Postmenopausal osteoporosis: visualization analysis of related signaling pathways

doi:10.12307/2026.724

Abstract

Abstract: BACKGROUND: Signaling pathways are important factors affecting bone metabolic stability and play an indispensable role in the onset and progression of postmenopausal osteoporosis.
OBJECTIVE: To perform a visual analysis of literature published over the past 20 years on signaling pathways related to postmenopausal osteoporosis and to explore the current state of development and research hotspots in this field.
METHODS: We retrieved the Web of Science Core Collection database for English-language literature on signaling pathways related to postmenopausal osteoporosis. The search period was from January 1, 2004 to October 20, 2024. Utilizing CiteSpace 6.3.R1 and R4.4.1 software, we conducted comprehensive statistical analyses of authors, countries, institutions, journals, cited references, and keywords, subsequently generating corresponding visualization maps.
RESULTS AND CONCLUSION: According to the inclusion and exclusion criteria, 853 articles were selected for analysis. The author with the highest number of publications was Xu Jiake, while China emerged as the leading country in publication output. Shanghai Jiao Tong University ranked as the institution with the highest number of publications. Among journals, Frontiers in Pharmacology demonstrated the highest publication volume, whereas Journal of Bone and Mineral Research received the most citations. Knowledge exchange occurred across molecular science, biology, genetics, and immunology disciplines. In recent years, “fracture prevention” and “bone resorption” become relatively stable research directions, while “network pharmacology” and “model” emerges as prominent keywords. Over the past two decades, publications on signaling pathways related to postmenopausal osteoporosis have shown an overall upward trend in the number of publications, reflecting increasing interdisciplinary integration. Among the top 10 most co-cited references, 5 studies validated the safety and efficacy of sclerostin monoclonal antibody through different approaches; 4 reviews summarized the diagnosis and treatment of osteoporosis or postmenopausal osteoporosis; and 1 study explored the role and mechanism of the Wnt signaling pathway in bone homeostasis and related diseases. Research hotspots in this field focus on elucidating signaling pathway mechanisms, particularly their associated cytokines and gene expression patterns in complex biological processes. Currently, the most prominent pathways under investigation include nuclear factor kappa B, phosphatase and tensin homolog, and nuclear factor of activated T-cells, cytoplasmic 1 pathways. In terms of treatments, the development of drugs targeting signaling pathway represents a promising direction for future treatment of postmenopausal osteoporosis, with traditional Chinese medicine applications gaining notable attention. Moreover, the combination of network pharmacology and animal models has emerged as a popular research approach in recent years.

Key words: postmenopausal osteoporosis, signaling pathway, visual analysis, bibliometrics, nuclear factor kappa B, herbal medicine

CLC Number:

Zou Shunyi, Yi Jin, Zeng Hao, Li Jianqi, Wu Zhongping. Postmenopausal osteoporosis: visualization analysis of related signaling pathways[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(16): 4229-4239.

Figures/Tables 14

2.1 绝经后骨质疏松症相关信号通路领域文献检索结果从Web of Science核心集数据库共检索到相关文献1 055篇，根据文献纳入标准和排除标准，最终纳入文献853篇，其中论著类文献684篇、综述类文献169篇。 2.2 绝经后骨质疏松症相关信号通路领域发文的年份特征绝经后骨质疏松症相关信号通路领域发文趋势可大致分为2个阶段，第一阶段为2004-2007年，这一阶段发文量总体较低且增长停滞；第二阶段为2008-2024年，该阶段发文量较为规律，呈阶段上升趋势，见图1。该领域近20年发文量年平均增长率为15.22%，总体增长较迅速，并于2017年年均发文量超过50篇，有较高的发文水平。由此可见，信号通路在绝经后骨质疏松症中的研究受到越来越多研究者的重视。 2.3 绝经后骨质疏松症相关信号通路领域发文作者分析纳入的853篇文献共包含5 083位发文作者，表1为绝经后骨质疏松症相关信号通路研究中发文量前10的作者。发文量最多的作者是XU JIAKE，发文量为19篇，其次是LIU QIAN和ZHAO JINMIN，发文量分别为16篇和12篇，他们在该领域研究开始于2015年，是近年较为活跃的研究者，共同形成了以XU JIAKE为代表的学术团体，团队中合作紧密；除此之外，其他作者合作网络较为松散，这就需要各研究团队之间进一步加强合作，优势互补；CHEN LIN和GATTI DAVIDE在该领域的研究从2011年持续至2023年，是时间跨度最长的研究者，具体见图2，3。 2.4 绝经后骨质疏松症相关信号通路领域发文国家与机构分析通过该领域发文国家的分析发现，近20年绝经后骨质疏松症相关信号通路领域发文量最多的国家是中国(516篇)，其次是美国(137篇)和韩国(46篇)，发文量排名前10的国家具体如表2所示。美国首次发文在2004年，在该领域起步最早，同时也有最高的中心性(0.31)。中国首次发文在2010年，虽起步较晚但近10年增长迅速，总发文量远高于其他国家。从国家合作图(图4)中可以看出，各节点间连线较多，说明国家间的合作较为紧密。发文量排名前10的机构如表3所示，该领域发文量最多的机构是上"

