Abstract
Objective: We studied the influence of bile duct obstruction (BDO) after 28 days on bone metabolism status and their modification by resveratrol in male Wistar rats. Methods: The rats were divided into 3 groups: Sham group with laparotomy and vehiculum application, group BDO—bile duct obstruction and vehiculum application, and group RBDO—bile duct obstruction and resveratrol application (10 mg/kg dose of resveratrol orally once daily). The bone mineral density (BMD; g/cm2) and body composition were measured by dual energy X-ray absorptiometry. The physiccal strenght of femur was examined by controlled break biomechanical testing. The osteocalcin, procollagen type I N-terminal propeptide (PINP) and carboxy-terminal collagen crosslinks (CTX) were analysed by EIA in the bone tissue homogenate. Results: The total BMD was lower in group BDO (0.176 ± 0.005; p = 0.01) and R-BDO (0.181 ± 0.004; p = 0.052) vs Sham (0.209 ± 0.003). BMD of femur diaphysis in BDO group decreased significantly (p = 0.01) but not in R-BDO animals (p = 0.052). Body fat (g, median) was lower in BDO (19.0) and R-BDO (26.0) than in Sham (35.0). The force needed for fracture of femurs (N) significantly decreased in BDO (154 ± 6) and R-BDO (151 ± 13) vs Sham group (208 ± 7). The force needed for neck fracture decreased in BDO (105 ± 3) and R-BDO (115 ± 8) vs Sham (135 ± 9). The osteocalcin decrease in group R-BDO (2.9 ± 0.1) vs Sham (3.7 ± 0.4). Higher PINP/CTX were in BDO (20 ± 5/0.49 ± 0.08) and R-BDO (30 ± 4/0.55 ± 0.07) vs Sham (16 ± 4/0.48 ± 0.11). Conclusions: Our findings suggest that subchronic bile duct obstruction decreased body fat quantity and BMD with decrease of bone rigidity. Resveratrol showed protective effect on liver injury and consequently positive influence on bone tissue.
Highlights
The osteoporosis has been recognized among others as a complication of chronic liver diseases such as haemochromatosis, alcoholic liver disease and cholestatic disorders, namely primary biliary cirrhosis and primary sclerosing cholangitis
We studied the influence of bile duct obstruction (BDO) after 28 days on bone metabolism status and their modification by resveratrol in male Wistar rats
Our findings suggest that subchronic bile duct obstruction decreased body fat quantity and bone mineral density (BMD) with decrease of bone rigidity
Summary
The osteoporosis has been recognized among others as a complication of chronic liver diseases such as haemochromatosis, alcoholic liver disease and cholestatic disorders, namely primary biliary cirrhosis and primary sclerosing cholangitis. These patients have an increased risk of spontaneous or low-trauma fractures leading to significant morbidity, deterioration of quality of life, and even mortality [1,2]. The underlying mechanisms are not completely understood, an imbalance in vitamine D turnover, calcium absorption or humoral signals such as IGF-1 deficiency or hyperbilirubinemia seems to be involved [4] Advantageous in this situation is the possibility of using the reliable animal model based on the induction of long-term extrahepatic cholestasis in rats by bile duct obstruction or ligation. We analyse the effects of BDO and the resveratrol on body composition, on the BMD, and on the related biomechanical characteristics and metabolic markers of bone tissue
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