Skip to main content

Attenuation of Osteoporosis by n-3 Lipids and Soy Protein

  • Chapter
Book cover Nutrition and Bone Health

Part of the book series: Nutrition and Health ((NH))

Abstract

Osteoporosis has become a major health and economic issue in our fast-growing elderly population (1–3). After attaining peak bone mass between the ages of 20 and 30, both men and women start losing bone at a rate of about 0.5–1% per year (4). In the United States alone, nearly $14 billion is spent each year for treatment of complications of osteoporosis (5). As life expectancy increases, there will be an increase in the financial burden on society. It is estimated that by the year 2050, the cost of osteoporosis-related treatments will increase to $131 billion (6). Osteoporosis is characterized by decreased bone mineral density resulting in susceptibility to fractures with minor to moderate trauma. Osteoporosis has been divided into two types (7). Type I osteoporosis, also designated postmenopausal osteoporosis, is the result of estrogen deficiency, whereas type II osteoporosis occurs in the entire aging population of both men and women.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Nevitt MC. Epidemiology of osteoporosis. Rheum Dis Clin N Am 1994; 20:535–559.

    CAS  Google Scholar 

  2. Melton LJ 3rd. How many women have osteoporosis now? J Bone Miner Res 1995; 10:175–177.

    Article  PubMed  Google Scholar 

  3. Mundy G, Garrett R, Harris S, et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999; 286:1946–1949.

    Article  PubMed  CAS  Google Scholar 

  4. McGarry KA, Kiel DP. Postmenopausal osteoporosis. Strategies for preventing bone loss, avoiding fracture. Postgrad Med 2000; 108:79–82, 85–78, 91.

    Article  PubMed  CAS  Google Scholar 

  5. Ray NF, Chan JK, Thamer M, Melton LJ 3rd. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997; 12:24–35.

    Article  PubMed  CAS  Google Scholar 

  6. Johnell O. The socioeconomic burden of fractures: today and in the 21st century. Am J Med 1997; 103:20S–25S; discussion 25S–26S.

    Article  PubMed  CAS  Google Scholar 

  7. Kassem M, Melton LI, Riggs B. The type I and type II model for involutional osteoporosis. In: Marcus R, Feldman D, Kelsey J, eds. Osteoporosis. Academic, New York, 1996, pp. 691–702.

    Google Scholar 

  8. Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science 2000; 289:1501–1504.

    Article  PubMed  CAS  Google Scholar 

  9. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000; 289:1504–1508.

    Article  PubMed  CAS  Google Scholar 

  10. Baylink DJ, Finkelman RD, Mohan S. Growth factors to stimulate bone formation. J Bone Miner Res 1993; 8(suppl 2):S565–S572.

    PubMed  Google Scholar 

  11. Mundy GR. Cytokines and growth factors in the regulation of bone remodeling. J Bone Miner Res 1993; 8(suppl 2):S505–S510.

    PubMed  Google Scholar 

  12. Raisz LG. Bone cell biology: new approaches and unanswered questions. J Bone Miner Res 1993; 8(suppl 2):S457–S465.

    PubMed  Google Scholar 

  13. Canalis E. Regulation of bone remodeling. In: Favus M, ed. Pimer on the Metabolic Bone Diseases and Disorders of mineral Metabolism. Raven, New York, 1993, pp. 33–37.

    Google Scholar 

  14. Blair HC, Schlesinger PH, Ross FP, Teitelbaum SL. Recent advances toward understanding osteoclast physiology. Clin Orthoped 1993; 294:7–22.

    Google Scholar 

  15. Lindsay R. Sex steroids in the pathogenesis and prevention of osteoporosis. In: Riggs B, Melton LI, eds. Osteoporosis: Etiology, Diagnosis and Management. Raven, New York, 1988.

    Google Scholar 

  16. Sanborn CF, Martin BJ, Wagner WW Jr. Is athletic amenorrhea specific to runners? Am J Obstet Gynecol 1982; 143:859–861.

