Association Between Post-trauma Platelet-lymphocyte Ratio and Nonunion in Patients With Extremity Fractures: a Multicenter Retrospective Cohort Studys

Background Post-traumatic coagulation and inflammatory activation are associated with various clinical outcomes, and impairments of haematoma formation and inflammatory cell recruitment in the early phases potentially adversely affect bone healing. We aimed to explore and quantify the association between serum platelet-lymphocyte ratio (PLR) levels and postoperative nonunion in patients undergoing extremity fracture Surgery. Methods This retrospective, multicenter cohort study analyzed data from five tertiary hospitals, including adult patients who underwent surgery for limb fractures between January 2020 and December 2022. The exposure was the post-trauma platelet-to-lymphocyte ratio (PLR), calculated by dividing the platelet count by the lymphocyte count. The outcome of interest was fracture nonunion, defined as the failure of fracture healing for a minimum of 9 months, without evidence of progression toward healing over the preceding 3 months, which was confirmed through a comprehensive review of medical records, telephone follow-ups, and outpatient assessments. Dose–response analysis using restricted cubic spline (RCS) function and multivariate logistic regression were conducted to evaluate the relationship between PLR and nonunion risk. Results In total, 30,791 patients were included, with an average age of 49.1 ± 16.5 years, and 60.5% were males. Nonunion occurred in 656 patients (2.1%). RCS analysis showed a significant negative non-linear dose–response relationship between PLR and nonunion risk (P-nonlinearity < 0.001, P-overall < 0.001), and the cutoff value for the risk-protective effect was 145.0. Compared to high PLR levels (≥ 145.0), lower PLR levels (< 145.0) were associated with higher nonunion risk (odds ratio = 1.613; 95% CI, 1.379–1.887; P < 0.001); and this risk effect remained evident after adjustment (adjusted odds ratio = 1.265; 95% CI, 1.057–1.515; P = 0.010). Results are robust across several prespecified sensitivity or exploratory analyses. Subgroup analyses revealed heterogeneity of association according to surgery site and fixation methods (P values for interaction < 0.050). Conclusion This study demonstrates that reduced post-trauma PLR levels are associated with an increased risk of nonunion, serving as a potential biomarker for risk stratification and personalized intervention planning during the critical bone healing window.