Pathophysiological aspects of the mechanisms of action of osteotropic drugs in an in vitro experiment on the blood mononuclear cells of patients with frontal bone injuries
Authors: Bondarchuk Oleksandr D. , Melnikov Oleg F. , Timchenko Мarina D. , Didyk Natalia D. 
Published: July 2023

Relevance: Pathogenetic treatment of head injuries should be based on the development of post-traumat ic disease, including the role of immune reactions in bone matrix regeneration processes. Repair of bone structures depends on activating stimuli from cells of the immune system. Currently, there is research on the importance of vitamin D in metabolic processes in mesenchymal tissue that affect the formation of the bone matrix and general mineralization of bones, as well as the drug osteogenon, the basis of which are ossein-hydroxyapatite compounds, which stimulate local regulators of bone tissue remodelling and calcium-phosphorus metabolism. Taking into account these data, it will be appropriate to determine the effect of drugs on the processes of bone tissue regeneration in patients with injuries of the frontal bone.
Purpose: to determine the effect of various drugs used in the treatment of frontal skull injuries on the pathophysiological mechanisms of inflammation (interleukin-1β, interleukin-10, γ-interferon), stabilization of cell membranes, and the level of regenerative cytokines.
Materials and methods: The authors conducted immunological studies on the determination of cytokine factors of inflammation and regeneration in 29 patients with frontal bone injury under the influence of various osteotropic drugs: ossein-hydroxyapatite compounds, osteogenon and vitamin D3 (water-soluble form – aquadetrim), both individually and in combination with each other. The research was carried out in an in vitro experiment in RPMI-1640 medium (Serva, Germany) with blood mononuclear cells from patients. γ-interferon), anti-inflammatory regeneration factor (transforming growth factor-TGF-1β). In the conditions of the experiment, the membrane-protective properties of the above-mentioned osteotropic drugs were investigated on cultures of peritoneal tissue basophils under the conditions of using protamine sulfate as a damaging factor.
Results and discussion: it was established that osteogenon and aquadetrim (vit. D3) have a positive effect on the production of cytokines by mononuclear cells in the blood of patients with TLC: they reduce the level of in vitro pro-inflammatory production and increase the production of anti-inflammatory cytokines, especially when used together. Protamine sulphate (liberator) was able to destroy 61% of tissue basophils, SK and osteogenon reduced this percentage, but not reliably. Reliable data were obtained under the action of vitamin, and combinations of ossein-hydroxyapatite compounds + vitamin and osteogenon + vitamin (р=0.01). The use of a general mixture of all drugs did not cancel the effect of liberation of TB. It can be assumed that the main membrane protector is vitamin D3 in the form of a water-soluble form – aquadetrim, which has various directions of pathophysiological influence on the mechanisms of inflammation and regeneration.
Conclusions: The growth factor was better stimulated with a mixture of all drugs (~1.7 μg/ml) in combination with vitamin D3. Membrane-protective properties were better expressed under the action of vitamin D3 and combinations of osseinhydroxyapatite compounds + vitamin D3 and osteogenon + vitamin D3. The most effective in activating immunocompetent blood cells were combinations of osteotropic drugs that reduced the level of proinflammatory cytokines and increased the content of anti-inflammatory interleukin-10 in the culture fluid.