Bidirectional Mendelian randomization analysis reveals no causal association between Helicobacter pylori infection and osteoporosis risk

Despite the widespread controversy surrounding the existence of a causal link between contracting Helicobacter pylori (H pylori) and the risk of osteoporosis (OP), this study aimed to ascertain this link using bidirectional two-sample Mendelian randomization (MR) analysis powered by genome-wide association data. Various analysis methods were used, including the inverse variance-weighted (IVW) method, weighted model, simple model, MR-Egger regression, and the weighted median method. The MR-Egger regression intercept term, MR-PRESSO, Cochran Q test, and leave-one-out cross-validation technique were used for sensitivity analysis. The IVW method of two-sample MR showed no causal relationship with anti-H pylori IgG seropositivity and OP (OR: 1.03; 95% CI: 0.90-1.18; P = .69), and the level of H pylori vacuolating cytotoxin A (VacA) antibody (OR: 1.00; 95% CI: 1.00-1.00; P = .28) or H pylori cytotoxin-associated gene A protein (CagA) antibody level (OR: 0.95; 95% CI: 0.86-1.05; P = .31). Using MR, a bidirectional analysis revealed no causal association between H pylori infection and OP. This finding was consistent across the 4 complementary analytical methods, and the sensitivity analyses identified no violations of the underlying MR assumptions. Our results suggest that there is no evidence of a causal relationship between H pylori infection and OP.