Gut microbiome and avascular necrosis: A scoping review of current evidence and knowledge gaps

Avascular necrosis (AVN) is a progressive bone disorder characterized by impaired blood supply, osteocyte death, and structural collapse, most commonly affecting the femoral head. In recent years, growing evidence has suggested that gut microbiota may influence skeletal health through immune, metabolic, and vascular pathways. This scoping review aimed to systematically map current evidence on the relationship between gut microbiota and AVN and to identify key knowledge gaps. Following Joanna Briggs Institute methodology and PRISMA-ScR guidelines, a comprehensive search of PubMed, EMBASE, ScienceDirect, Web of Science Core Collection, ClinicalTrials.gov, and Cochrane CENTRAL was conducted. Thirteen eligible studies, including experimental, clinical, multi-omics, and Mendelian randomization analyses, were included. The available evidence indicates that AVN, particularly glucocorticoid- and alcohol-associated forms, is consistently associated with intestinal dysbiosis, reduced production of short-chain fatty acids, immune activation, vascular impairment, and altered bone remodeling. Animal and translational studies demonstrate partial reversal of pathological changes through microbiota-targeted interventions, while human studies reveal etiology-specific microbiota-metabolome signatures. Genetic analyses further support a potential causal contribution of selected microbial taxa and pathways. Overall, current data support the existence of a multidimensional gut-bone axis in AVN. However, most evidence remains indirect - derived from animal models, cross-sectional human studies, and genetic inference rather than from direct interventional testing in patients. Well-designed longitudinal and interventional investigations are needed to clarify causality and therapeutic potential.