Drugs & Aging

, Volume 13, Issue 6, pp 421–434 | Cite as

Osteoporosis in Men

New Insights into Aetiology, Pathogenesis, Prevention and Management
Review Article Disease Management

Abstract

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake.

Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or ‘andropause’ comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged >65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites.

It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men.

It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway.

Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.

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References

  1. 1.
    Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev 1995; 16: 87–116PubMedGoogle Scholar
  2. 2.
    Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a worldwide projection. Osteoporosis Int 1992; 2: 285–9CrossRefGoogle Scholar
  3. 3.
    Cooper C, Atkinson EJ, O’Fallon MW, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota 1985–1989. J Bone Miner Res 1992; 7: 221–7PubMedCrossRefGoogle Scholar
  4. 4.
    Seeman E. Osteoporosis in men: epidemiology, pathophysiology and treatment possibilities. Am J Med 1993; 95: 225–85CrossRefGoogle Scholar
  5. 5.
    Parfitt AM, Duncan H. Metabolic bone disease affecting the spine. In: Rothman R, editor. The spine. 2nd ed. Philadelphia: Saunders, 1982; 775–905Google Scholar
  6. 6.
    Jones G, Nguyen T, Sambrook PN, et al. Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES). Osteoporosis Int 1994; 4: 277–82CrossRefGoogle Scholar
  7. 7.
    Melton LJ III, Thamer M, Ray NF, et al. Fractures attributable to osteoporosis: report from the National Osteoporosis Foundation. J Bone Miner Res 1997; 12: 16–23PubMedCrossRefGoogle Scholar
  8. 8.
    Poor G, Atkinson EJ, Lewallen DG, et al. Age-related hip fractures in men: clinical spectrum and short term outcomes. Osteoporosis Int 1995; 5: 419–26CrossRefGoogle Scholar
  9. 9.
    Burger H, Van Daele PLA, Grasluis K, et al. Vertebral deformities and functional impairment in men and women. J Bone Miner Res 1997; 12: 152–7PubMedCrossRefGoogle Scholar
  10. 10.
    Randell A, Sambrook PN, Nguyen TV, et al. Direct clinical and welfare costs of osteoporotic fractures in elderly men and women. Osteoporosis Int 1995; 5: 427–32CrossRefGoogle Scholar
  11. 11.
    Ross PD, Kim S, Wasnich RD. Bone density predicts vertebral fracture risk in both men and women [abstract]. J Bone Miner Res 1996; 11 (S1): A132Google Scholar
  12. 12.
    Nguyen TV, Eisman JA, Kelly PJ, et al. Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 1996; 144: 255–63PubMedCrossRefGoogle Scholar
  13. 13.
    Poor G, Atkinson EJ, O’Fallon WM, et al. Predictors of hip fractures in elderly men. J Bone Miner Res 1995; 10: 1900–7PubMedCrossRefGoogle Scholar
  14. 14.
    Stanley HL, Schmitt BP, Poses RM, et al. Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture. J Am Geriatr Soc 1991; 39: 766–71PubMedGoogle Scholar
  15. 15.
    Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis corticosteroid therapy and hip fracture. Ann Rheum Dis 1995; 54: 49–52PubMedCrossRefGoogle Scholar
  16. 16.
    Christian JC, Yu P-L, Slemenda CW, et al. Hereditability of bone mass: a longitudinal study of aging male twins. Am J Hum Genet 1989; 44: 429–33PubMedGoogle Scholar
  17. 17.
    Pocock NA, Eisman JA, Hopper JL, et al. Genetic determinants of bone mass in adults. J Clin Invest 1987; 80: 706–10PubMedCrossRefGoogle Scholar
  18. 18.
    Snow-Harter CR, Whalen K, Mybrugh S, et al. Bone mineral density, muscle strength, and recreational exercise in men. J Bone Miner Res 1992; 7: 1291–6PubMedCrossRefGoogle Scholar
  19. 19.
    Slemenda CW, Christian JC, Reed T, et al. Long-term bone loss in men: effects of genetic and environmental factors. Ann Intern Med 1992; 117: 286–91PubMedGoogle Scholar
