title: Hepatic osteodystrophy in rats results mainly from portasystemic shunting.
abstract: OBJECTIVE
  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 alpha (TNF-alpha) 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-alpha 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-alpha and low testosterone and 25-OH vit D levels may play a role.
authors.affiliation: Department of Internal Medicine and Gastroenterology, University of Pretoria, South Africa. svdm@intekom.co.za
authors.forename: S W
authors.initials: SW
authors.lastname: van der Merwe
authors.forename: J B
authors.initials: JB
authors.lastname: van den Bogaerde
authors.forename: C
authors.initials: C
authors.lastname: Goosen
authors.forename: F F
authors.initials: FF
authors.lastname: Maree
authors.forename: R J
authors.initials: RJ
authors.lastname: Milner
authors.forename: C M
authors.initials: CM
authors.lastname: Schnitzler
authors.forename: A
authors.initials: A
authors.lastname: Biscardi
authors.forename: J M
authors.initials: JM
authors.lastname: Mesquita
authors.forename: G
authors.initials: G
authors.lastname: Engelbrecht
authors.forename: D
authors.initials: D
authors.lastname: Kahn
authors.forename: J
authors.initials: J
authors.lastname: Fevery
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D005260:Female; D006975:Hypertension, Portal / Q000150:complications*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications*; D008297:Male; D010024:Osteoporosis / Q000209:etiology*; D011170:Portasystemic Shunt, Surgical / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride