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Hepatic osteodystrophy in rats results mainly from portasystemic shunting
  1. S W van der Merwe1,
  2. J B van den Bogaerde1,
  3. C Goosen1,
  4. F F Maree1,
  5. R J Milner1,
  6. C M Schnitzler2,
  7. A Biscardi2,
  8. J M Mesquita2,
  9. G Engelbrecht3,
  10. D Kahn3,
  11. J Fevery4
  1. 1Department of Internal Medicine and Gastroenterology, University of Pretoria, South Africa
  2. 2Department of Orthopaedic Surgery and MRC Mineral Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa
  3. 3Department of Surgery, Grootte Schuur Hospital, University of Cape Town, South Africa
  4. 4Departments of Hepatology and Internal Medicine, Catholic University of Leuven, Belgium
  1. Correspondence to:
    Dr S W van der Merwe, Department of Internal Medicine and Gastroenterology, University of Pretoria, PO Box 1649, Faerie Glen, Pretoria 0043, South Africa;
    svdm{at}intekom.co.za

Abstract

Background and aims: In chronic liver disease, bone disease frequently develops. The contributions of the different features of liver disease such as parenchymal inflammation, portal hypertension, and portasystemic shunting on bone metabolism have not been systematically studied. The aim of this study was to identify the features of liver disease contributing to bone disease using rat models.

Methods: Parenchymal liver disease was induced by carbon tetrachloride administration, portal hypertension by partial portal vein ligation, and portasystemic shunting by end to side anastomosis of the portal vein to the inferior vena cava. Normal and sham operated surgical animals served as controls. Serum calcium, 25-hydroxy vitamin D (25-OH vit D), and osteocalcin levels, and urinary deoxypyridinoline excretion were analysed. Testosterone and oestradiol levels were determined in male and female rats, respectively. Interleukin 1, interleukin 6, and tumour necrosis factor α (TNF-α) were determined in serum. Bone density was measured in all groups and in addition, in the surgical groups, histomorphometry was performed on undecalcified specimens of the proximal tibia. The calcium content of the femurs, removed at termination and ashed, was determined.

Results: Early parenchymal disease and portal hypertension did not affect bone metabolism or body mass. Portasystemic shunting increased bone resorption, decreased bone formation, bone density, and trabecular bone volume which were commensurate with a reduction in body mass. TNF-α levels were elevated and testosterone levels were low in male portasystemic shunted rats.

Conclusions: Portasystemic shunting in the rat adversely affects bone metabolism as part of a generalised catabolic state where high TNF-α and low testosterone and 25-OH vit D levels may play a role.

  • osteopenia
  • liver disease
  • cirrhosis
  • vitamin D
  • portasystemic shunting
  • PSS, portasystemic shunting
  • PPVL, partial portal vein ligation
  • SC, sham operated surgical controls
  • 25-OH vit D, 25-hydroxy vitamin D
  • CCl4, carbon tetrachloride
  • u-DPD, urinary deoxypyridinoline
  • BMD, bone mineral density
  • BMC, bone mineral content
  • CRP, C reactive protein
  • TNF-α, tumour necrosis factor α
  • ALT, alanine aminotransferase
  • ALP, alkaline phosphatase
  • IL, interleukin

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