REVIEW article
Front. Endocrinol.
Sec. Bone Research
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1625969
This article is part of the Research TopicStem Cells and Extracellular Vesicles in Bone Health, Disease and Regeneration - Volume IIView all 4 articles
Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Osteoporosis Models: A Systematic Review and Meta-Analysis of Preclinical Studies
Provisionally accepted
Ying Zhang1*
Chao Wang2- 1Department of Orthopedic Surgery, The 920th Hospital of Joint Logistics Support Force, Kunming, China
- 2The first Affiliated Hospital of Kunming Medical University, kunming, China
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Objective: Traditional pharmacological treatments for osteoporosis face challenges due to various limitations, including long-term safety concerns and limited bone anabolic effects. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free alternative therapy. However, their preclinical efficacy and the factors driving heterogeneity still require systematic evaluation. Methods: A systematic search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science (from inception to February 2025). Two independent authors performed literature screening, data extraction, and risk of bias assessment. A random-effects model was used to pool and analyze bone mineral density (BMD), bone volume fraction (BV/TV), trabecular/cortical structural parameters, and biomechanical test results. Publication bias was assessed using funnel plots and Egger's test, while leave-one-out sensitivity analysis was performed to evaluate the stability of the results. Subgroup analyses were conducted based on animal type, EVs source, synthesis method, engineering approach, intervention route, frequency, and treatment duration. Results: A total of 17 studies were included. The results demonstrated that, compared to the control group, MSC-EVs significantly increased BMD, BV/TV, trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th), mineral apposition rate (MAR), and the ultimate load-bearing capacity of the femur, while reducing trabecular separation (Tb.Sp). Significant heterogeneity and publication bias were observed in all analyses. Sensitivity analysis confirmed the robustness of all results. Conclusions: MSC-EVs demonstrate significant improvements in preclinical osteoporosis models, highlighting its potential for clinical translation. However, further standardized studies are needed to evaluate the long-term efficacy and safety of MSC-EVs.
Keywords: Extracellular vesicle, Osteoporosis, mesenchymal stem cell, bone mineral density, Animal Models, Meta-analysis
Received: 09 May 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ying Zhang, Department of Orthopedic Surgery, The 920th Hospital of Joint Logistics Support Force, Kunming, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.