氧化应激介导的脑-骨轴失调的机制和疾病关联：基于文献计量学的知识图谱和趋势分析

摘要(中文译文)

氧化应激以活性氧和抗氧化防御之间的系统性失衡为特征，越来越被认为是驱动脑骨轴失调的核心病理联系。尽管积累了经验证据，但仍然缺乏对该领域知识结构和主题进展的系统描述。本研究采用多数据库文献计量方法，绘制了氧化应激介导的神经骨骼串扰的研究图景，并确定了新兴的研究前沿。从Web of Science Core Collection、Scopus和PubMed数据库开始到2025年4月30日，对其进行了系统搜索。经过基于预定义标准的严格筛选过程，纳入了717篇相关出版物。使用CiteSpace、VOSviewer和Bibliometrix R包进行文献计量映射和网络分析，以评估协作模式、共引结构和关键字演变。分析显示，自2009年以来，研究产出稳步增长，具有不同的发展阶段。早期的研究主要集中在基本的氧化损伤机制上，而随后的研究则转向系统性疾病关联（如阿尔茨海默病和骨质疏松症）和有针对性的干预策略，包括间充质干细胞治疗和褪黑素。最近的趋势表明，方法论和主题转向了高分辨率的翻译主题，如神经免疫调节和“肠-脑-骨”轴。值得注意的是，“肠道微生物群”和“细胞外囊泡”已成为高中心性节点，反映出对器官间通讯和全身氧化还原调节的日益关注。本研究首次全面绘制了氧化应激介导的脑骨轴领域的研究轨迹。这些发现描绘了从孤立的机制研究向集成的多系统框架的明显进展，强调了向精准医学和转化应用的转变。通过识别当前的研究差距和新兴热点，该分析为未来的跨学科研究和神经骨骼并发症的靶向治疗策略的发展提供了系统的参考。

Abstract

Oxidative stress, characterized by the systemic imbalance between reactive oxygen species and antioxidant defenses, is increasingly recognized as a central pathological nexus driving the dysregulation of the brain-bone axis. Despite the accumulation of empirical evidence, a systematic characterization of the field's intellectual structure and thematic progression remains absent. This study employs a multi-database bibliometric approach to map the research landscape of oxidative stress-mediated neuro-skeletal crosstalk and identify emerging research frontiers. A systematic search was performed across the Web of Science Core Collection, Scopus, and PubMed databases from their inception to April 30, 2025. Following a rigorous screening process based on predefined criteria, 717 relevant publications were included. Bibliometric mapping and network analyses were conducted using CiteSpace, VOSviewer, and the Bibliometrix R-package to evaluate collaboration patterns, co-citation structures, and keyword evolution. The analysis reveals a steady increase in research output since 2009, marked by distinct developmental phases. Early investigations primarily focused on fundamental oxidative damage mechanisms, while subsequent research transitioned toward systemic disease associations (e.g., Alzheimer's disease and osteoporosis) and targeted intervention strategies, including mesenchymal stem cell therapy and melatonin. Recent trends indicate a methodological and thematic shift toward high-resolution translational themes, such as neuroimmune regulation and the "gut-brain-bone" axis. Notably, "gut microbiota" and "extracellular vesicles" have emerged as high-centrality nodes, reflecting an increasing focus on inter-organ communication and systemic redox modulation. This study provides the first comprehensive mapping of the research trajectories within the oxidative stress-mediated brain-bone axis field. The findings delineate a clear progression from isolated mechanistic studies toward integrated, multi-system frameworks, underscoring the shift toward precision medicine and translational applications. By identifying current research gaps and emerging hotspots, this analysis offers a systematic reference for future interdisciplinary investigations and the development of targeted therapeutic strategies for neuro-skeletal comorbidities.

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