Purpose <p>This study aimed to investigate the correlation between serum T helper 1/T helper 2 (Th1/Th2) balance and the risk of osteoporosis (OP) in patients with Helicobacter pylori (Hp) infection.</p> Methods <p>All patients were tested for both Hp and bone mineral density (BMD). A total of 200 patients were categorized into Hp non-infected (<i>n</i> = 100) and Hp infected (<i>n</i> = 100) groups based on ¹⁴C urea breath test results. Subsequently, patients were further divided into non-OP (<i>n</i> = 110) and OP (<i>n</i> = 90) groups according to BMD measurements. Serum levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were measured to calculate the IFN-γ/IL-4 ratio, reflecting the Th1/Th2 balance. Bone metabolism markers, bone alkaline phosphatase (BALP) and bone gal protein (BGP), were also assessed.</p> Results <p>The Hp infected group exhibited significantly lower BMD (0.97 vs. 1.02&#xa0;g/cm², <i>P</i> = 0.024), higher BALP (19.28 vs. 18.25&#xa0;µg/L, <i>P</i> = 0.026), lower BGP (17.35 vs. 18.91&#xa0;µg/L, <i>P</i> = 0.017), a higher IFN-γ/IL-4 ratio (18.26 vs. 15.87, <i>P</i> &lt; 0.001), and a higher OP prevalence (54% vs. 36%, <i>P</i> = 0.011) compared to the non-infected group. The OP group had a higher IFN-γ/IL-4 ratio (18.09 vs. 16.23, <i>P</i> &lt; 0.001). Correlation analysis revealed that OP risk positively correlated with the IFN-γ/IL-4 ratio (<i>r</i> = 0.313), IFN-γ (<i>r</i> = 0.212), age (<i>r</i> = 0.160), and smoking (<i>r</i> = 0.170), and negatively with male (<i>r</i>=-0.159, all <i>P</i> &lt; 0.05). Multivariate analysis identified the IFN-γ/IL-4 ratio as an independent risk factor for OP (OR = 1.257, <i>P</i> &lt; 0.001).</p> Conclusion <p>Hp infection may be associated with an increased risk of OP, potentially mediated by a shift towards a Th1-dominant immune response.</p>