DOI QR코드

DOI QR Code

Age-Related Male Osteoporosis, and Soy, Its Alternative Therapy - Review-

  • Soung, Do-Yu (Department of Nutritional Sciences, Oklahoma State University, Stillwater) ;
  • Chung, Hae-Young (College of Pharmacy) ;
  • Rhee, Sook-Hee (Department of Food Science and Nutrition, Pusan National University) ;
  • Park, Kun-Young (Department of Food Science and Nutrition, Pusan National University)
  • Published : 2005.09.01

Abstract

As the population of the elderly grows, the prevalence of osteoporosis and its related fractures will increase in both men and women. The etiology, preventive and curative strategies of male osteoporosis are relatively unknown and understudied in comparison with those of female osteoporosis. Even currently approved therapies, e.g. bisphophonates, parathyroid hormone, and testosterone for male osteoporosis are in need of further investigation to test their safety and efficacy. Isoflavones which are found in soy have been shown to positively affect bone by stimulating bone formation while concurrently slowing down bone resorption. These observations mainly come from studies that have employed women or female animal models of osteoporosis. Therefore, there is a need to explore the role of soy and its isoflavones in preventing bone loss or rebuilding bone utilizing men or animal models of .male osteoporosis. From the review of existing literature it is too early to state the extent to which men with osteoporosis can benefit from consumption of soy or its isoflavones. In this review, the efficacy of soy and its isoflavones as alternative and/or adjunctive treatment for male osteoporosis will be discussed.

Keywords

References

  1. Stein B, Ashok S. 2002. Osteoporosis and the aging male. Med Health R I 85: 160-162
  2. Shin A, Choi JY, Chung HW, Park SK, Shin CS, Choi YH, Cho SI, Kim DS, Kim DI, Lee KM, Lee KH, Yoo KY, Kang D. 2004. Prevalence and risk factors of distal radius and calcaneus bone mineral density in Korean population. Osteoporos Int 15: 639-644
  3. Schuit SC, van der KM, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA. 2004. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam study. Bone 34: 195-202 https://doi.org/10.1016/j.bone.2003.10.001
  4. Elliott ME, Drinka PJ, Krause P, Binkley NC, Mahoney JE. 2004. Osteoporosis assessment strategies for male nursing home residents. Maturitas 48: 225-233 https://doi.org/10.1016/j.maturitas.2003.11.005
  5. Holt G, Khaw KT, Reid DM, Compston JE, Bhalla A, Woolf AD, Crabtree NJ, Dalzell N, Wardley-Smith B, Lunt M, Reeve J. 2002. Prevalence of osteoporotic bone mineral density at the hip in Britain differs substantially from the US over 50 years of age: implications for clinical densitometry. Br J Radiol 75: 736-742 https://doi.org/10.1259/bjr.75.897.750736
  6. de Laet CE, van der KM, Hofman A, Pols HA. 2002. Osteoporosis in men and women: a story about bone mineral density thresholds and hip fracture risk. J Bone Miner Res 17: 2231-2236 https://doi.org/10.1359/jbmr.2002.17.12.2231
  7. Fujiwara S, Kasagi F, Masunari N, Naito K, Suzuki G, Fukunaga M. 2002. Fracture prediction from bone mineral density in Japanese men and women. J Bone Miner Res 18: 1547-1553 https://doi.org/10.1359/jbmr.2003.18.8.1547
  8. Alonso CG, Curiel M, Carranza FH, Cano RP, Perez AD. 2000. Femoral bone mineral density, neck-shaft angle and mean femoral neck width as predictors of hip fracture in men and women. Multicenter project for research in osteoporosis. Osteoporos Int 11: 714-720 https://doi.org/10.1007/s001980070071
  9. Cauley JA, Zmuda JM, Wisniewski SR, Krishnaswami S, Palermo L, Stone KL, Black DM, Nevitt MC. 2004. Bone mineral density and prevalent vertebral fractures in men and women. Osteoporos Int 15: 32-37 https://doi.org/10.1007/s00198-003-1462-8
  10. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B. 2001. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 12: 989-995 https://doi.org/10.1007/s001980170006
