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Chronic non-cholestatic liver disease is not associated with an increased fracture rate in children

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Abstract

Chronic liver disease in adults is a risk factor of osteoporosis, but little is known about risk of fractures in children with non-cholestatic liver disease. The aim of this study was to investigate associations among the severity of liver fibrosis, bone mass and low-energy fractures in children. History of fractures, anthropometry, and bone mass and size were examined in 39 Caucasian children (25 boys, 14 girls) aged 7.1–18 years (mean 11.9 ± 3.1) with chronic hepatitis B and liver fibrosis evidenced by liver biopsy. Severity of liver fibrosis was based on histological classification according to the method of Batts and Ludwig (mild, 1–2 scores; advanced, 3 scores) and Ishak (1–3 and 4–5 scores, respectively). Bone mineral content (BMC), density (BMD) and body composition were determined in the total body and lumbar spine using dual energy X-ray absorptiometry. Seven subjects (4 girls, 3 boys; 18% of the sample) had low BMD in the total body and lumbar spine region (Z-scores below −2.0). No associations were found among BMC, BMD, bone size and the severity of liver fibrosis. Nine boys (36% of all boys) and one girl reported repeated fractures (forearm, wrist, tibia, ankle, humerus), showing trends similar to the prevalence in general population. Fractures were neither associated with lower BMD/BMC nor with scores of liver fibrosis. Deficits in BMD in children with chronic hepatitis B are not associated with the severity of liver fibrosis. This study suggests that non-cholestatic liver disease does not increase the risk of low-energy fractures during growth. From the practical perspective, however, children with chronic liver disease should be screened for history and clinical risk factors for fractures rather than referred to bone density testing.

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References

  1. Gallego-Rojo FJ, Gonzalez-Calvin JL, Munoz-Torres M, Mundi JL, Fernandez-Perez R, Rodrigo-Moreno D (1998) Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis. Hepatology 28:695–699

    Article  PubMed  CAS  Google Scholar 

  2. Masaki K, Shiomi S, Kuroki T, Tanaka T, Monna T, Ochi H (1998) Longitudinal changes of bone mineral content with age in patients with cirrhosis of the liver. J Gastroenterol 33:236–240

    Article  PubMed  CAS  Google Scholar 

  3. Sokhi RP, Anantharaju A, Kondaveeti R, Creech SD, Islam KK, Van Thiel DH (2004) Bone mineral density among cirrhotic patients awaiting liver transplantation. Liver Transpl 10:648–653

    Article  PubMed  Google Scholar 

  4. Gonzalez-Calvin JL, Gallego-Rojo F, Fernandez-Perez R, Casado-Caballero F, Ruiz-Escolano E, Olivares EG (2004) Osteoporosis, mineral metabolism, and serum soluble tumor necrosis factor receptor p55 in viral cirrhosis. J Clin Endocrinol Metab 89:4325–4330

    Article  PubMed  CAS  Google Scholar 

  5. Bonkovsky HL, Hawkins M, Steinberg K, Hersh T, Galambos JT, Henderson JM, Millikan WJ, Galloway JR (1990) Prevalence and prediction of osteopenia in chronic liver disease. Hepatology 12:273–280

    Article  PubMed  CAS  Google Scholar 

  6. Springer JE, Cole DE, Rubin LA, Cauch-Dudek K, Harewood L, Evrovski J, Peltekova VD, Heathcote EJ (2000) Vitamin D-receptor genotypes as independent genetic predictors of decreased bone mineral density in primary biliary cirrhosis. Gastroenterology 118:145–151

    Article  PubMed  CAS  Google Scholar 

  7. Bagur A, Mautalen C, Findor J, Sorda J, Somoza J (1998) Risk factors for the development of vertebral and total skeleton osteoporosis in patients with primary biliary cirrhosis. Calcif Tissue Int 63:385–390

    Article  PubMed  CAS  Google Scholar 

  8. Newton J, Francis R, Prince M, James O, Bassendine M, Rawlings D, Jones D (2001) Osteoporosis in primary biliary cirrhosis revisited. Gut 49:282–287

    Article  PubMed  CAS  Google Scholar 

  9. Hirano Y, Kishimoto H, Hagino H, Teshima R (1999) The change of bone mineral density in secondary osteoporosis and vertebral fracture incidence. J Bone Miner Metab 17:119–124

    Article  PubMed  CAS  Google Scholar 

  10. Olsson R, Johansson C, Lindstedt G, Mellstrom D (1994) Risk factors for bone loss in chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol 29:753–756

    Article  PubMed  CAS  Google Scholar 

  11. Isaia G, Di Stefano M, Roggia C, Ardissone P, Rosina F (1998) Bone disorders in cholestatic liver diseases. Forum (Genova) 8:28–38

    CAS  Google Scholar 

  12. Sylvester FA (1999) Bone abnormalities in gastrointestinal and hepatic disease. Curr Opin Pediatr 11:402–407

    Article  PubMed  CAS  Google Scholar 

  13. Baroncelli GI, Federico G, Bertelloni S, Sodini F, De Terlizzi F, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136

    Article  PubMed  Google Scholar 

  14. Tanner JM (1978) Physical growth and development. In: Forfar J, Arnell CC (eds) Textbook of pediatrics, 2nd edn. Edinbourgh, Scotland, pp 249–303

