Exosomes as Emerging Therapeutic Strategies in Primary Osteoporosis: A Narrative Review

Primary osteoporosis imposes a growing global burden. While antiresorptive and anabolic agents reduce fractures, long-term adherence, adverse events, and limited tissue targeting leave unmet needs. Exosomes have emerged as promising, cell-free candidates.

We conducted a narrative synthesis of English-language studies (2010-May 2025) indexed in PubMed and Web of Science on exosomes and primary osteoporosis, including mechanistic, preclinical efficacy, delivery, and safety data.

Exosomes modulate bone remodeling via osteoanabolic signaling, osteoclast inhibition, and antioxidative pathways. Across cell and animal models, exosome preparations improved osteoblast viability and function, enhanced mineralization, and mitigated glucocorticoid- or estrogen-deficiency-related bone loss. Key translational variables include source selection, isolation/characterization, cargo loading, dosing, route, targeting, and biocompatibility. Safety signals are preliminarily favorable but heterogeneous across platforms. The current evidence base is predominantly preclinical; standardized manufacturing, biodistribution and persistence profiling, and dose-response relationships remain insufficient.

Exosome-based approaches are promising adjuncts rather than immediate replacements for current osteoporosis therapies. Priorities include harmonized release criteria, head-to-head comparisons with standard agents, validated pharmacodynamic biomarkers, and early-phase clinical trials.

For patients who are intolerant of or inadequately controlled by approved agents, exosome strategies may offer future targeted adjuncts once quality, safety, and efficacy are established in humans.