From mechanisms to therapeutics: a narrative review on pyroptosis and autophagy in osteoporosis.

BACKGROUND

Osteoporosis (OP) is a globally prevalent metabolic bone disorder, particularly affecting aging populations, and is characterized by an imbalance between bone resorption and formation. The pathogenesis of OP involves a complex interplay of genetic predisposition, hormonal changes, and chronic inflammatory pathways. Emerging evidence now indicates that pyroptosis, an inflammasome-mediated form of programmed cell death, and autophagy, a conserved intracellular catabolic process, are critical regulators of osteocyte viability and bone metabolism homeostasis.

METHODS

A systematic literature search was performed using PubMed and Web of Science for studies published from 2010 to 2024, with a focus on recent evidence (2020-2024). Seminal earlier publications were also considered. Inclusion criteria covered studies addressing both osteoporosis and pyroptosis/autophagy, their interaction, or related interventional strategies. Exclusions comprised articles not involving these mechanisms or lacking mechanistic insight into bone metabolism. Priority was given to experimental and clinical studies. Literature screening adhered to these criteria through title/abstract and full-text review.

RESULTS

The analysis confirmed that pyroptosis accelerated bone loss by activating inflammatory cascades, while autophagy exerted cytoprotective effects to maintain bone integrity. A dynamic interaction existed between these processes within osteocytes, forming a critical regulatory axis. Furthermore, specific natural compounds demonstrated the ability to modulate bone metabolism by targeting this axis, thereby offering novel mechanistic insights and promising therapeutic strategies for OP.

CONCLUSIONS

Pyroptosis-autophagy crosstalk represents a pivotal therapeutic target for osteoporosis. Future research should focus on developing dual-target therapies and conducting in vivo studies to elucidate the spatiotemporal dynamics of these interconnected processes.