Skip to main content

Advertisement

SpringerLink
Log in

Association between iron overload and osteoporosis in patients with hereditary hemochromatosis

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

In 87 patients with hereditary hemochromatosis, osteoporosis was detected in 25%, and osteopenia in 41%. Bone mineral density was independently associated with BMI, ALP levels, hypogonadism/menopause, and the amount of iron removed to reach depletion, but not with cirrhosis. Osteoporosis is influenced by iron overload in hemochromatosis.

Introduction

To analyze prevalence, clinical characteristics and genetic background associated with osteoporosis in a retrospective study in Italian patients with hereditary hemochromatosis (HHC).

Methods

In 87 consecutive patients with HHC, bone mineral density was systematically evaluated by dual energy x-ray absorptiometry of the lumbar spine (n = 87) and femoral neck (n = 66).

Results

Osteoporosis was detected in 22 (25.3%), and osteopenia in 36 (41.4%) patients. Mean Z scores were −0.92 ± 1.42 at lumbar spine and −0.35 ± 1.41 at femoral neck. Lumbar spine T-score was independently associated with total ALP (p = 0.002), hypogonadism/menopause (p = 0.026), and iron overload (p = 0.033 for ferritin and p = 0.017 for iron removed). We observed a borderline significance for BMI (p = 0.069) and smoking status (p = 0.086). Lumbar spine osteoporosis was independently associated with lower BMI (OR 0.73, 95% CI 0.54–0.94), total ALP (OR 1.17, 95% CI 1–1.39 per 10 unit increase) and the amount of iron removed (OR 1.53, 95% CI 1–2.5 per 5 g increase). HFE genotypes did not differ between patients with and without osteoporosis.

Conclusions

Osteoporosis is observed in a quarter of unselected patients with HHC, independently of the genetic background, and is associated with ALP, hypogonadism, body weight, and severity of iron overload.

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.

Similar content being viewed by others

References

  1. Pietrangelo A (2004) Hereditary hemochromatosis-a new look at an old disease. N Engl J Med 350:2383–2397

    Article  PubMed  CAS  Google Scholar 

  2. Feder JN, Gnirke A, Thomas W et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    Article  PubMed  CAS  Google Scholar 

  3. Camaschella C (2005) Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106:3710–3717

    Article  PubMed  CAS  Google Scholar 

  4. Valenti L, Pulixi EA, Arosio P et al (2007) Relative contribution of iron genes, dysmetabolism and hepatitis C virus (HCV) in the pathogenesis of altered iron regulation in HCV chronic hepatitis. Haematologica 92:1037–1042

    Article  PubMed  CAS  Google Scholar 

  5. Nagashima M, Kudo M, Chung H et al (2006) Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 36:288–293

    Article  PubMed  CAS  Google Scholar 

  6. Harrison-Findik DD, Klein E, Crist C et al (2007) Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol. Hepatology 46:1979–1985

    Article  PubMed  CAS  Google Scholar 

  7. Sinigaglia L, Fargion S, Fracanzani AL et al (1997) Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol 24:1809–1813

    PubMed  CAS  Google Scholar 

  8. Guggenbuhl P, Deugnier Y, Boisdet JF et al (2005) Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporos Int 16:1809–1814

    Article  PubMed  CAS  Google Scholar 

  9. Conte D, Caraceni MP, Duriez J et al (1989) Bone involvement in primary hemochromatosis and alcoholic cirrhosis. Am J Gastroenterol 84:1231–1234

    PubMed  CAS  Google Scholar 

  10. Diamond T, Stiel D, Posen S (1989) Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors? Ann Intern Med 110:430–436

    PubMed  CAS  Google Scholar 

  11. Diamond T, Pojer R, Stiel D et al (1991) Does iron affect osteoblast function? Studies in vitro and in patients with chronic liver disease. Calcif Tissue Int 48:373–379

    Article  PubMed  CAS  Google Scholar 

  12. de Vernejoul MC, Pointillart A, Golenzer CC et al (1984) Effects of iron overload on bone remodeling in pigs. Am J Pathol 116:377–384

    PubMed  Google Scholar 

  13. Diamond T, Stiel D, Posen S (1991) Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis. J Bone Miner Res 6:39–43

    Article  PubMed  CAS  Google Scholar 

  14. Angelopoulos NG, Goula AK, Papanikolaou G et al (2006) Osteoporosis in HFE2 juvenile hemochromatosis. A case report and review of the literature. Osteoporos Int 17:150–155

