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Androgens and bone

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Abstract

Androgen receptors are present at low densities in osteoblasts. Androgens are also metabolized in bone. (Non)aromatizable androgens probably induce proliferation of osteoblasts and differentiation. A direct effect of androgens on osteoclasts has not been demonstrated. Androgens may however inhibit bone resorption indirectly, by an inhibition of the recruitment of osteoclast precursors from bone marrow, by decreased secretion of interleukin-6 and/or prostaglandin E2, and/or by an increased sensitivity of marrow cells or osteoblasts for bone resorption stimulating factors such as PTH. The recent demonstration of androgen receptors in bone marrow stromal and osteoclast-like cells opens new perspectives in this respect. During puberty, androgens stimulate bone growth both directly and indirectly. Observations in androgen-resistant animals clearly demonstrated that the sexual dimorphism of bone depends on the presence of a functional androgen receptor. Optimal peak bone mass seems related to an appropriately timed androgen secretion. In adults, androgens are also involved in maintenance of the male skeleton. Androgen replacement may prevent further bone loss in hypogonadal men, however, it seems difficult to fully correct bone mass in these men.

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References

  1. Riggs BL, Melton LJ III (1986) Involutional osteoporosis. N Engl J Med 314:1676–1686

    Google Scholar 

  2. Anderson DC (1992) Osteoporosis in men. Br Med J 305:489–490

    Google Scholar 

  3. Gallagher JC, Melton LM, Riggs BL, Bergstrath E (1980) Epidemiology of fractures of the proximal femur in Rochester, Minnesota. Clin Orthop 150:163–171

    Google Scholar 

  4. Grisso JA, Chiu GY, Maislin G, Steinmann WC, Portate J (1991) Risk factors for hip fractures in men: a preliminary study. J Bone Miner Res 6:865–868

    Google Scholar 

  5. Lindsay R, Coutts JRT, Sweeney A, Hart DM (1977) Endogenous estrogen and bone loss following oöphorectomy. Calcif Tissue Int 22:213–216

    Google Scholar 

  6. Smith DAS, Walker MS (1977) Changes in plasma steroids and bone density in Klinefelter's syndrome. Calcif Tissue Int 22: 225–229

    Google Scholar 

  7. Horowitz M, Wishart JM, O'Loughin PD, Morris HA, Need AG, Nordin BEC (1992) Osteoporosis and Klinefelter's syndrome. Clin Endocrinol 36:113–118

    Google Scholar 

  8. Wong FHW, Pun KK, Wang C (1993) Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement. Osteoporosis Int 3:3–7

    Google Scholar 

  9. Greenspan SL, Neer RM, Ridgway C, Klibanski A (1986) Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Int Med 104:777–782

    Google Scholar 

  10. Finkelstein JS, Klibanski A, Neer RM, Doppelt SH, Rosenthal DI, Segre GV, Crowley WF Jr (1989) Increases in bone density during treatment of men with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 69:776–783

    Google Scholar 

  11. Devogelaer JP, Decooman S, Dedeuxchaines CN (1992) Low bone mass in hypogonadal males. Maturitas 15:17–27

    Google Scholar 

  12. Francis RM, Peacock M, Aaron JE, Selby PI, Taylor GA, Thompson J, Marshall DH, Horsman A (1986) Osteoporosis in hypogonadal men: role of decreased plasma 1,25-dihydroxyvitamin D, calcium malabsorption and low bone formation. Bone 7:261–268

    Google Scholar 

  13. Stepan JJ, Lachman M, Zverina J, Pacovscky V, Baylink DJ (1989) Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 69:523–527

    Google Scholar 

  14. Goldray D, Weisman Y, Jaccard N, Merdler C, Chen J, Matzin H (1993) Decreased bone density in elderly men treated with the gonadotropin-releasing hormone against Decapeptyl. J Clin Endocrinol Metab 76:288–290

    Google Scholar 

  15. Canalis E, Raisz LG (1978) Effects of steroids on bone collagen synthesis in vitro. Calcif Tissue Int 25:105–110

    Google Scholar 

  16. Caputo CB, Meadows D, Raisz LG (1976) Failure of estrogens and androgens to inhibit bone resorption in tissue culture. Endocrinology 98:1065–1068

