Abstract
Background
Osteomyelitis, primarily caused by Staphylococcus aureus, is influenced by risk factors like smoking and high BMI, potentially through immune alterations. Our study employs Mendelian randomization (MR) to explore these links and underlying mechanisms.
Methods
Utilizing a large genome-wide association study repository, we selected instrumental variables and conducted two-sample MR analyses to investigate relationships between smoking/BMI, lymphocyte counts, and osteomyelitis. Bidirectional, multivariable MR, and sensitivity analyses strengthened findings.
Results
Our findings revealed a positive correlation between smoking and lymphocyte counts (OR: 1.074, P = 0.002), with smoking also showing a significant association with an elevated risk of osteomyelitis (OR: 1.451, P = 0.001). Similarly, higher BMI was positively correlated with increased lymphocyte counts (OR: 1.182, P = 6×10^-5) and was found to augment the risk of osteomyelitis (OR: 1.795, 95% CI: 1.294–2.290, P = 5 × 10^-4). An incremented lymphocyte count level, in turn, was associated with a heightened risk of osteomyelitis (OR: 1.532, P = 0.002). In our mediation analysis, lymphocytes exhibited a solitary mediating effect of 7.8% for smoking and 11.8% for BMI. When both risk factors—smoking and high BMI—were concurrently present, the proportion mediated by lymphocytes rose to 9.4% for the link between smoking and osteomyelitis, and to 13.7% for the relationship between BMI and osteomyelitis.
Conclusion
Our MR study confirms smoking and high BMI as osteomyelitis risk factors, implicating lymphocytes as mediators. Elevated lymphocyte counts suggest a mechanism where pathogens may exploit and deplete these immune cells, exacerbating infection risk and severity. This suggests that changes in the immune system are important pathways through which smoking and BMI influence the development of osteomyelitis.