Probiotic Extracellular Vesicles Enable Oral Alendronate Therapy for Glucocorticoid-Induced Osteoporosis.

Authors

Jing Ruan, Yilei Ma, Ke Zhang, Baoting Wu, Ting Xu, Xinlu Wang, Chengzheng Duan, Shiyu Xu, Jiali Xu, Xianmei Yu, Hanbing Wang, Rongbing Chen, Yongwei Cheng, Zhigang Zheng, Dongjuan He, Da Sun, Cheng Luo

Published in

Advanced healthcare materials. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

Glucocorticoid-induced osteoporosis (GIOP) involves impaired bone remodeling, intestinal dysbiosis, and immune imbalance, which together limit the long-term benefit of conventional oral bisphosphonate therapy. Here, we report LpEVs@ALN, a probiotic extracellular vesicle-based oral nanoplatform constructed by loading alendronate (ALN) into Lacticaseibacillus paracasei-derived extracellular vesicles. LpEVs@ALN maintains vesicle integrity and epithelial compatibility, improves ALN retention under acidic exposure, and enables sustained ALN release at intestinal pH conditions. In dexamethasone-suppressed BMSCs, LpEVs@ALN enhances osteogenic differentiation, as evidenced by increased ALP activity and matrix mineralization. In zebrafish GIOP models, LpEVs@ALN improves cranial mineralization, new bone formation, scale regeneration, and locomotor/shoaling performance; accompanied by reduced inflammatory tone, improved ALP/RANKL-associated bone turnover readouts, and rebalanced oxidative-stress indices. Microbiome profiling shows recovery of richness/diversity and reduced Proteobacteria dominance, while scale RNA-seq reveals broad reversal of glucocorticoid-driven dysregulation toward pro-osteogenic and anti-inflammatory programs. Integrated correlation analysis further linked microbial remodeling with systemic and skeletal responses, suggesting involvement of the gut-immune-bone axis. Collectively, LpEVs@ALN alleviates GIOP by combining ALN-mediated bone protection with probiotic extracellular vesicle-associated regulation of intestinal and systemic homeostasis, highlighting its potential as an oral therapeutic strategy for GIOP.

PMID:
42926358
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.

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