: the French situation. Bone. 2002 Apr;30(4):631-6.

4. Duan Y, Seeman E. Bone fragility in Asian and Caucasian men. Ann Acad Med Singapore. 2002 Jan;31(1):54-66.

5. Seeman E. Unresolved issues in osteoporosis in men. Rev Endocr Metab Disord. 2001 Jan;2(1):45-64.

6. Moyad MA. Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormone-releasing hormone treatment/orchiectomy for prostate cancer: a review and assessment of the need for more research. Urology. 2002 Apr;59(4 Suppl 1):34-40.

7. Higano CS. Management of bone loss in men with prostate cancer. J Urol. 2003 Dec;170(6 Pt 2):S59-S63.

8. Khosla S, Melton LJ, III, Riggs BL. Osteoporosis: gender differences and similarities. Lupus. 1999;8(5):393-6.

9. Jalava T, Sarna S, Pylkkanen L, et al. Association between vertebral fracture and increased mortality in osteoporotic patients. J Bone Miner Res. 2003 Jul;18(7):1254-60.

10. Haentjens P, Johnell O, Kanis JA, et al. Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles’ or spine fracture: Colles’ fracture as an early and sensitive marker of skeletal fragility in white men. J Bone Miner Res. 2004 Dec;19(12):1933-44.

11. Siqueira FV, Facchini LA, Hallal PC. The burden of fractures in Brazil: a population-based study. Bone. 2005 Aug;37(2):261-6.

12. Seeman E. The structural basis of bone fragility in men. Bone. 1999 Jul;25(1):143-7.

13. Hijazi RA, Cunningham GR. Andropause: is androgen replacement therapy indicated for the aging male? Annu Rev Med. 2005;56:117-37.

14. Skouby SO, Al-Azzawi F, Barlow D, et al. Climacteric medicine: European Menopause and Andropause Society (EMAS) 2004/2005 position statements on peri- and postmenopausal hormone replacement therapy. Maturitas. 2005 May 16;51(1):8-14.

15. Cherrier MM, Asthana S, Plymate S, et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 2001 Jul 10;57(1):80-8.

16. Genazzani AR, Inglese S, Lombardi I, et al. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male. 2004 Jun;7(2):133-43.

17. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000 Aug 31;343(9):604-10.

18. Morales A. Andropause (or symptomatic late-onset hypogonadism): facts, fiction and controversies. Aging Male. 2004 Dec;7(4):297-303.

19. Dovio A, Perazzolo L, Osella G, et al. Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab. 2004 Oct;89(10):4923-8.

20. Kannisto S, Laatikainen A, Taivainen A, et al. Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients. Eur J Endocrinol. 2004 May;150(5):687-90.

21. Conde FA, Aronson WJ. Risk factors for male osteoporosis. Urol Oncol. 2003 Sep;21(5):380-3.

22. Hussain SA, Weston R, Stephenson RN, George E, Parr NJ. Immediate dual energy X-ray absorptiometry reveals a high incidence of osteoporosis in patients with advanced prostate cancer before hormonal manipulation. BJU Int. 2003 Nov;92(7):690-4.

23. Rashid MH, Chaudhary UB. Intermittent androgen deprivation therapy for prostate cancer. Oncologist. 2004;9(3):295-301.

24. Dawson-Hughes B. Racial/ethnic considerations in making recommendations for vitamin D for adult and elderly men and women. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1763S-6S.

25. Monier-Faugere MC, Mawad H, Qi Q, Friedler RM, Malluche HH. High prevalence of low bone turnover and occurrence of osteomalacia after kidney transplantation. J Am Soc Nephrol. 2000 Jun;11(6):1093-9.

26. Dodidou P, Bruckner T, Hosch S, et al. Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation. Osteoporos Int. 2003 Jan;14(1):82-9.