    PubMed  CAS  Google Scholar 

  17. Bilezikian JP. Estrogens and postmenopausal osteoporosis: was Albright right after all? J Bone Miner Res 1998; 13:774–776.

    Article  PubMed  CAS  Google Scholar 

  18. Weaver CM. The growing years and prevention of osteoporosis in later life. Proc Nutr Soc 2000; 59:303–306.

    Article  PubMed  CAS  Google Scholar 

  19. Weaver CM, Heaney RP. Dairy consumption and bone health. Am J Clin Nutr 2001; 73:660–661.

    PubMed  CAS  Google Scholar 

  20. Weaver CM, Teegarden D, Lyle RM, et al. Impact of exercise on bone health and contraindication of oral contraceptive use in young women. Med Sci Sports Exerc 2001; 33:873–880.

    Article  PubMed  CAS  Google Scholar 

  21. Weaver CM. Calcium requirements of physically active people. Am J Clin Nutr 2000; 72:579S–584S.

    PubMed  CAS  Google Scholar 

  22. Lacey JV Jr, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002; 288:334–341.

    Article  PubMed  CAS  Google Scholar 

  23. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288:321–333.

    Google Scholar 

  24. Karpf DB, Shapiro DR, Seeman E, et al. Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups. JAMA 1997; 277:1159–1164.

    Article  PubMed  CAS  Google Scholar 

  25. Stevenson JC, Abeyasekera G, Hillyard CJ, et al. Calcitonin and the calcium-regulating hormones in postmenopausal women: effect of oestrogens. Lancet 1981; 1:693–695.

    Article  PubMed  CAS  Google Scholar 

  26. Tiegs RD, Body JJ, Wahner HW, Barta J, Riggs BL, Heath H 3rd. Calcitonin secretion in postmenopausal osteoporosis. N Engl J Med 1985; 312:1097–1100.

    Article  PubMed  CAS  Google Scholar 

  27. Riggs BL, Melton LJ 3rd. Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 1983; 75:899–901.

    Article  PubMed  CAS  Google Scholar 

  28. Horowitz MC, Xi Y, Wilson K, Kacena MA. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev 2001; 12:9–18.

    Article  PubMed  CAS  Google Scholar 

  29. Calder PC. Dietary fatty acids and the immune system. Lipids 1999; 34:S137–S140.

    Article  PubMed  CAS  Google Scholar 

  30. Fernandes G. Nutrition and immunity. In: Dulbecco R, ed. Encyclopedia of Human Biology. Vol. 5. Academic, New York, 1991, pp. 503–516.

    Google Scholar 

  31. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990; 323:645–655.

    Article  PubMed  CAS  Google Scholar 

  32. Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3 PUFA on the synthesis of IL-1 and TNF by mononuclear cells. N Engl J Med 1989; 320:265–271.

    Article  PubMed  CAS  Google Scholar 

  33. Wang H, Chen X, Fisher EA. N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes. J Clin Invest 1993; 91:1380–1389.

    Article  PubMed  CAS  Google Scholar 

  34. Hwang D, Rhee SH. Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids. Am J Clin Nutr 1999; 70:545–556.

    PubMed  CAS  Google Scholar 

  35. Speizer LA, Watson MJ, Brunton LL. Differential effects of omega-3 fish oils on protein kinase activities in vitro. Am J Physiol 1991; 261:E109–E114.

    PubMed  CAS  Google Scholar 

  36. Simopoulos AP. Evolutionary aspects of omega-3 fatty acids in the food supply. Prostaglandins Leukot Essent Fatty Acids 1999; 60:421–429.

    Article  PubMed  CAS  Google Scholar 

  37. Mirnikjoo B, Brown SE, Kim HF, Marangell LB, Sweatt JD, Weeber EJ. Protein kinase inhibition by omega-3 fatty acids. J Biol Chem 2001; 276:10888–10896.

    Article  PubMed  CAS  Google Scholar 

  38. Kehn P, Fernandes G. The importance of omega-3 fatty acids in the attenuation of immunemediated diseases. J Clin Immunol 2001; 21:99–101.

