Skip to main content
SpringerLink
Log in

Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

GH deficiency (GHD) in adults is accompanied by reduced bone mass that may revert only after 2 yr of GH replacement. However, it is unclear whether the gender may modify bone responsiveness to GH replacement in adults. In this study we have evaluated whether bone mineral density (BMD) and turnover improve after GH replacement according to patients’ gender. BMD at lumbar spine (LS) and femoral neck (FN), serum osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) were assessed in 64 hypopituitaric patients (35 men, 30–50 yr) before and 2 yr after the beginning of GH replacement. Values of IGF-I and BMD at LS and at FN were expressed as Z-scores. At study entry, IGF-I and BMD resulted similar among men and women with GHD. During GH replacement, IGF-I levels increased in both men and women without any difference in the percentage of IGF-I increase between the genders (p=0.47). In women receiving estrogen replacement, however, the percentage of IGF-I increase (p<0.05), and the Z IGF-I score (p<0.001) were significant lower than estrogen untreated women, although IGF-I levels were similar in the 2 groups (p=0.53). The GH dose adjusted for body weight required to restore normal age- and sex-matched IGF-I levels was lower in men than in women (p<0.001), and was higher in women receiving than in those not receiving estrogen replacement (p<0.05). In contrast, hypogonadal men treated with testosterone and eugonadal men received a similar GH dose (p=0.97). Also OC, Ntx levels, lumbar and femoral BMD improved (p<0.001) in all patients. Nevertheless, a greater increase in lumbar BMD increase was observed in men than in women (8.0±2.1 vs 2.6±0.4%; p<0.05). No significant difference was revealed in bone parameters in women treated or untreated with estrogen replacement and in men treated or not with testosterone replacement for concomitant hypogonadism. At the multiple correlation analysis, gender was a stronger predictor for the required GH dose than the age (p<0.001 and p=0.02, respectively). In conclusion, a 2-yr GH replacement normalizes IGF-I levels, increases bone mass and improves bone turnover both in men and in women with GHD without any difference between the 2 groups, provided that the dose of GH was modulated on the basis of IGF-I levels. Women receiving oral estrogens should receive a GH dose approximately doubled, as compared to men and women not receiving oral estrogens, to achieve similar effects on bone density and turnover. In particular, GH replacement dose, to be successful on bone mass and turnover, depends on gender in hypopituitary patients aged below 50 yr.

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. Wüster C. Growth hormone and bone metabolism. Acta Endocrinol (Copenh) 1993, 128 (Suppl 2): 14–8.

    Google Scholar 

  2. Ohlsson C, Bengtsson BA, Isaksson OGP, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev 1998, 19: 55–79.

    PubMed  CAS  Google Scholar 

  3. De Boer H, Block G-J, Van der Veen EA. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995, 16: 63–86.

    Article  PubMed  Google Scholar 

  4. Hitz MF, Jensen JE, Eskildsen PC. Bone mineral density in patients with growth hormone deficiency: does a gender difference exist? Clin Endocrinol 2006, 65: 783–91.

    Article  CAS  Google Scholar 

  5. Wasnich RD, Ross PD, Heibrun LK, Vogel JM. Prediction of postmenopausal fracture risk with use of bone mineral measurements. Am J Obstr Gynecol 1985, 153: 745–51.

    Article  CAS  Google Scholar 

  6. Rosén T, Wilhelmensem L, Landin-Wilhelsem K, Lappas G, Bengtsson BA. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 1997, 137: 240–5.

    Article  PubMed  Google Scholar 

  7. Wuster C, Abs R, Bengtsson BA, et al. on behalf of the KIMS Study Group and the KIMS International board. Pharmacia & Upjohn International Metabolic Database. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res 2001, 16: 398–405.

    Article  PubMed  CAS  Google Scholar 

  8. Mazziotti G, Bianchi A, Bonadonna S, et al. Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J Bone Miner Res 2006, 21: 520–8.

    Article  PubMed  CAS  Google Scholar 

  9. Kaufman JM, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992, 74: 118–23.

    PubMed  CAS  Google Scholar 

  10. Holmes SJ, Economou G, Whitehouse RW, Adams JE, Shalet SS. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994, 78: 669–74.

