Association Between Simvastatin Therapy and Bone Health in Cyclophosphamide-Induced Osteoporosis in Rats

Osteoporosis, including drug-induced type, is a crucial health problem because it affects directly the quality of life and increases mortality. Simvastatin (SIM), shares the mevalonate pathway as nitrogen-containing bisphosphonate drugs which may impose a beneficial effect on bone health. This study aimed to explore the beneficial effects of SIM alone or in combination with alendronate (ALD) to prevent cyclophosphamide (CPA)-induced osteoporosis in rats. Six study groups (n = 7 rats each) were generated from 42 healthy female albino rats at the age of six months: Group 1 (control) received 1 ml/day of 0.9% NaCl orally for 6 weeks. Group 2 received CPA (4.5 mg/kg/day) orally for 15 days. Group 3 received ALD (1 mg/kg/day) orally for 6 weeks plus CPA. Group 4 received SIM (20 mg/kg/day) orally for 6 weeks plus CPA. Group 5 received a combination of the corresponding doses of ALD plus SIM in addition to CPA. Group 6 received SIM alone orally for 6 weeks. Finally, serum receptor activator of nuclear factor kappa-β ligand (RANKL) and tartrate-resistant acid phosphatase-5b (TRACP-5b) levels were evaluated in addition to the histopathological analysis of the right tibia. The osteoporosis effect of CPA was significantly reduced by SIM. Additionally, it is interesting to note that ALD plus SIM combination demonstrated an additional protective effect against osteoporosis compared to mono-therapy. Our findings suggest that SIM may be associated with bone-protective effect, the combination therapy administered group demonstrated an extra protective effect compared to mono-therapy.