Objective Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor‐α (TNF‐α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta‐analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. Methods The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. Results A total of 15 studies involving 5273 subjects were included in our meta‐analysis. The GG genotype of TNF‐α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51‐0.77, P < 0.0001, I2 = 31%). Additionally, we also observed a significant association between G308A polymorphism and BMD of lumbar spine (AA vs GG: P = 0.01, I2 = 53%). However, TNF‐α T1031C, C857T and C863A polymorphisms had no obvious impacts on osteoporosis risk. Conclusions The present meta‐analysis demonstrated that TNF‐α G308A polymorphism may act as a potential candidate biomarker for screening, diagnosis, and treatment of osteoporosis, which will help improve individualized therapy of osteoporosis patients in clinics.

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