Osteonecrosis of the Femoral Head: A Dysbiotic Condition?

Abstract

Osteonecrosis of the femoral head (ONFH) is a progressive and disabling condition of the hip joint that primarily affects young and active individuals, leading to progressive collapse of subchondral bone and often secondary arthritis. Despite extensive investigation, the precise etiology often remains unclear. While high-dose corticosteroids, chronic alcohol ingestion, and smoking are known associated risk factors, approximately 20 to 30% of ONFH cases are classified as idiopathic. Recently, the concept of gut dysbiosis, i.e., disruption of the normal intestinal microbial balance, has gained increasing attention due to its systemic immunologic and metabolic implications. Dysbiosis is associated with an increase in gut permeability, leading to the translocation of bacteria and their metabolic products, including lipopolysaccharides and short-chain fatty acids, into the systemic circulation. This may stimulate proinflammatory cascades throughout the body, including the joints, initiating a bone remodeling process. Emerging evidence from preclinical and human research suggests that specific gut microbiota taxa may influence key mechanisms involved in the pathogenesis of ONFH. In addition, early findings support the therapeutic potential of microbiota-targeted therapies such as probiotics, short-chain fatty acids-enriched diets, and fecal microbiota transplantation. Although a growing number of descriptive studies support this link, the current evidence remains associative rather than causal, as no longitudinal cohort studies have confirmed this relationship. Future investigations are needed to establish causality between gut dysbiosis and ONFH. To our knowledge, this review offers the first comprehensive synthesis of the literature aiming to explore current evidence and the potential link between gut dysbiosis and ONFH, highlighting future directions for microbiome-based therapeutic interventions. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.