Key Takeaways & Executive Findings
- ā¢ā¢ Publication volume on the bone-brain axis increased significantly from 2015 to 2024, with the USA and China leading in research output. ā¢ Core research themes include bone marrow, stem cells, osteoporosis, and neuroinflammation, with emerging focus on extracellular vesicles and Alzheimer's disease. ā¢ The journal Bone is the primary publication platform, while PLOS ONE exhibits high citation impact in this field. ā¢ Future research should prioritize understanding molecular mechanisms and fostering international collaboration to translate findings into clinical practice.
Abstract
BACKGROUND: In recent years, numerous studies have confirmed a close relationship between the skeletal system and the central nervous system, making the bone-brain axis a research hotspot in interdisciplinary fields; however, no studies have yet conducted a bibliometric and visualization analysis of this field. OBJECTIVE: To comprehensively analyze the research trends, hotspots, and future development directions in the bone-brain axis field utilizing bibliometric methods, providing data support and reference for subsequent studies. METHODS: A systematic literature search was conducted in the Web of Science Core Collection database to collect studies related to bone-brain axis published between 2015 and 2024. Visualization tools such as VOSviewer and CiteSpace were employed to analyze publication trends, collaboration networks, institutional contributions, and keyword co-occurrence patterns. RESULTS AND CONCLUSION: ā A total of 7,461 publications were included, showing a significant upward trend in publication volume over the past decade (2015-2024), indicating that bone-brain axis research has become an academic hotspot with increasing attention. ā”The United States and China dominated the field, with the USA publishing 2,397 papers (32.1%) and China 2,307 papers (30.9%). Harvard Medical School and Zhejiang University were the most productive and central institutions. ā¢Professor Wang Wei was the most prolific author, focusing on the interaction between bone marrow and neuroinflammation. ā£The journal Bone published the most papers (over 800), while PLOS ONE had the highest average citations per paper (45), indicating its influence. ā¤Core keywords included 'Bone Marrow', 'Stem Cells', 'Osteoporosis', and 'Neuroinflammation', reflecting fundamental research directions. Emerging frontiers included 'Extracellular Vesicles', 'Alzheimer's Disease', 'Inflammation', and 'Oxidative Stress', highlighting the importance of inflammation and neurodegenerative diseases. ā„Future research directions include exploring the specific mechanisms of osteogenic factors and neurotransmitters in the bone-brain axis, elucidating the molecular mechanisms of inflammation, oxidative stress, and extracellular vesicles in neurodegenerative diseases and bone metabolic disorders, and promoting the translation of basic research to clinical applications.
1. Introduction
The skeletal system and the central nervous system are not independent organs; recent research has revealed that they interact through a complex bidirectional signaling network, known as the 'bone-brain axis'. After bone was established as an endocrine organ, the regulatory effects of bone-derived factors on brain function have attracted widespread attention [1-2]. For example, hormones such as osteocalcin secreted by osteoblasts can enter the bloodstream and cross the blood-brain barrier, influencing brain development, learning, memory, and emotional regulation. Additionally, bone releases molecules like fibroblast growth factor 23 that act on the central nervous system. Conversely, the brain regulates bone remodeling through neurotransmitter pathways such as serotonin, balancing bone formation and resorption. Brain-derived factors also participate in bone metabolism regulation; for instance, brain-derived neurotrophic factor not only plays a crucial role in the central nervous system but is also expressed by bone cells and promotes osteogenic differentiation and bone formation [3].
The interaction between bone and the nervous system extends beyond physiological states to various pathological conditions. Proper innervation is essential for normal bone development and fracture repair, while disruption of sympathetic innervation may accelerate pathological states such as osteoporosis [4]. Moreover, certain neurological diseases, such as neurodegenerative disorders, are closely associated with skeletal diseases like osteoporosis, possibly due to the complex signaling network between the nervous system and bone [5]. Furthermore, bidirectional communication between bone and the central nervous system plays a significant role in energy metabolism regulation; the central nervous system communicates with bone via sympathetic and parasympathetic nerve fibers, modulating bone metabolic activity, while bone-secreted factors can cross the blood-brain barrier and affect brain function. This bone-to-brain signaling may contribute to the beneficial effects of exercise on brain function [6]. Thus, bone tissue and the brain form a close bidirectional regulatory mechanism through mediators such as osteoblasts, bone-derived hormones, neurotransmitters, and brain-derived factors, constituting an important axis in homeostasis and disease.
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WANG Degang, MEI Junhua, WANG Junli, ZHENG Li, CHEN Guohua (2026). Bibliometric and visualization analysis of the mechanism of osteogenic factors and neurotransmitters in the bone-brain axis. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21436
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Frequently Asked Questions
What is the bone-brain axis?
The bone-brain axis refers to the complex bidirectional signaling network between the skeletal system and the central nervous system, involving interactions through bone-derived factors, neurotransmitters, and other mediators that influence both physiological and pathological processes.
What are the main research hotspots in the bone-brain axis field?
Core research hotspots include bone marrow, stem cells, osteoporosis, and neuroinflammation. Emerging frontiers include extracellular vesicles, Alzheimer's disease, inflammation, and oxidative stress, indicating a growing focus on neurodegenerative diseases and molecular mechanisms.
Which countries lead in bone-brain axis research?
The United States and China are the leading contributors, with the USA publishing 2,397 papers (32.1%) and China 2,307 papers (30.9%) of the total 7,461 publications from 2015 to 2024.
What are the future research directions in this field?
Future research should focus on elucidating the specific mechanisms of osteogenic factors and neurotransmitters in the bone-brain axis, understanding the roles of inflammation, oxidative stress, and extracellular vesicles in neurodegenerative and bone metabolic diseases, and promoting the translation of basic research into clinical applications.
Why is bibliometric analysis important for the bone-brain axis?
Bibliometric analysis provides a quantitative overview of research trends, key contributors, and emerging topics, helping researchers identify gaps and opportunities for future studies, and facilitating evidence-based decision-making for funding and collaboration.
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