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 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.
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 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: A M Parfitt; M K Drezner; F H Glorieux; J A Kanis; H Malluche; P J Meunier; S M Ott; R R Recker Journal: J Bone Miner Res Date: 1987-12 Impact factor: 6.741
Authors: H L Bonkovsky; M Hawkins; K Steinberg; T Hersh; J T Galambos; J M Henderson; W J Millikan; J R Galloway Journal: Hepatology Date: 1990-08 Impact factor: 17.425
Authors: I S Benjamin; C J Ryan; G H Engelbrecht; J A Campbell; R van Hoorn-Hickman; L H Blumgart Journal: Hepatology Date: 1984 Jul-Aug Impact factor: 17.425
Authors: Schalk W van der Merwe; Maria M Conradie; Robert Bond; Brenda J Olivier; Elongo Fritz; Martin Nieuwoudt; Rhena Delport; Tomas Slavik; Gert Engelbrecht; Del Kahn; Enid G Shephard; Maritha J Kotze; Nico P de Villiers; Stephen Hough Journal: World J Gastroenterol Date: 2006-07-28 Impact factor: 5.742
Authors: Caren E Petrie Aronin; Karim W Sadik; Ann L Lay; Dave B Rion; Sunil S Tholpady; Roy C Ogle; Edward A Botchwey Journal: J Biomed Mater Res A Date: 2009-06 Impact factor: 4.396