Induction of bone loss by bile duct ligation in rats.

: Metabolic bone loss is the most common complication of chronic liver disease. However, there is little information available about bone loss in rats with a ligated bile duct, a biliary-type of experimental cirrhosis model. Therefore, in this study, the effect of bile duct ligation (BDL) on bone mineral density (BMD) and plasma insulin-like growth factor-I (IGF-I) levels was examined in rats. Two weeks after BDL operation, the rats with a ligated bile duct showed a pronounced and significant decrease in both trabecular and cortical BMD of the femur. In these rats, decreases in food intake and plasma IGF-I levels plus elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin were also observed. When the effect of dietary restriction (30% or 50%) over 2 weeks was then investigated in normal rats, 50% food restriction resulted in a significant decrease in femoral trabecular bone density although BMD was unchanged by 30% dietary restriction. The plasma levels of IGF-I were also decreased in food-restricted rats. Thus, the decrease in femoral bone density in 50% food-restricted rats was less potent compared with BDL rats; nevertheless, the decrease in plasma levels of IGF-I was almost equally potent in both BDL and food-restricted rats. Overall, this study showed that BDL operation resulted in a pronounced bone loss in rats, but also that this bone loss might not be merely due to the decreases in food intake and plasma IGF-I levels. These results suggest that BDL in rats is a useful experimental cirrhosis model for evaluating the bone loss associated with chronic liver disease.