COMBINED EFFECT OF PYRAZOLE-CONTAINING BISPHOSPHONATES AND VITAMIN D3 IN THE CORRECTION OF MINERAL METABOLISM IN ALIMENTARY OSTEOPOROSIS IN RATS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2020.v.i3.11513Keywords:
pyrazole-containing bisphosphonates, alimentary osteoporosis, mineral metabolism, vitamin D3, 25OHDAbstract
Introduction. According to the WHO, osteoporosis ranks central position among all known diseases as a cause of premature disability and mortality, and therefore the development of effective treatment strategies for this disease is one of the priority research areas for scientific and medical institutions. One of these areas is the development of new modern bisphosphonates and the study of their therapeutic effects in animal models.
The aim of the study – to explore the effectiveness of combined action of synthesized nitrogen-containing bisphosphonates (pyrazole-containing analogs), which inhibit osteoclast activity and bone resorption, and vitamin D3 – the main regulator of bone remodeling and osteogenesis, in the correction of mineral metabolism disturbances accompanying the development of osteoporosis.
Research Methods. The study of the biological effectiveness of the synthesized pyrazole-containing bisphosphonates was carried out on female Wistar rats (1 month old, initial weight (90±5) g). Alimentary osteoporosis was induced by keeping the rats for 30 days on a D-hypovitaminosis diet according to GOST 11222-65, balanced in calcium and phosphorus. Pyrazole-containing bisphosphonates (1.7 mg/kg) and cholecalciferol (400 IU/kg body weight) were used per os as corrective compounds. Serum 25OHD was tested by ELISA. The quantitative analysis of the components of mineral metabolism in the blood serum and bone tissue was determined by routine biochemical methods.
Results and Discussion. Our pyrazole-containing bisphosphonates inhibited the process of bone tissue demineralization (resorption) and enhanced mineral metabolism in rats with alimentary osteoporosis with various efficiency. After bisphosphonate supplementation, the content of calcium and inorganic phosphate increased, while the activity of alkaline phosphatase and its isoenzymes in blood serum decreased. The ash content and the levels of calcium and phosphorus in the ash of the tibia have been increased. The combination of pyrazole-containing bisphosphonates with vitamin D3, which normalizes the serum 25OHD content and provides the synthesis of biologically active hydroxylated forms of cholecalciferol, has been effective in the correction of mineral metabolism abnormalities in osteoporotic rats.
Conclusions. The study of the combined action of vitamin D3 and bisphosphonate I-12, as the substance with the highest biological efficiency in enhancing the bone remodeling through a balanced combination of bone resorption and formation, is most promising for further research.
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