Skip to main content
SpringerLink
Log in

The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50 years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen’s method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (β = −0.139 for osteocalcin and β = −0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50 years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bachrach LK (2001) Acquisition of optimal bone mass in childhood and adolescence. Trends Endocrinol Metab 12:22–28

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Alibhai SM, Gogov S, Allibhai Z (2006) Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: a systematic literature review. Crit Rev Oncol Hematol 60:201–215

    Article  PubMed  Google Scholar 

  4. Stepan JJ, Lachman M, Zverina J, Pacovsky 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

    Article  CAS  PubMed  Google Scholar 

  5. Lee EY, Kim D, Kim KM, Kim KJ, Choi HS, Rhee Y, Lim SK (2012) Age-related bone mineral density patterns in Koreans (KNHANES IV). J Clin Endocrinol Metab 97:3310–3318

    Article  CAS  PubMed  Google Scholar 

  6. Iranmanesh A, Lizarralde G, Veldhuis JD (1991) Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 73:1081–1088

    Article  CAS  PubMed  Google Scholar 

  7. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR, Baltimore Longitudinal Study of A (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86:724–731

    Article  Google Scholar 

  8. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB (2002) Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 87:589–598

    Article  CAS  PubMed  Google Scholar 

  9. Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, Flicker L (2007) In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study. Eur J Endocrinol 156:585–594

    Article  CAS  PubMed  Google Scholar 

  10. Pye SR, Almusalam B, Boonen S, Vanderschueren D, Borghs H et al (2011) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Szulc P, Joly-Pharaboz MO, Marchand F, Delmas PD (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  CAS  PubMed  Google Scholar 

  12. Cauley JA, Ewing SK, Taylor BC, Fink HA, Ensrud KE, Bauer DC, Barrett-Connor E, Marshall L, Orwoll ES, Osteoporotic Fractures in Men Study Research G (2010) Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density—the osteoporotic fractures in men study. J Clin Endocrinol Metab 95:4314–4323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Paller CJ, Shiels MS, Rohrmann S, Basaria S, Rifai N, Nelson W, Platz EA, Dobs A (2009) Relationship of sex steroid hormones with bone mineral density (BMD) in a nationally representative sample of men. Clin Endocrinol (Oxf) 70:26–34

    Article  CAS  Google Scholar 

  14. Kuchuk NO, van Schoor NM, Pluijm SM, Smit JH, de Ronde W, Lips P (2007) The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol (Oxf) 67:295–303

    Article  CAS  Google Scholar 

  15. Boonen S, Pye SR, O’Neill TW, Szulc P, Gielen E et al (2011) Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS). Eur J Endocrinol 165:977–986

    Article  CAS  PubMed  Google Scholar 

  16. Hsu B, Cumming RG, Seibel MJ, Naganathan V, Blyth FM, Bleicher K, Dave A, Le Couteur DG, Waite LM, Handelsman DJ (2015) Reproductive hormones and longitudinal change in bone mineral density and incident fracture risk in older men: the concord health and aging in men project. J Bone Miner Res 30:1701–1708

    Article  CAS  PubMed  Google Scholar 

  17. Vanderschueren D, Pye SR, Venken K, Borghs H, Gaytant J et al (2010) Gonadal sex steroid status and bone health in middle-aged and elderly European men. Osteoporos Int 21:1331–1339

    Article  CAS  PubMed  Google Scholar 

  18. 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  CAS  PubMed  Google Scholar 

  19. Ferlin A, Selice R, Carraro U, Foresta C (2013) Testicular function and bone metabolism—beyond testosterone. Nat Rev Endocrinol 9:548–554

    Article  CAS  PubMed  Google Scholar 

  20. Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, Orwoll ES (2006) Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab 91:3908–3915

    Article  CAS  PubMed  Google Scholar 

  21. Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C (2006) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Miner Res 21:529–535

    Article  PubMed  Google Scholar 

  22. Rucker D, Ezzat S, Diamandi A, Khosravi J, Hanley DA (2004) IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men. Clin Endocrinol (Oxf) 60:491–499

    Article  CAS  Google Scholar 

  23. Zha XY, Hu Y, Pang XN, Zhu JH, Chang GL, Li L (2014) Sex hormone-binding globulin (SHBG) as an independent determinant of bone mineral density (BMD) among Chinese middle-aged and elderly men. Endocrine 47:590–597

    Article  CAS  PubMed  Google Scholar 

  24. Keles I, Aydin G, Basar MM, Hayran M, Atalar E, Orkun S, Batislam E (2006) Endogenous sex steroids and bone mineral density in healthy men. Joint Bone Spine 73:80–85

    Article  CAS  PubMed  Google Scholar 

  25. Bo T, Zhu JM (2014) Low levels of free testosterone correlated with bone mineral densities of femoral necks in aged healthy Shanghainese men. Horm Metab Res 46:697–701

    Article  CAS  PubMed  Google Scholar 

  26. Vandenput L, Mellstrom D, Kindmark A, Johansson H, Lorentzon M, Leung J, Redlund-Johnell I, Rosengren BE, Karlsson MK, Wang YX, Kwok T, Ohlsson C (2016) High serum SHBG predicts incident vertebral fractures in elderly men. J Bone Miner Res 31:683–689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cawthon PM, Schousboe JT, Harrison SL, Ensrud KE, Black D, Cauley JA, Cummings SR, LeBlanc ES, Laughlin GA, Nielson CM, Broughton A, Kado DM, Hoffman AR, Jamal SA, Barrett-Connor E, Orwoll ES, Osteoporotic Fractures in Men Study Research G (2016) Sex hormones, sex hormone binding globulin, and vertebral fractures in older men. Bone 84:271–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cauley JA (2015) Estrogen and bone health in men and women. Steroids 99:11–15

    Article  CAS  PubMed  Google Scholar 

  29. Dunn JF, Nisula BC, Rodbard D (1981) Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 53:58–68

    Article  CAS  PubMed  Google Scholar 

  30. Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA (2010) Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol 316:79–85

    Article  CAS  PubMed  Google Scholar 

  31. Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bredella MA, Gerweck AV, Barber LA, Breggia A, Rosen CJ, Torriani M, Miller KK (2014) Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women. Bone 62:29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sneppen SB, Hoeck HC, Kollerup G, Sorensen OH, Laurberg P, Feldt-Rasmussen U (2002) Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults–an 18-month randomised, placebo-controlled, double blinded trial. Eur J Endocrinol 146:187–195

    Article  CAS  PubMed  Google Scholar 

  34. Niemann I, Hannemann A, Nauck M, Spielhagen C, Volzke H, Wallaschofski H, Friedrich N (2013) The association between insulin-like growth factor I and bone turnover markers in the general adult population. Bone 56:184–190

    Article  CAS  PubMed  Google Scholar 

  35. Amin S, Riggs BL, Melton LJ 3rd, Achenbach SJ, Atkinson EJ, Khosla S (2007) High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. J Bone Miner Res 22:799–807

    Article  CAS  PubMed  Google Scholar 

  36. Gurlek A, Gedik O (2001) Endogenous sex steroid, GH and IGF-I levels in normal elderly men: relationships with bone mineral density and markers of bone turnover. J Endocrinol Invest 24:408–414

    Article  CAS  PubMed  Google Scholar 

  37. Botella S, Restituto P, Monreal I, Colina I, Calleja A, Varo N (2013) Traditional and novel bone remodeling markers in premenopausal and postmenopausal women. J Clin Endocrinol Metab 98:E1740–E1748

    Article  CAS  PubMed  Google Scholar 

  38. Hsing AW, Stanczyk FZ, Belanger A, Schroeder P, Chang L, Falk RT, Fears TR (2007) Reproducibility of serum sex steroid assays in men by RIA and mass spectrometry. Cancer Epidemiol Biomarkers Prev 16:1004–1008

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank to all staffs of CHA Health Promotion Center for the quality control of our data.

Author information

Authors and Affiliations

  1. Department of Family Medicine, Green-cross I-MED, 06647, Seoul, South Korea

    Hye-Jung Kim

  2. Department of Family Medicine, Dongguk University Bundang Oriental Hospital, 13601, Seongnam, South Korea

    Hyung Suk Koo

  3. Department of Family Medicine, CHA Bundang Medical Centre, CHA University, 59 Yatap-ro, Bundang-gu, 13496, Seongnam-Si, Gyeonggi-do, South Korea

    Young-Sang Kim, Moon Jong Kim & Ji-hee Haam

  4. Department of Family Practice and Community Health, School of Medicine, Ajou University, 16499, Suwon, South Korea

    Kwang-Min Kim & Nam-Seok Joo

Authors
  1. Hye-Jung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyung Suk Koo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young-Sang Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moon Jong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kwang-Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nam-Seok Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ji-hee Haam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young-Sang Kim.

Ethics declarations

Conflict of interest

None of the authors has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the contents of the paper.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, HJ., Koo, H.S., Kim, YS. et al. The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older. J Bone Miner Metab 35, 659–665 (2017). https://doi.org/10.1007/s00774-016-0803-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-016-0803-6

Keywords

Search

Navigation