STUDY OF ENDOTHELIAL PROTECTIVE AND OSTEOPROTECTIVE PROPERTIES OF ROSUVASTATIN, L-NORVALINE AND THEIR COMBINATIONS IN EXPERIMENTAL OSTEOPOROSIS

Aim. Study of the effectiveness of pharmacological management of experimental osteoporosis with rosuvastatin, L-norvaline and their combination in comparison with strontium ranelate. Materials and methods. Simulation of hypoestrogenic osteoporosis was performed by bilateral oophorectomy in female Wistar rats. Four weeks after the surgery, the animals were administered study drugs during 4 weeks. After 12 weeks in the experimental animals, the parameters of intraosseous microcirculation of the proximal metaphysis of the femur were analyzed and the coefficient of endothelial dysfunction was calculated on the basis of laser Doppler flowmetry data. Calculation and registration of parameters of microcirculation were performed using the Biopac systems MP-150 laser doppler flowmeter and the TSD-144 needle sensor, and the results were processed using the AcqKnowledge version 4.1-4.2 software. For a comprehensive assessment of the formation of osteoporotic shifts and the effectiveness of therapy with the drugs studied, histomorphometry of the proximal metaphysis of the femurs was performed. When calculating the width of the bone trabecula, ImageJ version 1.39 was used. Results. It was found that L-norvaline and rosuvastatin in the doses under study in monotherapy and in combination significantly increase the parameters of regional intraosseous microcirculation of the vertex femur region. The investigated drugs and their combination, in comparison with the reference preparation, have an endothelial protective activity. This circumstance favorably affects intraosseous microcirculation, which contributes to the stable course of bone remodeling and prevents progression of osteoporotic disorders. In a morphometric study, it was established that L-norvaline, rosuvastatin, and their combination in these dosages prevented a decrease in the average width of bone trabeculae to the level of animals with experimental osteoporosis. Conclusion. L-norvaline, rosuvastatin and their combination in these dosages have a significant osteoprotective effect.

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