Significance of Stem Cell-Derived Exosomes in Femoral Head Necrosis: A Systematic Review and Meta-Analysis of...

Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive and refractory orthopedic disorder characterized by deterioration of the subchondral bone microstructure and eventual femoral head collapse, leading to hip joint dysfunction. Current therapeutic strategies offer limited efficacy and fail to reverse the necrotic process, with approximately 70% of patients eventually requiring total hip arthroplasty. Therefore, developing novel treatments capable of halting disease progression and promoting bone repair is crucial for addressing this clinical challenge. Exosomes, bioactive nanovesicles that regulate apoptosis, angiogenesis, and inflammation, represent a promising regenerative modality. In particular, stem cell-derived exosomes are considered to play a key role in the treatment of SONFH by promoting osteogenesis and angiogenesis and modulating inflammatory responses. However, the efficacy and mechanisms underlying exosome-based therapy for SONFH have not been systematically evaluated. A comprehensive synthesis of current evidence is urgently needed to inform future clinical translation.

By synthesizing preclinical evidence, this study explored the mechanism and therapeutic potential of stem cell-derived exosomes in SONFH and identified key methodological limitations to provide a roadmap for future research.

Systematic review and meta-analysis.

A comprehensive literature search was conducted in PubMed, Web of Science, the Cochrane Library, and Embase for preclinical studies published from database inception until August 2025, with a focus on exosome-based therapy for osteonecrosis of the femoral head. Studies meeting the predefined inclusion criteria were rigorously selected and assessed for methodological quality, and relevant data were extracted. All the statistical analyses were performed via Review Manager (RevMan) version 5.4 software.

A total of 12 studies were included, all of which involved rat models of SONFH. The results of the meta-analysis revealed that exosome intervention significantly increased bone mineral density (BMD), thickness of trabecula, percentage of bone mass, the number of trabecula, vascular length, vascular volume and vascular area and reduced trabecular bone dissociation.

Exosomes rescue SONFH through multiple pathways. By promoting angiogenesis and osteogenesis, they effectively reverse the core pathological process of femoral head necrosis.