海交通大学，发文量为35篇，其次是广州中医药大学和中国科学院，发文量分别为25篇和21篇。中心性最高的机构是上海交通大学、西澳大学和哈佛大学，中心性均为0.11，同时发文量≥15篇，这3所高校兼具较高的发文量与中心性，是该领域各机构的重要合作中心。发文量排名前10的机构中高校占绝大多数，这与高校浓厚的学术氛围密不可分，具体见图5。 2.5 绝经后骨质疏松症相关信号通路领域发文期刊分析纳入的853篇文献共发表在326种期刊上，其中收录文献数量最多的期刊是《Frontiers In Pharmacology》，收录文献40篇，其次是《Bone》和《International Journal Of Molecular Sciences》分别收录文献35篇和26篇。被引期刊中被引频次最多的是《Journal of Bone and Mineral Research》，被引频次为697次，其次是《Bone》和《Journal of Biological Inorganic Chemistry》，被引频次分别为629次和488次。绝经后骨质疏松症相关信号通路领域发文量和被引量排名前10的期刊具体如表4所示。期刊双图叠加反应了施引期刊和被引期刊之间的引用关系，从期刊双图叠加(图6)中可以发现，绝经后骨质疏松症相关信号通路领域知识流动最频繁的是学科是molecular(分子科学)、biology(生物学)、genetics(遗传学)、immunology(免疫学)。 2.6 绝经后骨质疏松症相关信号通路领域共被引文献分析绝经后骨质疏松症相关信号通路领域共被引文献共现图，如图7所示。在被引频次前10的文献中，5篇文献通过不同方式验证了硬骨素单克隆抗体的安全性和有效性，4篇文献综述了骨质疏松症或绝经后骨折疏松症的诊断与治疗，1篇文献探讨了Wnt信号在骨稳态和骨相关疾病中的作用机制。其中文献共被引频次最多的是Compston JE于2019年发表在期刊《LANCET》上的综述类文章，共被引次数为56次，中心性为0.02，文章主要介绍了骨质疏松症的流行病学、临床表现、治疗"

方法等，是骨质疏松症的基础文献，为临床上骨质疏松症的诊断与治疗提供了重要的指导作用[7]；发文文献共被引中心性最高的文献是McClung MR于2014年发表在《NEW ENGL J MED》的随机对照试验，共被引次数为33次，中心性为0.24，该文通过随机对照试验比较了洛莫索珠单抗与阿仑膦酸盐类及特立帕肽的治疗作用，证明了洛莫索珠单抗的有效性和安全性，为洛莫索珠单抗的使用提供了一定的循证医学证据[8]。这些文献的高被引频次说明相关研究被广泛认可，是该领域较为重要的文献，具体见表5[7-13]。 2.7 绝经后骨质疏松症相关信号通路领域文献的关键词分析 2.7.1 关键词共现分析关键词是文章主要内容的精炼与核心，通过对文章关键词进行统计分析，可以很好地把握某一领域的研究热点和发展势态。通过CiteSpace软件分析得到节点数为 497、连线为1 028、网络密度为0.008 3的关键词共现网络图，见图8。绝经后骨质疏松症相关信号通路领域共现频次及中心性排名前10的关键词如表6所示。共现频次最高的是postmenopausal women(绝经后女性)，其次是postmenopausal osteoporosis(绝经后骨质疏松症)和gene expression(基因表达)；中心性最高的关键词是growth factor(生长因子)，其次是bone loss(骨质流失)和mechanism(作用机制)，由此可知，揭示绝经后骨质疏松症的作用机制及关键调控基因是目前研究的主要方向。 2.7.2 关键词聚类分析通过对数自然似算法对关键词进行聚类，如图9所示。关键词聚类以聚类模块值(Q)及聚类平局轮廓值(S)为评判标准，该聚类Q=0.726 6、S=0.874 4，说明该聚类社团结构显著，聚类结果合理。聚类标签反映该聚类研究的主要内容，聚类序号反应该聚类的规模，聚类序号越小则聚类规模越大，所包含的关键词越多。聚类规模前10的聚类"

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