Zhao Yixin, Wang Jihan, Xu Lijuan, Xu Haofeng, Yan Yu, Zhao Heping, Yan Yuzhu
Clinical Laboratory of Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, China.
Yan'an Medical College, Yan'an University, Yan'an 716000, China.
Biomedicines. 2025 Jun 12;13(6):1443. doi: 10.3390/biomedicines13061443.
Osteoporosis is a systemic bone disorder characterized by decreased bone mass and deteriorated microarchitecture, leading to an increased risk of fractures. Recent studies have revealed that its pathogenesis involves complex biological processes beyond bone remodeling, including oxidative stress, chronic inflammation, cellular senescence, osteoimmunology, gut microbiota alterations, and epigenetic modifications. Oxidative stress disrupts bone homeostasis by promoting excessive free radical production and osteoclast activity. Chronic inflammation and the accumulation of senescent cells impair skeletal repair mechanisms. Advances in osteoimmunology have highlighted the critical role of immune-bone crosstalk in regulating bone resorption and formation. Moreover, the gut-bone axis, mediated by microbial metabolites, influences bone metabolism through immune and endocrine pathways. Epigenetic changes, such as DNA methylation and histone modification, contribute to gene-environment interactions, affecting disease progression. Multi-omics approaches (genomics, proteomics, and metabolomics) systematically identify molecular networks and comorbid links with diabetes/cardiovascular diseases, revealing pathological feedback loops that exacerbate bone loss. In conclusion, osteoporosis pathogenesis extends beyond bone remodeling to encompass systemic inflammation, immunometabolic dysregulation, and gut microbiota-host interactions. Future research should focus on integrating multi-omics biomarkers with targeted therapies to advance precision medicine strategies for osteoporosis prevention and treatment.
骨质疏松症是一种全身性骨病，其特征是骨量减少和微结构恶化，导致骨折风险增加。最近的研究表明，其发病机制涉及骨重塑之外的复杂生物学过程，包括氧化应激、慢性炎症、细胞衰老、骨免疫学、肠道微生物群改变和表观遗传修饰。氧化应激通过促进过量自由基产生和破骨细胞活性来破坏骨稳态。慢性炎症和衰老细胞的积累会损害骨骼修复机制。骨免疫学的进展突出了免疫-骨相互作用在调节骨吸收和形成中的关键作用。此外，由微生物代谢产物介导的肠-骨轴通过免疫和内分泌途径影响骨代谢。表观遗传变化，如DNA甲基化和组蛋白修饰，有助于基因-环境相互作用，影响疾病进展。多组学方法（基因组学、蛋白质组学和代谢组学）系统地识别与糖尿病/心血管疾病的分子网络和共病联系，揭示加剧骨质流失的病理反馈回路。总之，骨质疏松症的发病机制不仅限于骨重塑，还包括全身炎症、免疫代谢失调以及肠道微生物群与宿主的相互作用。未来的研究应专注于将多组学生物标志物与靶向治疗相结合，以推进骨质疏松症预防和治疗的精准医学策略。
