Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Abstract

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

“…Corroborating previous studies that showed the impact of chronic hepatic disorder on the skeleton, the present study contributes to advancements in this line of investigation. Based on the previous experience of our group in the study of bone disturbances in cholestasis (clinical and experimental) 10 - 12 , 19 , we observed conspicuous differences in bone remodeling using an experimental model of cirrhosis. While the predominant bone impairment seems to be low osteoblastic activity in cholestasis, in hepatocellular disease, increased osteoclastic action appears to be the major mechanism of bone loss.…”

Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats

“…Nevertheless, NTX injection did not lead to a statistically significant increase in these parameters. Nevertheless, additional studies have shown notable reductions in one or a combination of these indices in rats undergoing BDL-induced cholestasis 41 – 43 . Decreased levels of these parameters may indicate the successful execution of our BDL surgery.…”