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Bone mineral density in men with genetic hemochromatosis and HFE gene mutation

Osteoporosis International volume 16, pages 1809–1814 (2005)Cite this article

Abstract

Genetic hemochromatosis (GH) is an iron overload disorder mainly due to the C282Y mutation of the HFE gene. The possibility of bone involvement was only recently recognized. The aims of this study were to assess bone mineral density (BMD) and bone remodeling in men with GH, and to examine the influence of iron overload. Thirty-eight men (mean age 47.2±9.4 years) with well-defined HFE-related GH were studied. They had an important iron overload with liver iron concentration to age ratio >2.5, no previous venesection therapy and were C282Y homozygotes ( n =37) or compound C282Y/H63D heterozygote ( n =1). BMD measured by DXA was 0.925±0.15 g/cm2 at the lumbar spine (LS) and 0.778±0.13 g/cm2 at the femoral neck (FN). Osteopenia (T-score <−1 SD) was observed in 78.9% of patients and osteoporosis (T-score <−2.5 SD) in 34.2%. Vitamin D levels were normal, and no 1–84 parathyroid hormone dysfunction was found. Hypogonadism was found in only 13.2% of patients. Patients with hypogonadism had lower LS BMD than eugonadal patients (0.788±0.16 and 0.954±0.14 g/cm2). Bone remodeling and parathyroid hormone levels were lower in patients with cirrhosis, but BMD values were similar to those in patients without cirrhosis. FN BMD appeared to fall with rising hepatic iron concentrations ( r =−0.399). We conclude that there is significant bone loss in HFE-related hemochromatosis that cannot solely be explained by hypogonadism or cirrhosis. Further investigations are needed to determine the role of iron overload itself.

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References

  1. Yaouanq J, Feingold J, Lacombe D (1999) Hémochromatose. Ann Genet 42:234–240

    CAS  PubMed  Google Scholar 

  2. Feder JN, Gnirke A, Thomas W, Tshuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK (1996) A novel MHC class-I like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    Article  CAS  PubMed  Google Scholar 

  3. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, Ramm GA (2003) Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homeostasis. Lancet 361:699–673

    Article  Google Scholar 

  4. Jouanolle AM, Gandon G, Jezequel P, Blayau M, Campion ML, Yaouanq J, Mosser J, Fergelot P, Chauvel B, Bouric P, Carn G, Andrieux N, Gicquel I, Le Gall JY, David V (1996) Haemochromatosis and HLA-H. Nat Genet 13:251–252

    Article  Google Scholar 

  5. Brissot P, Troadec MB, Loreal O (2004) The clinical relevance of new insights in iron transport and metabolism. Curr Hematol Rep 3:107–115

    PubMed  Google Scholar 

  6. Delbarre F (1960) L’ostéoporose des hémochromatoses. Sem Hop Paris 36:3279–3295

    CAS  PubMed  Google Scholar 

  7. Pawlotsky Y, Lancien G, Roudier G, Hany Y, Louboutin JY, Ferrand B, Bourel M (1979) Histomorphométrie osseuse et manifestations ostéo-articulaires de l’hémochromatose idiopathique. Rev Rhum Mal Osteoartic 46:91–99

    CAS  PubMed  Google Scholar 

  8. Pawlotsky Y, Le Dantec P, Moirand R, Guggenbuhl P, Jouanolle AM, Catheline M, Meadeb J, Brissot P, Deugnier Y, Chalès G (1999) Elevated parathyroid hormone 44–68 and osteoarticular changes in patients with genetic hemochromatosis. Arthritis Rheum 42:799–806

    Article  CAS  PubMed  Google Scholar 

  9. Sinigaglia L, Fargion S, Fracanzani AL, Binelli L, Battafarano N, Varenna M, Piperno A, Fiorelli G (1997) Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol 24:1809–1813

    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

    CAS  PubMed  Google Scholar 

  11. Bisbocci D, Marinone C, Ballanti P, Villata E, Suriano A, Vallauri P, Chiandussi L (1991) Bone involvement in primary hemochromatosis : osteoporosis and hormonal bone pattern in hemochromatosis. In: Gentilini P, Dianzani MU (eds) Experimental and clinical hepatology. Elsevier, London, pp 163–169

