Assessing the impact of tobacco smoke exposure on earlyonset osteoarthritis: A cross-sectional analysis of secondary data from the National Health and Nutrition Examination Survey (NHANES), 1999-2020.

Introduction: There is evidence that exposure to tobacco smoke is associated to a number of chronic diseases, but the evidence for an association with osteoarthritis (OA) is sparse and inconclusive. The aim of this study was to investigate whether exposure to tobacco smoke for an adult is associated with developing OA at a young age, and to assess dose-response patterns.

Methods: We conducted a pooled, cross-sectional analysis of secondary data from the National Health and Nutrition Examination Survey (NHANES) 1999-2020 among US adults aged 20-54 years (n=26145). Tobacco smoke exposure was quantified by serum cotinine. Multivariable logistic regression, restricted cubic splines, and threshold analyses were used to estimate the dose-response relationship between cotinine and self-reported physician-diagnosed early-onset OA.

Results: Overall, 1086 participants (4.2%) reported early-onset OA. After full adjusted odds ratio (AOR), serum cotinine ≥3 ng/mL was associated with a 52% increase in odds of early-onset OA (AOR=1.52; 95% CI: 1.30-1.79), compared with <0.05 ng/mL. A non-linear, positively saturated relationship was observed between the cotinine levels after the natural logarithm (LN) transformation and early-onset OA, with an inflection point at approximately 2.90 ng/mL (AOR=1.38; 95 % CI: 1.17-1.63, p=0.00). Subgroup analyses confirmed the robustness of this association across demographic and clinical strata.

Conclusions: This study, based on a nationally representative sample from the United States, suggests that high levels of tobacco smoke exposure significantly increase the likelihood of early-onset OA, highlighting the need for further research into factors associated with early-onset OA.