Abstract
BACKGROUND: Vertebral fractures, which account for 40% of osteoporotic fractures, often lack early clinical symptoms. Previous studies have shown that neutrophil-to-lymphocyte ratio (NLR) has potential predictive value for vertebral fractures, but evidence-based conclusions are lacking. This meta-analysis is the latest to evaluate the link between NLR and vertebral fracture risk in patients with osteoporosis. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane, Wanfang and CNKI (up to March 2025). The search was performed using the following keywords: "Neutrophils", "Lymphocytes", "Osteoporosis", and "Fracture". Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (CIs) were used for the data synthesis of categorical and continuous variables, respectively. Sensitivity analysis was performed to explore the stability of the results and possible sources of heterogeneity. All analyses were performed using Review Manger 5.4 and STATA 15.0. RESULTS: Six observational studies (n=938) were included. Categorical data showed a significantly higher vertebral fracture risk in high-NLR groups (OR = 3.75, 95% CI:1.79-7.86; P = 0.0005). However, continuous data revealed no significant NLR difference between fracture and non-fracture groups (SMD = 0.51, 95% CI: -0.06-1.08; P = 0.08). Sensitivity analysis revealed that when the data of Li et al., 2023 were excluded, the results of continuous data shifted from insignificant to significant (SMD: 0.27; 95% CI: 0.08, 0.46; P = 0.004), and the heterogeneity decreased significantly. CONCLUSION: Higher NLR values in osteoporotic patients are significantly associated with an increased risk of vertebral fractures, but the strength of this evidence is limited by high heterogeneity and the instability of results from continuous variables. Current findings support NLR as a potential inflammation-related biomarker for vertebral fractures, but its clinical application requires careful interpretation. Future research should focus on conducting more high-quality, large-sample prospective studies to standardize NLR thresholds and validate its practical value in risk stratification for osteoporotic fractures. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251023391.