Two-sample Mendelian randomization investigating the causal association between endocarditis and osteomyelitis: A validation analysis using UK Biobank and FinnGen databases.

We conducted this study to explore the causal relationship between infective endocarditis (IE) and osteomyelitis (OM). We conducted a systematic search of PubMed, Cochrane Library, Web of Science, and Embase for relevant studies up to January 10, 2025. A meta-analysis was performed to evaluate the co-occurrence rates of IE and OM. Subsequently, 2-sample Mendelian randomization (MR) and multivariable MR analyses were employed to explore potential causal relationships, with using GWAS data from the UK Biobank and FinnGen databases. Meta-analysis revealed that 14% of OM patients had concurrent IE (95% confidence intervals [CI] = 10-18%), while 6% of IE patients exhibited comorbid OM (95% CI = 4-9%). However, all MR analyses demonstrated non-significant causal associations between IE and OM. Pooled results from meta-analysis of inverse variance weighted estimates showed: when IE was the exposure and OM the outcome: odds ratio = 1.01 (95% CI = 0.96-1.07). When OM was the exposure and IE the outcome: odds ratio = 0.87 (95% CI = 0.75-1.00). Despite the statistically non-significant MR results, the clinically observed association between IE and OM cannot be dismissed. The mediating role of bacteremia in their relationship warrants further investigation.