  20. 20.
    Jones G, Nguyen T, Sambrook P, et al. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo Osteoporosis Epidemiology Study. BMJ 1995; 309: 691–5CrossRefGoogle Scholar
  21. 21.
    Riggs BL, Melton LJ III. Involutional Osteoporosis. N Engl J Med 1986; 314: 1676–86PubMedCrossRefGoogle Scholar
  22. 22.
    Garn SM, Sullivan TV, Decker SA, et al. Continuing bone expansion and increasing bone loss over a two-decade period in men and women from a total community sample. Am J Hum Biol 1992; 4: 57–67CrossRefGoogle Scholar
  23. 23.
    Mosekilde L, Mosekilde L. Normal vertebral body size and compressive strength relations to age and to vertebral and iliac bone compressive strength. Bone 1986; 7: 207–12PubMedCrossRefGoogle Scholar
  24. 24.
    Compston JE, Mellish RWE, Groucher P, et al. Structural mechanisms of trabecular bone loss in men. Bone Miner 1989; 6: 339–50PubMedCrossRefGoogle Scholar
  25. 25.
    Beck TJ, Ruff CB, Scott Jr WW, et al. Sex differences in geometry of femoral neck with aging: a structural analysis of bone mineral data. Calcif Tissue Int 1992; 50: 24–9PubMedCrossRefGoogle Scholar
  26. 26.
    Ebeling PR, Petrson JM, Riggs BL. Utility of type I procollagen propeptide assays for assessing abnormalities in metabolic bone diseases. J Bone Miner Res 1992; 7: 1243–50PubMedCrossRefGoogle Scholar
  27. 27.
    Tsai KS, Pan WH, Hsu SH, et al. Sexual differences in bone markers and bone mineral density of normal Chinese. Calcif Tissue Int 1996; 59: 454–60PubMedGoogle Scholar
  28. 28.
    Schneider DL, Barett-Connor EL. Urinary N-telopeptide levels discriminate normal osteopenic and osteoporotic bone mineral density. Arch Intern Med 1997; 157: 1241–5PubMedCrossRefGoogle Scholar
  29. 29.
    Sone T, Miyake M, Takeda N, et al. Urinary excretion of type I N-telopeptides in healthy Japanese adults: age- and sex-related changes and reference limits. Bone 1995; 17: 335–9PubMedCrossRefGoogle Scholar
  30. 30.
    Krall EA, Dawson-Hughes B, Hirst K, et al. Bone mineral density and biochemical markers of bone turnover in healthy elderly men and women. J Gerontol A Biol Sci Med Sci 1997; 52: M61–7PubMedCrossRefGoogle Scholar
  31. 31.
    Endres DB, Morgan CH, Garry PJ, et al. Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women. J Clin Endocrinol Metab 1987; 65: 724–31PubMedCrossRefGoogle Scholar
  32. 32.
    Orwoll ES, Meier DE. Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia. J Clin Endocrinol Metab 1986; 63: 1262–9PubMedCrossRefGoogle Scholar
  33. 33.
    Slovik DM, Adams JS, Neer RM, et al. Deficient production of 1,25-dihydroxy vitamin D in elderly osteoporotic patients. N Engl J Med 1981; 305: 372–4PubMedCrossRefGoogle Scholar
  34. 34.
    Halloran BP, Portale AA, Lonergan ET, et al. Production and metabolic clearance of 1,25-dihydroxy vitamin D in men: effect of advancing age. J Clin Endocrinol Metab 1990; 70: 318–23PubMedCrossRefGoogle Scholar
  35. 35.
    Ebeling PR, Sandgren ME, Di Magno EP, et al. Evidence of an age-related decrease in intestinal responsiveness to vitamin D: relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptors in normal women. J Clin Endocrinol Metab 1992; 75: 176–82PubMedCrossRefGoogle Scholar
  36. 36.
    Kinyamu HK, Gallagher JC, Prahl JM, et al. Association between intestinal vitamin D receptor, calcium absorption, and serum 1,25 dihydroxyvitamin D in normal young and elderly women. J Bone Miner Res 1997; 12: 922–8PubMedCrossRefGoogle Scholar
  37. 37.
    Morrison NA, Qi JC, Tokita A, Kelly PJ, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367: 284–7PubMedCrossRefGoogle Scholar
  38. 38.
    Krall EA, Parry P, Lichter JB, et al. Vitamin D receptor alleles and rates of bone loss: influences of years since menopause and calcium intake. J Bone Miner Res 1995; 10: 978–84PubMedCrossRefGoogle Scholar
  39. 39.
