Nanomaterial-powered therapeutic strategies for osteoporosis: From mechanistic insights to functional regeneration

Osteoporosis is a kind of systemic skeletal disorder. Its core mechanism lies in imbalanced bone remodeling, which could result in progressive bone loss and structural compromise. Current clinical drugs and therapeutics are greatly limited, mostly due to their low bioavailability, poor bone-targeting specificity, and an overreliance on single molecular targets, hindering effective modulation of the disease's complex pathological microenvironment. In recent years, with the advent of nanotechnology, a transformative strategy has arisen to overcome these shortcomings in conventional osteoporosis management. This review begins with the pathophysiological mechanisms underlying osteoporosis and provides a comprehensive overview of nanomaterial-based therapeutic approaches, including nanocarriers engineered for targeted drug or biomacromolecule delivery, nanoplatforms designed to remodel the bone microenvironment, advanced scaffolds tailored to support severe bone defects and guide tissue regeneration, and bioactive systems aimed at regulating the gut-bone axis for systemic bone homeostasis. We summarize recent progress and advantages of these nanotechnologies, critically address persistent challenges and highlight emerging strategies to tackle them, and provide an outlook on potential future research directions and technologies.