The mediating effect of body mass index on the relationship between smoking and hip or knee replacement due to primary osteoarthritis. A population-based cohort study (the HUNT Study)

To investigate the total effect of smoking on total hip or knee replacement (THR/TKR) due to primary osteoarthritis (OA) and to quantify the indirect effect of smoking through body mass index (BMI). Participants from the Nord-Trøndelag Health Study (the HUNT Study) were linked to the Norwegian Arthroplasty Register to detect the first THR or TKR due to primary OA. A mediation analysis was used to decompose the total effect of smoking into a direct and indirect effect. BMI was considered a mediator in the analysis. All effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). The indirect effect of smoking mediated through BMI was expressed as a percentage (proportion*100). In total 55 188 participants were followed up during 17.2 years (median). We identified 1322 THRs and 754 TKRs. For men, the total effect of current vs. never smoking revealed a decreased risk of THR (HR 0.59, 95% CI 0.46-0.76) and TKR (HR 0.47, 95% CI 0.32-0.66). For women, current smoking increased the risk of THR (HR 1.34, 95% CI 1.11-1.60). For men, 6% and 7% of the risk reduction for THR and TKR, respectively, was mediated by BMI. We found a negative association between smoking and THR or TKR for men. On the contrary, smoking was associated with increased risk of THR for women. Most of the effect of smoking on joint replacement risk remained unexplained by BMI.