  11. Pande I, O'Neill TW, Pritchard C, Scott DL, Woolf AD. 2000. Bone mineral density, hip axis length and risk of hip fracture in men: results from the cornwall hip fracture study. Osteoporos Int 11: 866-870 https://doi.org/10.1007/s001980070046
  12. The European prospective osteoporosis study group. 2002. The relationship between bone density and incident vertebral fracture in men and women. J Bone Miner Res 17: 2214-2221 https://doi.org/10.1359/jbmr.2002.17.12.2214
  13. Tuck SP, Raj N, Summers GD. 2002. Is distal forearm fracture in men due to osteoporosis? Osteoporos Int 13: 630-636 https://doi.org/10.1007/s001980200085
  14. Melton LJ III, Thamer M, Ray NF, Chan JK, Chesnut CH III, Einhorn TA, Johnston CC, Raisz LG, Silverman SL, Siris ES. 1997. Fractures attributable to osteoporosis: report from the National Osteoporosis Foundation. J Bone Miner Res 12: 16-23 https://doi.org/10.1359/jbmr.1997.12.1.16
  15. Gehlbach SH, Burge RT, Puleo E, Klar J. 2003. Hospital care of osteoporosis-related vertebral fractures. Osteoporos Int 14: 53-60 https://doi.org/10.1007/s00198-002-1313-z
  16. Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B. 2004. Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 15: 108-112 https://doi.org/10.1007/s00198-003-1516-y
  17. Trombetti A, Herrmann F, Hoffmeyer P, Schurch MA, Bonjour JP, Rizzoli R. 2002. Survival and potential years of life lost after hip fracture in men and age-matched women. Osteoporos Int 13: 731-737 https://doi.org/10.1007/s001980200100
  18. Wehren LE, Hawkes WG, Orwig DL, Hebel JR, Zimmerman SI, Magaziner J. 2003. Gender differences in mortality after hip fracture: the role of infection. J Bone Miner Res 18: 2231-2237 https://doi.org/10.1359/jbmr.2003.18.12.2231
  19. Randell A, Sambrook PN, Nguyen TV, Lapsley H, Jones G, Kelly PJ, Eisman JA. 1995. Direct clinical and welfare costs of osteoporotic fractures in elderly men and women. Osteoporos Int 5: 427-432 https://doi.org/10.1007/BF01626603
  20. Adachi JD, loannidis G, Pickard L, Berger C, Prior JC, Joseph L, Hanley DA, Olszynski WP, Murray TM, Anastassiades T, Hopman W, Brown JP, Kirkland S, Joyce C, Papaioannou A, Poliquin S, Tenenhouse A, Papadimitropoulos EA. 2003. The association between osteoporotic fractures and healthrelated quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 14: 895-904 https://doi.org/10.1007/s00198-003-1483-3
  21. Cockerill W, Lunt M, Silman AJ, Cooper C, Lips P, Bhalla AK, Cannata JB, Eastell R, Felsenberg D, Gennari C, Johnell O, Kanis JA, Kiss C, Masaryk P, Naves M, Poor G, Raspe H, Reid DM, Reeve J, Stepan J, Todd C, Woolf AD, O'Neill TW. 2004. Health-related quality of life and radiographic vertebral fracture. Osteoporos Int 15: 113-119 https://doi.org/10.1007/s00198-003-1547-4
  22. Hall SE, Williams JA, Senior JA, Goldswain PR, Criddle RA. 2000. Hip fracture outcomes: quality of life and functional status in older adults living in the community. Aust N Z J Med 30: 327-332 https://doi.org/10.1111/j.1445-5994.2000.tb00833.x
  23. Peterson MG, Allegrante JP, Cornell CN, MacKenzie CR, Robbins L, Horton R, Ganz SB, Augurt A. 2002. Measuring recovery after a hip fracture using the SF-36 and Cummings scales. Osteoporos Int 13: 296-302 https://doi.org/10.1007/s001980200029
  24. Amin SH, Kuhle CL, Fitzpatrick LA. 2003. Comprehensive evaluation of the older woman. Mayo Clin Proc 78: 1157-1185
  25. Campion JM, Maricic MJ. 2003. Osteoporosis in men. Am Fam Physician 67: 1521-1526
  26. Ebeling PR. 1998. Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. Drugs Aging 13: 421-434 https://doi.org/10.2165/00002512-199813060-00002
  27. Ebeling PR. 1999. Secondary causes of osteoporosis. In Osteoporosis in men. Orwoll ES, ed. Academic press, California. p 483-504
