Skip to main content
SpringerLink
Log in

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major

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

Abstract

Purpose

Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures.

Methods

We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5–83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder.

Results

Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%).

Conclusion

Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article.

References

  1. Weatherall DJ (1998) Pathophysiology of thalassaemia. Baillieres Clin Haematol 11(1):127–146

    Article  CAS  PubMed  Google Scholar 

  2. De Sanctis V, Soliman AT, Angastiniotis M, Eleftheriou A, Kattamis C, Karimi M et al (2012) International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow. Georgian Med News 205:52–57

    Google Scholar 

  3. Smaldone A (2008) Glycemic control and hemoglobinopathy: when A1C may not be reliable. Diabetes Spectr 21(1):46–49

    Article  Google Scholar 

  4. De Sanctis V (2002) Growth and puberty and its management in thalassaemia. Horm Res 58(Suppl 1):72–79

    PubMed  Google Scholar 

  5. Magro S, Puzzonia P, Consarino C, Galati MC, Morgione S, Porcelli D et al (1990) Hypothyroidism in patients with thalassemia syndromes. Acta Haematol 84(2):72–76

    Article  CAS  PubMed  Google Scholar 

  6. Poomthavorn P, Isaradisaikul B, Chuansumrit A, Khlairit P, Sriphrapradang A, Mahachoklertwattana P (2010) High prevalence of “biochemical” adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin? J Clin Endocrinol Metab 95(10):4609–4615

    Article  CAS  PubMed  Google Scholar 

  7. Karimi M, Rasekhi AR, Rasekh M, Nabavizadeh SA, Assadsangabi R, Amirhakimi GH (2009) Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major. Eur J Radiol 70(3):481–484

    Article  CAS  PubMed  Google Scholar 

  8. Gaudio A, Morabito N, Catalano A, Rapisarda R, Xourafa A, Lasco A (2019) Pathogenesis of thalassemia major-associated osteoporosis: a review with insights from clinical experience. J Clin Res Pediatr Endocrinol 11(2):110–117

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lasco A, Morabito N, Gaudio A, Crisafulli A, Meo A, Denuzzo G et al (2002) Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis. J Endocrinol Invest 25(4):338–344

    Article  CAS  PubMed  Google Scholar 

  10. Soliman AT, El Banna N, Ansari BM (1998) GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia. Eur J Endocrinol 138(4):394–400

    Article  CAS  PubMed  Google Scholar 

  11. Soliman AT, De Sanctis V, Elalaily R, Yassin M (2015) Insulin-like growth factor- I and factors affecting it in thalassemia major. Indian J Endocrinol Metab 19(2):245–251

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hyldstrup L, Conway GS, Racz K, Keller A, Chanson P, Zacharin M et al (2012) Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency. Osteoporos Int 23(8):2219–2226

    Article  CAS  PubMed  Google Scholar 

  13. Locatelli V, Bianchi VE (2014) Effect of GH/IGF-1 on bone metabolism and osteoporsosis. Int J Endocrinol 2014:235060

    Article  PubMed  PubMed Central  Google Scholar 

  14. Liu JM, Zhao HY, Ning G, Chen Y, Zhang LZ, Sun LH et al (2008) IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 26(2):159–164

    Article  CAS  PubMed  Google Scholar 

  15. Paccou J, Dewailly J, Cortet B (2012) Reduced levels of serum IGF-1 is related to the presence of osteoporotic fractures in male idiopathic osteoporosis. Joint Bone Spine 79(1):78–82

    Article  CAS  PubMed  Google Scholar 

  16. Ohlsson C, Mellström D, Carlzon D, Orwoll E, Ljunggren O, Karlsson MK et al (2011) Older men with low serum IGF-1 have an increased risk of incident fractures: the MrOS Sweden study. J Bone Miner Res Off J Am Soc Bone Miner Res 26(4):865–872

    Article  CAS  Google Scholar 

  17. ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D et al (2023) Summary of revisions: standards of care in diabetes-2023. Diabetes Care 46(Suppl 1):S5-9

    Article  PubMed  Google Scholar 

  18. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM et al (2018) Testosterone therapy in men with hypogonadism: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab 103(5):1715–1744

    Article  PubMed  Google Scholar 

  19. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI et al (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American association of clinical endocrinologists and the American thyroid association. Thyroid Off J Am Thyroid Assoc 22(12):1200–1235

    Article  CAS  Google Scholar 

  20. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD et al (2016) Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 101(2):364–389

