# The effect of bone marrow mesenchymal stem cell-derived extracellular vesicles on bone mineral density and microstructure in osteoporosis: A systematic review and meta-analysis of preclinical studies

## TL;DR

This study reviews preclinical research on using bone marrow stem cell-derived extracellular vesicles to improve bone density and structure in osteoporosis models.

## Contribution

A systematic review and meta-analysis of BMSC-EVs effects on bone parameters in osteoporosis animal models.

## Key findings

- BMSC-EV treatment significantly increased bone mineral density and improved trabecular microstructure.
- Treatment also enhanced cortical thickness and biomechanical properties in osteoporosis models.
- Publication bias was observed in some parameters, though results remained stable after sensitivity analysis.

## Abstract

The treatment of osteoporosis is challenged by limited bone regeneration and side effects. Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have gained widespread attention as a potential therapeutic approach. This study aims to evaluate the effects of BMSC-EVs on bone density, trabecular microstructure, and biomechanical properties in animal models of osteoporosis, providing evidence to support clinical translation and mechanism exploration.

A systematic search was conducted in the PubMed, Cochrane, Web of Science, and Embase (inception to January 2025) databases for preclinical studies on BMSC-EV intervention in osteoporosis models. A random-effects model was used to synthesize and analyze seven key parameters (BMD, BV/TV, Tb.N, Tb.Sp, Tb.Th, Ct.Th, and ultimate load-bearing capacity). Subgroup analysis was performed based on species (rats/mice), EVs engineering targets/methods, injection frequency, and treatment duration. The quality of the studies was assessed using SYRCLE’s risk of bias tool.

The meta-analysis of 10 studies (355 animals) showed that, compared to the control group, BMSC-EV treatment significantly increased BMD, BV/TV, Tb.N, Tb.Th, Ct.Th, and ultimate load-bearing capacity, while reducing Tb.Sp in the osteoporosis model. A publication bias was found in the summary analysis for Tb.N. However, sensitivity analysis confirmed that all summary results were relatively stable.

Compared to the control group, BMSC-EV treatment demonstrated positive effects in increasing BMD, improving trabecular microstructure, cortical thickness, and biomechanical properties in the osteoporosis model. However, clinical translation still requires standardized EV characterization and preclinical safety assessments.