Mechanisms and disease associations of oxidative stress-mediated brain-bone axis dysregulation: a knowledge mapping...

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.