    Kroger H, Laitinen K. Bone mineral density measured by dual-energy x-ray absorptiometry in normal men. Eur J Clin Invest 1992; 22: 454–60PubMedCrossRefGoogle Scholar
  40. 40.
    Kelly PJ, Pocock NA, Sambrook PN, et al. Dietary calcium, sex hormones and bone mineral density in men. BMJ 1990; 300: 1361–4PubMedCrossRefGoogle Scholar
  41. 41.
    Looker AC, Harris TB, Madans JH, et al. Dietary calcium and hip fracture risk: the NHANES epidemiologic follow-up study. Osteoporosis Int 1993; 3: 177–84CrossRefGoogle Scholar
  42. 42.
    Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337: 670–6PubMedCrossRefGoogle Scholar
  43. 43.
    Francis RM, Peacock M, Marshall DH, et al. Spinal osteoporosis in men. Bone Miner 1989; 5: 347–57PubMedCrossRefGoogle Scholar
  44. 44.
    MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986; 104: 648–51PubMedGoogle Scholar
  45. 45.
    Chavassieux P, Serre CM, Vernaud P. In vitro evaluation of dose-effect of ethanol on human osteoblastic cells. Bone Miner 1993; 22: 95–103PubMedCrossRefGoogle Scholar
  46. 46.
    Diamond T, Stiel D, Lunzer M, et al. Ethanol reduced bone formation and may cause osteoporosis. Am J Med 1989; 86: 282–8PubMedCrossRefGoogle Scholar
  47. 47.
    Hopper JL, Seeman E. The bone density of female twins discordant for smoking. N Engl J Med 1994; 330: 387–92PubMedCrossRefGoogle Scholar
  48. 48.
    Seeman E, Melton LJ III. Risk factors for spinal osteoporosis in males. Am J Med 1983; 75: 977–83PubMedCrossRefGoogle Scholar
  49. 49.
    Francis RM, Peacock M, Marshall DH, et al. Spinal osteoporosis in men. Bone Miner 1989; 5: 347–57PubMedCrossRefGoogle Scholar
  50. 50.
    Francis RM, Peacock M. Osteoporosis in hypogonadal men: role of decreased plasma 1,25-dihydroxy vitamin D, calcium malabsorption and low bone formation. Bone 1986; 261–8Google Scholar
  51. 51.
    Parfitt AM, Duncan H. Metabolic bone disease affecting the spine. In: Rothman R, editor. The spine. 2nd ed. Philadelphia: Saunders, 1982: 775–905Google Scholar
  52. 52.
    Nordin BEC, Aaron J, Speed R, et al. Bone formation and resorption as the determinants of trabecular bone volume in normal and osteoporotic men. Scott Med J 1984; 29: 171–5PubMedGoogle Scholar
  53. 53.
    Aaron JE, Francis RM, Peacock M, et al. Contrasting microanatomy of idiopathic and corticosteroid-induced osteoporosis. Clin Orthop 1989; 243: 294–305PubMedGoogle Scholar
  54. 54.
    Ferrini RL, Barrett-Connort E. Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bio-available fractions in community-dwelling men. Am J Epidemiol 1998; 15: 750–4CrossRefGoogle Scholar
  55. 55.
    Clarke BL, Ebeling PR, Wahner HW, et al. Steroid hormones influence bone histomorphometric parameters in healthy men [abstract]. Calcif Tissue Int 1994; 54: 334Google Scholar
  56. 56.
    Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992; 75: 1092–8PubMedCrossRefGoogle Scholar
  57. 57.
    Orwoll ES, Oviatt S. Transdermal testosterone supplementation in normal older men [abstract]. Proc Endocr Soc 1992; A1071Google Scholar
  58. 58.
    Jackson JA, Kleerekoper M. Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis. J Clin Endocrinol Metab 1987; 65: 53–8PubMedCrossRefGoogle Scholar
  59. 59.
    Stepan JJ, Lachman M. Castrated men with bone loss: effect of calcitonin on biochemical indices of bone remodelling. J Clin Endocrinol Metab 1989; 69: 523–7PubMedCrossRefGoogle Scholar
  60. 60.
    Katznelson L, Finklestein JS, Schoenfeld DA, et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996; 81: 4358–65PubMedCrossRefGoogle Scholar
  61. 61.
    Devogelaer JP, De Cooman S, Nagant de Deuxchaisnes C. Low bone mass in hypogonadal males: effect of testosterone substitution therapy, a densitometric study. Maturitas 1992; 15: 17–23PubMedCrossRefGoogle Scholar
  62. 62.