    Article  CAS  PubMed  Google Scholar 

  21. Clarke BL (2022) Hypoparathyroidism: update of guidelines from the 2022 international task force. Arch Endocrinol Metab 66(5):604–610

    Article  PubMed  PubMed Central  Google Scholar 

  22. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(6):1587–1609

    Article  CAS  PubMed  Google Scholar 

  23. Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, Giannini S et al (2016) Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo 68(1):1–39

    Article  CAS  PubMed  Google Scholar 

  24. Nuti R, Brandi ML, Checchia G, Di Munno O, Dominguez L, Falaschi P et al (2019) Guidelines for the management of osteoporosis and fragility fractures. Intern Emerg Med 14(1):85–102

    Article  PubMed  Google Scholar 

  25. Ardawi MSM, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA et al (2013) Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 56(2):355–362

    Article  CAS  PubMed  Google Scholar 

  26. Langlois JA, Rosen CJ, Visser M, Hannan MT, Harris T, Wilson PWF et al (1998) Association between insulin-like growth factor I and bone mineral density in older women and men: the framingham heart study1. J Clin Endocrinol Metab 83(12):4257–4262

    CAS  PubMed  Google Scholar 

  27. 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(8):1343–1349

    Article  CAS  PubMed  Google Scholar 

  28. Garnero P, Sornay-Rendu E, Delmas PD (2000) Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. The Lancet 355(9207):898–899

    Article  CAS  Google Scholar 

  29. Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS et al (1989) Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci U S A 86(3):854–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Martin-Millan M, Almeida M, Ambrogini E, Han L, Zhao H, Weinstein RS et al (2010) The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol Baltim Md 24(2):323–334

    Article  CAS  Google Scholar 

  31. Venken K, De Gendt K, Boonen S, Ophoff J, Bouillon R, Swinnen JV et al (2006) Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. J Bone Miner Res 21(4):576–585

    Article  CAS  PubMed  Google Scholar 

  32. Callewaert F, Sinnesael M, Gielen E, Boonen S, Vanderschueren D (2010) Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1, and mechanical loading. J Endocrinol 207(2):127–134

    Article  CAS  PubMed  Google Scholar 

  33. Vandenput L, Boonen S, Van Herck E, Swinnen JV, Bouillon R, Vanderschueren D (2002) Evidence from the aged orchidectomized male rat model that 17beta-estradiol is a more effective bone-sparing and anabolic agent than 5alpha-dihydrotestosterone. J Bone Miner Res Off J Am Soc Bone Miner Res 17(11):2080–2086

    Article  CAS  Google Scholar 

  34. Weissberger AJ, Ho KK (1993) Activation of the somatotropic axis by testosterone in adult males: evidence for the role of aromatization. J Clin Endocrinol Metab 76(6):1407–1412

    CAS  PubMed  Google Scholar 

  35. Krishnan V, Bryant HU, MacDougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116(5):1202–1209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Diacinti D, Guglielmi G (2019) How to define an osteoporotic vertebral fracture? Quant Imaging Med Surg 9(9):1485–1494

    Article  PubMed  PubMed Central  Google Scholar 

  37. Scacchi M, Danesi L, Cattaneo A, Sciortino G, Radin R, Ambrogio AG et al (2016) Bone turnover and mineral density in adult thalassemic patients: relationships with growth hormone secretory status and circulating somatomedins. Endocrine 53(2):551–557

    Article  CAS  PubMed  Google Scholar 

  38. Poggi M, Pascucci C, Monti S, Pugliese P, Lauri C, Amodeo G et al (2010) Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters. J Endocrinol Invest 33(8):534–538

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, 95122, Catania, Italy

    G. Costanzo, A. Naselli, M. L. Arpi, T. Piticchio, R. Le Moli, A. Belfiore & F. Frasca

Authors
  1. G. Costanzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Naselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. L. Arpi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Piticchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Le Moli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Belfiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Frasca
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors G. Costanzo, A. Naselli, and F. Frasca were directly involved in data collection and statistical analysis. All of the authors contributed to and approved the final draft of the manuscript.

Corresponding author

Correspondence to F. Frasca.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures involving human participants were in accordance with the ethical standards of the institutional Research Committee and with the Helsinki declaration as revised in 2013.

Informed consent

Informed consent regarding publishing their data was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costanzo, G., Naselli, A., Arpi, M.L. et al. Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-023-02270-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40618-023-02270-6

Keywords

Search

Navigation