  28. Chan GK, Duque G. 2002. Age-related bone loss: old bone, new facts. Gerontology 48: 62-71 https://doi.org/10.1159/000048929
  29. Clarke BL, Ebeling PR, Jones JD, Wahner HW, O'Fallon WM, Riggs BL, Fitzpatrick LA. 2002. Predictors of bone mineral density in aging healthy men varies by skeletal site. Calcif Tissue Int 70: 137-145 https://doi.org/10.1007/s00223-001-1072-4
  30. Falahati-Nini A, Riggs BL, Atkinson EJ, O'Fallon WM, Eastell R, Khosla S. 2000. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106: 1553-1560 https://doi.org/10.1172/JCI10942
  31. Lee GS, Choi KC, Park SM, An BS, Cho MC, Jeung EB. 2003. Expression of human Calbindin-D (9k) correlated with age, vitamin D receptor and blood calcium level in the gastrointestinal tissues. Clin Biochem 36: 255-261 https://doi.org/10.1016/S0009-9120(03)00010-9
  32. Rucker D, Ezzat S, Diamandi A, Khosravi J, Hanley DA. 2004. IGF-I and testosterone levels as predictors of bone mineral densityin healthy, community-dwelling men. Clin Endocrinol (Oxf) 60: 491-499 https://doi.org/10.1111/j.1365-2265.2004.02006.x
  33. Bilezikian JP, Kurland ES, Rosen CJ 2005. Idiopathic osteoporosis in men. In Osteoporosis in men. Orwoll ES, ed. Academic Press, San Diego. p 395-416
  34. Gillberg P, Johansson AG, Blum WF, Groth T, Ljunghall S. 2001. Growth hormone secretion and sensitivity in men with idiopathic osteoporosis. Calcif Tissue Int 68: 67-73 https://doi.org/10.1007/BF02678143
  35. Van PI, Goemaere S, Zmierczak H, Kaufman JM. 2004. Perturbed sex steroid status in men with idiopathic osteoporosis and their sons. J Clin Endocrinol Metab 89: 4949-4953 https://doi.org/10.1210/jc.2003-032081
  36. Hasegawa J, Nagashima M, Yamamoto M, Nishijima T, Katsumata S, Yoshino S. 2003. Bone resorption and inflammatory inhibition efficacy of intermittent cyclical etidronate therapy in rheumatoid arthritis. J Rheumatol 30: 474-479 https://doi.org/10.1093/rheumatology/30.6.474
  37. Jahnsen J, Falch JA, Mowinckel P, Aadland E. 2002. Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol 37: 192-199 https://doi.org/10.1080/003655202753416876
  38. Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O'Donnell CJ, Wilson PW. 2001. Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham heart study. Calcif Tissue Int 68: 271-276 https://doi.org/10.1007/BF02390833
  39. Boling EP. 2004. Secondary osteoporosis: underlying disease and the risk for glucocorticoid-induced osteoporosis. Clin Ther 26: 1-14 https://doi.org/10.1016/S0149-2918(04)90001-X
  40. Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL. 2004. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 89: 503-510 https://doi.org/10.1210/jc.2003-031110
  41. Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A. 2000. Alendronate for the treatment of osteoporosis in men. N Engl J Med 343: 604-610 https://doi.org/10.1056/NEJM200008313430902
  42. Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman JM, Clancy A, Gaich GA. 2003. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res 18: 9-17. https://doi.org/10.1359/jbmr.2003.18.1.9
  43. Ringe JD, Faber H, Dorst A. 2001. Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective study. J Clin Endocrinol Metab 86: 5252-5255 https://doi.org/10.1210/jc.86.11.5252
  44. Ringe JD, Dorst A, Faber H, Ibach K. 2004. Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study. Rheumatol Int 24: 110-113 https://doi.org/10.1007/s00296-003-0388-y
  45. Schubert M, Bullmann C, Minnemann T, Reiners C, Krone W, Jockenhovel F. 2003. Osteoporosis in male hypogonadism: responses to androgen substitution differ among men with primary and secondary hypogonadism. Horm Res 60: 21-28
  46. Drake WM, Kendler DL, Rosen CJ, Orwoll ES. 2003. An investigation of the predictors of bone mineral density and response to therapy with alendronate in osteoporotic men. J Clin Endocrinol Metab 88: 5759-5765 https://doi.org/10.1210/jc.2002-021654