27. Kapoor D, Jones TH. Smoking and hormones in health and endocrine disorders. Eur J Endocrinol. 2005 Apr;152(4):491-9.

28. Wawrzynska L, Tomkowski WZ, Przedlacki J, Hajduk B, Torbicki A. Changes in bone density during long-term administration of low-molecular-weight heparins or acenocoumarol for secondary prophylaxis of venous thromboembolism. Pathophysiol Haemost Thromb. 2003 Mar;33(2):64-7.

29. Wong SY, Lau EM, Lau WW, Lynn HS. Is dietary counselling effective in increasing dietary calcium, protein and energy intake in patients with osteoporotic fractures? A randomized controlled clinical trial. J Hum Nutr Diet. 2004 Aug;17(4):359-64.

30. Kerstetter JE, O’Brien KO, Insogna KL. Dietary protein, calcium metabolism, and skeletal homeostasis revisited. Am J Clin Nutr. 2003 Sep;78(3 Suppl):584S-92S.

31. Haderslev KV, Tjellesen L, Sorensen HA, Staun M. Effect of cyclical intravenous clodronate therapy on bone mineral density and markers of bone turnover in patients receiving home parenteral nutrition. Am J Clin Nutr. 2002 Aug;76(2):482-8.

32. Robbins J, Hirsch C, Whitmer R, Cauley J, Harris T. The association of bone mineral density and depression in an older population. J Am Geriatr Soc. 2001 Jun;49(6):732-6.

33. Geusens PP. Review of guidelines for testing and treatment of osteoporosis. Curr Osteoporos Rep. 2003 Sep;1(2):59-65.

34. Heidenreich A. Bisphosphonates in the management of metastatic prostate cancer. Oncology. 2003;65 Suppl 15-11.

35. Graham DY, Malaty HM. Alendronate gastric ulcers. Aliment Pharmacol Ther. 1999 Apr;13(4):515-9.

36. Marshall JK, Rainsford KD, James C, Hunt RH. A randomized controlled trial to assess alendronate-associated injury of the upper gastrointestinal tract. Aliment Pharmacol Ther. 2000 Nov;14(11):1451-7.

37. Francis RM. Non-response to osteoporosis treatment. J Br Menopause Soc. 2004 Jun;10(2):76-80.

38. Papaioannou A, Giangregorio L, Kvern B, et al. The osteoporosis care gap in Canada. BMC Musculoskelet Disord. 2004 Apr 6;511.

39. Peacock M, Liu G, Carey M, et al. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab. 2000 Sep;85(9):3011-9.

40. Siffledeen JS, Fedorak RN, Siminoski K, et al. Randomized trial of etidronate plus calcium and vitamin D for treatment of low bone mineral density in Crohn’s disease. Clin Gastroenterol Hepatol. 2005 Feb;3(2):122-32.

41. Cortet B, Vasseur J, Grardel B, et al. Management of male osteoporosis. Joint Bone Spine. 2001 May;68(3):252-6.

42. Kubodera N, Tsuji N, Uchiyama Y, Endo K. A new active vitamin D analog, ED-71, causes increase in bone mass with preferential effects on bone in osteoporotic patients. J Cell Biochem. 2003 Feb 1;88(2):286-9.

43. Moyad MA. Promoting general health during androgen deprivation therapy (ADT): a rapid 10-step review for your patients. Urol Oncol. 2005 Jan;23(1):56-64.

44. Resch H, Gollob E, Kudlacek S, Pietschmann P. Osteoporosis in the man. Wien Med Wochenschr. 2001;151(18-20):457-63.

45. Elliott ME, Farrah RM, Binkley NC, Carnes ML, Gudmundsson A. Management of glucocorticoid-induced osteoporosis in male veterans. Ann Pharmacother. 2000 Dec;34(12):1380-4.

46. Devogelaer JP, Goemaere S, Boonen S, et al. Evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: a consensus document of the Belgian Bone Club. Osteoporos Int. 2005 Oct 11.