    Article  PubMed  CAS  Google Scholar 

  39. Calder PC. Immunomodulatory and anti-inflammatory effects of omega-3 polyunsaturated fatty acids. Proc Nutr Soc 1996; 55:737–774.

    Article  PubMed  CAS  Google Scholar 

  40. Robinson DR, Knoell CT, Urakaze M, et al. Suppression of autoimmune disease by omega-3 fatty acids. Biochem Soc Trans 1995; 23:287–291.

    PubMed  CAS  Google Scholar 

  41. Robinson DR, Kremer JM. Rheumatoid arthritis and inflammatory mediators. World Rev Nutr Diet 1991; 66:44–47.

    PubMed  CAS  Google Scholar 

  42. Prickett JD, Robinson DR, Steinberg AD. Dietary enrichment with the PUFA eicosapentaenoic prevents proteinuria and prolongs survival in NZB×NZWF1 mice. J Clin Invest 1981; 658:556–559.

    Article  Google Scholar 

  43. Kelley VE, Ferretti A, Izui S, Strom TB. A fish oil diet rich in eicosapentanoic acid reduces cyclooxygenese metabolites and suppresses lupus in MRL/lpr mice. J Immunol 1985; 134:1914–1919.

    PubMed  CAS  Google Scholar 

  44. Fernandes G. Effect of dietary fish oil supplement on autoimmune disease: changes in lymphoid cell subsets, oncogene mRNA expression and neuroendocrine hormones. In: Chandra R, ed. Health Effects of Fish and Fish Oils. ARTS Biomedical Publications, St. John’s, Newfoundland, Canada, 1989, pp. 409–433.

    Google Scholar 

  45. Jeng KC, Fernandes G. Effect of fish oil diet on immune response and proteinurea in mice. Proc Natl Sci Council ROC 1991; 15(2):105–110.

    CAS  Google Scholar 

  46. Fernandes G, Venkatraman J. Role of w-3 fatty acids in health and disease. Nutr Res 1993; 13:S19–S45.

    Article  CAS  Google Scholar 

  47. Venkatraman JT, Chandrasekar B, Kim JD, Fernandes G. Effects of n-3 and n-6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZB×NZW F1 mice. Lipids 1994; 29:561–568.

    Article  PubMed  CAS  Google Scholar 

  48. Fernandes G, Bysani C, Venkatraman JT, Tomar V, Zhao W. Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice. J Immunol 1994; 152:5979–5987.

    PubMed  CAS  Google Scholar 

  49. Fernandes G. Dietary lipids and risk of autoimmune disease. Clin Immunol Immunopathol 1994; 72:193–197.

    Article  PubMed  CAS  Google Scholar 

  50. Fernandes G. Effect of calorie restriction and omega-3 fatty acids on autoimmunity and aging. Nutr Rev 1995; 53:S72–S79.

    PubMed  CAS  Google Scholar 

  51. Fernandes G, Chandrasekar B, Luan X, Troyer DA. Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. Lipids 1996; 31(suppl):S91–S96.

    Article  PubMed  CAS  Google Scholar 

  52. Chandrasekar B, Fernandes G. Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by ω-3 lipids in murine lupus nephritis. Biochem Biophys Res Commun 1994; 200:893–898.

    Article  PubMed  CAS  Google Scholar 

  53. Chandrasekar B, Troyer DA, Venkatraman JT, Fernandes G. Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. J Autoimmun 1995; 8:381–393.

    Article  PubMed  CAS  Google Scholar 

  54. Chandrasekar B, McGuff HS, Aufdermorte TB, Troyer DA, Talal N, Fernandes G. Effects of calorie restriction on transforming growth factor beta 1 and proinflammatory cytokines in murine Sjogren’s syndrome. Clin Immunol Immunopathol 1995; 76:291–296.

    Article  PubMed  CAS  Google Scholar 

  55. Horowitz MC. Cytokines and estrogen in bone: anti-osteoporotic effects. Science 1993; 260:626–627.

    Article  PubMed  CAS  Google Scholar 

  56. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332:305–311.

