Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL RELEVANCE: 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.