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Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study

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Abstract

The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40–79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E2), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E2, and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.

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References

  1. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559

    Article  PubMed  CAS  Google Scholar 

  2. Fall C, Hindmarsh P, Dennison E et al (1998) Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis. J Clin Endocrinol Metab 83:135–139

    Article  PubMed  CAS  Google Scholar 

  3. Gillberg P, Olofsson H, Mallmin H et al (2002) Bone mineral density in femoral neck is positively correlated to circulating insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in Swedish men. Calcif Tissue Int 70:22–29

    Article  PubMed  CAS  Google Scholar 

  4. Janssen JA, Burger H, Stolk RP et al (1998) Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women. Eur J Endocrinol 138:627–632

    Article  PubMed  CAS  Google Scholar 

  5. Krassas GE, Papadopoulou P, Koliakos G et al (2003) Growth hormone, insulin growth factor-1, and IGF binding protein-3 axis relationship with bone mineral density among healthy men. Arch Androl 49:191–199

    Article  PubMed  CAS  Google Scholar 

  6. Patel MB, Arden NK, Masterson LM et al (2005) Investigating the role of the growth hormone–insulin-like growth factor (GH–IGF) axis as a determinant of male bone mineral density (BMD). Bone 37:833–841

    Article  PubMed  CAS  Google Scholar 

  7. Sugimoto T, Nishiyama K, Kuribayashi F et al (1997) Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 12:1272–1279

    Article  PubMed  CAS  Google Scholar 

  8. Rucker D, Ezzat S, Diamandi A et al (2004) IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men. Clin Endocrinol 60:491–499

    Article  CAS  Google Scholar 

  9. Barrett-Connor E, Goodman-Gruen D (1998) Gender differences in insulin-like growth factor and bone mineral density association in old age: the Rancho Bernardo Study. J Bone Miner Res 13:1343–1349

    Article  PubMed  CAS  Google Scholar 

  10. Jehle PM, Jehle DR, Mohan S et al (1998) Serum levels of insulin-like growth factor system components and relationship to bone metabolism in type 1 and type 2 diabetes mellitus patients. J Endocrinol 159:297–306

    Article  PubMed  CAS  Google Scholar 

  11. Rosen CJ (1999) Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implications. Clin Chem 45:1384–1390

    PubMed  CAS  Google Scholar 

  12. Conover CA, Bale LK, Clarkson JT et al (1993) Potentiation of insulin-like growth factor action by insulin-like growth factor binding protein-3: studies of underlying mechanism. Growth Regul 3:87–88

    PubMed  CAS  Google Scholar 

  13. Szulc P, Joly-Pharaboz MO, Marchand F et al (2004) Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study. Calcif Tissue Int 74:322–329

    Article  PubMed  CAS  Google Scholar 

  14. Johansson AG, Eriksen EF, Lindh E et al (1997) Reduced serum levels of the growth hormone-dependent insulin-like growth factor binding protein and a negative bone balance at the level of individual remodeling units in idiopathic osteoporosis in men. J Clin Endocrinol Metab 82:2795–2798

    Article  PubMed  CAS  Google Scholar 

  15. Conover CA, Lee PD, Riggs BL et al (1996) Insulin-like growth factor-binding protein-1 expression in cultured human bone cells: regulation by insulin and glucocorticoid. Endocrinology 137:3295–3301

    Article  PubMed  CAS  Google Scholar 

  16. Jassal SK, von Muhlen D, Barrett-Connor E et al (2005) Serum insulin-like growth factor binding protein-1 levels and bone mineral density in older adults: the Rancho Bernardo Study. Osteoporos Int 16:1948–1954

    Article  PubMed  CAS  Google Scholar 

  17. Lee DM, O’Neill TW, Pye SR et al (2009) The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl 32:11–24

    Article  PubMed  Google Scholar 

  18. Washburn RA, Smith KW, Jette AM et al (1993) The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol 46:153–162

    Article  PubMed  CAS  Google Scholar 

  19. Wu FC, Tajar A, Pye SR et al (2008) Hypothalamic–pituitary–testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 93:2737–2745

    Article  PubMed  CAS  Google Scholar 

  20. Labrie F, Belanger A, Belanger P et al (2007) Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol 103:178–188

    Article  PubMed  CAS  Google Scholar 

  21. Labrie F, Belanger A, Belanger P et al (2006) Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol 99:182–188

    Article  PubMed  CAS  Google Scholar 

  22. Van Pottelbergh I, Goemaere S, Kaufman JM (2003) Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age. J Clin Endocrinol Metab 88:3075–3081

    Article  PubMed  Google Scholar 

  23. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672

    Article  PubMed  CAS  Google Scholar 

  24. Pye SR, Devakumar V, Boonen S et al (2010) Influence of lifestyle factors on quantitative heel ultrasound measurements in middle-aged and elderly men. Calcif Tissue Int 86:211–219

    Article  PubMed  CAS  Google Scholar 

  25. Kurland ES, Rosen CJ, Cosman F et al (1997) Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 82:2799–2805

    Article  PubMed  CAS  Google Scholar 

  26. Ohlsson C, Bengtsson BA, Isaksson OG et al (1998) Growth hormone and bone. Endocr Rev 19:55–79

    Article  PubMed  CAS  Google Scholar 

  27. Rosen CJ, Donahue LR, Hunter SJ (1994) Insulin-like growth factors and bone: the osteoporosis connection. Proc Soc Exp Biol Med 206:83–102

