Immunology of Osteoporosis: From Mechanisms to Therapeutic Strategies

This review provides an overview of current understanding of the role of adaptive immunity in the pathogenesis of osteoporosis and the prospects for immunotherapy. Osteoporosis has long been considered a metabolic disease, but the development of osteoimmunology has led to a fundamental shift in our understanding of its pathogenesis. This review presents the current evidence (2021—2026) on the role of adaptive immunity in the development of osteoporosis and the potential of immunotherapeutic approaches. The key molecular mechanisms of osteoimmun interactions are considered, including the RANK/RANKL/OPG system and pro-inflammatory cytokines. Special attention is paid to the concept of «immunoporosis» — immunologically mediated osteoporosis associated with age-related immune system aging and chronic low-level inflammation. The role of T-lymphocyte subpopulations (Th17, Treg, Th1, Th2) and B-cells in the regulation of bone remodeling is analyzed in detail, as well as the significance of the imbalance between pro-inflammatory and anti-inflammatory immune mechanisms. Epidemiological data on the global burden of osteoporosis are presented, emphasizing the need for new therapeutic strategies. Promising areas of immunotherapy are being discussed: the use of monoclonal antibodies to pro-inflammatory cytokines (TNF-α, IL-6, IL-17), modulation of the function of regulatory T cells (Treg), the use of JAK/STAT inhibitors and senolytics to eliminate aging immune cells, and the impact on the gut-immune-bone axis. The problems and challenges associated with the introduction of immunotherapeutic approaches into clinical practice are considered, including the need to identify biomarkers for personalized selection of means of prevention and treatment of osteoporosis in the aging population.