  47. Weber TJ, Drezner MK. 2001. Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Metabolism 50: 912-915 https://doi.org/10.1053/meta.2001.24925
  48. Reid DM, Adami S, Devogelaer JP, Chines AA. 2001. Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy. Calcif Tissue Int 69: 242-247 https://doi.org/10.1007/s00223-001-1060-8
  49. Wallach S, Cohen S, Reid DM, Hughes RA, Hosking DJ, Laan RF, Doherty SM, Maricic M, Rosen C, Brown J, Barton I, Chines AA. 2000. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 67: 277-285 https://doi.org/10.1007/s002230001146
  50. Sato S, Ohosone Y, Suwa A, Yasuoka H, Nojima T, Fujii T, Kuwana M, Nakamura K, Mimori T, Hirakata M. 2003. Effect of intermittent cyclical etidronate therapy on corticosteroidinduced osteoporosis in Japanese patients with connective tissue disease: 3 year followup. J Rheumatol 30: 2673-2679
  51. Baron R. 2003. General principles of bone biology. In Primer on the metabolic bone diseases and disorders of mineral metabolism. Favus MJ, ed. The American society for bone and mineral research, Washington, DC. p 1-8
  52. Niall HD, Sauer RT, Jacobs JW, Keutmann HT, Segre GV, O'Riordan JL, Ambach GD, Potts JT Jr. 1974. The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone. Proc Natl Acad Sci USA 71: 384-388
  53. Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A, Dore RK, Correa-Rotter R, Papaioannou A, Cumming DC, Hodsman AB. 2002. A randomized doubleblind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 87: 4528-4535. https://doi.org/10.1210/jc.2002-020334
  54. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. 2003. Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 18: 1932-1941. https://doi.org/10.1359/jbmr.2003.18.11.1932
  55. Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. 2000. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85: 3069-3076 https://doi.org/10.1210/jc.85.9.3069
  56. Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R. 2003. Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88: 1150-1156 https://doi.org/10.1210/jc.2002-021988
  57. Slovik DM, Rosenthal DI, Doppelt SH, Potts JT Jr, Daly MA, Campbell JA, Neer RM. 1986. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1-34) and 1,25-dihydroxyvitamin D. J Bone Miner Res 1: 377-381 https://doi.org/10.1002/jbmr.5650010411
  58. Kenny AM, Prestwood KM, Marcello KM, Raisz LG. 2000. Determinants of bone density in healthy older men with low testosterone levels. J Gerontol A Biol Sci Med Sci 55: M492-M497 https://doi.org/10.1093/gerona/55.9.M492
  59. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL. 2000. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 85: 2670-2677 https://doi.org/10.1210/jc.85.8.2670
  60. Matsumoto AM, Tenover L, McClung M, Mobley D, Geller J, Sullivan M, Grayhack J, Wessells H, Kadmon D, Flanagan M, Zhang GK, Schmidt J, Taylor AM, Lee M, Waldstreicher J. 2002. The long-term effect of specific type II 5alpha-reductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial. J Urol 167: 2105-2108 https://doi.org/10.1016/S0022-5347(05)65095-1
  61. Fujita T, Kawata T, Tokimasa C, Tanne K. 2001. Influence of oestrogen and androgen on modelling of the mandibular condylar bone in ovariectomized and orchiectomized growing mice. Arch Oral Biol 46: 57-65 https://doi.org/10.1016/S0003-9969(00)00094-7
  62. Vandenput L, Boonen S, Van Herck E, Swinnen JV, Bouillon R, Vanderschueren D. 2002. Evidence from the aged orchidectomized male rat model that 17beta-estradiol is a more effective bone-sparing and anabolic agent than 5alpha-dihydrotestosterone. J Bone Miner Res 17: 2080-2086 https://doi.org/10.1359/jbmr.2002.17.11.2080
  63. Alexandersen P, Christiansen C. 2004. The aging male: testosterone deficiency and testosterone replacement. An up-date. Atherosclerosis 173: 157-169 https://doi.org/10.1016/S0021-9150(03)00242-9