    Google Scholar 

  17. Albright F, Reifenstein EC (1948) Metabolic bone disease: osteoporosis. In: Albright F, Reifenstein EC (eds) The parathyroid glands and metabolic bone disease. Williams and Wilkins, Baltimore, pp 145–204

    Google Scholar 

  18. Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS, Riggs BL, Spelsberg TC (1989) Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci 86:854–857

    Google Scholar 

  19. Orwoll ES, Stribrska L, Ramsey EB, Keenan EJ (1991) Androgen receptors in osteoblast-like cells. Calcif Tissue Int 49:183–187

    Google Scholar 

  20. Benz DJ, Haussler MR, Thomas MA, Speelman B, Komm BS (1991) High-affinity androgen binding and androgenic regulation of alfal(I)-procollagen and transforming growth factor-β steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells. Endocrinology 128:2723–2730

    Google Scholar 

  21. Masuyama A, Ouchi Y, Sato F, Hosoi T, Nakamura T, Orimo H (1992) Characteristics of steroid hormone receptors in cultured LC3T3-E1 osteoblastic cells and effect of steroid hormones on cell proliferation. Calcif Tissue Int 51:376–381

    Google Scholar 

  22. Tanaka S, Haji M, Nishi Y, Yanase T, Takayanagi R, Nawata H (1993) Aromatase activity in human osteoblast-like osteosarcoma cell. Calcif Tissue Int 52:107–109

    Google Scholar 

  23. Purohit A, Flanagan AM, Reed MJ (1992) Estrogen synthesis by osteoblast cell lines. J Clin Endocrinol Metab 61:152–157

    Google Scholar 

  24. Bruch HB, Wolf L, Budde R, Romalo G, Schweikert HU (1992) Androstenedione metabolism in cultured human osteoblast-like cells. J Clin Endocrinol Metab 75:101–105

    Google Scholar 

  25. Turner RT, Bleriberg BB, Colvard DS, Keeting PE, Evans G, Spelsberg TC (1990) Failure of isolated rat tibial periosteal cells to 5 alfa-reduce testosterone to 5 alfa-dihydrotestosterone. J Bone Miner Res 5:775–779

    Google Scholar 

  26. Vittek J, Altman K, Gordon GG, Southren AL (1974) The metabolism of testosterone by rat mandibular bone. Endocrinology 94:325–329

    Google Scholar 

  27. Schweikert HU, Rulf W, Niederle N, Schafer I, Keck E, Kruck F (1980) Testosterone metabolism in human bone. Acta Endocrinol 95:258–264

    Google Scholar 

  28. Kasperk C, Wergedal JE, Farley JR, Linkhart TA, Turner RT, Baylink D (1989) Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 124:1576–1579

    Google Scholar 

  29. Gray C, Colston KW, Mac Kay AG, Taylor L, Arnett TR (1989) Interaction of androgen and 1,25-dihydroxyvitamin D3: effects on normal rat bone cells. J Bone Miner Res 7:41–46

    Google Scholar 

  30. Weisman Y, Cassorla F, Malozowski S, Krieg RJ, Goldray D, Kaye AM, Sömjen D (1993) Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females and in testicular feminized male rats. Steroids 58:126–133

    Google Scholar 

  31. Kasperk C, Fitzsimmons R, Strong D, Mohan S, Jennings J, Wergedal J, Baylink D (1990) Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells. J Clin Endocrinol Metab 71:1322–1329

    Google Scholar 

  32. Bellido T, Girasole G, Jilka RL, Crabb D, Manolagas SC (1993) Demonstration of androgen receptors in bone marrow stromal cells and their role in the regulation of transcription from the human interleukin-6 (IL-6) gene promoter. J Bone Miner Res 8:S1:57

    Google Scholar 

  33. Ryaby JT, Magee FP, Khin NA, Fitzsimmons RJ, Baylink DJ (1993) Downregulation of osteoclastogenic potential in vivo by combined ac/dc magnetic fields. J Bone Miner Res 8:S1:626

    Google Scholar 

  34. Girasole G, Jilka RL, Passeri G, Scott B,Boder G, Williams DC, Manolagas SC (1992) Estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro. A potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89:883–891

    Google Scholar 

  35. Pilbeam CC, Raisz LG (1990) Effects of androgens on parathyroid and interleukin-1-stimulated prostaglandin production in cultured neonatal mouse calvariae. J Bone Miner Res 5:1183–1188

    Google Scholar 

  36. Fukayama S, Tashjan AH (1989) Direct modulation by androgens of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTRrp. Endocrinology 125: 1789–1794

    Google Scholar 

  37. Mizuno Y, Hosoi T, Inoue S, Ikegami A, Kaneki M, Akedo Y, Nakamura T, Ouchi Y, Chang C, Orimo H (1994) Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells. Calcif Tissue Int 54:325–326

    Google Scholar 

  38. Tobias JH, Chambers TJ (1991) The effect of sex hormone on bone resorption by rat osteoclasts. Acta Endocrinol124:121–127

    Google Scholar 

  39. Oursler MJ, Osdoby P, Pyfferoen J, Riggs BL, Spelsberg TC (1991) Avian osteoclast cells as estrogen target cells. Proc Natl Acad Sci USA 88:6613–6617

    Google Scholar 

  40. Oursler MJ, Pederson L, Pyfferoen J, Osdoby P, Fitzpatrick L, Spelsberg TC (1993) Estrogen modulation of avian osteoclast lysosomal gene expression. Endocrinology 132:1313–1380

    Google Scholar 

  41. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC (1992) Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257:88–91

    Google Scholar 

  42. Wronski TJ, Schenck PA, Cintron M,Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Res 40:155–159

    Google Scholar 

  43. Kalu DN, Hardin RR, Cockermam R (1984) Evaluation of the pathogenesis of skeletal changes in ovariectomized rats. Endocrinology 115:507–512

    Google Scholar 

  44. Vanderschueren D, Van Herck E, Suiker AMH, Visser WJ, Schot LPC, Bouillon R (1992) Bone and mineral metabolism in aged male rats: short- and long-term effects of androgen deficiency. Endocrinology 130:2906–2916

    Google Scholar 

  45. Schoutens A, Verhas M, L'Hermite-Baleriaux, L'Hermite M, Verschaeren A, Dourov N, Mone M, Heilporn A, Tricot A (1984) Growth and bone haemodynamic responses to castration in male rats. Reversibility by testosterone. Acta Endocrinol 107:428–432

    Google Scholar 

  46. Wakley GK, Schritte HD, Kathleen SH, Turner RT (1991) Androgen treatment prevents loss of cancellous bone in the orchidectomized rat. J Bone Miner Res 6:325–330

    Google Scholar 

  47. Saville PD (1969) Changes in skeletal mass and fragility with castration in the rat: a model for osteoporosis. Am Geriatr Soc 17:155–166

    Google Scholar 

  48. Hock JM, Fonseca J, Gunness-Hey, Kemp BE, Martin TJ (1989) Comparison of the anabolic effects of synthetic parathyroid hormone-related protein (PTHrP)1-34 and PTH 1–34 on bone in rats. Endocrinology 125:2022–2027

    Google Scholar 

  49. Turner RT, Hannon KS, Demers LM, Buchanan J, Bell NH (1989) Differential effects of gonadal function on bone histomorphometry in male and female rats. J Bone Miner Res 4:557–563

    Google Scholar 

  50. Wink CS, Felts WJL (1980) Effects of castration on the bone structure of male rats: a model for osteoporosis. Calcif Tissue Int 32:77–82

    Google Scholar 

  51. Verhas M, Schoutens A, L'Hermite-Baleriaux, Dourov N, Verschaeren A, Mone M, Heilporn A (1986) The effect of orchidectomy on bone metabolism in aging rats. Calcif Tissue Int 39:74–77

    Google Scholar 

  52. Danielson CC, Mosekilde L, Andreassen TT (1992) Long-term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties. Calcif Tissue Int 50:169–174

    Google Scholar 

  53. Turner RT, Wakley GK, Hannon KS (1990) Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats. J Orthop Res 8:612–617

    Google Scholar 

  54. Wink CS (1986) A scanning electronic-microscopic study of femoral bone surfaces from castrate rats treated with dichloromethylene biphosphonate. Acta Anat 126:57–62

    Google Scholar 

  55. Vanderschueren D, Van Herck E, Schot L, Rush E, Einhorn T, Geusens P, Bouillon R (1993) The aged male rat as a model for human osteoporosis: evaluation by nondestructive measurements and biomechanical testing. Calcif Tissue Int 53:342–347

