Osteoporosis International

, Volume 17, Issue 11, pp 1577–1583

Bone fragility in men - where are we?

  • E. Seeman
  • G. Bianchi
  • S. Khosla
  • J. A. Kanis
  • E. Orwoll
Review
  • 168 Downloads

Abstract

Introduction

This is a summary of several aspects of the epidemiology, pathogenesis and treatment arising directly and indirectly from the proceedings of the Third International Osteoporosis in Men meeting held in Genoa in May 2005. Advances in the study of bone fragility in men have taken place, but many challenges remain.

Observations

Although the epidemiology of hip fractures is well documented, the epidemiology of other non-vertebral fractures is less well defined even though these fractures contribute substantially to the global burden of fractures in men. The epidemiology of vertebral fragility fractures is derived mostly from cross sectional data. The comparable prevalence of vertebral fractures in men and women is likely to be misleading because of traumatic vertebral fractures that arise in young men. Prospective studies are needed to define the proportion of these fractures that are traumatic. After the age of 50 years, the incidence of vertebral fractures in men is about one third to one half of that in women. As in women, most vertebral and non-vertebral fragility fractures occur in persons without osteoporosis. Identifying these individuals is an unmet challenge. The absolute risk for fractures appears no different by sex in men and women of the same age and bone mineral density (BMD) so that the diagnostic threshold for osteoporosis in women can be used in men. Fracture risk varies around the world and is unlikely to be explained solely by variations in BMD, though there are few data comparing men and women of different races. Both the notion that men lose less bone than women from the endosteal envelope and that they gain more on the periosteal envelope during advancing age needs reassessment as recent evidence challenges these observations. Sex differences in the net gain and loss from these surfaces are likely to be site specific, and research is needed to specify this heterogeneity and the reasons for it. The independent and co-dependent effects of sex hormones and the growth hormone/insulin like growth factor 1 axis on periosteal and endosteal modeling and remodeling during growth as well as ageing are poorly defined. The anti-fracture efficacy and safety of androgens and other agents remain incompletely investigated in men.

Conclusion

A great deal of research is needed to advance our understanding of bone fragility in men.