  64. Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, Lucani B, Dal Canto N, Valenti R, Gennari C, Nuti R. 2003. Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab 88: 5327-5333 https://doi.org/10.1210/jc.2003-030736
  65. Gillberg P, Johansson AG, Ljunghall S. 1999. Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis. Calcif Tissue Int 64: 209-213 https://doi.org/10.1007/s002239900604
  66. Ongphiphadhanakul B, Thamprajamchit S, Chanprasertyothin S, Chailurkit L, Rajatanavin R. 2002. Effect of estrogen replacement on insulin sensitivity, serum lipid and bone resorption marker in hypogonadal males. Maturitas 42: 85-89 https://doi.org/10.1016/S0378-5122(02)00026-9
  67. Szulc P, Munoz F, Claustrat B, Garnero P, Marchand F, Duboeuf F, Delmas PD. 2001. Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab 86: 192-199 https://doi.org/10.1210/jc.86.1.192
  68. Ishimi Y, Yoshida M, Wakimoto S, Wu J, Chiba H, Wang X, Takeda K, Iyaura C. 2002. Genistein, a soybean isoflavone, affects bone marrow lymphopoiesis and prevents bone loss in castrated male mice. Bone 31: 180-185 https://doi.org/10.1016/S8756-3282(02)00780-9
  69. Ringe JD, Dorst A, Kipshoven C, Rovati LC, Setnikar I. 1998. A voidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate. Osteoporos Int 8: 47-52 https://doi.org/10.1007/s001980050047
  70. Ringe JD, Rovati LC. 2001. Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates. Calcif Tissue Int 69: 252-255 https://doi.org/10.1007/s00223-001-1050-x
  71. Schoofs MW, van der KM, Hofman A, de Laet CE, Herings RM, Stijnen T, Pols HA, Stricker BH. 2003. Thiazide diuretics and the risk for hip fracture. Ann Intern Med 139: 476-482 https://doi.org/10.7326/0003-4819-139-6-200309160-00010
  72. LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE. 2000. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 133: 516-526 https://doi.org/10.7326/0003-4819-133-7-200010030-00010
  73. Legroux-Gerot I, Catanzariti L, Marchandise X, Duquesnoy B, Cortet B. 2004. Bone mineral density changes in hypercalciuretic osteoporotic men treated with thiazide diuretics. Joint Bone Spine 71: 51-55 https://doi.org/10.1016/j.jbspin.2003.09.009
  74. Deftos LL. 2004. Calcitonin. In Primer on the metabolic bone diseases and disorders of mineral metabolism. Favus MJ, ed. The American society for bone and mineral research, Washington DC. p 137-141
  75. Ikegame M, Ejiri S, Ozawa H. 2004. Calcitonin-induced change in serum calcium levels and its relationship to osteoclast morphology and number of calcitonin receptors. Bone 35: 27-33 https://doi.org/10.1016/j.bone.2004.03.018
  76. Erlacher L, Kettenbach J, Kiener H, Graninger W, Kainberger F, Pietschmann P. 1997. Salmon calcitonin and calcium in the treatment of male osteoporosis: the effect on bone mineral density. Wien Klin Wochenschr 109: 270-274
  77. Trovas GP, Lyritis GP, Galanos A, Raptou P, Constantelou E. 2002. A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. J Bone Miner Res 17: 521-527 https://doi.org/10.1359/jbmr.2002.17.3.521
  78. Axelson M, Sjovall J, Gustafsson BE, Setchell KD. 1984. Soya--a dietary source of the non-steroidal oestrogen equol in man and animals. J Endocrinol 102: 49-56 https://doi.org/10.1677/joe.0.1020049
  79. Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M. 1984. Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 40: 569-578
  80. Baum JA, Teng H, Erdman JW Jr, Weigel RM, Klein BP, Persky VW, Freels S, Surya P, Bakhit RM, Ramos E, Shay NF, Potter SM. 1998. Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr 68: 545-551
  81. Merz-Demlow BE, Duncan AM, Wangen KE, Xu X, Carr TP, Phipps WR, Kurzer MS. 2000. Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. Am J Clin Nutr 71: 1462-1469
  82. Messina MJ. 1999. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 70: 439S-450S
  83. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. 2000. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72: 844-852
