OBJECTIVE: Our meta-analysis aims to assess the efficacy of genetically modified stem cell therapy in preclinical osteoporosis models. METHODS: We executed a thorough literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to September 15, 2023. We used a random-effect model for pooled analysis of the effect of genetically modified stem cell therapy on animals with osteoporosis. The primary outcomes included bone mineral density (BMD) and bone volume fraction. (BV/TV). All meta-analyses were performed employing the Cochrane Collaboration's Review Manager (version 5.3) in conjunction with Stata 15.0 statistical software. RESULTS: A total of 2567 articles were reviewed, of which 16 articles met inclusion criteria. Of these, 13 studies evaluated the BMD and 11 studies evaluated BV/TV. Compared to the control group, genetically modified stem cell therapy was associated with significantly improved BMD (standardized mean difference [SMD] = 1.85, 95% Confidence Interval [CI]: 1.06-2.63, P <
0.001, I CONCLUSION: Genetically modified stem cell therapy is a safe and effective method that can significantly improve the BMD and BV/TV in animal models of osteoporosis. These results provide an important basis for future translational clinical studies of genetically modified stem cells.