References

  1. 1.
    Cooper C, Dennison EM, Leufkens HGM, Bishop N, Van Staa TP (2004) Epidemiology of childhood fractures in Britain: a study using the general practice research database. J Bone Miner Res 19:1976–1981PubMedCrossRefGoogle Scholar
  2. 2.
    Johnell O, Kanis JA, Jonsson B, Oden A, Johansson H, De Laet C (2005) The burden of hospitalised fractures in Sweden. Osteoporos Int 16:222–228PubMedCrossRefGoogle Scholar
  3. 3.
    Jiang HX, Majumdar SR, Dick DA, Moreau M, Raso J, Otto DD, Johnston DWC (2005) Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res 20:494–500PubMedCrossRefGoogle Scholar
  4. 4.
    Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK (2003) The components of excess mortality after hip fracture. Bone 32:468–473PubMedCrossRefGoogle Scholar
  5. 5.
    Khosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ (1994) Epidemiology and clinical-features of osteoporosis in young individuals. Bone 15:551–555PubMedCrossRefGoogle Scholar
  6. 6.
    Orwoll ES, Klein RF (1995) Osteoporosis in men. Endocr Rev 16:87–116PubMedCrossRefGoogle Scholar
  7. 7.
    Schuit SCE, van der Klift M, Weel AEAM, de Laet CEDH, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JPTM, Pols HAP (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34:195–202PubMedCrossRefGoogle Scholar
  8. 8.
    Szulc P, Munoz F, Duboeuf F, Marchand F, Delmas PD (2005) Bone mineral density predicts osteoporotic fractures in elderly men: the MINOS study. Osteoporos Int 16:1184–1192PubMedCrossRefGoogle Scholar
  9. 9.
    Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Pierre D, Delmas PDD (2005) The identification of osteopenic women at high risk of fracture: the OFELY Study. J Bone Miner Res 20:1929–1943PubMedCrossRefGoogle Scholar
  10. 10.
    Kanis JA, Johnell O, Oden A et al (2001) Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 12:989–995PubMedCrossRefGoogle Scholar
  11. 11.
    Kanis JA, Oden A, Johnell O et al (2001) The burden of osteoporotic fractures: a method of setting intervention thresholds. Osteoporos Int 12:417–427PubMedCrossRefGoogle Scholar
  12. 12.
    Kanis JA, Johnell O, Oden A et al (2005) Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden. Osteoporos Int 16:6–14PubMedCrossRefGoogle Scholar
  13. 13.
    Kanis JA, Borgstrom F, Zethraeus Z et al (2005) Intervention thresholds for osteoporosis in men and women. Bone 36:22–32PubMedCrossRefGoogle Scholar
  14. 14.
    Duan Y, Turner CH, Kim BT, Seeman E (2001) Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss. J Bone Miner Res 16:2267–2274PubMedCrossRefGoogle Scholar
  15. 15.
    Duan Y, Beck TJ, Wang X-F, Seeman E (2003) Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res 18:1766–1774PubMedCrossRefGoogle Scholar
  16. 16.
    Wang XF, Duan Y, Beck T, Seeman ER (2005) Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone 36:978–986PubMedCrossRefGoogle Scholar
  17. 17.
    Seeman E (2003) Periosteal bone formation - a neglected determinant of bone strength. New Eng J Med 349:320–323PubMedCrossRefGoogle Scholar
  18. 18.
    Ahlborg HG Johnell O, Turner CH, Rannevik G, Karlsson MK (2003) Bone loss and bone size after the menopause. N Engl J Med 349:327–334PubMedCrossRefGoogle Scholar
  19. 19.
    Ruff CB, Trinkaus E, Walker A, Larsen CS (1993) Postcranial robusticity in Homo. 1: temporal trends and mechanical interpretation. Am J Phys Anthropol 91:21–53PubMedCrossRefGoogle Scholar
  20. 20.
    Balena R, Shih M-S, Parfitt (1992) Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women. J Bone Miner Res 7:1475–1482PubMedCrossRefGoogle Scholar
  21. 21.
    Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S (2004) A population-based study of age and sex differences in bone volumetric density, size, geometry and structure at different skeletal sites. J Bone Miner Res 19:1945–1954PubMedCrossRefGoogle Scholar
  22. 22.
    Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, Peterson JM, Melton LJ 3rd (2006) Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res 21:124–131PubMedCrossRefGoogle Scholar
  23. 23.
    Aaron JE, Makins NB, Sagreiy K (1987) The microanatomy of trabecular bone loss in normal aging men and women. Clin Orth RR 215:260–271Google Scholar
  24. 24.
    Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB (2004) Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts male aging study. J Clin Endocrinol Metab 89:5920–5926PubMedCrossRefGoogle Scholar
  25. 25.
    Bouillon R, Bex M, Vanderschueren D, Boonen S (2004) Estrogens are essential for male pubertal periosteal bone expansion. J Clin Endocrinol Metab 89:6025–6029PubMedCrossRefGoogle Scholar
  26. 26.
    Khosla S, Melton LJ, Riggs BL (2002) Estrogen and the male skeleton. J Clin Endocrinol Metab 87:1443–1450PubMedCrossRefGoogle Scholar
  27. 27.
    Khosla S, Melton LJ, Atkinson EJ, O’Fallon WM (2001) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 86:3555–3561PubMedCrossRefGoogle Scholar
  28. 28.
    Khosla S, Riggs BL, Robb RA, Camp JJ, Achenbach SJ, Oberg AL, Rouleau PA, Melton LJ III (2005) Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in men. J Clin Endocrinol Metab 90:5096–5103PubMedCrossRefGoogle Scholar
  29. 29.
    Orwoll ES (2003) Toward an expanded understanding of the role of the periosteum in skeletal helath. J Bone Miner Res 18:949–954PubMedCrossRefGoogle Scholar
  30. 30.
    Sims NA, Dupont S, Krust A, Clement-LaCroix P, Minet D, Resche-Rigon M, Gaillard Kelly M, Baron R (2002) Deletion of estrogen receptors reveals a regulatory role for estrogen receptors beta in bone remodeling in females but not in males. Bone 30:18–25PubMedCrossRefGoogle Scholar
  31. 31.
    Sims NA, Clement-Lacroix P, Minet D, Fraslon-Vanhulle C, Gaillard-Kelly M, Resche-Rigon M, Baron R (2003) A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor-deficient mice. J Clin Invest 111:1319–1327PubMedCrossRefGoogle Scholar
  32. 32.
    Szulc P, Garnero P, Marchand F, Duboeuf F, Delmas PD (2005) Biochemical markers of bone formation reflect endosteal bone loss in elderly men-MINOS study. Bone 36:13–21PubMedCrossRefGoogle Scholar
  33. 33.
    Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA (2005) Bone resorption and osteoporotic fractures in elderly men: the Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res 20:579–587PubMedCrossRefGoogle Scholar
  34. 34.
    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 343:604–610PubMedCrossRefGoogle Scholar
  35. 35.
    Sato Y, Iwamoto J, Kanoko T, Satoh K (2005) Risedronate sodium therapy for prevention of hip fracture in men 65 years or older after stroke. Arch Intern Med 165:1743–1748PubMedCrossRefGoogle Scholar
  36. 36.
    Ringe JD, Faber H, Farahmand P, Dorst A (2005) Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study. Rheumatol Int 7:1–5Google Scholar
  37. 37.
    Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP (2000) Therapy of idiopathic osteoporosis in men with parathyroid hormone: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–3076PubMedCrossRefGoogle Scholar
  38. 38.
    Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, Kaufman J-M, Clancy AD, Gaich GA (2003) The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Min Res 18:9–17CrossRefGoogle Scholar
  39. 39.
    Kaufman J-M, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, Lindsay R, Mitlak BH (2005) Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int 16:510–516PubMedCrossRefGoogle Scholar
  40. 40.
    Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226PubMedCrossRefGoogle Scholar
  41. 41.
    Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP (2004) The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1–34)]. Osteoporos Int 15:992–997PubMedCrossRefGoogle Scholar
  42. 42.
    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 89:503–510PubMedCrossRefGoogle Scholar
  43. 43.
    Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, JSantanna J, Kapoor SC, Attie MF, Haddad JG Jr (1999) Strom BL Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84:1966–1972PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • E. Seeman
    • 1
  • G. Bianchi
    • 2
  • S. Khosla
    • 3
  • J. A. Kanis
    • 4
  • E. Orwoll
    • 5
  1. 1.Austin Health, Centaur BuildingHeidelbergAustralia
  2. 2.GenovaItaly
  3. 3.Department of EndocrinologyMayo ClinicRochesterUSA
  4. 4.Centre for Metabolic Bone DiseaseUniversity of Sheffield Medical SchoolBeech Road SheffieldUK
  5. 5.Professor of MedicineOregon Health & Science UniversityPortlandUSA

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