Pharmacological correction of experimental osteoporosis and fractures related to it by means of rosuvastatin, L-norvaline and their combination

Аннотация

Introduction: osteoporosis (OP) is a multifactorial disease which is based on a dynamic decrease in bone mass and, as a result, disruption of bone structure, leading to higher chances of skeletal fractures. Endothelial dysfunction is a key cause of impaired blood supply to the bone, resulting in a decreased perfusion, disrupted osteogenesis and, as a consequence, osteoporotic changes. According to modern literature and available research, L-norvaline and rosuvastatin have a powerful endotheliotropic effect. However, there is no information that the osteoprotective properties of these drugs used as a monotherapy and as their combination have ever been studied.

Materials and Methods: Simulation of experimental osteoporosis was performed on 120 white female Wistar rats. After eight weeks, the operated rats developed hypoestrogenic osteoporosis. L-norvaline and rosuvastatin, both as a monotherapy and in their combination, were used from week 9 to week 12, inclusive. The extent of changes on the background of osteoporosis was estimated twelve weeks after oophorectomy. Simulation of closed osteoporotic fractures of the femurs and their osteosynthesis were performed on 120 white female Wistar rats. Experimental osteoporosis was modeled on all animals (except the control group). Eight weeks after the removal of the ovaries on the background of developing osteoporosis, fractures of the femur were simulated. The test drugs and their combination were applied from week 1 to week 4, inclusive, after the modeling of osteoporotic fractures and their osteosynthesis. Twelve weeks after the start of the experiment, the results of fracture consolidation were analyzed.

Results and Discussion: Rosuvastatin at a dose of 0.86 mg/kg, L-norvaline at a dose of 10 mg/kg, and their combination prevented a decrease in the level of microcirculation in the callus, had an anti-osteoporotic effect, and also contributed to an increased number of healed experimental fractures. The osteoprotective effect of the test drugs is, apparently, due to their endothelial-protective action.

Conclusion: The range of the pleiotropic action of drugs with endothelial-protective properties can be extended by adding an osteoprotective element, which, however, requires additional research.