Smoking Amplifies Comorbidity-Associated Risk in Orthopaedic Surgery: A Multiplicative Interaction

<b>Background:</b> The success of orthopaedic surgery is fundamentally biological, yet the synergistic effect of smoking and comorbidities on surgical outcomes is not well quantified. We hypothesised that active smoking multiplies the risk conferred by common comorbidities. <b>Methods:</b> In this retrospective cohort study, we analysed 3123 orthopaedic procedures from 2020 to 2024. Patients were stratified by comorbidity (diabetes, anemia, hepatic dysfunction, chronic venous disease) and smoking status. Primary outcomes were orthopaedic-specific complications, including non-union, periprosthetic joint infection (PJI), and revision surgery. We used multivariate logistic regression to calculate adjusted odds ratios (aORs) and formal tests for interaction to quantify synergy. <b>Results:</b> A significant synergistic effect was observed. In analyses adjusted for age, sex, and procedure acuity, diabetic smokers had significantly higher rates of non-union (8.6% vs. 3.3%; aOR 3.0, 95% CI 1.1-8.2), periprosthetic joint infection (8.2% vs. 2.8%; aOR 3.1, 95% CI 1.1-8.9), and revision surgery (12.2% vs. 5.0%; aOR 2.7, 95% CI 1.2-6.1). Significant interaction effects confirmed this synergy. Smokers with hepatic dysfunction had higher haematoma rates, while smoking with severe anemia was associated with markedly increased mortality (5.0%; aOR 8.9, 95% CI 1.8-43.1). Former smokers' outcomes were consistently intermediate between active and non-smokers. For example, in the diabetic cohort, the adjusted odds of non-union were elevated for both former (aOR 2.1, 95% CI 0.8-5.5) and active smokers (aOR 3.0, 95% CI 1.1-8.2) compared to non-smokers (reference), demonstrating a gradient of risk. <b>Conclusions:</b> Smoking is associated with a multiplicative increase in comorbidity risk, creating a distinct high-risk phenotype that severely compromises healing. These findings strongly support that verified smoking cessation should be a foundational component of preoperative optimisation before elective orthopaedic surgery.