    PubMed  CAS  Google Scholar 

  11. Colao A, Di Somma C, Pivonello R, et al. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999, 84: 1919–24.

    Article  PubMed  CAS  Google Scholar 

  12. Gatford KL, Egan AR, Clarke IJ, Owens PC. Sexual dimorphism of the somatotrophic axis. J. Endocrinol 1998, 157: 373–89.

    Article  PubMed  CAS  Google Scholar 

  13. Johansson AG. Gender difference in growth hormone response in adults. J Endocrinol Invest 1999, 22 (5 Suppl): 58–60.

    PubMed  CAS  Google Scholar 

  14. Johansson AG, Engström BE, Ljunghall S, Karlsson FA, Burman P. Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency. J Clin Endocrinol Metab 1999, 84: 2002–7.

    PubMed  CAS  Google Scholar 

  15. Span JP, Pieters GF, Sweep FG, Hermus AR, Smals AG. Gender differences in rhGH-induced changes in body composition in GH-deficient adults. J Clin Endocrinol Metab 2001, 86: 4161–5.

    Article  PubMed  CAS  Google Scholar 

  16. Holloway L, Butterfield G, Hintz RL, Gesundheit N, Marcus R. Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. J Clin Endocrinol Metab 1994, 79: 470–9.

    PubMed  CAS  Google Scholar 

  17. Colao A, Di Somma C, Filippella M, et al. Insulin-like growth factor-I deficiency determines increased intimamedia thickness at common carotid arteries in adult patients with growth hormone deficiency. Clin Endocrinol (Oxf) 2004, 61: 360–6.

    Article  CAS  Google Scholar 

  18. Colao A, Di Somma C, Cuocolo A, et al. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab 2004, 89: 5908–6004.

    Article  CAS  Google Scholar 

  19. Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism. Ann Intern Med 1989, 111: 567–73.

    Article  PubMed  CAS  Google Scholar 

  20. Di Somma C, Colao A, Pivonello R, et al. Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing’s disease. Clin Endocrinol (Oxf) 1998, 48: 655–62.

    Article  Google Scholar 

  21. Di Somma C, Colao A, Di Sarno A, et al. Bone density and bone marker responses to dopamine agonist therapy in hyperprolactinemic males. J Clin Endocrinol Metab 1998, 83: 807–13.

    Article  PubMed  Google Scholar 

  22. Ghigo E, Goffi S, Nicolosi M, et al. Growth hormone (GH) responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man. J Clin Endocrinol Metab 1990, 71: 1481–5.

    Article  PubMed  CAS  Google Scholar 

  23. Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. EurJ Endocrinol 1996, 134: 352–6.

    Article  CAS  Google Scholar 

  24. Aimaretti G, Corneli G, Razzore P, et al. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone+arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 1998, 83: 1615–8.

    PubMed  CAS  Google Scholar 

  25. Aimaretti G, Corneli G, Rovere S, Croce CG, Ghigo E, Procopio M. Is GH therapy useful to preserve bone mass in transition-phase patients with GH deficiency? J Endocrinol Invest 2005, 28 (10 Suppl): 28–32.

    PubMed  CAS  Google Scholar 

  26. Carroll PV, Christ ER, Bengtsson BA, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 1998, 83: 382–95.

    Article  PubMed  CAS  Google Scholar 

  27. Amato G, Carella C, Fazio S, et al. Body composition, bone metabolism and heart structure and function in growth hormone deficient adult before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993, 77: 1671–6.

    PubMed  CAS  Google Scholar 

  28. Holmes SJ, Whitehouse RW, Swindell R, Economou G, Adams JE, Shalet SM. Effect of growth hormone replacement on bone mass in adults with adult onset of growth hormone deficiency. Clin Endocrinol (Oxf) 1995, 42: 627–33.

    Article  CAS  Google Scholar 

  29. Finkenstedt G, Gasser RW, Höfle G, Watfah C, Fridrich L. Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up. Eur J Endocrinol 1997, 136: 282–9.

