Effect of Simvastatin, Hydrochlorothiazide and Combined Treatment on Bone Formation and Lipid Profile of Corticosteroid-Induced Osteoporosis in Albino Rats

Abstract

Statins and thiazides which are widely prescribed for the treatment of hyperlipidemia and hypertension play an important role in bone metabolism and may have potential therapeutic implications for osteoporosis.  Moreover, concomitant use of statins and thiazides may offer additive effects on bone metabolism and might be of value in attenuation of dyslipidemia that may be induced by the use of thiazides. Therefore, the present study was conducted to investigate the effects of statins, thiazides and combined treatment of both drugs on bone metabolism and lipid profile in corticosteroid-induced osteoporosis in albino rats. Five groups of rats were used; 15 rats each. The first group received no medication and served as normal control. Osteoporosis was induced in the other four groups by daily oral administration of prednisone for thirty days. Then,    osteoporotic groups were randomized into four groups; one received no medication and served as control osteoporotic group for other osteoporotic groups.  The third, fourth and fifth groups received daily treatment of either hydrochlorothiazide (HCT, 10 mg/kg/ day), simvastatin (SIM, 10mg/kg/day)or combined SIM-HCT orally for 90 days. Then, the effects of the test drugs on bone metabolism were evaluated biochemically (estimating serum alkaline phosphatase, serum calcium and parathyroid hormone level, and by histopathological examination of the tibia. Moreover, serum lipid profile was investigated and compared between all test groups. Also, the vascular reactivity of the isolated rats' aortic rings was studied. The results obtained revealed significant treatment - dependent effect of all test drugs on serum calcium level which was further confirmed histologically by significant (p<0.05) increase in cortical and trabecular bone thickness. Moreover, a significant decrease in LDL and TG was only obtained with the combined group while SIM group only produced the significant increase in HDL However, HCT group showed a significant increase in LDL and TG and cholesterol. Furthermore, all tested groups exhibited improvement in the lowering effect of endothelium-dependent relaxations induced by osteoporotic group compared to normal control group with the insignificant difference between combined and normal groups P>0.05). In conclusion, the present study clearly demonstrated that combined statins and thiazides may offer additional beneficial effects in corticosteroid-induced osteoporotic rats by additive mechanisms on bone metabolism, reduction of thiazide-induced dyslipidemia and by further improvement in the vascular reactivity of the aorta.