CURRENT IDEAS ON THE PATHOGENESIS OF OSTEOPOROSIS IN CHRONIC LYMPHATIC LEUKEMIA (LITERATURE REVIEW); [СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О ПАТОГЕНЕЗЕ ОСТЕОПОРОЗА ПРИ ХРОНИЧЕСКОМ ЛИМФОЛЕЙКОЗЕ (ОБЗОР ЛИТЕРАТУРЫ)]

Background. Chronic lymphocytic leukemia (CLL) is the second most common hematologicalmalignancy without a trendtowards a decrease in its incidence. 66% of patients with CLL experience bone fractures as a result of osteoporosis in all age groups, andthe detection frequency is no more than 15%. Insufficientunderstanding of the osteoporosis pathogenesis in CLL leads to problems in diagnosis, prevention and therapy. The aim of the study. To analyze modern data on the features of the osteoporosis pathogenesis in chronic lymphocytic leukemia. Results and discussion. Osteoporosis is formed when osteoresorption prevails over osteosynthesis due to intercellular interactions of bone tissue and the immune system, dysregulation of intracellular signaling pathways RANKL/RANK/OPG, Wnt, FoxO, RUNX2, initiatedby cytokines, growthfactors, prostaglandins, andhormones. The degree of osteoresorption in CLL is associated with the severity of the clinical course, chemotherapy and hormonal deprivation. The osteoporosis pathogenesis in CLLis consideredas partofa complex setofevents, including, firstly, the interaction between leukemic cells (overexpression of PTHrP, RANKL) and bone cells (synthesis of growthfactors), whichforms a vicious circle ofosteoresorption andtumor growth. Secondly, pro-inflammatory markers in CLL (tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-11, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, transforming growthfactor β, prostaglandin E2) limit osteoblast-induced osteosynthesis and stimulate the expansion of osteoclasts from monocytic suppressor cells of myeloid origin with or without the participation of the RANKL/RANK system. Thirdly, oxidative stress in CLL and impaired efficiency of antioxidant protection with the participation of fibroblast growth factor 23, transcription factor Nrf-2withactivation ofJNK, ERK1/2, NF-κB, andalso an increase in the RANKL/OPG ratio lead to inhibition of osteoblastogenesis. Conclusion. Analyzing and systematizing data on the osteoporosis pathogenesis in CLL are instrumental for the development of diagnostic criteria for osteoporosis in chronic lymphocytic leukemia that are much-needed in clinical practice and for the improvement of therapeutic tactics. © 2024 Scientific Centre for Family Health and Human Reproduction Problems. All rights reserved.