47. Boonen S, Rizzoli R, Meunier PJ, et al. The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report. Osteoporos Int. 2004 Jul;15(7):511-9.

48. Reginster JY, Zegels B, Lejeune E, et al. Influence of daily regimen calcium and vitamin D supplementation on parathyroid hormone secretion. Calcif Tissue Int. 2002 Feb;70(2):78-82.

49. Ringe JD, Dorst A, Kipshoven C, Rovati LC, Setnikar I. Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate. Osteoporos Int. 1998;8(1):47-52.

50. Erlacher L, Kettenbach J, Kiener H, et al. Salmon calcitonin and calcium in the treatment of male osteoporosis: the effect on bone mineral density. Wien Klin Wochenschr. 1997 Apr 25;109(8):270-4.

51. von Bothmer MI, Fridlund B. Gender differences in health habits and in motivation for a healthy lifestyle among Swedish university students. Nurs Health Sci. 2005 Jun;7(2):107-18.

52. Patel A, Coates PS, Nelson JB, et al. Does bone mineral density and knowledge influence health-related behaviors of elderly men at risk for osteoporosis? J Clin Densitom. 2003;6(4):323-30.

53. Bisse E, Epting T, Beil A, et al. Reference values for serum silicon in adults. Anal Biochem. 2005 Feb 1;337(1):130-5.

54. Hayter J. Trace elements: implications for nursing. J Adv Nurs. 1980 Jan;5(1):91-101.

55. Perez-Granados AM, Vaquero MP. Silicon, aluminium, arsenic and lithium: essentiality and human health implications. J Nutr Health Aging. 2002;6(2):154-62.

56. Jugdaohsingh R, Tucker KL, Qiao N, et al. Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort. J Bone Miner Res. 2004 Feb;19(2):297-307.

57. Chapuy MC, Meunier PJ. Prevention and treatment of osteoporosis. Aging (Milano.). 1995 Aug;7(4):164-73.

58. Tucker KL. Dietary intake and bone status with aging. Curr Pharm Des. 2003;9(32):2687-704.

59. Hott M, de PC, Modrowski D, Marie PJ. Short-term effects of organic silicon on trabecular bone in mature ovariectomized rats. Calcif Tissue Int. 1993 Sep;53(3):174-9.

60. Rico H, Gallego-Lago JL, Hernandez ER, et al. Effect of silicon supplement on osteopenia induced by ovariectomy in rats. Calcif Tissue Int. 2000 Jan;66(1):53-5.

61. Lang KJ, Nielsen BD, Waite KL, Hill GM, Orth MW. Supplemental silicon increases plasma and milk silicon concentrations in horses. J Anim Sci. 2001 Oct;79(10):2627-33.

62. Eisinger J, Clairet D. Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a retrospective study. Magnes Res. 1993 Sep;6(3):247-9.

63. Jugdaohsingh R, Anderson SH, Tucker KL, et al. Dietary silicon intake and absorption. Am J Clin Nutr. 2002 May;75(5):887-93.

64. Spector TD, Callome MR, Anderson S, et al. Effect on bone turnover and BMD of low-dose oral silicon as an adjunct to calcium/vitamin D3 in a randomized, placebo-controlled trial. 2005 Sep; Washington, DC, USA: American Society for Bone and Mineral Research; 2005.

65. Dimai HP, Porta S, Wirnsberger G, et al. Daily oral magnesium supplementation suppresses bone turnover in young adult males. J Clin Endocrinol Metab. 1998 Aug;83(8):2742-8.

66. Available at: Accessed October 27, 2005.

67. Plaza SM, Lamson DW. Vitamin K2 in bone metabolism and osteoporosis. Altern Med Rev. 2005 Mar;10(1):24-35.

68. Villareal DT. Effects of dehydroepiandrosterone on bone mineral density: what implications for therapy? Treat Endocrinol. 2002;1(6):349-57.

