Circulating and Tissue Biomarkers Associated with Disease Severity and Progression in Adolescent Idiopathic Scoliosis: A Systematic Review.

Adolescent idiopathic scoliosis (AIS) is a multifactorial spinal deformity with variable progression patterns, making early risk stratification challenging. Circulating and tissue biomarkers, including inflammatory, metabolic, endocrine, epigenetic, and bone-related markers, have recently been investigated as potential predictors of disease severity and progression. This systematic review evaluated the current evidence on circulating and tissue biomarkers associated with AIS severity and progression. PubMed, Scopus, and Web of Science were searched for studies published between April 2016 and April 2026. Studies assessing circulating or tissue-based inflammatory, metabolic, epigenetic, and bone-related biomarkers in AIS patients were included. Data on study design, biomarker type, analytical methods, and associations with curve severity or progression were extracted. Twenty-nine studies involving more than 4000 participants were included. Biomarkers identified included inflammatory cytokines, microRNAs, metabolic hormones, and bone metabolism markers. Most studies reported significant associations between biomarkers and curve severity, particularly for inflammatory mediators, epigenetic regulators, and bone-related markers. However, few studies evaluated longitudinal progression, and only a limited number of studies identified predictive biomarkers, including circulating miRNA panels and spermidine levels. ROBINS-I assessment showed substantial risk of bias, mainly related to confounding and selective reporting. Heterogeneity was observed across study designs and outcome definitions. Current evidence supports associations between biomarkers and AIS severity, but predictive value for progression remains limited.