  84. Dalais FS, Rice GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R, Strauss BJ. 1998. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1: 124-129 https://doi.org/10.3109/13697139809085527
  85. Ho SC, Chan SG, Yi Q, Wong E, Leung PC. 2001. Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women. J Bone Miner Res 16: 1363-1369 https://doi.org/10.1359/jbmr.2001.16.7.1363
  86. Horiuchi T, Onouchi T, Takahashi M, Ito H, Orimo H. 2000. Effect of soy protein on bone metabolism in postmenopausal Japanese women. Osteoporos Int 11: 721-724 https://doi.org/10.1007/s001980070072
  87. Hsu CS, Shen WW, Hsueh YM, Yeh SL. 2001. Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids, antioxidant enzyme activities and bone density. J Reprod Med 46: 221-226
  88. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr. 1998. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68: 1375S-1379S
  89. Scheiber MD, Liu JH, Subbiah MT, Rebar RW, Setchell KD. 2001. Dietary. inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause 8: 384-392 https://doi.org/10.1097/00042192-200109000-00015
  90. Setchell KD, Lydeking-Olsen E. 2003. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. Am J Clin Nutr 78: 593S-609S
  91. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS. 2000. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 85: 3043-3048 https://doi.org/10.1210/jc.85.9.3043
  92. Bacon WE, Maggi S, Looker A, Harris T, Nair CR, Giaconi J, Honkanen R, Ho SC, Peffers KA, Torring O, Gass R, Gonzalez N. 1996. International comparison of hip fracture rates in 1988-89. Osteoporos Int 6: 69-75 https://doi.org/10.1007/BF01626541
  93. Ho SC, Bacon WE, Harris T, Looker A, Maggi S. 1993. Hip fracture rates in Hong Kong and the United States, 1988 through 1989. Am J Public Health 83: 694-697 https://doi.org/10.2105/AJPH.83.5.694
  94. Khalil DA, Lucas EA, Juma S, Smith BJ, Payton ME, Arjmandi BH. 2002. 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 132: 2605-2608
  95. Khalil DA, Lucas EA, Smith BJ, Soung DY, Devareddy L, Juma S, Akhter MP, Recker R, Arjmandi BH. 2005. Soy isoflavones may protect against orchidectomy-induced bone loss in aged male rats. Calcif Tissue Int 76: 56-62 https://doi.org/10.1007/s00223-004-0018-z
  96. Chen XW, Garner SC, Anderson JJ. 2002. Isoflavones regulate interleukin-6 and osteoprotegerin synthesis during osteoblast cell differentiation via an estrogen-receptor-dependent pathway. Biochem Biophys Res Commun 295: 417- 422 https://doi.org/10.1016/S0006-291X(02)00667-8
  97. Choi EM, Suh KS, Kim YS, Choue RW, Koo SJ. 2001. Soybean ethanol extract increases the function of osteoblastic MC3T3-E1 cells. Phytochemistry 56: 733-739 https://doi.org/10.1016/S0031-9422(00)00484-2
  98. Gao YH, Yamaguchi M. 1999a. Anabolic effect of daidzein on cortical bone in tissue culture: comparison with gen istein effect. Mol Cell Biochem 194: 93-97 https://doi.org/10.1023/A:1006949912266
  99. Gao YH, Yamaguchi M. 1999b. Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures. Biochem Pharmacol 58: 767-772 https://doi.org/10.1016/S0006-2952(99)00162-8
  100. Gao YH, Yamaguchi M. 1999c. Suppressive effect of genistein on rat bone osteoclasts: apoptosis is induced through Ca2+ signaling. Biol Pharm Bull 22: 805-809 https://doi.org/10.1248/bpb.22.805
  101. Gao YH, Yamaguchi M. 2000. Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation. Int J Mol Med 5: 261-267
  102. Heim M, Frank O, Kampmann G, Sochocky N, Pennimpede T, Fuchs P, Hunziker W, Weber P, Martin I, Bendik I. 2000. The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells. Endocrinology 145: 848-859 https://doi.org/10.1210/en.2003-1014
  103. Jia TL, Wang HZ, Xie LP, Wang XY, Zhang RQ. 2003. Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production. Biochem Pharmacol 65: 709-715 https://doi.org/10.1016/S0006-2952(02)01585-X
