Metabolic Derangements are Independent Additive Risk Factors for Tibial Diaphyseal Nonunion.

OBJECTIVES: To evaluate whether altered metabolic factors (metabolic comorbidities) increase the risk of postoperative tibial diaphyseal nonunion following fracture fixation, and to determine whether additional metabolic risk factors contribute cumulatively. METHODS: Design: Retrospective cohort analysis. SETTING: The TriNetX Research Network. PATIENT SELECTION CRITERIA: Patients with operatively treated tibial diaphyseal fractures (AO/OTA 42) between January 1, 2013 and December 31, 2023 were identified. A minimum of 1 year of follow-up was required. Patients with a prior diagnosis of tibial nonunion or underlying metabolic bone disease were excluded. OUTCOMES MEASURES AND COMPARISONS: The primary outcome was tibial diaphyseal nonunion following the index fracture. Outcomes were compared between patients with and without each metabolic comorbidity of interest (obesity, hypertension, diabetes, and dyslipidemia), as well as across groups stratified by cumulative metabolic burden to evaluate additive risk. RESULTS: A total of 36,474 patients (mean age 41.5 years, range 18-90; 62.7% male) were included in the analysis. Metabolic comorbidities were independently associated with a higher risk of nonunion, including diabetes (Hazard Ratio(HR) 2.82, p<0.001), hypertension (HR 1.87, p<0.001), obesity (HR 1.45, p<0.001), and dyslipidemia (HR 1.25, p<0.001).When stratified by obesity class, the risk of nonunion remained consistently elevated across all BMI categories, including BMI 30-35 (HR 1.44, 95% CI 1.46-1.82; p<0.001), BMI 35-40 (HR 1.50, 95% CI 1.30-1.73; p<0.001), and BMI ≥40 (HR 1.46, 95% CI 1.22-1.74; p<0.001), without a clear dose-response gradient across increasing obesity severity. Importantly, absolute event rates increased in a graded fashion with cumulative metabolic burden. Patients without metabolic derangements had a nonunion incidence of 5.0% (506/10,082). This increased to 8.5% (493/5,767) with one condition, 10.4% (316/3,036) with two conditions, and 11.8% (142/1,208) with three or more conditions. Correspondingly, the hazard of nonunion increased stepwise: one condition (HR 1.59, 95% CI 1.38-1.83; p<0.001), two conditions (HR 2.62, 95% CI 2.21-3.11; p<0.001), three conditions (HR 3.16, 95% CI 2.50-3.99; p<0.001), and four conditions (HR 3.37, 95% CI 2.35-4.84; p<0.001). A similar graded increase was observed for odds of nonunion, with one (OR 1.63), two (OR 2.78), three (OR 3.80), and four conditions (OR 4.21) (all p<0.001). CONCLUSIONS: Metabolic comorbidities, including diabetes, hypertension, obesity, and dyslipidemia, were independently associated with an increased risk of tibial diaphyseal nonunion following fracture fixation. The risk of nonunion increases in a graded fashion as additional metabolic conditions are present, indicating that cumulative metabolic burden confers substantially higher risk. LEVEL OF EVIDENCE: Level III.