    Google Scholar 

  56. Hodgkinson A (1979) Effects of calcium deprivation and orchidectomy on bone composition in the rat. Horm Metab Res 11: 516–519

    Google Scholar 

  57. Gürkan L, Ekeland A, Gautvik KM, Langeland N, Ronningen H, Solheim LF (1986) Bone changes after castration in rats. Acta Orthop Scand 57:67–70

    Google Scholar 

  58. Li XJ, Jee WSS, Ke HZ, Mori S, Akamine T (1991) Age-related changes of cancellous and cortical bone histomorphometry in female Sprague-Dawley rats. Cells Materials (suppl 1):25–35

    Google Scholar 

  59. Chow JWM, Badve S, Chambers TJ (1993) A comparison of microanatomic basis for coupling between bone formation and bone resorption in man and the rat. Bone 14:355–360B

    Google Scholar 

  60. Eriksen EF, Mosekilde L (1990) Estrogens and bone. In: Heersche JNM, Kanis JA (eds) Bone and mineral research/7. Elsevier Science Publishers BV, (Biomedical Division) New York, pp 273–311

    Google Scholar 

  61. Uesugi Y, Taguchi O, Noumara T, Iguchi T (1992) Effects of sex steroids on the development of sexual dimorphism in mouse innominate bone. Anat Rec 234:541–548

    Google Scholar 

  62. Vanderschueren D, Van Herck E, Suiker AMH, Visser WJ, Geussens P, Schot LPC, Bouillon R, Rush EB, Einhorn TA (1993) Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat. J Bone Miner Res 8:799–807

    Google Scholar 

  63. Vanderschueren D, Van Herck E, Geusens P, Bouillon R (1994) Androgen resistance and deficiency have different effects on the growing skeleton of the rat. Calcif Tissue Int 55:198–203

    Google Scholar 

  64. Seeman E, Melton LJ III (1983) Risk factors for osteoporosis in men. Am J Med 75:977–983

    Google Scholar 

  65. Stanley HL, Schmitt BP, Poses RM, Deiss WP (1991) Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men. J Am Geriatr Soc 39:766–771

    Google Scholar 

  66. Jackson JA, Kleerekoper M, Parfitt AM, Rao DS, Villanueva AR, Frame B (1987) Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis. J Clin Endocrinol Metab 65:53–58

    Google Scholar 

  67. Vermeulen A, Rubens R, Verdonck L (1972) Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab 34:730–735

    Google Scholar 

  68. Finkelstein JS, Neer RM, Biller BMK, Crawford JD, Klibanski A (1992) Osteopenia in men with a history of delayed puberty. N Engl J Med 326:600–604

    Google Scholar 

  69. Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER (1993) Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab 75:996–1001

    Google Scholar 

  70. Attie KM, Ramirez NR, Conte FA, Kaplan SL, Grumbach MM (1990) The pubertal growth spurt in eight patients with true precocious puberty and growth hormone deficiency: evidence for a direct role of sex steroids. J Clin Endocrinol Metab 71: 975–983

    Google Scholar 

  71. Kerrigan JR, Rogal AD (1992) The impact of gonadal steroid secretion during childhood and adolescence. Endocrinol Rev 13:281–298

    Google Scholar 

  72. Jansson J-O, Eden S, Isaksson O (1985) Sexual dimorphism in the control of growth hormone secretion. Endocrinol Rev 6: 128–150

    Google Scholar 

  73. Ulloa-Aguirre A, Blizzard RM, Garcia-Rubi E, Rogal AD, Link K, Christie CM, Johnson ML, Veldhuis JD (1990) Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin Endocrinol Metab 71:846–855

    Google Scholar 

  74. Harris DA, Van Vliet G, Egli CA, Grumbach MM, Kaplan SL, Styne DM, Vainsel M (1985) Somatomedin-C in normal puberty and in true precocious puberty before and after treatment with potent luteinizing hormone-releasing hormone antagonist. J Clin Endocrinol Metab 61:152–157

    Google Scholar 

  75. Johansen AS, Giwercman A, Hartwell D, Nielsen T, Price PA, Christiansen C, Skakkebaek N (1988) Serum bone gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor and serum testosterone. J Clin Endocrinol Metab 67:273–278

    Google Scholar 

  76. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056–1061

    Google Scholar 

  77. Tenover JS (1992) Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75:1092–1098

    Google Scholar 

  78. McElduff A, Wilkinson M, Ward P, Posen S (1988) Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations. Bone 9:281–283

