title: Metabolic and structural bone disturbances induced by hyperlipidic diet in mice treated with simvastatin.
abstract: Simvastatin can modulate lipid and bone metabolism. However, information related to the interaction between diet and simvastatin on bone structure and biomechanics is scarce. Thus, this study evaluated the effects of simvastatin on femoral biomechanics and cortical/trabecular bone structure in wild-type mice nourished with a hyperlipidic diet. Three-month-old male wild-type mice (C57BL6 strain) were divided into four groups: (1) group W, nourished with a standard diet; (2) group WH, fed a hyperlipidic diet; (3) group WS, nourished with a standard diet plus oral simvastatin (20 mg/kg/day); and (4) group WHS, fed a hyperlipidic diet plus oral simvastatin (20 mg/kg/day). All animals received only their specific diet and water for 60 days. Blood samples were collected for the analysis of calcium, triglycerides, total cholesterol (TC) and fraction serum levels. Diet manipulation was able to induce a dyslipidaemic status in mice, characterized by triglyceride and TC rise in WH animals. Simvastatin prevented hypercholesterolaemia and reduced TC and LDL serum levels, but did not prevent hypertriglyceridaemia and HDL serum levels in the WHS group. In the WH mice the hyperlipidaemia was associated with reduction in trabecular bone thickness, femur structural and material property alterations. Simvastatin prevented these morphological alterations and minimized femur biomechanical changes in WHS mice. Taken together, the results indicated that the hyperlipidic diet intake acts as a risk factor for bone integrity, generating bones with reduced resistance and more susceptible to fractures, an effect attenuated by simvastatin that is potentially related to the modulatory action of this drug on lipid and bone metabolism.
authors.affiliation: Department of Anatomy, Federal University of Alfenas (UNIFAL), Alfenas, Brazil.
authors.forename: Evelise Aline
authors.initials: EA
authors.lastname: Soares
authors.affiliation: Department of Structural Biology, Federal University of Alfenas (UNIFAL), Alfenas, Brazil.
authors.forename: Rômulo Dias
authors.initials: RD
authors.lastname: Novaes
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Wilson Romero
authors.initials: WR
authors.lastname: Nakagaki
authors.affiliation: Department of Anatomy, Federal University of Alfenas (UNIFAL), Alfenas, Brazil.
authors.forename: Geraldo José Medeiros
authors.initials: GJ
authors.lastname: Fernandes
authors.affiliation: Nucleus of Experimental Research in Pharmacology and Experimental Surgery, University José Rosário Vellano (UNIFENAS), Alfenas, Brazil.
authors.forename: José Antônio Dias
authors.initials: JA
authors.lastname: Garcia
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: José Angelo
authors.initials: JA
authors.lastname: Camilli
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: bone tissue; hyperlipidaemia; mechanical properties; pathology; simvastatin