| Summary: | Aim of the work: This is the first experimental study to assess the possible synergistic effects of simvastatin combination with residronate, strontium ranelate and raloxifene on glucocorticoid induced osteoporosis (GIO) in female albino rats. Materials and methods: 48 mature healthy female albino rats were randomly allocated into 6 main groups (8 rats /group) and received all drugs daily orally for 6 weeks. (G1) negative control group; (G2) osteoporotic group that received prednisolone at 15 mg/kg/day; (G3) prednisolone + 10 mg/kg/day simvastatin; (G4) received prednisolone + simvastatin + residronate 1 mg/kg/day; (G5) prednisolone + simvastatin + strontium ranelate 600 mg/kg/day; (G6) prednisolone + simvastatin + raloxifene at 1.25 mg/kg/day. After 6 weeks, mean arterial blood pressure (MAP), ejection fraction and left ventricular diameter were assessed. Bone histomorphometry, serum level of bone specific alkaline phosphatase (BsALP), osteocalcin (OCN), calcium, phosphorus, AST and ALT and bone mineral assessment by DEXA. Results: Simvastatin combined regimens-treated groups exerted significant marked amelioration of osteoporotic changes by achieving the highest histopathological score, bone mineral density by DEXA scan, increase in serum Ca, OCN and decrease in BsALP especially in simvastatin combined groups (G4 and G5) whereas, simvastatin combined groups (G4 and G6) exerted more significant improvement in cardiovascular adverse events regarding the elevated MAP, cardiac hypertrophy and dysfunction as compared to osteoporotic non-treated group2 (p < 0.0001). Conclusion: Simvastatin combined regimens have promising synergistic effects on bone microarchitecture with cardiovascular protective effects which might be considered by clinicians as valid preventive and therapeutic strategy in patients with osteoporosis with or highly susceptible to cardiovascular disease. Keywords: Anti-resorptive medications, Simvastatin, Glucocorticoids, Cardiovascular protection, Bone markers turnover
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