    Google Scholar 

  79. Forresta C, Ruzza G, Mioni R, Guarneri G, Gribaldo R, Meneghello A, Mastrogiacomo I (1984) Osteoporosis and decline of gonadal function in the elderly. Horm Res 19:18–22

    Google Scholar 

  80. Murphy S, Khaw KT, Cassidy A, Compston JE (1993) Sex hormones and bone mineral density in elderly men. Bone Miner 20:133–140

    Google Scholar 

  81. Meier DE, Orwoll ES, Keena EJ, Fagerstrom RM (1987) Marked decline in trabecular bone mineral in healthy men with age: lack of association with sex steroid levels. J Am Geriatr Soc 35:189–197

    Google Scholar 

  82. Buchanan JR, Hospodar, Myers C, Leuenberger P, Demers LM (1988) Effect of excess endogenous androgens on bone density in young women. J Clin Endocrinol Metab 67:937–943

    Google Scholar 

  83. Haffner SM, Bauer RL (1992) Excess androgenicity only partially explains the relationship between obesity and bone density in premenopausal women. Int J Obesity 16:869–874

    Google Scholar 

  84. Steinberg KK, Freni-Titulaer LW, DePeuy EG, Miller DT, Sgoutas DS, Coralli CH, Philips DL, Rogers TN, Clark RV (1989) Sex steroids and bone density in premenopausal and perimenopausal women. J Clin Endocrinol Metab 69:533–539

    Google Scholar 

  85. Nordin BEC, Roberson A, Seamark RF, Bridges A, Philcox JC, Nedd AG, Horowitz M, Morris HA, Deam S (1985) The relation between calcium absorption, serum dehydroepiandrostenedione, and vertebral mineral density in postmenopausal women. J Clin Endocrinol Metab 60:651–657

    Google Scholar 

  86. Davidson BJ, Riggs BL, Wahner HW, Judd HI (1983) Endogeneous cortisol and sex steroids in patients with osteoporotic spinal fractures. Obstet Gynecol 61:275–278

    Google Scholar 

  87. Davidson BJ, Riggs BL, Paganini-Hill A, Hammond GD, Siiteri PK, Judd LH (1982) Total, and free androgens and estrogens in postmenopausal women with hip fractures. J Clin Endocrinol Metab 54:115–120

    Google Scholar 

  88. Klibanski A, Biller BMK, Rosenthal DI, Schoenfeld DA, Saxe V (1988) Effects of prolactin and estrogen deficiency in amenorroic bone loss. J Clin Endocrinol Metab 67:124–130

    Google Scholar 

  89. Manolagas SC, Anderson DC, Lindsay R (1979) Adrenal steroids and the development of osteoporosis in oophorectomized women. Lancet 2:597–600

    Google Scholar 

  90. Ohta H, Ikeda T, Masuzawa T, Makita K, Suda Y, Nozawa S (1993) Differences in axial bone mineral density, serum levels of sex steroids, and bone metabolism between postmenopausal and age- and body size-matched premenopausal subjects. Bone 14:111–116

    Google Scholar 

  91. Goulding A, Gold E (1993) Flutamide-mediated androgen blockade evokes osteopenia in the female rat. J Bone Miner Res 8:763–769

    Google Scholar 

  92. Foresta C, Scanelli G, Zanatta GP, Busnardo B, Scandallari C (1987) Reduced calcitonin reserve in young hypogonadic osteoporotic men. Horm Metab Res 19:275–277

    Google Scholar 

  93. Foresta C, Busnardo BB, Ruzza G, Mioni R (1983) Lower calcitonin levels in young hypogonadal men with osteoporosis. Horm Metab Res 15:206–207

    Google Scholar 

  94. Isaia G, Mussetta M, Pecchio F, Sciolla A, Distefano M, Molinatti GM (1992) Effect of testosterone on bone in hypogonadal males. Maturitas 15:47–51

    Google Scholar 

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  1. Laboratorium voor experimentele geneeskunde en endocrinologie, Onderwijs en navorsing, UZ Gasthuisberg, B 3000, Leuven, Belgium

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Vanderschueren, D., Bouillon, R. Androgens and bone. Calcif Tissue Int 56, 341–346 (1995). https://doi.org/10.1007/BF00301598

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