    Article  PubMed  Google Scholar 

  15. Valenti L, Fracanzani AL, Rossi V et al (2008) The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload. J Rheumatol 35:153–158

    PubMed  CAS  Google Scholar 

  16. Guillygomarc’h A, Mendler MH, Moirand R et al (2001) Venesection therapy of insulin resistance-associated hepatic iron overload. J Hepatol 35:344–349

    Article  PubMed  CAS  Google Scholar 

  17. Scheuer PG, Williams R, Muir AR (1962) Hepatic pathology in relatives of patients with hemochromatosis. J Pathol Bacteriol 84:1–85

    Article  Google Scholar 

  18. Barry M, Sherlock S (1971) Measurement of liver iron concentration in needle biopsy specimens. Lancet 1:100–103

    Article  PubMed  CAS  Google Scholar 

  19. Sampietro M, Piperno A, Lupica L et al (1998) High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda. Hepatology 27:181–184

    Article  PubMed  CAS  Google Scholar 

  20. Adams PC, Reboussin DM, Barton JC et al (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778

    Article  PubMed  CAS  Google Scholar 

  21. McDermott JH, Walsh CH (2005) Hypogonadism in hereditary hemochromatosis. J Clin Endocrinol Metab 90:2451–2455

    Article  PubMed  CAS  Google Scholar 

  22. Cundy T, Bomford A, Butler J et al (1989) Hypogonadism and sexual dysfunction in hemochromatosis: the effects of cirrhosis and diabetes. J Clin Endocrinol Metab 69:110–116

    Article  PubMed  CAS  Google Scholar 

  23. Group WHOs (1994) Osteoporosis. In: (eds)(1994) Assesment of fracture risk and its application to screening for post-menopausal osteoporosis. WHO technical report series 843. WHO, Geneva pp

  24. Pedrazzoni M, Girasole G, Bertoldo F et al (2003) Definition of a population-specific DXA reference standard in Italian women: the Densitometric Italian Normative Study (DINS). Osteoporos Int 14:978–982

    Article  PubMed  CAS  Google Scholar 

  25. Varenna M, Binelli L, Zucchi F et al (1997) Is the metatarsal fracture in postmenopausal women an osteoporotic fracture? A cross-sectional study on 113 cases. Osteoporos Int 7:558–563

    Article  PubMed  CAS  Google Scholar 

  26. Mandelli C, Cesarini L, Piperno A et al (1992) Saturability of hepatic iron deposits in genetic hemochromatosis. Hepatology 16:956–959

    Article  PubMed  CAS  Google Scholar 

  27. Cundy T, Butler J, Bomford A et al (1993) Reversibility of hypogonadotrophic hypogonadism associated with genetic haemochromatosis. Clin Endocrinol (Oxf) 38:617–620

    Article  CAS  Google Scholar 

  28. Szulc P, Montella A, Delmas PD (2007) High bone turnover is associated with accelerated bone loss but not with increased fracture risk in men aged 50 and over - prospective MINOS study. Ann Rheum Dis

  29. Pratelli L, Verri E, Fortini M et al (2006) Chelation therapy and bone metabolism markers in thalassemia major. J Pediatr Endocrinol Metab 19:1335–1342

    PubMed  CAS  Google Scholar 

  30. Salama OS, Al-Tonbary YA, Shahin RA et al (2006) Unbalanced bone turnover in children with beta-thalassemia. Hematology 11:197–202

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements and Funding

This paper was supported by COFIN 2004, FIRST 2004, FIRST 2005, Ricerca Corrente Ospedale Maggiore Policlinico Mangiagalli Regina Elena IRCCS 2004, 2005, 2006. Centro Universitario per lo Studio e la Cura delle Malattie Metaboliche del Fegato.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli, Universita degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Via F Sforza 35, 20122, Milan, Italy

    L. Valenti, A. L. Fracanzani & S. Fargion

  2. Department of Rheumatology, Gaetano Pini Institute, Milan, Italy

    M. Varenna, V. Rossi & L. Sinigaglia

Authors
  1. L. Valenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Varenna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. L. Fracanzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Fargion
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Sinigaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Fargion.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valenti, L., Varenna, M., Fracanzani, A.L. et al. Association between iron overload and osteoporosis in patients with hereditary hemochromatosis. Osteoporos Int 20, 549–555 (2009). https://doi.org/10.1007/s00198-008-0701-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-008-0701-4

Keywords

Search

Navigation