    Article  PubMed  CAS  Google Scholar 

  57. Pacifici R. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 1996; 11:1043–1051.

    Article  PubMed  CAS  Google Scholar 

  58. Lorenzo JA, Naprta A, Rao Y, et al. Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology 1998; 139:3022–3025.

    Article  PubMed  CAS  Google Scholar 

  59. Cenci S, Weitzmann MN, Roggia C, et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 2000; 106:1229–1237.

    Article  PubMed  CAS  Google Scholar 

  60. Kanematsu M, Sato T, Takai H, Watanabe K, Ikeda K, Yamada Y. Prostaglandin E2 induces expression of receptor activator of nuclear factor-kappa B ligans/osteoprotegrin ligand on pre-B cells: implications for accelerated osteoclastogenesis in estrogen deficiency. J Bone Miner Res 2000; 15:1321–1329.

    Article  PubMed  CAS  Google Scholar 

  61. Das UN. Essential fatty acids and osteoporosis [editorial]. Nutrition 2000; 16:386–390.

    Article  PubMed  CAS  Google Scholar 

  62. Kruger MC, Horrobin DF. Calcium metabolism, osteoporosis and essential fatty acids: a review. Prog Lipid Res 1997; 36:131–151.

    Article  PubMed  CAS  Google Scholar 

  63. Watkins BA, Lippman HE, Le Bouteiller L, Li Y, Seifert MF. Bioactive fatty acids: role in bone biology and bone cell function. Prog Lipid Res 2001; 40:125–148.

    Article  PubMed  CAS  Google Scholar 

  64. Das UN. Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular disease. Prostaglandins Leukot Essent Fatty Acids 1991; 44:201–210.

    Article  PubMed  CAS  Google Scholar 

  65. Li Y, Seifert MF, Ney DM, et al. Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids. J Bone Miner Res 1999; 14:1153–1162.

    Article  PubMed  CAS  Google Scholar 

  66. Teegarden D, Lyle RM, Proulx WR, Johnston CC, Weaver CM. Previous milk consumption is associated with greater bone density in young women. Am J Clin Nutr 1999; 69:1014–1017.

    PubMed  CAS  Google Scholar 

  67. Weaver CM, Peacock M, Johnston CC Jr. Adolescent nutrition in the prevention of postmenopausal osteoporosis. J Clin Endocrinol Metab 1999; 84:1839–1843.

    Article  PubMed  CAS  Google Scholar 

  68. Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gammalinolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano) 1998; 10:385–394.

    CAS  Google Scholar 

  69. Schlemmer CK, Coetzer H, Claassen N, Kruger MC. Oestrogen and essential fatty acid supplementation corrects bone loss due to ovariectomy in the female Sprague Dawley rat. Prostaglandins Leukot Essent Fatty Acids 1999; 61:381–390.

    Article  PubMed  CAS  Google Scholar 

  70. Claassen N, Coetzer H, Steinmann CM, Kruger MC. The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Prostaglandins Leukot Essent Fatty Acids 1995; 53:13–19.

    Article  PubMed  CAS  Google Scholar 

  71. Wohl GR, Loehrke L, Watkins BA, Zernicke RF. Effects of high-fat diet on mature bone mineral content, structure, and mechanical properties. Calcif Tissue Int 1998; 63:74–79.

    Article  PubMed  CAS  Google Scholar 

  72. Sakaguchi K, Morita I, Murota S. Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. Prostaglandins Leukot Essent Fatty Acids 1994; 50:81–84.

    Article  PubMed  CAS  Google Scholar 

  73. Kruger M, Claassen N, Smuts C, Potgeiter H. Correlation between essential fatty acids and parameters of bone formation and degradation. Asia Pacific J Clin Nutr 1997; 6:235–238.

    Google Scholar 

  74. Coetzer H, Claassen N, van Papendorp DH, Kruger MC. Calcium transport by isolated brush border and basolateral membrane vesicles: role of essential fatty acid supplementation. Prostaglandins Leukot Essent Fatty Acids 1994; 50:257–266.