  104. Lee Y, Chen X, Anderson JJ. 2001. Physiological concentrations of genistein stimulate the proliferation and protect against free radical-induced oxidative damage of MC3T3-E1 osteoblast-like cells. Nutr Res 21: 1287-1298 https://doi.org/10.1016/S0271-5317(01)00340-2
  105. Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G. 2002. Down-regulation of osteoclast differentiation by daidzein via caspase 3. J Bone Miner Res 17: 630-638 https://doi.org/10.1359/jbmr.2002.17.4.630
  106. Sik SK, Koh G, Young PC, Taek WK, Woon KS, Woo KJ, Kook PI, Seol KY. 2003. Soybean isoflavones inhibit tumor necrosis factor-alpha-induced apoptosis and the production of interleukin-6 and prostaglandin E(2) in osteoblastic cells. Phytochemistry 63: 209-215 https://doi.org/10.1016/S0031-9422(03)00101-8
  107. Sugimoto E, Yamaguchi M. 2000a. Anabolic effect of genistein in osteoblastic MC3T3-E1 cells. Int J Mol Med 5: 515-520
  108. Sugimoto E, Yamaguchi M. 2000b. Stimulatory effect of daidzein in osteoblastic MC3T3-E1 cells. Biochem Pharmacol 59: 471-475 https://doi.org/10.1016/S0006-2952(99)00351-2
  109. Viereck V, Grundker C, Blaschke S, Siggelkow H, Emons G, Hofbauer LC. 2002. Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. J Cell Biochem 84: 725-735 https://doi.org/10.1002/jcb.10087
  110. Yamagishi T, Otsuka E, Hagiwara H. 2001. Reciprocal control of expression of mRNAs for osteoclast differentiation factor and OPG in osteogenic stromal cells by genistein: evidence for the involvement of topoisomerase II in osteoclastogenesis. Endocrinology 142: 3632-3637 https://doi.org/10.1210/en.142.8.3632
  111. Yamaguchi M, Gao YH.1998. Anabolic effect of genistein and genistin on bone metabolism in the femoral-metaphyseal tissues of elderly rats: the genistein effect is enhanced by zinc. Mol Cell Biochem 178: 377-382 https://doi.org/10.1023/A:1006809031836
  112. Yamaguchi M, Sugimoto E. 2000. Stimulatory effect of genistein and daidzein on protein synthesis in osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase. Mol Cell Biochem 214: 97-102 https://doi.org/10.1023/A:1007199120295
  113. Yoon HK, Chen K, Baylink DJ, Lau KH. 1998. Differential effects of two protein tyrosine kinase inhibitors, tyrphostin and genistein, on human bone cell proliferation as compared with differentiation. Calcif Tissue Int 63: 243-249 https://doi.org/10.1007/s002239900521
  114. Arjmandi BH, Smith BJ. 2002. Soy isoflavones' osteoprotective role in postmenopausal women: mechanism of action. J Nutr Biochem 13: 130-137 https://doi.org/10.1016/S0955-2863(02)00172-9
  115. Blum SC, Heaton SN, Bowman BM, Hegsted M, Miller SC. 2003. Dietary soy protein maintains some indices of bone mineral density and bone formation in aged ovariectomized rats. J Nutr 133: 1244-1249
  116. Fanti P, Monier-Faugere MC, Geng Z, Schmidt J, Morris PE, Cohen D, Malluche HH. 1998. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int 8: 274-281 https://doi.org/10.1007/s001980050065
  117. Ishimi Y, Miyaura C, Ohmura M, Onoe Y, Sato T, Uchiyama Y, Ito M, Wang X, Suda T, Ikegami S. 1999. Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology 140: 1893-1900 https://doi.org/10.1210/en.140.4.1893
  118. Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. 2003. Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 88: 1048-1054 https://doi.org/10.1210/jc.2002-020849
  119. Crisafulli A, Altavilla D, Squadrito G, Romeo A, Adamo EB, Marini R, Inferrera MA, Marini H, Bitto A, D'Anna R, Corrado F, Bartolone S, Frisina N, Squadrito F. 2004. Effects of the phytoestrogen genistein on the circulating soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin system in early postmenopausal women. J Clin Endocrinol Metab 89: 188-192 https://doi.org/10.1210/jc.2003-030891
  120. Morabito N, Crisafulli A, Vergara C, Gaudio A, Lasco A, Frisina N, D'Anna R, Corrado F, Pizzoleo MA, Cincotta M, Altavilla D, Ientile R, Squadrito F. 2002. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res 17: 1904-1912 https://doi.org/10.1359/jbmr.2002.17.10.1904
