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Bone status and fractures in 85 adults with Wilson’s disease

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Abstract

Summary

Wilson’s disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.

Introduction

Wilson’s disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients.

Methods

In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67 %) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied.

Results

Mean LS and FN Z-score was normal (−0.37 ± 1.20 at LS and −0.06 ± 1.20 at FN). BMI <19 kg/m2 and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51 %) and VF in 7 (8 %) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF.

Conclusion

Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.

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References

  1. Trocello JM, Chappuis P, Chaine P, Rémy P, Debray D, Duclos-Vallée JC, Woimant F (2009) Maladie de Wilson. Presse Med 38:1089–1098

    Article  PubMed  Google Scholar 

  2. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML (2007) Wilson’s disease. Lancet 367:397–408

    Article  Google Scholar 

  3. Wiggelinkhuizen M, Tilanus ME, Bollen CW, Houwen RH (2009) Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson’s disease. Aliment Pharmacol Ther 29:947–958

    Article  PubMed  CAS  Google Scholar 

  4. Kataoka M, Tsumura H, Itonaga I, Kaku N, Torisu T (2004) Subchondral cyst of the tibia secondary to Wilson disease. Clin Rheumatol 23:460–463

    Article  PubMed  Google Scholar 

  5. Kramer U, Weinberger A, Yarom R, Zoldan J, Bahar A, Godoth N (1993) Synovial copper deposition as a possible explanation of arthropathy in Wilson’s disease. Bull Hosp Jt Dis 52:46–49

    PubMed  CAS  Google Scholar 

  6. Menerey KA, Eider W, Brewer GJ, Braunstein EM, Schumacher HR, Fox IH (1988) The arthropathy of Wilson’s disease: clinical and pathologic features. J Rheumatol 15:331–337

    PubMed  CAS  Google Scholar 

  7. Kaklamanis P, Spengos M (1973) Osteoarticular changes and synovial biopsy findings in Wilson’s disease. Ann Rheum Dis 32:422–427

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Xie YZ, Zhang XZ, Xu XH, Zhang ZX, Feng YK (1985) Radiologic study of 42 cases of Wilson disease. Skelet Radiol 13:114–119

    Article  CAS  Google Scholar 

  9. Canelas HM, Carvalho N, Scaff M, Vitule A, Barbosa ER, Azevedo EM (1978) Osteoarthropathy of hepatolenticular degeneration. Acta Neurol Scand 57:481–487

    Article  PubMed  CAS  Google Scholar 

  10. Golding DN, Walshe JM (1977) Arthropathy of Wilson’s disease. Study of clinical and radiological features in 32 patients. Ann Rheum Dis 36:99–111

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Boudin G, Pépin B, Hubault A, Goldstein B, Lidy C (1977) Arthropathies dans la maladie de Wilson. Ann Méd Interne (Paris) 128:853–856

    CAS  Google Scholar 

  12. Stavrakakis G, Spengos M, Scarpalezos S (1975) Skeletal mass conversions in hepatolenticular degeneration. Neuroradiology 10:169–172

    Article  PubMed  CAS  Google Scholar 

  13. Aksoy M, Camli N, Dilşen G, Koçak N, Erdem S, Ozdogan E, Dinçol K, Dinçol G (1975) Osteoarticular pains and changes in Wilson’s disease: a radiological study in fourteen patients in nine Turkish families. Acta Hepatogastroenterol (Stuttg) 22:164–170

    CAS  Google Scholar 

  14. Golding DN, Walshe JM (1975) Proceedings: the musculoskeletal features of Wilson’s disease: a clinical, radiological, and serological survey. Ann Rheum Dis 34:201

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Rosenoer VM, Michell RC (1959) Skeletal changes in Wilson’s disease. Br J Radiol 32:805–809

    Article  PubMed  CAS  Google Scholar 

  16. Feller ER, Schumacher HR (1972) Osteoarticular changes in Wilson’s disease. Arthritis Rheum 15:259–266

    Article  PubMed  CAS  Google Scholar 

  17. Aksoy M, Camli N, Dincol K, Erdem S, Akgün T (1972) Osseous changes in Wilson’s disease. A radiologic study of nine patients. Radiology 102:505–509

    Article  PubMed  CAS  Google Scholar 

  18. Mindelzun R, Elkin M, Scheinberg IH, Sternlieb I (1970) Skeletal changes in Wilson’s disease. A radiological study. Radiology 94:127–132

    Article  PubMed  CAS  Google Scholar 

  19. Hu R (1994) Severe spinal degeneration in Wilson’s disease. Spine 19:372–375

    Article  PubMed  CAS  Google Scholar 

  20. Rodriges Nieva N, Vernet Bori A (2004) Osteoarthropathy in three siblings with Wilson’s disease. Ann Pediatr (Barc) 61:181–184

    Article  Google Scholar 

  21. Finby N, Bearn AG (1958) Roentgenographic abnormalities of the skeletal system in Wilson’s disease. Am J Roentgenol Radium Ther Nucl Med 79:603–611

    PubMed  CAS  Google Scholar 

  22. Zakraoui L, Amara N, Hamza M, Mrabet A, Hamza M, Hila A, Haddad S (1986) Atteinte articulaire dans la maladie de Wilson. Rev Rhum Mal Osteoartic 53:345–348

    PubMed  CAS  Google Scholar 

  23. Pan HY, Huang CY, Lai CL (1985) Wilson’s disease in a patient presenting with skeletal abnormalities. Orthopedics 8:742–744

    PubMed  CAS  Google Scholar 

  24. Boudin G, Pépin B (1964) Arthropathies dans la maladie de Wilson. Rev Rhum Mal Osteoartic 31:594–598

    PubMed  CAS  Google Scholar 

  25. Hegedus D, Ferencz V, Lakatos PL, Meszaros S, Lakatos P, Horvath C, Szalay F (2002) Decreased bone density, elevated serum osteoprotegerin, and beta-cross-laps in Wilson disease. J Bone Miner Res 17:1961–1967

    Article  PubMed  CAS  Google Scholar 

  26. Selimoglu MA, Ertekin V, Doneray H, Yildirim M (2008) Bone mineral density of children with Wilson disease: efficacy of penicillamine and zinc therapy. J Clin Gastroenterol 42:194–198

    Article  PubMed  CAS  Google Scholar 

  27. Cztonkowska A, Tarnaka B, Möller JC, Leinweber B, Bandmann O, Woimant F, Oertel WH (2007) Unified Wilson’s disease Rating Scale—a proposal for the neurological scoring of Wilson’s disease patients. Neurol I Neurochir Pol 41(1):1–2

    Google Scholar 

  28. Infante-Rivard C, Esnaola S, Villeneuve JP (1987) Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics. Hepatology 7:660–664

    Article  PubMed  CAS  Google Scholar 

  29. Fardellone P, Sebert JL, Bouraya M, Bonidan O, Leclercq G, Doutrellot C, Bellony R, Dubreuil A (1991) Evaluation of the calcium content of diet by frequential self-questionnaire. Rev Rhum Mal Osteoartic 58:99–103

    PubMed  CAS  Google Scholar 

  30. Fardellone P, Cotté FE, Roux C, Lespessailles E, Mercier F, Gaudin AF (2010) Calcium intake and the risk of osteoporosis and fractures in French women. Joint Bone Spine 77:154–158

    Article  PubMed  CAS  Google Scholar 

  31. Epstein S (1988) Serum and urinary markers of bone remodeling: assessment of bone turnover. Endocr Rev 9:437–448

    Article  PubMed  CAS  Google Scholar 

  32. Van Straalen JP, Sanders E, Prummel MF, Sanders GTB (1991) Bone alkaline phosphatase as indicator of bone formation. Clin Chim Acta 201:27–33

    Article  PubMed  Google Scholar 

  33. Bonde M, Garnero P, Fledelius C, Qvist P, Delmas PD, Christiansen C (1997) Measurement of bone degradation products in serum using antibodies reactive with an isomerized from of an 8 amino acid sequence of the C-telopeptide of Type I collagen. J Bone Miner Res 12:1028–1034

    Article  PubMed  CAS  Google Scholar 

  34. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  PubMed  CAS  Google Scholar 

  35. Lewiecki EM, Watts NB, McClung MR, Petak SM, Bachrach LK, Shepherd JA, Downs RW Jr (2004) International society for clinical densitometry. Official positions of the international society for clinical densitometry. J Clin Endocrinol Metab 89:3651–3655

    Article  PubMed  CAS  Google Scholar 

  36. Taes Y, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM (2010) Early smoking is associated with peak bone mass and prevalent fractures in young, healthy men. J Bone Miner Res 25(2):379–387

    Article  PubMed  Google Scholar 

  37. Lutsenko S (2008) Atp7b-/- mice as a model for studies of Wilson’s disease. Biomech Soc Trans 36:1233–1238

    Article  CAS  Google Scholar 

  38. Rest JR (1976) The histological effects of copper and zinc on chick embryo skeletal tissues in organ culture. Br J Nutr 36(2):243–254

    Article  PubMed  CAS  Google Scholar 

  39. Li S, Wang M, Chen X, Li SF, Li-Ling J, Xie HQ (2014) Inhibition of osteogenic differentiation of mesenchymal stem cells by copper supplementation. Cell Prolif 47(1):81–90

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

All authors have approved the final version; FL has supervised the study and will act as the corresponding author. We are grateful to Florence Baudouin and Anny Présent for their contribution to study monitoring. English correction was funded by the “Association pour la Recherche en Pathologie Synoviale” (ARPS).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Paris Diderot University, Sorbonne Paris-Cité, 75205, Paris, France

    H.-K. Ea, M.-C. de Vernejoul & F. Lioté

  2. Service de Rhumatologie, Pole Appareil Locomoteur, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Lariboisière, 75010, Paris, France

    A.-S. Quemeneur, H.-K. Ea, M.-C. de Vernejoul & F. Lioté

  3. Centre National de Référence de la Maladie de Wilson, Service de Neurologie, AP-HP, Hôpital Lariboisière, 75010, Paris, France

    J.-M. Trocello, A. Leyendecker & F. Woimant

  4. Inserm, UMR 1132, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010, Paris, France

    H.-K. Ea, A. Ostertag, M.-C. de Vernejoul & F. Lioté

  5. Centre National de Référence de la Maladie de Wilson, Centre Hépato-Biliaire, AP-HP, Hôpital Paul Brousse, 94800, Villejuif, France

    J.-C. Duclos-Vallée

  6. Coordinateur du DHU Hepatinov, Centre Hépato-Biliaire, Université Paris-Sud, UMR-S 785, 94800, Villejuif, France

    J.-C. Duclos-Vallée

  7. Inserm, U 785, 94800, Villejuif, France

    J.-C. Duclos-Vallée

Authors
  1. A.-S. Quemeneur
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  2. J.-M. Trocello
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  3. H.-K. Ea
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  4. A. Ostertag
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  5. A. Leyendecker
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  6. J.-C. Duclos-Vallée
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  7. M.-C. de Vernejoul
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  8. F. Woimant
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  9. F. Lioté
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Corresponding author

Correspondence to F. Lioté.

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Quemeneur, AS., Trocello, JM., Ea, HK. et al. Bone status and fractures in 85 adults with Wilson’s disease. Osteoporos Int 25, 2573–2580 (2014). https://doi.org/10.1007/s00198-014-2806-2

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  • DOI: https://doi.org/10.1007/s00198-014-2806-2

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