Persistent CRP Elevation at 4 Weeks Is Associated with Delayed Union After Polytrauma: An Exploratory Retrospective Cohort Study

Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication.