A. A. Shaev

The review focuses on current concepts of the role of obesity, the chronic systemic inflammation it induces, and lipid metabolism disorders in the pathogenesis of osteonecrosis of the femoral head (ONFH) in order to substantiate new approaches to its prevention and treatment. This review analyzes modern fundamental and clinical studies focusing on the relationship between metabolic disorders, chronic inflammation, and osteonecrosis. Specifically, we examine research investigating the molecular mechanisms of adipose tissue dysfunction, lipotoxicity, oxidative stress, and their impact on bone tissue homeostasis.The analysis established that obesity acts as a systemic risk factor for ONFH development, functioning not merely as a source of mechanical load but also as an initiator of a pathogenic cascade. Dysfunctional adipose tissue leads to chronic low-grade systemic inflammation and oxidative stress. Together, these factors provoke endothelial dysfunction, impair perfusion of the femoral head bone tissue, and induce lipotoxicity in the bone marrow. Consequently, at the local level, this cascade suppresses osteogenesis, simultaneously enhances bone resorption, and triggers osteocyte apoptosis.Systemic metabolic and inflammatory disruptions initiated by obesity underlie impaired bone remodeling, ischemia, and necrosis of the femoral head subchondral bone. Therefore, the correction of body weight and associated metabolic disorders should be considered an integral part of a comprehensive strategy for treating ONFH and preventing its progression. This integrated approach may improve the outcomes of joint-preserving interventions and delay the need for total hip arthroplasty in young patients.

The potential association between dysbiosis of the gut microbiota and osteoarthritis is confirming by a growing number of studies. Given the social significance, the high prevalence of osteoarthritis, and evidences that quantitative and qualitative modification of the gut microbiota affects its progression, it seems important to clarify the underlying mechanisms of this association. Osteoarthritis is a multifactorial joint disease, which is based primarily on the progressive degeneration of articular cartilage. Impaired metabolic activity of chondrocytes, consisting in an imbalance in the extracellular matrix synthesis and degradation processes, causes the persistent release of molecular patterns associated with damage. This leads to the activation of a wide range of innate immune cells receptors and is the basis for the development of an inflammatory reaction in the joint. The involvement of macrophages in the synovial membrane and their activation leads to the production of pro-inflammatory cytokines, leading to the development of chronic low-grade inflammation in the joint, supporting the synthesis of catabolic enzymes by chondrocytes and escalating the cartilage degeneration. Microbial dysbiosis, defined as an adverse modification in the diversity, structure, or metabolic activity of the gut microbiota, is a hidden risk factor, accompanied by metabolic endotoxemia and, consequently, by increased production of pro-inflammatory cytokines, that support the systematic low-grade inflammation and pathophysiological mechanisms of osteoarthritis. It has been shown that dysbiosis of the gut microbiota intestinal takes part in the formation of other osteoarthritis risk factors for, for example, obesity and metabolic disorders. The identification of important interrelated pathophysiological mechanisms of these pathologies will contribute to the development of new pathogenetic treatment methods with their subsequent active introduction into clinical practice.