Bone-targeted nanocarrier systems in osteoporotic therapy: design strategies and therapeutic potential

Osteoporosis is characterized by reduced bone mineral density and deteriorated bone microarchitecture, and has become a growing global health challenge owing to increased fracture susceptibility. Despite diverse pharmacotherapeutic options, systemic toxicity, poor bioavailability, and patient non-compliance constrain clinical management. With the advent of nanomedicine, osteoporotic therapy is shifting from systemic drug exposure toward precise bone targeting. This review summarizes recent advances in bone-targeting nanocarrier systems. Literature within the past five years was identified through Scopus, Web of Science, Google Scholar, and PubMed using combinations of keywords including "Biomimetic Extracellular Vesicles," "Bone Targeting nanocarrier," "Bisphosphonates," "Hydroxyapatite," "Osteoporosis," and "Stimuli-Responsive." The review focuses on the pathophysiological basis for targeting and on active targeting strategies coupled with stimuli-responsive mechanisms triggered by the enzymatic and acidic bone microenvironment. It further discusses the potential of inorganic, lipid, and polymeric platforms for delivering bioactive compounds, nucleic acids, and small molecules, and scrutinizes critical barriers to clinical translation, including long-term biocompatibility, manufacturing scalability, and bone penetration depth. Collectively, this review highlights how the gap between therapeutic efficacy and safety of bone-targeting nanocarriers may be bridged, pointing toward the future of precision bone medicine.