Traditional Chinese medicine-derived monomers improve bone metabolic imbalance and delay osteoporosis progression by regulating mitochondrial homeostasis.

Abstract

Osteoporosis is a systemic metabolic bone disease characterized by reduced bone mass, microarchitectural deterioration, and increased fracture risk. Its pathogenesis is driven by an imbalance between insufficient osteoblast-mediated bone formation and excessive osteoclast-mediated bone resorption. In recent years, mitochondrial homeostasis has emerged as an important pathological hub in this process. Beyond energy production, mitochondria regulate redox balance, mitophagy, apoptosis, senescence, and metabolic adaptation in bone cells. When mitochondrial homeostasis is disrupted, excessive reactive oxygen species accumulation, impaired membrane potential, defective quality control, and metabolic insufficiency collectively suppress osteogenic capacity while promoting osteoclastic activity, ultimately aggravating bone loss. A growing body of evidence suggests that monomers derived from traditional Chinese medicine can partially restore bone metabolic balance by improving mitochondrial function, reducing oxidative stress, and modulating mitochondrial quality control. These compounds have been reported to promote osteoblast survival and differentiation while suppressing osteoclastogenesis and bone resorption. However, the current evidence remains uneven in depth and quality. Most studies are still based on in vitro experiments and animal models, whereas direct evidence supporting mitochondria-specific targeting, long-term safety, bioavailability, and clinical applicability remains limited. This review summarizes the pathological role of mitochondrial homeostasis imbalance in osteoporosis and discusses how representative TCM-derived monomers regulate osteogenic and osteoclastic metabolism through mitochondrial mechanisms. It also critically evaluates current limitations and highlights future directions for improving mechanistic rigor and translational value.