Alterations in Circulating miRNAs and Their Potential Role in Aseptic Loosening After Total Hip Replacement: An Observational, Cross-Sectional Study

<b>Background/Objectives:</b> Aseptic loosening (AL) is among the most common causes of late failure following total hip arthroplasty (THA), often necessitating complex revision surgery. Current diagnostic tools, mainly based on clinical and radiological findings, are primarily able to identify advanced changes of periprosthetic osteolysis (PPOL). Therefore, early detection of AL remains a challenge. Circulating microRNAs (miRNAs) have emerged as promising, minimally invasive biomarkers in musculoskeletal disorders. This study investigates the expression of inflammation-related miRNAs let-7i-5p, let-7e-5p, miR-15a-5p, miR-30a-3p and miR-130a-3p in patients with confirmed AL after THA to evaluate their potential role in AL. <b>Methods:</b> AL patients undergoing revision were compared with asymptomatic post-THA individuals and controls with degenerative osteoarthritis. Preoperative, peripheral blood samples were collected; total RNA was extracted; and quantitative real-time PCR (qRT-PCR) was performed to quantify miRNA expression. The relative expression of miRNAs was calculated using the 2-ΔΔCt method after proper normalization of Ct values. Statistical analysis assessed differences between groups. <b>Results:</b> The under investigation miRNAs exhibited distinct expression patterns. Several targets demonstrated significant downregulation in AL patients, suggesting a potential link to inflammatory and osteolytic pathways like Toll-like receptor 4 (TLR4)-Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, NLRP3 inflammasome activation and macrophage polarization. <b>Conclusions:</b> The observed alterations in circulating miRNAs support their capability as biomarkers for early detection of AL following THA. Larger cohorts could facilitate translation into routine clinical diagnostics.