    Article  PubMed  CAS  Google Scholar 

  75. Pacifici R, Rifas L, Teitelbaum S, et al. Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci USA 1987; 84:4616–4620.

    Article  PubMed  CAS  Google Scholar 

  76. Lowik CW, van der Pluijm G, Bloys H, et al. Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclastogenesis. Biochem Biophys Res Commun 1989; 162:1546–1552.

    Article  PubMed  CAS  Google Scholar 

  77. Votta BJ, Bertolini DR. Cytokine suppressive anti-inflammatory compounds inhibit bone resorption in vitro. Bone 1994; 15:533–538.

    Article  PubMed  CAS  Google Scholar 

  78. Kumar G, Das U, Kumar V. Effect of n-6 and n-3 fatty acids on the proliferation and secretion of TNF and IL-2 by human lymphocytes in vitro. Nutr Res 1992; 12:815–823.

    Article  CAS  Google Scholar 

  79. Kumar GS, Das UN. Effect of prostaglandins and their precursors on the proliferation of human lymphocytes and their secretion of tumor necrosis factor and various interleukins. Prostaglandins Leukot Essent Fatty Acids 1994; 50:331–334.

    Article  PubMed  CAS  Google Scholar 

  80. Santoli D, Zurier R. Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. J Immunol 1989; 143:1303–1309.

    PubMed  CAS  Google Scholar 

  81. Purasiri P, Murray A, Richardson S, Heys SD, Horrobin D, Eremin O. Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer. Clin Sci (Colch) 1994; 87:711–717.

    CAS  Google Scholar 

  82. Wachman A, Bernstein DS. Diet and osteoporosis. Lancet 1968; 1:958–959.

    Article  PubMed  CAS  Google Scholar 

  83. Sellmeyer DE, Stone KL, Sebastian A, Cummings SR. A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. Am J Clin Nutr 2001; 73:118–122.

    PubMed  CAS  Google Scholar 

  84. Margen S, Chu JY, Kaufmann NA, Calloway DH. Studies in calcium metabolism. I. The calciuretic effect of dietary protein. Am J Clin Nutr 1974; 27:584–589.

    PubMed  CAS  Google Scholar 

  85. Schuette SA, Zemel MB, Linkswiler HM. Studies on the mechanism of protein-induced hypercalciuria in older men and women. J Nutr 1980; 110:305–315.

    PubMed  CAS  Google Scholar 

  86. Heaney RP, Recker RR. Effects of nitrogen, phosphorus, and caffeine on calcium balance in women. J Lab Clin Med 1982; 99:46–55.

    PubMed  CAS  Google Scholar 

  87. Hegsted M, Linkswiler HM. Long-term effects of level of protein intake on calcium metabolism in young adult women. J Nutr 1981; 111:244–251.

    PubMed  CAS  Google Scholar 

  88. Spencer H, Kramer L, Osis D. Do protein and phosphorus cause calcium loss? J Nutr 1988; 118:657–660.

    PubMed  CAS  Google Scholar 

  89. Lutz J, Linkswiler HM. Calcium metabolism in postmenopausal and osteoporotic women consuming two levels of dietary protein. Am J Clin Nutr 1981; 34:2178–2186.

    PubMed  CAS  Google Scholar 

  90. Hegsted DM. Calcium and osteoporosis. J Nutr 1986; 116:2316–2319.

    PubMed  CAS  Google Scholar 

  91. Abelow BJ, Holford TR, Insogna KL. Cross-cultural association between dietary animal protein and hip fracture: a hypothesis. Calcif Tissue Int 1992; 50:14–18.

    Article  PubMed  CAS  Google Scholar 

  92. Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998; 128:801–809.

    PubMed  CAS  Google Scholar 

  93. Delmi M, Rapin CH, Bengoa JM, Delmas PD, Vasey H, Bonjour JP. Dietary supplementation in elderly patients with fractured neck of the femur. Lancet 1990; 335:1013–1016.