    Bagchi MK, Tsai MJ, O’Malley BW, et al. Analysis of the mechanism of steroid hormone receptor-dependent gene activation in cell-free systems. Endocr Rev 1992; 13: 525–35PubMedGoogle Scholar
  63. 63.
    Lubahn DB, Joseph DR, Sar M, et al. The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis, and gene expression in prostate. Mol Endocrinol 1988; 2: 1265–75PubMedCrossRefGoogle Scholar
  64. 64.
    Edwards A, Hammond HA, Jin L, et al. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics 1992; 12: 241–53PubMedCrossRefGoogle Scholar
  65. 65.
    Sleddens HF, Oostra BA, Brinkmann AO, et al. Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene. Hum Mol Genet 1995; 2: 493–7CrossRefGoogle Scholar
  66. 66.
    Kazemi-Esfarjani P, Trifiro M, Pinsky L. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenic relevance for the (CAG)n-expanded neuropathies. Hum Mol Genet 1995; 4: 523–7PubMedCrossRefGoogle Scholar
  67. 67.
    Cohen P, Peehl DM, Graves HC, et al. Biological effects of prostate specific antigens as an insulin-like growth factor binding protein-3 protease. J Endocrinol 1994; 142: 407–15PubMedCrossRefGoogle Scholar
  68. 68.
    Brass AL, Barnard J, Patai BL, et al. Androgen up-regulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing human androgen receptor. Cancer Res 1995; 54: 3197–203Google Scholar
  69. 69.
    Wilding G, Valverius E, Knabbe C, et al. Role of transforming growth factor in a human prostate cancer cell growth. Prostate 1989; 15: 1–12PubMedCrossRefGoogle Scholar
  70. 70.
    Marcelli M, Haidacher SJ, Plymate SR, et al. Altered growth and insulin-like growth factor binding protein-3 production in PC3 prostate carcinoma cells stably transfected with a constitutively active androgen receptor complementary deoxyribonucleic acid. Endocrinology 1995; 136: 1040–8PubMedCrossRefGoogle Scholar
  71. 71.
    Ebeling PR, Jones JD, O’Fallon WM, et al. Short-term effects of recombinant hIGF-I on bone turnover in normal women. J Clin Endocrinol Metab 1993; 77: 1384–7PubMedCrossRefGoogle Scholar
  72. 72.
    Kurland ES, Rosen CJ, Cosman F, et al. Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 1997; 82: 2799–805PubMedCrossRefGoogle Scholar
  73. 73.
    Spotila LD, Constantinos CD, Sereda L, et al. Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genetic overlap with mild osteogenesis imperfecta. Proc Natl Acad Sci U S A 1991; 88: 5423–7PubMedCrossRefGoogle Scholar
  74. 74.
    Grant SFA, Reid DM, Ralston SH. Osteoporotic fracture and reduced bone density related to a polymorphism in the transcriptional control region of the collagen type I a 1 gene [abstract]. J Bone Miner Res 1995; 10 (S1): A106Google Scholar
  75. 75.
    Vanderscheueren D, Van Herck E, De Coster R, et al. Aromatisation of androgens is important for skeletal maintenance of aged male rats. Calcif Tissue Int 1996; 59: 179–83CrossRefGoogle Scholar
  76. 76.
    Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056–61PubMedCrossRefGoogle Scholar
  77. 77.
    Kenan Q, Fisher CR, Grumbach MM, et al. Aromatase deficiency in a male subject: characterization of a mutation in the CYP gene in an affected family [abstract]. Endocrinol Soc 1995; A P3–27Google Scholar
  78. 78.
    Bilezikian JP, Morishima A, Bell J, et al. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. N Engl J Med 1998; 339: 599–603PubMedCrossRefGoogle Scholar
  79. 79.
    Slemenda CW, Longcope C, Zhou L, et al. Sex steroids and bone mass in older men: positive associations with serum estrogens and negative associations with androgens. J Clin Invest 1997; 100: 1755–9PubMedCrossRefGoogle Scholar
  80. 80.
    Van Kesteren, Lips P, Deville W, et al. The effect of one-year cross-sex hormonal treatment on bone metabolism and serum insulin-like growth factor-I treatment in transsexuals. J Clin Endocrinol Metab 1996; 81: 2227–32PubMedCrossRefGoogle Scholar
  81. 81.
