EVALUATION OF THE OSTEOMODULATOR AND CARDIOVASCULAR PROTECTIVE IN COMBINATION WITH RISEDRONATE, RALOXIFENE AND STRONTIUM RANELATE IN AN OSTEOPOROTIC RAT MODEL

Citation:
EVALUATION OF THE OSTEOMODULATOR AND CARDIOVASCULAR PROTECTIVE IN COMBINATION WITH RISEDRONATE, RALOXIFENE AND STRONTIUM RANELATE IN AN OSTEOPOROTIC RAT MODEL, karam Mahmoud, Amira, Diab Soheir Abou Elazm, mohamed zaher Hashem Ghada Abdel, and Youssef Mira Farouk , Giza, (2018)

Thesis Type:

PHD

Abstract:

Background: Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. The side-effects of the currently available osteoporotic therapies and their ability to increase bone mass is relatively small not more than 2% per year so, there is a need for novel drug therapies for the treatment of osteoporosis. Evidence that osteoporosis and cardiovascular diseases are positively correlated. Therefore, the attention has driven toward the importance of possible synergism that might occur from combination of anti resorpative medications with simvastatin.
Aim of the work: assess the osteomodulatory and cardio vascular protective effect of Simvastatin, residronate, strontium ranelate and raloxifene separately and their combination with simvastatin in rat model of glucocorticoid induced osteoporosis
Methodology: A 72Mature healthy albino rats of both sex are randomly allocated into 9 main groups and received drugs for 6weeks by oral gavage .G1: normal control group,G2:osteoprotic treated group received prednisolone (pred) at 30 mg/kg per 2 days ,G3:Simvastatin(Sim)- treated group received simvastatin at10mg/kg/day,G4:Residronate (Residr)- treated group received residronate at 1mg/kg/day), G5:strontium(SR)-treated group received strontium at 600mg/kg/day,G6:raloxifene(RAL)-treated group, received raloxifene at 1.25mg/kg/day,G7:SIM+Residr-treated group,G8:Sim +SR treated group and G9:Sim +RAL treated group. At the end of 6weeks ,all studied groups were assessed pharmacologically by measurement of mean arterial blood pressure(MAP), ECG and echocardiography, Biochemically, by measurement of serum Ca, P, osteocalcin(OCN), bone specific alkaline phosphatase (BSAP),ALT and AST. Histologically by assessment of bone cortical thickness, histopathological scoring and bone mineral density by DEXA scan was also recorded.

Results: The result revealed Significant elevation of mean arterial blood pressure, decrease in LVEDD , decrease in ejection fraction with decrease in Ach induced aortic relaxation .In addition to the significant elevation of serum BSAP, significant decrease in the serum level of osteocalcin , Ca and compansatory increase in serum level of Pin osteoporotic non treated group as compared to normal control group. Separately treated groups 3,4,5,6 showed significant amelioration of the above mentioned changes with variable degrees, with a net results of enhanced of bone architecture and biochemical markers compared osteoporotic group.

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