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Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis

Published online by Cambridge University Press:  26 July 2017

Priscila L. Sequetto ,
Reggiani V. Gonçalves ,
Aloísio S. Pinto ,
Maria G. A. Oliveira ,
Izabel R. S. C. Maldonado ,
Tânia T. Oliveira  and
Rômulo D. Novaes
Priscila L. Sequetto
Affiliation:
Department of Pharmaceutical Sciences – Health Area, Universidade Federal de Juiz de Fora, Governador Valadares, 35020-220, MG, Brazil Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, 36570-000, MG, Brazil
Reggiani V. Gonçalves
Affiliation:
Department of Animal Biology, Universidade Federal de Viçosa, MG, Brazil
Aloísio S. Pinto
Affiliation:
Department of Veterinary Medicine, Universidade Federal de Viçosa, Viçosa, 36570-000, MG, Brazil
Maria G. A. Oliveira
Affiliation:
Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, 36570-000, MG, Brazil
Izabel R. S. C. Maldonado
Affiliation:
Department of General Biology, Universidade Federal de Viçosa, Viçosa, 36570-000, MG, Brazil
Tânia T. Oliveira
Affiliation:
Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, 36570-000, MG, Brazil
Rômulo D. Novaes*
Affiliation:
Institute of Biomedical Sciences, Department Structural Biology, Universidade Federal de Alfenas, Alfenas, 37130-001, MG, Brazil
*
*Corresponding author. [email protected]
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Abstract

By using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.

Keywords

boneglucocorticoidmicroanalysispathologyscanning electron microscopy
Type
Biological Science Applications
Information
Microscopy and Microanalysis , Volume 23 , Issue 5 , October 2017 , pp. 989 - 1001
Copyright
© Microscopy Society of America 2017 

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