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Beyond the bladder: Escherichia coli UTIs drive systemic inflammation and RANKL-mediated bone resorption

Ir J Med Sci. 2025 Sep 25. doi: 10.1007/s11845-025-04093-1. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic inflammation associated with recurrent urinary tract infections (rUTIs) can adversely affect bone metabolism. This study aimed to explore the interactions between vitamin D status, inflammatory markers, and bone turnover in patients with rUTIs, with a focus on the differences between infections caused by Escherichia coli and those caused by non-E. coli pathogens.

METHODS: In this cross-sectional study, 50 patients with rUTIs (25 with E. coli-induced infections and 25 with infections caused by non-E. coli pathogens) were evaluated. The serum levels of 25-hydroxyvitamin D (vitamin D), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), receptor activator of nuclear factor kappa-Β ligand (RANKL), and the bone resorption marker C-terminal telopeptide of type I collagen (CTX-I) were measured. Statistical analyses included group comparisons, correlation assessments, receiver operating characteristic (ROC) curve analysis, and multiple linear regression.

RESULTS: Patients in the E. coli group had significantly lower serum vitamin D levels and elevated levels of IL-6, RANKL, and CTX-I than those in the non-E. coli group (all p < 0.001). Vitamin D levels showed a strong inverse correlation with RANKL levels (r = – 0.593). In the multiple regression analysis, IL-6 and RANKL emerged as the only independent predictors of CTX-I, collectively accounting for 60% of the variance (R2 = 0.60).

CONCLUSION: Recurrent urinary tract infections caused by E. coli are associated with a clinical profile characterized by vitamin D deficiency and inflammation-mediated bone resorption driven by the IL-6/RANKL signaling pathway. These findings highlight the previously underappreciated osteoimmunological impact of common bacterial infections and suggest that skeletal health should be an important consideration in the management of patients with rUTIs.

PMID:40996582 | DOI:10.1007/s11845-025-04093-1

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