Gut Microbiota and Dietary Modulation in Osteonecrosis: Mechanistic Insights and Food-Based Therapeutic Strategies

Osteonecrosis is a progressive and debilitating bone disease characterized by compromised vascular supply and impaired bone remodeling, currently lacks effective therapeutic strategies. Emerging evidence implicates the gut microbiota (GM) as a pivotal regulator of bone health via the gut-bone axis. Whereas GM dysbiosis, characterized by reduced beneficial taxa (e.g., Lactobacillus, Bifidobacterium) and increased pathobionts, undermines skeletal integrity through diminished short-chain fatty acids (SCFAs) production, compromised nutrient absorption, and heightened systemic inflammation. This review synthesizes current evidence on GM-derived mechanisms in osteonecrosis, focusing on dietary and microbial metabolites such as SCFAs, polyamines, and hydrogen sulfide (H₂S) as well as immune-nutritional crosstalk. We critically examine food-based and microbiota-targeted interventions, including probiotics and prebiotics that restore microbial balance and enhance SCFA synthesis; functional foods such as polyphenols and fiber-rich diets with osteoprotective and anti-inflammatory properties; postbiotics (e.g., microbial-derived exopolysaccharides) as direct immunomodulators; and emerging therapies such as fecal microbiota transplantation (FMT) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that offer metabolic and vascular bone benefits. Additionally, the potential of GM signatures as biomarkers for early diagnosis and the development of personalized nutrition strategies are discussed. Despite promising insights, challenges remain regarding interindividual variability, lack of standardized protocols, and limited clinical translation. By integrating advances in food science, microbial ecology, and translational medicine, this review underscores the potential of GM and diet-based therapeutics as novel, noninvasive strategies to mitigate osteonecrosis progression and improve bone health outcomes.