Association of elevated exosomal miR-21 levels with nonunion in clavicular fractures post-ORIF: A prospective analysis

Abstract

Background

This study investigates the relationship between plasma exosomal miRNAs and nonunion risk following open reduction and internal fixation (ORIF) of clavicle fractures, aiming to identify predictive molecule to enhance patient management and personalized orthopedic care.

Methods

Conducted as a prospective cohort study at Taian City Central Hospital, participants included individuals with unilateral, closed clavicle fractures who underwent ORIF (n = 763, 546 males and 217 females). Plasma samples were collected preoperatively for exosome isolation and miRNA extraction, specifically analyzing miR-100, miR-124, miR-125b, and miR-21 using quantitative polymerase chain reaction (qPCR). Patients were classified into union and nonunion groups based on follow-up outcomes at a minimum of three months post-surgery.

Results

Out of 763 patients, 720 achieved union while 43 developed nonunion. Notably, the nonunion group exhibited significantly elevated exosomal miR-21 expression levels. Univariate analysis demonstrated a significant association between high miR-21 expression and nonunion occurrence (Relative Risk [RR] = 1.82, P = 0.0004). Multivariate logistic regression analysis corroborated this association (RR > 1.8, P < 0.05), adjusting for covariates. High miR-21 levels (3.12 to 7.89) were robustly associated with nonunion outcomes (RR > 4), independent of other factors. Receiver operating characteristic (ROC) curve analysis indicated certain clinical diagnostic value of miR-21 for predicting nonunion (Area Under the Curve [AUC] = 0.7885).

Conclusions

The elevated preoperative levels of exosomal miR-21 were significantly associated with an increased risk of bone nonunion at three months ORIF in patients with clavicle fractures, indicating that miR-21 holds potential as a non-specific predictive molecule.