    Google Scholar 

  15. Batts KP, Ludwig J (1995) Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 19:1409–1417

    Article  PubMed  CAS  Google Scholar 

  16. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699

    Article  PubMed  CAS  Google Scholar 

  17. Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB, Rauch F (2008) Official positions of the international society for clinical densitometry and executive summary of the 2007 ISCD pediatric position development conference. J Clin Densitom 11:6–21

    Article  PubMed  Google Scholar 

  18. Pares A, Guanabens N, Alvarez L, De Osaba MJ, Oriola J, Pons F, Caballeria L, Monegal A, Salvador G, Jo J, Peris P, Rivera F, Ballesta AM, Rodes J (2001) Collagen type I alpha1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis. Hepatology 33:554–560

    Article  PubMed  CAS  Google Scholar 

  19. Duarte MP, Farias ML, Coelho HS, Mendonca LM, Stabnov LM, d Oliveira M, Lamy RA, Oliveira DS (2001) Calcium-parathyroid hormone-vitamin D axis and metabolic bone disease in chronic viral liver disease. J Gastroenterol Hepatol 16:1022–1027

    Article  PubMed  CAS  Google Scholar 

  20. Crawford BA, Kam C, Donaghy AJ, McCaughan GW (2003) The heterogeneity of bone disease in cirrhosis: a multivariate analysis. Osteoporos Int 14:987–994

    Article  PubMed  Google Scholar 

  21. Corazza GR, Trevisani F, Di Stefano M, De Notariis S, Veneto G, Cecchetti L, Minguzzi L, Gasbarrini G, Bernardi M (2000) Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis. Dig Dis Sci 45:1392–1399

    Article  PubMed  CAS  Google Scholar 

  22. Schiefke I, Fach A, Wiedmann M, Aretin AV, Schenker E, Borte G, Wiese M, Moessner J (2005) Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol 11:1843–1847

    PubMed  CAS  Google Scholar 

  23. Gur A, Dikici B, Nas K, Bosnak M, Haspolat K, Sarac AJ (2005) Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent osteoporosis? BMC Gastroenterol 5:30

    Article  PubMed  Google Scholar 

  24. Ma DQ, Jones G (2002) Clinical risk factors but not bone density are associated with prevalent fractures in prepubertal children. J Paediatr Child Health 38:497–500

    Article  PubMed  CAS  Google Scholar 

  25. Landin LA (1997) Epidemiology of children’s fractures. J Pediatr Orthop B 6:79–83

    Article  PubMed  CAS  Google Scholar 

  26. Khosla S, Melton LJ 3rd, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL (2003) Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA 290:1479–1485

    Article  PubMed  CAS  Google Scholar 

  27. Lyons RA, Delahunty AM, Kraus D, Heaven M, McCabe M, Allen H, Nash P (1999) Children’s fractures: a population based study. Inj Prev 5:129–132

    Article  PubMed  CAS  Google Scholar 

  28. Jones IE, Cannan R, Goulding A (2000) Distal forearm fractures in New Zealand children: annual rates in a geographically defined area. N Z Med J 113:443–445

    PubMed  CAS  Google Scholar 

  29. Hagino H, Yamamoto K, Ohshiro H, Nose T (2000) Increasing incidence of distal radius fractures in Japanese children and adolescents. J Orthop Sci 5:356–360

    Article  PubMed  CAS  Google Scholar 

  30. Jones IE, Williams SM, Dow N, Goulding A (2002) How many children remain fracture-free during growth? A longitudinal study of children and adolescents participating in the Dunedin Multidisciplinary Health and Development study. Osteoporos Int 13:990–995

    Article  PubMed  CAS  Google Scholar 

  31. Brudvik C, Hove LM (2003) Childhood fractures in Bergen, Norway: identifying high-risk groups and activities. J Pediatr Orthop 23:629–634

    Article  PubMed  Google Scholar 

  32. Konstantynowicz J, Bialokoz-Kalinowska I, Motkowski R, Abramowicz P, Piotrowska-Jastrzebska J, Sienkiewicz J, Seeman E (2005) The characteristics of fractures in Polish adolescents aged 16–20 years. Osteoporos Int 16:1397–1403

    Article  PubMed  Google Scholar 

  33. Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ (2001) Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy X-ray absorptiometry study. J Pediatr 139:509–515

    Article  PubMed  CAS  Google Scholar 

  34. Ma D, Jones G (2004) Soft drink and milk consumption, physical activity, bone mass, and upper limb fractures in children: a population-based case-control study. Calcif Tissue Int 75:286–291

    Article  PubMed  CAS  Google Scholar 

  35. Ma D, Morley R, Jones G (2004) Risk-taking, coordination and upper limb fractures in children: a population based case–control study. Osteoporos Int 15:633–638

    Article  PubMed  Google Scholar 

  36. Tsuneoka K, Tameda Y, Takase K, Nakano T (1996) Osteodystrophy in patients with chronic hepatitis and liver cirrhosis. J Gastroenterol 31:669–678

    Article  PubMed  CAS  Google Scholar 

  37. George J, Ganesh HK, Acharya S, Bandgar TR, Shivane V, Karvat A, Bhatia SJ, Shah S, Menon PS, Shah N (2009) Bone mineral density and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol 28:3516–3522

    Article  Google Scholar 

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Correspondence to Jerzy Konstantynowicz.

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Konstantynowicz, J., Lebensztejn, D.M., Skiba, E. et al. Chronic non-cholestatic liver disease is not associated with an increased fracture rate in children. J Bone Miner Metab 29, 315–320 (2011). https://doi.org/10.1007/s00774-010-0219-7

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  • DOI: https://doi.org/10.1007/s00774-010-0219-7

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