Microneedle-based transdermal delivery systems for metabolic bone diseases: advances, challenges, and future perspectives

Metabolic bone diseases (MBDs), such as osteoporosis and rickets, present significant clinical challenges due to the chronic nature of treatment and the limitations of conventional systemic therapies. Oral medications often suffer from low bioavailability and gastrointestinal intolerance, while injectable biologics are hampered by poor patient adherence. Microneedle (MN) systems have emerged as a transformative transdermal delivery platform capable of overcoming these barriers. This review provides a comprehensive overview of MN technology, detailing its classification, material properties, and advantages in bypassing the stratum corneum for painless administration. We analyze how MNs have evolved from physical conduits into intelligent therapeutic platforms that integrate bone-targeting ligands, stimuli-responsive release mechanisms, and immunomodulatory functions to precisely regulate the bone microenvironment. Furthermore, we summarize recent preclinical advances in MN applications for MBDs, highlighting their ability to improve pharmacokinetic profiles and therapeutic efficacy. Finally, the review critically examines current hurdles regarding manufacturing, safety, and clinical translation, and offers perspectives on next-generation systems that combine diagnostic sensing with adaptive therapy to realize personalized bone health management.