69. Yanase T, Suzuki S, Goto K, Nawata H, Takayanagi R. DHEA and bone metabolism. Clin Calcium. 2003 Nov;13(11):1419-24.

70. Khalil DA, Lucas EA, Juma S, Smith BJ, Payton ME, Arjmandi BH. Soy protein supplementation increases serum insulin-like growth factor-I in young and old men but does not affect markers of bone metabolism. J Nutr. 2002 Sep;132(9):2605-8.

71. Humfrey CD. Phytoestrogens and human health effects: weighing up the current evidence. Nat Toxins. 1998;6(2):51-9.

72. Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med. 2001 May 14;161(9):1161-72.

73. Harkness LS, Fiedler K, Sehgal AR, Oravec D, Lerner E. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health (Larchmt.). 2004 Nov;13(9):1000-7.

74. Chen X, Anderson JJ. Isoflavones and bone: animal and human evidence of efficacy. J Musculoskelet Neuronal Interact. 2002 Jun;2(4):352-9.

75. Messina M, Messina V. Soyfoods, soybean isoflavones, and bone health: a brief overview. J Ren Nutr. 2000 Apr;10(2):63-8.

76. Head KA. Ipriflavone: an important bone-building isoflavone. Altern Med Rev. 1999 Feb;4(1):10-22.

77. Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int. 1997;7(2):119-25.

78. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int. 1997;61 Suppl 1S19-S22.

79. Agnusdei D, Crepaldi G, Isaia G et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 1997 Aug;61(2):142-7.

80. Valente M, Bufalino L, Castiglione GN, et al. Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int. 1994 May;54(5):377-80.

81. Kovacs AB. Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions. 1994 Mar;41(1-2):86-7.

82. Passeri M, Biondi M, Costi D, et al. Effect of ipriflavone on bone mass in elderly osteoporotic women. Bone Miner. 1992 Oct;19 Suppl 1S57-S62.

83. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61 Suppl 1S23-7.

84. Messina MJ. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr. 1999 Sep;70(3 Suppl):439S-50S.

85. Civitelli R, bbasi-Jarhomi SH, Halstead LR, Dimarogonas A. Ipriflavone improves bone density and biomechanical properties of adult male rat bones. Calcif Tissue Int. 1995 Mar;56(3):215-9.

86. Ghezzo C, Civitelli R, Cadel S, et al. Ipriflavone does not alter bone apatite crystal structure in adult male rats. Calcif Tissue Int. 1996 Dec;59(6):496-9.

87. Smith MR, McGovern FJ, Fallon MA, Schoenfeld D, Kantoff PW, Finkelstein JS. Low bone mineral density in hormone-naive men with prostate carcinoma. Cancer. 2001 Jun 15;91(12):2238–45.

88. Strum SB, Scholz MC. Quantitative computerized tomography in prostate cancer. J Urol. 2003 (submitted).

89. Bolotin HH. Inaccuracies inherent in dual-energy X-ray absorptiometry in vivo bone mineral densitometry may flaw osteopenic/osteoporotic interpretations and mislead assessment of antiresorptive therapy effectiveness. Bone. 2001 May;28(5): 548–55.

90. Frahm C, Link J, Hakelberg K, et al. Densitometry in suspected preclinical osteoporosis: quantitative computerized tomography versus dual energy roentgen absorptiometry. Bildgebung. 1994 Dec;61(4):256–62.

91. von Stremple A, Prokopp M, Flindt C. A comparison of two noninvasive measurement methods for determining central osteoporosis taking into consideration the ash content. Aktuelle Radiol. 1993 Jan;3(1): 31–6.

92. Meirelles ES, Borelli A, Camargo OP. Influence of disease activity and chronicity on ankylosing spondylitis bone mass loss. Clin Rheumatol. 1999;18(5):364–8.

93. von der Recke P, Hansen MA, Overgaard K, Christiansen C. The impact of degenerative conditions in the spine on bone mineral density and fracture risk prediction. Osteoporos Int. 1996;6(1):43–9.