title: 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.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: F A
authors.initials: FA
authors.lastname: Pereira
authors.forename: R
authors.initials: R
authors.lastname: Mattar
authors.forename: I
authors.initials: I
authors.lastname: Facincani
authors.forename: H L A
authors.initials: HL
authors.lastname: Defino
authors.forename: L N Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: V
authors.initials: V
authors.lastname: Jorgetti
authors.forename: J B
authors.initials: JB
authors.lastname: Volpon
authors.forename: F J A
authors.initials: FJ
authors.lastname: de Paula
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002780:Cholestasis, Intrahepatic / Q000150:complications*; D002908:Chronic Disease; D004164:Diphosphonates / Q000627:therapeutic use*; D013006:Growth Hormone / Q000097:blood; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D000077268:Pamidronate; D017208:Rats, Wistar
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000077268:Pamidronate