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.

The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency

“…The inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and the subsequent reduction in isoprenoid synthesis tilt the bone remodeling process in favor of formation over resorption [ 10 ]. However, most animal studies indicated that statins at doses higher than the clinical hypocholesterolemia regimen are required to exploit its bone-protective potential [ 11 , 12 ]. High-dose statins are often accompanied by adverse side-effects, such as myopathy, rhabdomyolysis, increased circulating transaminase level and risk of diabetes mellitus [ 13 ].…”

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

“…However, alendronate and simvastatin, especially when combined, improved bone mechanical function, such as the maximum load and stiffness, at the same time that they improved inorganic and organic bone mass in a dose-dependent fashion. Mineral homeostasis is critical to bone structure and mechanical behavior (Weiner & Wagner, 1998;Soares et al, 2015, Zimmermann et al, 2015. Due to the co-dependent relationship between calcium and phosphorus in constructing the fundamental crystalline structure of the mineral bone matrix (i.e., hydroxyapatite crystals), the relative and Figure 4.…”

“…The right femurs were removed and submitted to the threepoint bending test until complete fracture at a velocity of 3 mm/min (Soares et al, 2015). A universal mechanical testing system (MTS) with a load cell of 10,00 kgf was used (5966 Dual Column Tabletop Model testing system; Instron, Grove City, PA, USA).…”

“…These data were used for the acquisition and calculation of the maximum load, displacement at maximum load, and extrinsic stiffness. The extrinsic stiffness was calculated as the slope of the linear portion of the elastic region of the load-displacement curve (Soares et al, 2015).…”

Ameliorative effects of Lipitor against hypercholesterolemia-induced nephrotoxicity in rats and their breast-feeding young

“…Furthermore Lipitor-treated alone or in combination with hypercholesterolemia was found to improve femoral epiphysis and renal tissue to some extent and not equal to normal ones. The antilipidemic drug simvastatin (Soares et al, 2015) and atorvastatin (Rajamannan, 2015) were found to improve the impairing bone integrity related to bone fracture in mice as a result of hyperlipidemia.…”