    Article  PubMed  CAS  Google Scholar 

  94. Tkatch L, Rapin CH, Rizzoli R, et al. Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. J Am Coll Nutr 1992; 11:519–525.

    PubMed  CAS  Google Scholar 

  95. Bastow MD, Rawlings J, Allison SP. Benefits of supplementary tube feeding after fractured neck of femur: a randomised controlled trial. Br Med J (Clin Res Ed) 1983; 287:1589–1592.

    Article  CAS  Google Scholar 

  96. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Protein consumption and bone fractures in women. Am J Epidemiol 1996; 143:472–479.

    Article  PubMed  CAS  Google Scholar 

  97. Munger RG, Cerhan JR, Chiu BC. Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women. Am J Clin Nutr 1999; 69:147–152.

    PubMed  CAS  Google Scholar 

  98. Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DP. Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 2000; 15:2504–2512.

    Article  PubMed  CAS  Google Scholar 

  99. Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Protein consumption and bone mineral density in the elderly : the Rancho Bernardo Study. Am J Epidemiol 2002; 155:636–644.

    Article  PubMed  Google Scholar 

  100. Meyer HE, Pedersen JI, Loken EB, Tverdal A. Dietary factors and the incidence of hip fracture in middle-aged Norwegians. A prospective study. Am J Epidemiol 1997; 145:117–123.

    Article  PubMed  CAS  Google Scholar 

  101. Marsh AG, Sanchez TV, Michelsen O, Chaffee FL, Fagal SM. Vegetarian lifestyle and bone mineral density. Am J Clin Nutr 1988; 48:837–841.

    PubMed  CAS  Google Scholar 

  102. Dawson-Hughes B, Harris SS. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am J Clin Nutr 2002; 75:773–779.

    PubMed  CAS  Google Scholar 

  103. Messina M, Messina V. Soyfoods, soybean isoflavones, and bone health: a brief overview. J Ren Nutr 2000; 10:63–68.

    Article  PubMed  CAS  Google Scholar 

  104. Kritz-Silverstein D, Goodman-Gruen DL. Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women. J Womens Health Gend Based Med 2002; 11:69–78.

    Article  PubMed  Google Scholar 

  105. Arjmandi BH. The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. J Am Coll Nutr 2001; 20:398S–402S; discussion 4175–4205.

    PubMed  CAS  Google Scholar 

  106. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000; 72:844–852.

    PubMed  CAS  Google Scholar 

  107. Ho SC, Chan SG, Yi Q, Wong E, Leung PC. Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women. J Bone Miner Res 2001; 16:1363–1369.

    Article  PubMed  CAS  Google Scholar 

  108. Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equola clue to the effectiveness of soy and its isoflavones. J Nutr 2002; 132:3577–3584.

    PubMed  CAS  Google Scholar 

  109. Setchell KD. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 1998; 68:1333S–1346S.

    PubMed  CAS  Google Scholar 

  110. Fernandes G, Sun D, Krishnan A, Zaman K, R L. Soy protein and n-3 fatty acids prevent receptor activator of NF-kB ligand (RANKL) expression and osteoporosis in ovariectomized mice. FASEB J 2002; 16:A625.

    Google Scholar 

  111. Fernandes G, Lawrence R, Sun D. Protective role of n-3 lipids and soy protein in osteoporosis. Prostaglandins Leukot Essent Fatty Acids. 2003; 68:361–372.

    Article  PubMed  CAS  Google Scholar 

  112. Heaney RP. Constructive interactions among nutrients and bone-active pharmacologic agents with principal emphasis on calcium, phosphorus, vitamin D and protein. J Am Coll Nutr 2001; 20:403S–409S; discussion 4175–4205.

    PubMed  CAS  Google Scholar 

  113. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93:165–176.

    Article  PubMed  CAS  Google Scholar 

  114. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999; 397:315–323.

    Article  PubMed  CAS  Google Scholar 

  115. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999; 20:345–357.

