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Osteoporosis International

, Volume 20, Issue 4, pp 549–555 | Cite as

Association between iron overload and osteoporosis in patients with hereditary hemochromatosis

  • L. Valenti
  • M. Varenna
  • A. L. Fracanzani
  • V. Rossi
  • S. FargionEmail author
  • L. Sinigaglia
Original Article

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.

Keywords

Bone mineral density Hemochromatosis Human HFE protein Iron overload Osteoporosis 

Notes

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.

References

  1. 1.
    Pietrangelo A (2004) Hereditary hemochromatosis-a new look at an old disease. N Engl J Med 350:2383–2397PubMedCrossRefGoogle Scholar
  2. 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 13:399–408PubMedCrossRefGoogle Scholar
  3. 3.
    Camaschella C (2005) Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106:3710–3717PubMedCrossRefGoogle Scholar
  4. 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 92:1037–1042PubMedCrossRefGoogle Scholar
  5. 5.
    Nagashima M, Kudo M, Chung H et al (2006) Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 36:288–293PubMedCrossRefGoogle Scholar
  6. 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 46:1979–1985PubMedCrossRefGoogle Scholar
  7. 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 24:1809–1813PubMedGoogle Scholar
  8. 8.
    Guggenbuhl P, Deugnier Y, Boisdet JF et al (2005) Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporos Int 16:1809–1814PubMedCrossRefGoogle Scholar
  9. 9.
    Conte D, Caraceni MP, Duriez J et al (1989) Bone involvement in primary hemochromatosis and alcoholic cirrhosis. Am J Gastroenterol 84:1231–1234PubMedGoogle Scholar
  10. 10.
    Diamond T, Stiel D, Posen S (1989) Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors? Ann Intern Med 110:430–436PubMedGoogle Scholar
  11. 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 48:373–379PubMedCrossRefGoogle Scholar
  12. 12.
    de Vernejoul MC, Pointillart A, Golenzer CC et al (1984) Effects of iron overload on bone remodeling in pigs. Am J Pathol 116:377–384PubMedGoogle Scholar
  13. 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 6:39–43PubMedCrossRefGoogle Scholar
  14. 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 17:150–155PubMedCrossRefGoogle Scholar
  15. 15.
    Valenti L, Fracanzani AL, Rossi V et al (2008) The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload. J Rheumatol 35:153–158PubMedGoogle Scholar
  16. 16.
    Guillygomarc’h A, Mendler MH, Moirand R et al (2001) Venesection therapy of insulin resistance-associated hepatic iron overload. J Hepatol 35:344–349PubMedCrossRefGoogle Scholar
  17. 17.
    Scheuer PG, Williams R, Muir AR (1962) Hepatic pathology in relatives of patients with hemochromatosis. J Pathol Bacteriol 84:1–85CrossRefGoogle Scholar
  18. 18.
    Barry M, Sherlock S (1971) Measurement of liver iron concentration in needle biopsy specimens. Lancet 1:100–103PubMedCrossRefGoogle Scholar
  19. 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 27:181–184PubMedCrossRefGoogle Scholar
  20. 20.
    Adams PC, Reboussin DM, Barton JC et al (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778PubMedCrossRefGoogle Scholar
  21. 21.
    McDermott JH, Walsh CH (2005) Hypogonadism in hereditary hemochromatosis. J Clin Endocrinol Metab 90:2451–2455PubMedCrossRefGoogle Scholar
  22. 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 69:110–116PubMedCrossRefGoogle Scholar
  23. 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 ppGoogle Scholar
  24. 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 14:978–982PubMedCrossRefGoogle Scholar
  25. 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 7:558–563PubMedCrossRefGoogle Scholar
  26. 26.
    Mandelli C, Cesarini L, Piperno A et al (1992) Saturability of hepatic iron deposits in genetic hemochromatosis. Hepatology 16:956–959PubMedCrossRefGoogle Scholar
  27. 27.
    Cundy T, Butler J, Bomford A et al (1993) Reversibility of hypogonadotrophic hypogonadism associated with genetic haemochromatosis. Clin Endocrinol (Oxf) 38:617–620CrossRefGoogle Scholar
  28. 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 DisGoogle Scholar
  29. 29.
    Pratelli L, Verri E, Fortini M et al (2006) Chelation therapy and bone metabolism markers in thalassemia major. J Pediatr Endocrinol Metab 19:1335–1342PubMedGoogle Scholar
  30. 30.
    Salama OS, Al-Tonbary YA, Shahin RA et al (2006) Unbalanced bone turnover in children with beta-thalassemia. Hematology 11:197–202PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • L. Valenti
    • 1
  • M. Varenna
    • 2
  • A. L. Fracanzani
    • 1
  • V. Rossi
    • 2
  • S. Fargion
    • 1
    Email author
  • L. Sinigaglia
    • 2
  1. 1.Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli, Universita degli Studi di MilanoOspedale Policlinico Mangialli e Regina Elena Fondazione IRCCSMilanItaly
  2. 2.Department of RheumatologyGaetano Pini InstituteMilanItaly

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