  12. Chalès G, Guggenbuhl P (2003) When and how should we screen for hereditary hemochromatosis? Joint Bone Spine 70:263–270

    Article  PubMed  Google Scholar 

  13. Barry M, Sherlock S (1971) Measurement of liver-iron concentration in needle-biopsy specimens. Lancet 328:100–103

    Article  Google Scholar 

  14. Gandon Y, Guyader D, Heautot JF, Reda MI, Yaouanq J, Buhe T, Brissot P, Carsin M, Deugnier Y (1994) Hemochromatosis : diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 193:533–538

    CAS  PubMed  Google Scholar 

  15. Gandon Y, Olivié D, Guyader D, Aubée C, Oberti F, Sebille V, Deugnier Y (2004) Non-invasive assessment of hepatic iron stores by MRI. Lancet 363:357–362

    Article  CAS  PubMed  Google Scholar 

  16. Guyader D, Jacquelinet C, Moirand R, Turlin B, Mendler MH, Chaperon J, David V, Brissot P, Adams P, Deugnier Y (1998) Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology 115:929–936

    CAS  PubMed  Google Scholar 

  17. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    CAS  PubMed  Google Scholar 

  18. Conte D, Caraceni M, Duriez J, Mandelli C, Corghi E, Cesana M, Ortolani S, Bianchi PA (1989) Bone involvement in primary hemochromatosis and alcoholic cirrhosis. Am J Gastroenterol 84:1231–1234

    CAS  PubMed  Google Scholar 

  19. Pawlotsky Y, Roussey M, Hany Y, Simon M, Bourel M (1974) Hyperparathormonémie dans l’hémochromatose idiopathique. Nouv Presse Med 3:1757–1758

    CAS  PubMed  Google Scholar 

  20. Audran M, Chappard D, Legrand E, Libouban H, Baslé MF (2001) Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model. Calcif Tissue Int 69:214–217

    Article  CAS  PubMed  Google Scholar 

  21. De Vernejoul MC, Pointillart A, Cywiner- Golenzer C, Morieux C, Bielakoff J, Modrowski D, Miravet L (1984) Effects of iron overload on bone remodelling pigs. Am J Pathol 116:377–384

    PubMed  Google Scholar 

  22. Ebina Y, Okada S, Hamazaki S, Toda Y, Midorikawa O (1991) Impairment of bone formation with aluminium and ferric nitriloacetate complexes. Calcif Tissue Int 48:28–36

    CAS  PubMed  Google Scholar 

  23. Guanabens N, Parés A, Alvarez L, Martinez de Osaba MJ, Monegal A, Peris P, Ballesta AM, Rodes J (1998) Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis. J Bone Miner Res 13:731–738

    CAS  PubMed  Google Scholar 

  24. Chales G, Guggenbuhl P (2001) Ostéoporose de l’hémochromatose génétique. Rev Rhum [Ed Fr] 68:749–751

    Google Scholar 

  25. Diamond T, Pojer R, Alfrey A, Posen S (1991) Does iron affect osteoblast function ? Studies in vitro and in patients with chronic liver disease. Calcif Tissue Int 48:373–379

    CAS  PubMed  Google Scholar 

  26. Diamond T, Stiel D, Lunzer M, McDowall D, Eckstein R, Posen S (1989) Hepatic osteodystrophy. Gastroenterology 96:213–221

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Rheumatology Department, University Hospital, Rennes, France

    P. Guggenbuhl, J. F. Boisdet, A. Perdriger, Y. Pawlotsky & G. Chalès

  2. Hepatology Department, University Hospital, Rennes, France

    Y. Deugnier

  3. Radiology Department, University Hospital, Rennes, France

    Y. Rolland

Authors
  1. P. Guggenbuhl
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  2. Y. Deugnier
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  3. J. F. Boisdet
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  4. Y. Rolland
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  5. A. Perdriger
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  6. Y. Pawlotsky
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  7. G. Chalès
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Correspondence to P. Guggenbuhl.

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Guggenbuhl, P., Deugnier, Y., Boisdet, J.F. et al. Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporos Int 16, 1809–1814 (2005). https://doi.org/10.1007/s00198-005-1934-0

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  • DOI: https://doi.org/10.1007/s00198-005-1934-0

Keywords

  • Bone mineral density
  • Hemochromatosis
  • Iron overload
  • Osteopenia
  • Osteoporosis