    Article  PubMed  CAS  Google Scholar 

  116. Olsen NJ, Kovacs WJ. Gonadal steroids and immunity. Endocr Rev 1996; 17:369–384.

    PubMed  CAS  Google Scholar 

  117. Bebo BF Jr, Schuster JC, Vandenbark AA, Offner H. Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells. J Immunol 1999; 162:35–40.

    PubMed  CAS  Google Scholar 

  118. Benten WP, Lieberherr M, Giese G, Wunderlich F. Estradiol binding to cell surface raises cytosolic free calcium in T cells. FEBS Lett 1998; 422:349–353.

    Article  PubMed  CAS  Google Scholar 

  119. Gilmore W, Weiner LP, Correale J. Effect of estradiol on cytokine secretion by proteolipid protein-specific T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol 1997; 158:446–451.

    PubMed  CAS  Google Scholar 

  120. Kong YY, Feige U, Sarosi I, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999; 402:304–309.

    Article  PubMed  CAS  Google Scholar 

  121. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 1999; 265:144–150.

    Article  PubMed  CAS  Google Scholar 

  122. Teng YT, Nguyen H, Gao X, et al. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest 2000; 106:R59–R67.

    Article  PubMed  CAS  Google Scholar 

  123. Grcevic D, Lee SK, Marusic A, Lorenzo JA. Depletion of CD4 and CD8 T lymphocytes in mice in vivo enhances 1,25-dihydroxyvitamin D3-stimulated osteoclast-like cell formation in vitro by a mechanism that is dependent on prostaglandin synthesis. J Immunol 2000; 165:4231–4238.

    PubMed  CAS  Google Scholar 

  124. Takayanagi H, Ogasawara K, Hida S, et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross- talk between RANKL and IFN-gamma. Nature 2000; 408:600–605.

    Article  PubMed  CAS  Google Scholar 

  125. Muthukumar AR, Jolly CA, Zaman K, Fernandes G. Calorie restriction decreases proinflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB × NZW)F1 mice. J Clin Immunol 2000; 20:354–361.

    Article  PubMed  CAS  Google Scholar 

  126. Jolly C, Muthukumar A, Reddy Avula C, Troyer D, Fernandes G. Life span is prolonged in food-restricted autoimmune-prone (NZB × NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr 2001; 131:2753–2760.

    PubMed  CAS  Google Scholar 

  127. Terada S, Takizawa M, Yamamoto S, Ezaki O, Itakura H, Akagawa KS. Suppressive mechanisms of EPA on human T cell proliferation. Microbiol Immunol 2001; 45:473–481.

    PubMed  CAS  Google Scholar 

  128. Schlemmer CK, Coetzer H, Claassen N, et al. Ectopic calcification of rat aortas and kidneys is reduced with n-3 fatty acid supplementation. Prostaglandins Leukot Essent Fatty Acids 1998; 59:221–227.

    Article  PubMed  CAS  Google Scholar 

  129. Claassen N, Potgieter HC, Seppa M, et al. Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content. Bone 1995; 16:385S–392S.

    Article  PubMed  CAS  Google Scholar 

  130. Manolagas SC, Bellido T, Jilka RL. New insights into the cellular, biochemical, and molecular basis of postmenopausal and senile osteoporosis: roles of IL-6 and gp 130. Int J Immunopharmacol 1995; 17:109–116.

    Article  PubMed  CAS  Google Scholar 

  131. Raisz LG. Physiologic and pathologic roles of prostaglandins and other eicosanoids in bone metabolism. J Nutr 1995; 125:2024S–2027S.

    PubMed  CAS  Google Scholar 

  132. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998; 95:3597–3602.

    Article  PubMed  CAS  Google Scholar 

  133. Sun D, Krishnan A, Zaman K, Lawrence R, Fernandes G. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res 2003; 18: 1206–1216.

    Article  PubMed  CAS  Google Scholar 

  134. Calder PC. Polyunsaturated fatty acids, inflammation, and immunity. Lipids 2001; 36:1007–1024.

    Article  PubMed  CAS  Google Scholar 

  135. Priante G, Bordin L, Musacchio E, Clari G, Baggio B. Fatty acids and cytokine mRNA expression in human osteoblastic cells: a specific effect of arachidonic acid. Clin Sci (Lond) 2002; 102:403–409.

