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

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-li...

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Main Authors: F.A. Pereira, R. Mattar, I. Facincani, H.L.A. Defino, L.N.Z. Ramalho, V. Jorgetti, J.B. Volpon, F.J.A. de Paula
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2012-12-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001200021&lng=en&tlng=en
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author F.A. Pereira
R. Mattar
I. Facincani
H.L.A. Defino
L.N.Z. Ramalho
V. Jorgetti
J.B. Volpon
F.J.A. de Paula
author_facet F.A. Pereira
R. Mattar
I. Facincani
H.L.A. Defino
L.N.Z. Ramalho
V. Jorgetti
J.B. Volpon
F.J.A. de Paula
author_sort F.A. Pereira
collection DOAJ
description 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.
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spelling doaj.art-54eaa5551c1e4c12a4539e18d44784802022-12-22T01:23:16ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2012-12-01451212551261S0100-879X2012001200021Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar ratsF.A. Pereira0R. Mattar1I. Facincani2H.L.A. Defino3L.N.Z. Ramalho4V. Jorgetti5J.B. Volpon6F.J.A. de Paula7Universidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloUniversidade de São PauloOsteoporosis 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001200021&lng=en&tlng=enHepatic osteodystrophyOsteoporosis pathogenesisGrowth factorsBiomechanicsAnimal modelsPamidronate
spellingShingle F.A. Pereira
R. Mattar
I. Facincani
H.L.A. Defino
L.N.Z. Ramalho
V. Jorgetti
J.B. Volpon
F.J.A. de Paula
Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
Brazilian Journal of Medical and Biological Research
Hepatic osteodystrophy
Osteoporosis pathogenesis
Growth factors
Biomechanics
Animal models
Pamidronate
title Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
title_full Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
title_fullStr Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
title_full_unstemmed Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
title_short Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats
title_sort pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in wistar rats
topic Hepatic osteodystrophy
Osteoporosis pathogenesis
Growth factors
Biomechanics
Animal models
Pamidronate
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012001200021&lng=en&tlng=en
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