Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis.
To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.
Nakano
A
A
Department of Pharmacology, Kinki University, School of Medicine, Osaka, Japan.
Kanda
T
T
Abe
H
H
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002251:Carbon Tetrachloride; D007421:Intestine, Small / Q000473:pathology; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010024:Osteoporosis / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D014807:Vitamin D / Q000097:blood
D013853:Thioacetamide; D014807:Vitamin D; D002251:Carbon Tetrachloride; D002118:Calcium