# Extracellular Vesicles for Treatment of Bone Resorption-Related Diseases in Animal Models: Systematic Review

## TL;DR

This review shows that extracellular vesicles (EVs) can help reduce bone loss in animal models by improving bone density and reducing harmful inflammation.

## Contribution

The study systematically evaluates the in vivo efficacy of EVs for bone resorption-related diseases using PRISMA guidelines.

## Key findings

- EV therapy reduced bone resorption by increasing osteoprotegerin and decreasing RANKL, TRAP, and osteoclasts.
- EVs enhanced bone formation markers like ALP, Runx2, and osteocalcin, leading to increased bone density.
- The review highlights the potential of EVs as a treatment but notes the need for more research on safety and dosing.

## Abstract

This systematic review aimed to analyze the usefulness of EV therapy in controlling bone resorption-related diseases in animal models. The study was conducted following the PRISMA guidelines. The search was conducted until November 2025 using PubMed/MEDLINE, Scopus, Cochrane Library, and OpenGrey databases to respond to the PICO question: Would therapy with EVs be efficient for the treatment of bone resorption-related diseases in vivo? The primary and secondary outcomes were the control of bone resorption and the molecular mechanisms involved, respectively. The risk of bias was examined according to the criteria of SYRCLE's RoB tool. A total of 1031 studies were reviewed, and after applying the eligibility criteria and excluding duplicates, 38 articles were included in the results. The usefulness of EVs in controlling bone resorption was established in the majority of studies. Increased levels of osteoprotegerin (OPG) and decreased levels of the pro-inflammatory cytokines, receptor activator of nuclear factor-kB ligand (RANKL), tartrate-resistant acid phosphatase (TRAP), and osteoclasts were reported. The studies also showed enhanced levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), contributing to increased bone density. EV is a promising treatment for bone resorption-related diseases in vivo. Further studies are needed to assess safety, optimal dosing, and ideal source cells, in order to confirm the findings and support potential investigations in humans.