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

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.

Is bone loss a physiological cost of reproduction in the Great fruit-eating bat Artibeus lituratus?

“…lituratus may be more influenced by other bone components rather than calcium or phosphorus. Connective tissue components such as collagen and elastin can influence force production during maximal effort, act on stability, responsiveness and also help maintaining bone strength [29].…”

Porous Chitosan/Nano-Hydroxyapatite Composite Scaffolds Incorporating Simvastatin-Loaded PLGA Microspheres for Bone Repair

“…In recent decades, scientists found that SIM also has other pharmacological actions which are beneficial to bone regeneration [Park, 2009]. Previous studies indicated that SIM can enhance bone formation by increasing the expression of osteogenesis-related genes in MSCs and reducing osteoblast apoptosis, as well as inhibit bone resorption via the inhibition of osteoclast proliferation and differentiation [Noronha Oliveira et al, 2017;Sequetto et al, 2017]. However, systemic administration of SIM is limited by low drug availability, and local injection at effective doses may cause excessive inflammation [Zhang et al, 2016].…”