The hidden driver of osteoporosis: mitochondria-dominated inflammation

Mitochondria are powerful multifunctional intracellular organelles involved in a wide array of cellular processes. Emerging evidence has highlighted mitochondria as pivotal activators of innate immunity and key participants in inflammatory responses, including in sterile inflammatory diseases, beyond their well-established role as the "powerhouse" of cells. Osteoporosis (OP) is a metabolic disorder characterized by chronic low-grade inflammation, suggesting potential therapeutic value for OP treatment by targeting mitochondria-driven inflammatory pathways. Current research on mitochondrial involvement in OP primarily focuses on its functions in energy metabolism, calcium signaling transduction, oxidative stress, and cell death. However, it remains elusive regarding the precise relationship between mitochondria-mediated inflammatory mechanisms and OP pathogenesis. Accordingly, this review aims to synthesize recent advancement in understanding mitochondria-mediated inflammatory mechanisms and their implications in OP development, to offer insights that may inform future mechanistic investigations and therapeutic strategy development.