Aptamers in Osteoimmune Regulation: Scientific Rationale, Emerging Evidence and Translational Challenges.

Osteoimmune disorders are difficult to treat because pathogenic signals are spatially restricted, temporally dynamic, and distributed across immune, skeletal, vascular, and microbial compartments. Aptamers provide a programmable recognition platform that may address these limitations, although their application in osteoimmune systems remains largely exploratory. This critical narrative review defines the scientific rationale for aptamer-based osteoimmune regulation, maps the current state of aptamer research across biological axes closely associated with osteoimmune regulation, and highlights potential targets for future therapeutic intervention. Aptamer contributions are classified into three distinct functional modes: direct molecular regulation, targeted navigation and niche reconditioning. We further analyze challenges imposed by acidic, nuclease-rich, and oxidizing skeletal environments, modification-dependent pharmacokinetics, and innate nucleic-acid sensing. Current evidence remains dominated by indirect and multicomponent systems, whereas direct aptamer-mediated osteoimmune pharmacology is supported by a comparatively limited number of studies. Future studies must establish aptamer-specific target engagement, causal immune-to-bone mechanisms, disease-relevant stability, and functional skeletal outcomes before clinical translation can be credibly pursued.