The combined effect of heavy metals and polycyclic aromatic hydrocarbons on arthritis, especially osteoarthritis, in the U.S. adult population

The evaluation of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) impact on arthritis is usually limited to the analysis of the arthritis subtype (rheumatoid arthritis, RA), whereas studies on osteoarthritis (OA) are relatively sparse. Furthermore, the combined effect of HMs and PAHs co-exposure on arthritis also has rarely been analyzed. Herein, we aimed to comprehensively estimate the association between HMs and PAHs (three blood HMs and six urinary PAHs metabolites) co-exposure and arthritis. Using data from the National Health and Nutrition Examination Survey (NHANES), 2003-2016, we included 9735 adults, of whom 2464 had total arthritis, 1371 had OA, and 468 had RA. The logistic regression model was conducted to estimate the single effect of HMs and PAHs on arthritis. Moreover, weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) were separately performed to assess the combined effect of HMs and PAHs co-exposure on arthritis. In the single-exposure analyses, cadmium (Cd) and lead (Pb) statistically grew the risk of total arthritis, OA, and RA. Among PAHs, 1-hydroxynaphthalene (1-NAP) and 3-hydroxyfluorene (3-FLU) showed a positive association with total arthritis, OA, and RA. Meanwhile, 2-NAP also was significantly associated with total arthritis. 2-NAP, 2-FLU, and 1-hydroxyphenanthrene (1-PHE) also were significantly associated with RA. Furthermore, the three complementary models consistently demonstrated that co-exposure to high levels of HMs and PAHs was positively associated with total arthritis, OA, and RA risk. The above associations were more obvious in young and medium-aged people. Interestingly, BKMR analyses indicated that 1-NAP might interact with Cd and 3-FLU in total arthritis, while Pb might interact with Cd in OA. Therefore, this study provided novel evidence that co-exposure to HMs and PAHs positively correlated with arthritis, especially OA, and these results were worthy of further prospective studies.