  121. Jilka RL. 2003. Biology of the basic multicellular unit and the pathophysiology of osteoporosis. Med Pediatr Oncol 41: 182-185 https://doi.org/10.1002/mpo.10334
  122. Tsuboi M, Kawakami A, Nakashima T, Matsuoka N, Urayama S, Kawabe Y, Fujiyama K, Kiriyama T, Aoyagi T, Maeda K, Eguchi K. 1999. Tumor necrosis factoralpha and interleukin-1beta increase the Fas-mediated apoptosis of human osteoblasts. J Lab Clin Med 134: 222-231 https://doi.org/10.1016/S0022-2143(99)90201-9
  123. Weinstein RS, Jia D, Powers CC, Stewart SA, Jilka RL, Parfitt AM, Manolagas SC. 2004. The skeletal effects of glucocorticoid excess override those of orchidectomy in mice. Endocrinology 145: 1980-1987 https://doi.org/10.1210/en.2003-1133
  124. Zhou S, Zilberman Y, Wassermann K, Bain SD, Sadovsky Y, Gazit D. 2001. Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice. J Cell Biochem 81: 144-155 https://doi.org/10.1002/jcb.1096
  125. Qu Q, Perala-Heape M, Kapanen A, Dahllund J, Salo J, Vaananen HK, Harkonen P. 1998. Estrogen enhances differentiation of osteoblasts in mouse bone marrow culture. Bone 22: 201-209 https://doi.org/10.1016/S8756-3282(97)00276-7
  126. Komori T. 2003. Requisite roles of Runx2 and Cbfb in skeletal development. J Bone Miner Metab 21: 193-197
  127. Otto F, Lubbert M, Stock M. 2003. Upstream and downstream targets of RUNX proteins. J Cell Biochem 89: 9-18 https://doi.org/10.1002/jcb.10491
  128. Figueroa JD, Hayman MJ. 2004. Differential effects of the Ski-interacting protein (SKIP) on differentiation induced by transforming growth factor-beta1 and bone morphogenetic protein-2 in C2C12 cells. Exp Cell Res 296: 163-172 https://doi.org/10.1016/j.yexcr.2004.01.025
  129. Sowa H, Kaji H, Hendy GN, Canaff L, Komori T, Sugimoto T, Chihara K. 2004. Menin is required for BMP-2- and TGF-beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem 279: 40267-40275 https://doi.org/10.1074/jbc.M401312200
  130. Sun L, Vitolo M, Passaniti A. 2001. Runt-related gene 2 in endothelial cells: inducible expression and specific regulation of cell migration and invasion. Cancer Res 61: 4994-5001
  131. Arjmandi BH, Birnbaum R, Goyal NV, Getlinger MJ, Juma S, Alekel L, Hasler CM, Drum ML, Hollis BW, Kukreja SC. 1998a. Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr 68: 1364S-1368S
  132. Arjmandi BH, Getlinger MJ, Goyal NV, Alekel L, Hasler CM, Juma S, Drum ML, Hollis BW, Kukreja SC. 1998b. Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats. Am J Clin Nutr 68: 1358S-1363S
  133. Ogasawara T, Katagiri M, Yamamoto A, Hoshi K, Takato T, Nakamura K, Tanaka S, Okayama H, Kawaguchi H. 2004. Osteoclast differentiation by RANKL requires NFkappaB-mediated downregulation of cyclin-dependent kinase 6 (Cdk6). J Bone Miner Res 19: 1128-1136 https://doi.org/10.1359/jbmr.2004.19.7.1128
  134. Wang C, Steer JH, Joyce DA, Yip KH, Zheng MH, Xu J. 2003. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits osteoclastogenesis by suppressing RANKL-induced NF-kappaB activation. J Bone Miner Res 18: 2159-2168 https://doi.org/10.1359/jbmr.2003.18.12.2159
  135. Choi C, Cho H, Park J, Cho C, Song Y. 2003. Suppressive effects of genistein on oxidative stress and NFkappaB activation in RAW 264.7 macrophages. Biosci Biotechnol Biochem 67: 1916-1922 https://doi.org/10.1271/bbb.67.1916
  136. Rowe SM, Jung ST, Lee JY. 1997. Epidemiology of osteoporosis in Korea. Osteoporos Int 7(suppl 3) 3: S88-90
  137. Rhee EJ, Oh KW, Lee WY, Kim SW, Oh ES, Baek KH, Kang MI, Park CY, Choi MG, Yoo HJ, Park SW. 2004. Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men. J Bone Miner Metab 22: 392-398
  138. Oh KW, Rhee EJ, Lee WY, Kim SW, Baek KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW. 2004. Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol (Oxf) 62: 92-98