    Article  PubMed  CAS  Google Scholar 

  30. Johansson G, Rosén T, Bengtsson BA. Four years of growth hormone replacement in adult with growth hormone deficiency: further increase in bone mineral density. Growth Horm IGF Res 1998, 8 (suppl B): 194 (abstract).

    Article  Google Scholar 

  31. Johansen JS, Pedersen SA, Jørgensen JO, et al. Effects of growth hormone (GH) on plasma Gla protein in GH-deficient adults. J Clin Endocrinol Metab 1990, 70: 916–9.

    Article  PubMed  CAS  Google Scholar 

  32. Schlemmer A, Johansen JS, Pedersen SA, Jørgensen JO, Hassager C, Christiansen C. The effect of growth hormone (GH) therapy on urinary pyridoline cross-links in GH-deficient adults. Clin Endocrinol (Oxf) 1991, 35: 471–576.

    Article  CAS  Google Scholar 

  33. Rahim A, Holmes SJ, Adams JE, Shalet SM. Long-term change in the bone mineral density of adult onset growth hormone (GH) deficiency in response to short or long-term GH replacement therapy. Clin Endocrinol (Oxf) 1998, 48: 463–9.

    Article  CAS  Google Scholar 

  34. Melton LJ 3rd, Crowson CS, O’Fallon WM, Wahner HW, Riggs BL. Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 2003, 18: 312–8.

    Article  PubMed  Google Scholar 

  35. Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993, 8: 1227–34.

    Article  PubMed  Google Scholar 

  36. Götherström G, Bengtsson BA, Bosaeus I, Johannsson G, Svensson J. Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency. Eur J Endocrinol 2007, 156: 55–64.

    Article  PubMed  CAS  Google Scholar 

  37. Drake WM, Rodríguez-Arnao J, Weaver JU, et al. The influence of gender on the short and long-term effects of growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults: a 5-year study. Clin Endocrinol 2001, 54: 525–32.

    Article  CAS  Google Scholar 

  38. Lang I, Schernthaner G, Pietschmann P, Kurz R, Stephenson JM, Templ H. Effects of sex and age on growth hormone response to growth hormone-releasing hormone in healthy individuals. J Clin Endocrinol Metab 1987, 65: 535–40.

    Article  PubMed  CAS  Google Scholar 

  39. Lieberman SA, Mitchell AM, Marcus R, Hintz RL, Hoffman AR. The insulin-like growth factor I generation test: resistance to growth hormone with aging and estrogen replacement therapy. Horm Metab Res 1994, 26: 229–33.

    Article  PubMed  CAS  Google Scholar 

  40. Murray RD, Howell SJ, Lissett CA, Shalet SM. Pre-treatment IGF-I levels is the major determinant of GH dosage in adult GH deficiency. Clin Endocrinol (Oxf) 2000, 52: 537–42.

    Article  CAS  Google Scholar 

  41. Abrahamsen B, Hangaard J, Horn HC, et al. Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies. Clin Endocrinol (Oxf) 2002, 57: 273–81.

    Article  CAS  Google Scholar 

  42. Kam GYW, Leung KC, Baxter RC, Ho KY. Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab 2000, 85: 1918–22.

    PubMed  CAS  Google Scholar 

  43. Cook DM, Ludlam WH, Cook MB. Route of estrogen administration helps to determine growth hormone (GH) replacement dose in GH-deficient adults. J Clin Endocrinol Metab 1999, 84: 3956–60.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Clinical Endocrinology and Oncology, “Federico II” University of Naples, via S. Pansini 5, 80131, Napoli, Italy

    F. Rota, M. C. Savanelli, L. Tauchmanova, S. Savastano, G. Lombardi, A. Colao MD, PhD & C. Di Somma

Authors
  1. F. Rota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Savanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Tauchmanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Savastano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Lombardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Colao MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Di Somma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Colao MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rota, F., Savanelli, M.C., Tauchmanova, L. et al. Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender. J Endocrinol Invest 31, 94–102 (2008). https://doi.org/10.1007/BF03345574

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345574

Key Words

Search

Navigation