    Lubahn DB, Moyer JS, Golding TS, et al. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S A 1993; 90: 11162–6PubMedCrossRefGoogle Scholar
  82. 82.
    Kobayashi S, Inoue S, Hosoi T, et al. Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res 1996; 11: 306–11PubMedCrossRefGoogle Scholar
  83. 83.
    Agrawal R, Wallack S, Cohn S, et al. Calcitonin treatment of osteoporosis. In: Pecile A, editor. Calcitonin. Amsterdam: Exerpta Medica, 1981; 540: 237Google Scholar
  84. 84.
    Selby PL, Rehman MT, Economou G, et al. Etidronate in male osteoporosis: evidence for a site-specific action [abstract]. In: Christiansen C, editor. Osteoporosis 1993. Aalborg: Aalborg APS, 1993: 197Google Scholar
  85. 85.
    Anderson FH, Francis RM, Bishop JC, et al. Effect of intermittent cyclical disodium etidronate therapy on bone mineral density in men with vertebral fractures. Age Ageing 1997; 26: 359–65PubMedCrossRefGoogle Scholar
  86. 86.
    Orme SM, Simpson M, Stewart SP, et al. Comparison of changes in idiopathic and secondary osteoporosis following therapy with disodium etidronate and high dose calcium supplementation. Clin Endocrinol (Oxf) 1994; 41: 245–50CrossRefGoogle Scholar
  87. 87.
    Anderson FH, Francis RM, Peaston RT, et al. Androgen supplementation in eugonadal men with osteoporosis: effects of six months treatment on markers of bone formation and bone resorption. J Bone Miner Res 1997; 12: 472–8PubMedCrossRefGoogle Scholar
  88. 88.
    Slovik DM, Rosenthal DI, Doppelt SH, et al. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1–34) and 1,25-dihydroxy vitamin D. J Bone Miner Res 1986; 1: 377–81PubMedCrossRefGoogle Scholar
  89. 89.
    Reeve J, Davis UM, Hesp R, et al. Human parathyroid peptide treatment of osteoporosis substantially increases spinal trabecular bone (with observations on the effects of sodium fluoride therapy). BMJ 1990; 301: 314–8 477PubMedCrossRefGoogle Scholar
  90. 90.
    Lindsay R, Cosman F, Shen V, et al. Bone mass increments induced by PTH treatment can be maintained by oestrogen [abstract]. J Bone Miner Res 1995; 10 (S2): A200Google Scholar
  91. 91.
    Hodsman AB, Steer BM, Fraher L, et al. Bone densitometric and histomorphometric responses to sequential human parathyroid hormone (1–38) and salmon calcitonin in osteoporotic patients. Bone Miner 1991; 14: 67–83PubMedCrossRefGoogle Scholar
  92. 92.
    Greenspan SL, Holland S, Maitland-Ramsey L, et al. Nocturnal stimulation of parathyroid hormone: a mechanism to explain the continued improvement in bone mineral density following alendronate therapy [abstract]. J Bone Miner Res 1995; 10 (S1): A449Google Scholar
  93. 93.
    Finkelsten JS, Klibanski A, Schafer EH, et al. Parathyroid hormone for the prevention of bone loss induced by oestrogen deficiency. N Engl J Med 1994; 331: 1618–23CrossRefGoogle Scholar
  94. 94.
    Rudman D, Feller AG, Hoskote S, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323: 1–6PubMedCrossRefGoogle Scholar
  95. 95.
    Holloway L, Kohlmeier L, Kent K, et al. Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women. J Clin Endocrinol Metab 1997; 82: 1111–7PubMedCrossRefGoogle Scholar
  96. 96.
    Ghiron LJ, Thompson JL, Holloway L, et al. Effects of recombinant insulin-like growth factor-1 and growth hormone on bone turnover in elderly women. J Bone Miner Res 1995; 10: 1844–52PubMedCrossRefGoogle Scholar
  97. 97.
    Orwoll ES, Oviatt S, McClung MR, et al. The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation. Ann Intern Med 1990; 112: 29–34PubMedGoogle Scholar
  98. 98.
    Dawson-Hughes B, Dallal GE, Krall EA, et al. Acontrolled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990; 323: 878–83PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Department of Diabetes and EndocrinologyThe Royal Melbourne HospitalMelbourneAustralia

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