Experimental findings reveal zoledronic acid reduces osteoblast function and increases Caspase9 in MRONJ, indicating critical pathways in disease progression.
Objective To elucidate the mechanism of medication‐related osteonecrosis of the jaw (MRONJ), which is challenging to prevent and treat, to facilitate the development of precise prevention and treatment strategies. Materials and Methods Osteoclast‐derived exosomes were extracted and their roles in cell migration, osteogenesis, angiogenesis, and the mechanism of MRONJ were investigated. Results Osteoclast‐derived exosomes were taken up by human umbilical vein endothelial cells and osteoblasts. Cell migration and vascularization decreased in cells treated with zoledronic acid (ZA)‐induced exosomes. VEGFR2 mRNA and protein expression decreased, while Caspase9 mRNA and protein expression increased. The migration and osteogenic differentiation of osteoblasts induced by exosomes from ZA‐treated osteoclasts decreased, and the mRNA and protein expression of Notch1‐Hes1/Hey increased. In vivo, ZA‐treated osteoclast‐derived exosomes caused decreased trabecular volume, number, and thickness and increased trabecular separation in the extraction sockets. Alkaline phosphatase and tartrate‐resistant acid phosphatase activities decreased, and the number of H‐type vessels decreased in the ZA‐treated group. Conclusion ZA may contribute to MRONJ by affecting the exocytotic components produced by osteoclasts through the VEGFR2‐Caspase9 and Notch1‐Hes1/Hey signaling pathways.
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Zhang et al. (2025) studied this question.
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