Khomenko A. Metabolism and regulatory role of vitamin D3 in glucocorticoid-induced osteoporosis

Object: vitamin D3 metabolism and its functions at action glucocorticoid - prednisolone. Aim: to clarify the features of the vitamin D3 metabolism and manifestations its functional activity with prolonged exposure to glucocorticoid drugs - prednisolone and experimentally justify the ways of correcting disturbance. Methods: biochemical (spectrophotometry, chromatography, radioisotope analysis and so forth), immunological (ELISA, Western blot analysis), histological and cytochemical methods, methods of light microscopy and flow cytometry, methods of mathematical statistics. It was proved that decrease in blood serum 25OHD3 was due to alteration of vitamin D3 metabolism in hepatocytes, namely inhibition of vitamin D3 25-hydroxylase activity and reduced expression of CYP27A1 and CYP2R isoforms. Prednisolone-evoked abnormalities of cholecalciferol metabolism in liver can be linked to intensification of ROS generation, destructive changes in cells, lowered ratio of proteins Bax/Bcl-2 and an increase in the amount of dead hepatic cells. Prednisolone administration was proven to be accompanied by the development of hypocalcemia, hypophosphatemia, increased activity of ALP and its isoenzymes in serum and decreased content of mineral components in bone tissue. Combined administration of vitamin D3 with vitamin E was shown to be most optimal for activation of vitamin D3 25-hydroxylase in hepatocytes, that led to an increase in 25OHD3 level and normalization of mineral metabolism in glucocorticoid-induced osteoporosis.