Association between urinary NNAL concentrations and osteoarthritis: Evidence from NHANES 2007-2012

Osteoarthritis (OA) is the most prevalent degenerative joint disorder globally, yet the impact of smoking on its development remains contentious. The compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a principal metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a well-recognized biomarker for smoking exposure. This study aimed to use urinary NNAL as a biomarker to evaluate the association between tobacco exposure and OA.

This study was a secondary cross-sectional analysis of pooled data from the 2007-2012 cycles of the National Health and Nutrition Examination Survey (NHANES), including 10848 adults. OA was assessed using self-reported physician diagnosis and radiographic examination, with a Kellgren-Lawrence grade ≥2 indicating radiographic OA; urinary NNAL concentration was used as the biomarker of tobacco exposure. Survey-weighted multivariable logistic regression analysis and subgroup analyses were performed after adjusting for confounding factors.

Elevated urinary NNAL concentrations were positively associated with greater odds of OA. In the fully adjusted model, urinary NNAL concentrations >0.077925 ng/mL were associated with greater odds of OA (adjusted odds ratio, AOR=1.55; 95% CI: 1.36-1.76). Evidence of interaction was observed for age (p for interaction <0.001), but not for sex (p=0.231) or BMI (p=0.127). Among adults aged <60 years, the AOR for the highest versus lowest NNAL category was 1.69 (95% CI: 1.46-1.95), whereas the corresponding AOR was 0.98 (95% CI: 0.82-1.17) among adults aged ≥60 years.

Higher urinary NNAL was associated with an increased likelihood of OA, with more prominent effects observed in middle-aged adults. Given the cross-sectional design, temporality and causality cannot be established, and the potential association requires confirmation in longitudinal and mechanistic studies.