    PubMed  CAS  Google Scholar 

  28. Ebeling PR, Jones JD, O’Fallon WM et al (1993) Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 77:1384–1387

    Article  PubMed  CAS  Google Scholar 

  29. Grinspoon S, Baum H, Lee K et al (1996) Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 81:3864–3870

    Article  PubMed  CAS  Google Scholar 

  30. Langlois JA, Rosen CJ, Visser M et al (1998) Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study. J Clin Endocrinol Metab 83:4257–4262

    Article  PubMed  CAS  Google Scholar 

  31. Bauer DC, Rosen C, Cauley J et al (1998) Low serum IGF-I but not IGFBP-3 predicts hip and spine fracture: the study of osteoporotic fracture. Bone 23(5 Suppl 1):S561

    Google Scholar 

  32. O’Neill TW, Marsden D, Matthis C et al (1995) Survey response rates: national and regional differences in a European multicentre study of vertebral osteoporosis. J Epidemiol Community Health 49:87–93

    Article  PubMed  Google Scholar 

  33. Feldman HA, Goldstein I, Hatzichristou DG et al (1994) Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151:54–61

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

EMAS is funded by the Commission of the European Communities Fifth Framework Programme “Quality of Life and Management of Living Resources” (grant QLK6-CT-2001-00258) and Arthritis Research UK. The principal investigator of EMAS is Professor Frederick Wu, MD (Department of Endocrinology, Manchester Royal Infirmary, UK). The authors thank the men who participated in the eight countries, the research/nursing staff in the eight centers: C. Pott, Manchester; E. Wouters, Leuven; M. Nilsson, Malmö; M. del Mar Fernandez, Santiago de Compostela; M. Jedrzejowska, Lodz; H.-M. Tabo, Tartu; A. Heredi, Szeged (for their data collection); and C. Moseley, Manchester (for data entry and project coordination). D. V. is a senior clinical investigator supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium. S. B. is a senior clinical investigator of the Fund for Scientific Research-Flanders, Belgium (F.W.O.-Vlaanderen), and holds the Leuven University Chair in Metabolic Bone Diseases.

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Authors and Affiliations

  1. Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M13 9PT, UK

    Stephen R. Pye, Bader Almusalam & Terence W. O’Neill

  2. Leuven University Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium

    Steven Boonen & Evelien Gielen

  3. Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium

    Steven Boonen, Dirk Vanderschueren, Herman Borghs & Evelien Gielen

  4. Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium

    Dirk Vanderschueren

  5. Clinical Radiology, Imaging Science and Biomedical Engineering, Royal Infirmary, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    Judith E. Adams & Kate A. Ward

  6. MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK

    Kate A. Ward

  7. Department of Obstetrics, Gynecology and Andrology, Albert Szent-Gyorgy Medical University, Szeged, Hungary

    Gyorgy Bartfai

  8. Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatología Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, Santiago de Compostela, Spain

    Felipe F. Casanueva

  9. Andrology Research Unit, Developmental & Regenerative Biomedicine Research Group, Manchester Royal Infirmary, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    Joseph D. Finn & Frederick C. W. Wu

  10. Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy

    Gianni Forti

  11. Reproductive Medicine Centre, Skåne University Hospital, University of Lund, Malmo, Sweden

    Aleksander Giwercman

  12. Department of Endocrinology, University College London, London, UK

    Thang S. Han

  13. Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK

    Ilpo T. Huhtaniemi

  14. Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland

    Krzysztof Kula

  15. Laboratory of Molecular Endocrinology and Oncology, Laval University, Quebec City, QC, Canada

    Fernand Labrie

  16. Department of Human Nutrition, University of Glasgow, Glasgow, Scotland

    Michael E. J. Lean

  17. School of Community Based Medicine, The University of Manchester, Salford Royal NHS Trust, Salford, UK

    Neil Pendleton

  18. Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia

    Margus Punab

  19. Arthritis Research UK, Chesterfield, UK

    Alan J. Silman

Authors
  1. Stephen R. Pye
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  2. Bader Almusalam
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  3. Steven Boonen
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  4. Dirk Vanderschueren
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  5. Herman Borghs
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  7. Judith E. Adams
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  8. Kate A. Ward
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  9. Gyorgy Bartfai
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  10. Felipe F. Casanueva
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  11. Joseph D. Finn
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  12. Gianni Forti
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  13. Aleksander Giwercman
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  14. Thang S. Han
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  15. Ilpo T. Huhtaniemi
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  16. Krzysztof Kula
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  17. Fernand Labrie
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  18. Michael E. J. Lean
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  19. Neil Pendleton
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  20. Margus Punab
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  21. Alan J. Silman
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  22. Frederick C. W. Wu
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  23. Terence W. O’Neill
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Consortia

The EMAS Study Group

Corresponding author

Correspondence to Terence W. O’Neill.

Additional information

The list of authors included in The EMAS Study Group are listed in Appendix.

The authors have stated that they have no conflict of interest.

Appendix

Appendix

The EMAS Study Group: Florence (Gianni Forti, Luisa Petrone, Giovanni Corona); Leuven (Dirk Vanderschueren, Steven Boonen, Herman Borghs); Lodz (Krzysztof Kula, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska); London (Ilpo Huhtaniemi); Malmö (Aleksander Giwercman); Manchester (Frederick Wu, Alan Silman, Terence O’Neill, Joseph Finn, Philip Steer, Abdelouahid Tajar, David Lee, Stephen Pye); Santiago (Felipe Casanueva, Mary Lage, Ana I Castro); Szeged (Gyorgy Bartfai, Imre Földesi, Imre Fejes); Tartu (Margus Punab, Paul Korrovitz); Turku (Min Jiang).

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Pye, S.R., Almusalam, B., Boonen, S. et al. Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study. Calcif Tissue Int 88, 503–510 (2011). https://doi.org/10.1007/s00223-011-9484-2

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