Personal history of irradiation and risk of osteomyelitis: A Mendelian randomization study

This study employed Mendelian randomization (MR) to clarify the causal relationship between personal radiation exposure and osteomyelitis onset. We used a 2-sample MR approach to examine the causal association between personal irradiation history and osteomyelitis, leveraging genome-wide association study datasets: radiation exposure data from the IEU genome-wide association study database (UK Biobank cohort, 463,010 European-ancestry participants with self-reported radiotherapy or occupational exposure) and osteomyelitis data from the FinnGen Consortium (842 cases and 209,575 controls of European ancestry). Inverse variance weighting was the primary analytical method, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analyses included Cochran Q test, MR-Egger intercept, and leave-one-out validation. After rigorous quality control, 98 instrumental variables strongly associated with radiation exposure were selected. Inverse variance weighting analysis revealed a significant positive causal association (odds ratio = 1.29, 95% confidence interval = 1.01-1.66, P = .04), indicating a 29% increased risk of osteomyelitis per unit of genetically proxied radiation exposure. Cochran Q test (P = .71) showed no significant heterogeneity, and the MR-Egger intercept (P = .33) ruled out horizontal pleiotropy. Leave-one-out analysis confirmed stable results. This study provides genetic evidence for a causal link between personal irradiation history and elevated osteomyelitis risk. Clinically, these findings underscore the need for enhanced monitoring of bone health in high-dose radiotherapy populations and support targeted preventive strategies to reduce infection susceptibility, with implications for optimizing care in at-risk individuals.