Abstract
OBJECTIVE: In recent years, stem cell-derived extracellular vesicles (SC-EVs) have garnered widespread attention for the treatment of osteoporosis. Based on all available data, we conducted a comprehensive evaluation of the efficacy of SC-EVs in preclinical studies, aiming to provide the latest evidence to support their clinical translation. METHODS: A comprehensive search was conducted in PubMed, Cochrane, Embase, and Web of Science databases for preclinical studies on SC-EVs for the treatment of osteoporosis, with the search period ending on November 10, 2024. Data extraction focused on three main aspects: general bone analysis parameters, histological quantification, and serum bone turnover markers. Additionally, the reporting quality and risk of bias of the studies were rigorously assessed. RESULTS: A total of 21 studies met the inclusion criteria and were included in the final meta-analysis. The results showed that SC-EVs treatment, compared to placebo, significantly increased bone mineral density, bone volume fraction, trabecular number, and trabecular thickness, while reducing trabecular separation. Furthermore, SC-EVs treatment promoted an increase in osteoblast numbers, inhibited osteoclast numbers, and enhanced bone mineralization. Despite the presence of heterogeneity and publication bias, the results were relatively robust. CONCLUSIONS: Compared with placebo, SC-EV treatment increased bone mass and strength, improved bone microarchitecture, and enhanced biomechanical properties. These effects may be associated with the regulation of bone homeostasis through osteoblasts and osteoclasts within trabecular bone. In summary, SC-EVs demonstrate great potential in regulating bone homeostasis in osteoporosis. However, rigorous and standardized quality control in future studies is essential to facilitate the clinical translation of SC-EVs.