    Article  CAS  Google Scholar 

  136. Hamilton LC, Mitchell JA, Tomlinson AM, Warner TD. Synergy between cyclo-oxygenase-2 induction and arachidonic acid supply in vivo: consequences for nonsteroidal antiinflammatory drug efficacy. FASEB J 1999; 13:245–251.

    PubMed  CAS  Google Scholar 

  137. Das UN. Estrogen, statins, and polyunsaturated fatty acids: similarities in their actions and benefits—is there a common link? Nutrition 2002; 18:178–188.

    Article  PubMed  CAS  Google Scholar 

  138. Das UN. Antiosteoporotic actions of estrogen, statins, and essential fatty Acids. Exp Biol Med 2002; 227:88–93.

    CAS  Google Scholar 

  139. Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med 1997; 3:1285–1289.

    Article  PubMed  CAS  Google Scholar 

  140. Zhang YH, Heulsmann A, Tondravi MM, Mukherjee A, Abu-Amer Y. Tumor necrosis factoralpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem 2001; 276:563–568.

    Article  PubMed  CAS  Google Scholar 

  141. Wong BR, Josien R, Lee SY, Vologodskaia M, Steinman RM, Choi Y. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. J Biol Chem 1998; 273:28355–28359.

    Article  PubMed  CAS  Google Scholar 

  142. Darnay BG, Haridas V, Ni J, Moore PA, Aggarwal BB. Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase. J Biol Chem 1998; 273:20551–20555.

    Article  PubMed  CAS  Google Scholar 

  143. Camandola S, Leonarduzzi G, Musso T, et al. Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid. Biochem Biophys Res Commun 1996; 229:643–647.

    Article  PubMed  CAS  Google Scholar 

  144. Erben RG, Raith S, Eberle J, Stangassinger M. Ovariectomy augments B lymphopoiesis and generation of monocyte-macrophage precursors in rat bone marrow. Am J Physiol 1998; 274:E476–483.

    PubMed  CAS  Google Scholar 

  145. Masuzawa T, Miyaura C, Onoe Y, et al. Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow. J Clin Invest 1994; 94:1090–1097.

    Article  PubMed  CAS  Google Scholar 

  146. Morony S, Capparelli C, Kostenuik P, Eli A, Scully W, Wiemann B. Osteoprotegerin prevents osteolytic bone destruction in both athymic and syngeneic models of experimental tumor metastasis to bone. J Bone Miner Res 1999; 14(suppl 1):1124.

    Google Scholar 

  147. Smithson G, Couse JF, Lubahn DB, Korach KS, Kincade PW. The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis. J Immunol 1998; 161:27–34.

    PubMed  CAS  Google Scholar 

  148. Ishimi Y, Miyaura C, Ohmura M, et al. Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology 1999; 140:1893–1900.

    Article  PubMed  CAS  Google Scholar 

  149. Miyaura C, Onoe Y, Inada M, et al. Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency. Proc Natl Acad Sci USA 1997; 94:9360–9365.

    Article  PubMed  CAS  Google Scholar 

  150. Onoe Y, Miyaura C, Ito M, Ohta H, Nozawa S, Suda T. Comparative effects of estrogen and raloxifene on B lymphopoiesis and bone loss induced by sex steroid deficiency in mice. J Bone Miner Res 2000; 15:541–549.

    Article  PubMed  CAS  Google Scholar 

  151. Manabe N, Kawaguchi H, Chikuda H, et al. Connection between B lymphocyte and osteoclast differentiation pathways. J Immunol 2001; 167:2625–2631.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Fernandes, G. (2004). Attenuation of Osteoporosis by n-3 Lipids and Soy Protein. In: Holick, M.F., Dawson-Hughes, B. (eds) Nutrition and Bone Health. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-740-6_31

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-740-6_31

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-451-7

  • Online ISBN: 978-1-59259-740-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics