Visual analysis of the literature on postmenopausal osteoporosis-related hormone research: Current status and future trends (2004-2024).

Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder. In China, it affects an estimated 70 million women, accounting for 77.78% of all osteoporosis cases in the country. The fractures and associated complications arising from PMOP are linked to a significantly high rate of disability and mortality. Projections indicate that by 2035, the financial burden of managing postmenopausal osteoporotic fractures in China will soar to 132 billion yuan, underscoring the issue as a formidable public health challenge. [ 1 ] Traditional therapeutic strategies for PMOP have centered on oral calcium supplementation, vitamin D administration, and pharmacological interventions, including teriparatide, bisphosphonates, and denosumab. [ 2 ] However, the long-term application of these medications is frequently complicated by safety concerns and tolerability issues. Consequently, there is an urgent imperative for researchers to delve into innovative therapeutic modalities to enhance the comprehensive efficacy of PMOP prevention and management. Hormones are cellular secretions that are released in response to specific signals or stimuli, playing a crucial role in maintaining the body’s homeostatic environment and regulating human metabolism. These biochemical messengers facilitate communication and coordination among the metabolic processes of various tissues and organs, thereby ensuring the stability of the internal milieu. [ 3 ] Evidence suggests that hormonal levels can modulate bone homeostasis by influencing the oxidative stress response, ferroptosis, and the copper death response in bone-related cells of postmenopausal women, as well as by impacting changes in the human intestinal microbiota. The regulation of hormonal levels may thus offer a novel avenue for the prevention and treatment of PMOP. [ 4 ] Investigating the levels of hormones related to PMOP sheds light on their role in the pathogenesis of the disease and paves the way for innovative preventative and therapeutic strategies. Bibliometrics, a methodological approach for the analysis of scientific literature, involves both quantitative and qualitative assessments of the distribution and evolutionary patterns of relevant information within scholarly texts. This method is instrumental in summarizing the current state and trends of a research domain, as well as in charting its future developmental trajectory. [ 5 ] Bibliometrics has been extensively applied across a spectrum of medical fields, including cancer, [ 6 ] osteoarthritis, [ 7 ] and liver disease. [ 8 ] However, its application to the study of hormonal levels associated with PMOP has been lacking. To address this research gap, the present study employs bibliometric and visual analysis techniques to synthesize the scientific literature on PMOP-related hormonal levels from the Web of Science database spanning 2 decades (2004–2024). The objective of this study is to pinpoint the principal contributors and the current state of research on PMOP-related hormonal levels, and to uncover global research hotspots and developmental trends, thereby offering guidance to scholars in this area.

Conceptualization: Bo Jin, Kunjian Li. Data curation: Bo Jin. Funding acquisition: Lin Meng. Methodology: Kunjian Li. Software: Shunyi Zou, Lin Meng. Visualization: Shunyi Zou. Writing – original draft: Yongjin Li. Writing – review & editing: Yongjin Li, Lin Meng.

This study was searched independently by 2 researchers. TS = (postmenopausal osteoporosis) AND (TS = (postmenopausal osteoporosis OR PMOP) AND TS = (hormones OR thyroid hormones OR estrogen OR follicle-stimulating hormone OR glucocorticoid OR steroid hormone OR hormone concentration OR hormone content OR TH OR E2 OR E1 OR E3 OR FSH OR GC)) were used to search articles in the WOS core collection database from 2004-09-01 to 2024-09-01. The article types are set to “Article” and “Review Article.” The retrieved English literature was exported in the format of “Text” and imported into NoteExpress software (Aegean Software, Beijing Aegean Software Center) to create a database for the first duplicate check. Two researchers manually performed the second duplicate check and screened the literature according to the inclusion criteria. If there was any disagreement, the third researcher would discuss. PMOP and hormone-related studies must be clearly involved and the literature information is complete and full text can be obtained, including important information such as author, institution, and country. For different versions of the same research results, only the one with the most complete content and the highest quality is retained; missing key data in the literature; and conference abstracts, letters, and comments were excluded. CiteSpace parameter setting: the selected Chinese and English literature were imported into CiteSpace 6.4.R1 (Chaomei Chen, Drexel University, College of Computing & Informatics) in “Refworks” and “Text” respectively, and the project was created. The time span was from January 2004 to 2024.09, and the time slice was 1 year. Topic, abstract and key words were selected as vocabulary sources. The node types included coauthors, institutions, countries, keywords, and cited literature. “ g -index = 25” was selected as the node filter mode, and Pathfinder, Pruning sliced networks and Pruning the merged network were selected as the pruning mode. And to check the robustness of the results, we tested the network structure of g -index under k  = 20 and k  = 30, respectively. The results showed that core cluster members, key turning point literature remained consistent, and only a small number of weak connections at the network edge differed, indicating that the main conclusions of this study were not sensitive to the choice of the g -index threshold, as depicted in Figure 1 . Flowchart of scientific literature screening. CiteSpace(6.3.R1) is a sophisticated software tool for document econometric analysis and visualization, developed by Professor Chen. [ 9 ] This tool is adept at uncovering the evolving trends and dynamics within a specific academic research domain. In this study, following the retrieval and filtration of pertinent literature from the Web of Science Core Collection (WoSCC) database in “Plaintextfile” format, we utilized CiteSpace to further analyze the “FullRecord and CitedReferences” data, importing the “download_xx.TXT” file to establish a database. The analytical timeframe was delineated from September 2004 to September 2024, with an annual time slice interval. The nodes of our analysis were categorized by Author, Country, Institution, Keywords, and CitedReferences, employing the g -index for node filtering with k  = 25. Nodes with higher intermediary centrality within the network are considered pivotal “bridges” or “intermediaries.” The PathFinder algorithm was engaged to systematically prune the network, focusing on keyword reduction, with subsequent steps following CiteSpace’s default parameters. The software was instrumental in conducting a visual analysis of publication counts, countries, institutions, authors, keywords, and co-cited literature, thereby generating informative visual maps. Additionally, Microsoft Excel was employed for the statistical analysis of our data and for the creation of pertinent tables.

Based on our search findings, a total of 7174 investigations pertaining to hormones associated with PMOP were identified over the span of 2 decades, comprising 5874 original articles and 1300 review articles. As illustrated in Figure 2 , the output of scientific literature reached its zenith in 2010 with 433 articles, succeeded by 2016 with 402 articles. During the initial decade from 2009 to 2010, the most notable surge occurred between 2011 and 2012, escalating from 330 to 433 articles, marking a 103-article increment and a 31.2% growth rate. In the subsequent decade from 2014 to 2024, the most significant leap was observed from 2015 to 2016, with an increase from 382 to 402 articles, resulting in an 80-article rise and a 20.9% growth rate. When examining the annual publication count, the scientific literature growth rate remained relatively consistent throughout the entire period from 2004 to 2024; despite minor fluctuations, it generally stabilized at around 350 publications annually. This underscores the substantial interest and attention that the research domain of PMOP-related hormones has garnered among the scientific community. Refer to Figure 2 for further details. Annual output of scientific literature on hormones related to PMOP. PMOP = postmenopausal osteoporosis. The scientific discourse in the realm of PMOP-related hormones is a global affair, with contributions from 104 countries and 572 institutions. The leading nations in terms of publication output are the United States, China, Japan, the United Kingdom, Italy, Germany, South Korea, Canada, France, and Spain, with a distribution that highlights Europe’s pronounced engagement in this field, boasting 5 European, 3 Asian, and 2 North American countries. Among these, the United States stands at the forefront with 2187 publications (30.15%), trailed by China (1218; 16.79%), Japan (496; 6.83%), the United Kingdom (472; 6.51%), and Italy (465; 6.41%). Collectively, China and the United States account for nearly half (46.94%) of the global scientific output, underscoring their pivotal roles in the research and publication landscape of this field. A visualization of the collaborative network among countries with over 100 scientific publications, as depicted in Figure 3 , reveals a substantial number of nodes but a limited number of connections, suggesting a need for enhanced international collaboration. Despite this, the centrality scores from Table 1 indicate a low degree of international cooperation, with closer ties within national borders. This observation implies that amplifying international collaborative efforts, while maintaining robust national partnerships, is essential for advancing research in this domain. For further insights, refer to Table 1 and Figure 3 . Top 10 countries and institutions for PMOP-related hormone research. The centrality values are rounded to 2 decimal places. A value of 0 indicates that the original centrality degree of the node is <0.01. PMOP = postmenopausal osteoporosis. National visualizations of relevant hormone studies in PMOP. Nodes in the figure represent countries. The larger the number of documents, the greater the number of nodes. The color of the node represents the year. Cooperation between countries is represented by connections between nodes. The more connections a country has, the more closely it cooperates with other countries. PMOP = postmenopausal osteoporosis. Among the top 10 institutions, 8 are based in the United States, with the remaining 2 in France and the United Kingdom. The University of California System (289; 3.89%), Harvard University (196; 2.70%), Columbia University (183; 2.52%), and Eli Lilly (159; 2.19%) are the most prolific publishers, all hailing from the United States, reflecting a strong institutional dominance that mirrors the country’s overall leadership in this field. Upon filtering and visualizing the 572 institutions with more than 100 scientific publications, a collaborative network was constructed, revealing a preponderance of national universities with extensive inter-institutional connections, as shown in Figure 4 . This pattern indicates that universities are the principal drivers of research in this field across various countries. The centrality analysis of the top 10 institutions in Table 1 reveals that the Institut National de la Santé et de la Recherche Médicale (Inserm) and Harvard University exhibit the highest centrality scores, signifying their central roles in the research and publication of scientific literature in this area. For a detailed examination, see Table 1 and Figure 4 . Institutional visual analysis of related hormone studies in patients with PMOP. Nodes represent institutions in the figure. The larger the number of documents, the larger the number of nodes. The color of the node represents the year. Cooperation between institutions is represented by connections between nodes. The more connections an institution has, the more closely it works with other institutions. PMOP = postmenopausal osteoporosis. The scientific discourse on PMOP is represented across 1678 journals, with the Journal of Osteoporosis International leading the publication count (n = 446, 5.87%), followed by the International Journal of Bone and Mineral Research (n = 317, 4.17%), the Journal of Bone and Mineral Research (n = 267, 3.51%), the Journal of Clinical Endocrinology and Metabolism (n = 160, 2.10%), and the Journal of Calcified Tissue International Research (n = 155, 2.04%). Within the top 10 journals, 4 are classified in the Journal Citation Reports’ (JCR) Q1 category, and 5 in Q2. Notably, the Journal of Bone and Mineral Research boasts the highest impact factor (IF = 6.2) and ranks within the top 3 for published papers, underscoring its significance in PMOP hormone-related research. This journal is a primary contributor to the scientific literature in this field. To elucidate the interrelationships among the predominant research topics within PMOP-related hormonal studies, a co-citation analysis was conducted across all 1678 journals. Subsequent clustering was performed based on journal titles, followed by a visual network graph analysis of the top 10 topics. The cluster sequence number indicates the scale of the cluster, with smaller numbers representing larger clusters and a greater inclusion of keywords. The cluster modularity value (Q) and average silhouette value (S) serve as metrics for assessing the robustness and validity of the clustering. Generally, a modularity value (Q) >0.3 and an average silhouette value (S) >0.7 are considered indicative of significant and efficient clustering, respectively. This study yielded a modularity value (Q) of 0.7793 and an average silhouette value (S) of 0.9128, signifying a significant and reliable group structure. The larger the number of journals within a cluster, the higher its ranking. Figure 5 illustrates the themes of the top 10 clusters, which include #0 Sequential treatment, #1 Glucocorticoid-induced osteoporosis, #2 Serum sclerostin level, #3 Elderly women, #4 Zoledronic acid, #5 Parathyroid hormone, #6 Hormone replacement therapy, #7 Conjugated estrogen, #8 Gut microbiota, and #9 Aromatase inhibitor. The main cited literature represented the research frontier, among which cluster #0 was the largest cluster with 173 nodes and a profile value of 0.89. The main cited literature of this cluster studied the standardized evaluation and management of osteoporosis and the prevention of fragility fractures for postmenopausal women and men aged 50 years and over. Gregson et al believe that by integrating the latest evidence and providing a unified and operational clinical framework for all medical staff involved in the management of osteoporosis, the incidence of fragility fractures in postmenopausal women and men over 50 years old in the UK can be reduced, and the health burden and economic cost of the disease can be reduced. Cluster #1 Glucocorticoid-induced osteoporosis has 161 nodes. The main cited literature of this cluster studied insights and implications of sexual dimorphism in osteoporosis. Zhang et al believe that the rapid decline of estrogen after menopause is the main cause of bone loss in women, which plays a role by inhibiting osteoclast activity and promoting osteoblast survival. In men, estrogen deficiency (such as aromatase deficiency) can also lead to decreased bone density, and estrogen receptor α is a key regulator of bone homeostasis in men and women. Cluster #2 Serum sclerostin level has 134 nodes, and the main cited literature for this cluster studies Osteoporosis update from the 2010 Santa Fe bone symposium. Lewiecki et al have shown that serum sclerostin is a potent inhibitor of the Wnt signaling pathway. Sclerostin can directly inhibit the process of bone formation by blocking the pathway, which is an important molecule leading to bone loss and increased bone fragility. Cluster #3 Elderly women had 121 nodes, and the main cited literature in this cluster studied Management of osteoporosis in postmenopausal women: 2006 position statement of the North American Menopause. Ettinger et al believe that although GnRH-a can be used to treat endometriosis and other diseases, it can induce bone loss by inducing iatrogenic hypogonadism, which leads to PMOP. Cluster #4 Zoledronic acid has 118 nodes. The main citations of this cluster were the same as cluster #3, but it proposed zoledronic acid as a “promising new therapy” that has been studied in some countries outside North America, but has not yet been approved for the routine treatment of postmenopausal women with osteoporosis in North America. Cluster #5 Parathyroid hormone had 113 nodes, and the main cited articles in this cluster studied Parathyroid hormone treatment for osteoporosis. Cosman et al concluded that PTH is the preferred anabolic drug for osteoporotic patients with high fracture risk, which can significantly improve bone microstructure and fracture risk, but it should be combined with anti-absorptive drugs after drug withdrawal to maintain its efficacy. Cluster #6 Hormone replacement therapy has 100 nodes, and the main cited articles of cluster #3 are also the same. The studies in this cluster show that hormone replacement therapy is an emerging method that can significantly delay bone loss, but should be strictly limited to postmenopausal women who are “symptomatic and at high risk of fracture.” Balancing Benefits and Risks with “Lower Doses, Shorter Courses”; Cluster #7 Conjugated estrogen has 87 nodes, The main cited literature of this cluster is the Development of conjugated estrogens/bazedoxifene, the first tissue-selective estrogen complex (TSEC) for management of menopausal hot flashes and postmenopausal bone loss. Komm et al have shown that estrogen binding complex (TSEC) can significantly act on bone, inhibit osteoclast activity, reduce bone resorption, and prevent postmenopausal bone loss. Compared with estrogen therapy alone, TSEC has better clinical efficacy. Cluster #8 Gut microbiota has 85 nodes, and the main cited literature of this cluster studies Oxidative stress and inflammation in osteoporosis: molecular mechanisms involved and the relationship with micrornas. Iantomasi et al have shown that the imbalance of intestinal flora can reduce the level of active estrogen and aggravate the bone loss related to estrogen deficiency. However, intestinal flora can regulate the activity of intestinal immune cells through its metabolites, maintain the systemic pro-inflammatory/anti-inflammatory balance, and then affect the function of bone cells. Cluster #9 Aromatase inhibitor has 82 nodes, and the main references in this cluster focus on bone health testing techniques, treatment strategies, bone health management in special populations (such as aromatase inhibitor users), hip fracture treatment pathways, and treatment monitoring, etc. Lewiecki et al have shown that Aromatase inhibitor can strongly inhibit aromatase with an inhibition rate of 96% to 99%, reduce circulating estrogen level to very low, relieve the inhibition of estrogen on bone resorption, and lead to hyperbone turnover and decreased bone mineral density, thereby significantly increasing the risk of osteoporosis and fracture in postmenopausal breast cancer patients. The interrelatedness of various research topics is instrumental in driving progress and innovation within the field. As per Table 2 , the Journal of Bone and Mineral Research is not only frequently cited at the top of the list (n = 5845) but also ranks second in centrality, indicating that the journal’s scientific literature is widely recognized and influential in research related to PMOP hormones, earning its reputation as a “trendsetter” in this domain. For further details, refer to Table 2 and Figure 5 . Top 10 journals in terms of publication volume of related hormone studies in PMOP. The centrality values are rounded to 2 decimal places. A value of 0 indicates that the original centrality degree of the node is <0.01. IF = impact factor, JCR = Journal Citation Reports, PMOP = postmenopausal osteoporosis. Topic clustering map of co-cited journals related to hormone studies in PMOP. In the figure, different color clusters represent different clusters, nodes represent the journals contained in the cluster, lines represent the co-occurrences of journal citations, and # represents different cluster labels: #0 estrogen receptor, #1 bone mineral density, #2 cortical bone, #3 breast cancer, #4 osteoblast differentiation, #5 teriparatide, #6 RANKL, #7 cathepsin K, #8 hip fracture, #9 hormone replacement therapy. PMOP = postmenopausal osteoporosis. A total of 941 authors have contributed to the field of PMOP-related hormone research, with the top 10 authors each publishing a minimum of 20 articles within the scientific canon. Subsequent to applying a screening criterion that filtered for authors with at least 10 scientific papers to their name, a visual analysis was conducted to construct a network diagram. As depicted in Figure 6 A, authors Bilezikian, John, Khosla, Sundeep, and Eastell, Richard are represented by larger nodes, signifying their prolific contributions to the literature and their status as active figures in PMOP-related hormone research. Their research directions are likely to be influential within the field. The network connections suggest a cooperative relationship between Bilezikian, John, and Khosla, Sundeep, whereas Eastell and Richard do not appear to have collaborative ties with the former duo. Although there is evidence of collaboration among other authors, these connections are not extensively intertwined. (A) Authors of relevant hormone studies in patients with PMOP. Nodes in the figure represent the author. The larger the number of papers, the larger the node; the color of the node represents the year; the collaboration between authors is represented by the lines between nodes, and the more lines there are, themore closely the author works with other authors. (B) Co-cited authors of related hormone studies in PMOP. The color of the nodes in the figure represents the year. The node represents the cited author. The larger the node, the higher the co-occurrence frequency of the cited author. The line between the nodes represents the co-cited relationship between the 2 cited authors. PMOP = postmenopausal osteoporosis. In a cohort of 252 co-cited authors, 11 have been cited more than 900 times, with Cummings (n = 1581), Anonymous (n = 1555), and Kanis (n = 1487) leading in citation frequency. This indicates that the scientific contributions of these 3 authors are highly representative and have garnered significant attention within the research community. By selecting authors with a minimum of 200 citations, a co-citation network was mapped. Figure 6 B illustrates a rich interconnectivity among these authors, indicative of robust collaborative relationships, such as those observed between Rossouw and Greenspan, and Khosla and Rosen. These connections are instrumental in facilitating both the horizontal expansion and vertical deepening of research within the field. For further details, refer to Table 3 , Figure 6 A, B. Top 10 authors and co-cited authors of related hormone studies in PMOP. PMOP = postmenopausal osteoporosis. Between 2004 and 2024, the field of PMOP research referenced a cumulative total of 1,59,139 articles within the scientific discourse on hormonal studies. Within the stratum of the top 10 most frequently cited scientific studies, [ 10 - 19 ] each has garnered a minimum of 119 citations. Notably, the publication “Rossouw JE, 2002, JAMA-JAMMEDASSOC” [ 10 ] secured the premier position, amassing 327 citations – a figure significantly exceeding that of other entries. This substantial citation count underscores the study’s widespread acknowledgments and influence among scholars in the domain of PMOP-related hormone research. For the construction of a visual network diagram, we have identified and included scientific literature with citation counts exceeding 70. As delineated in Figure 7 , a robust co-citation nexus is evident among numerous studies. Specifically, the works “Saag KG, 2017, NEWENGLJMED” and “Miller PD, 2016, JAMA-JAMMEDASSOC,” as well as “Cosman F, 2016, NEWENGLJMED” and “Cummings SR, 2009, NEWENGLJMED,” demonstrate affirmative co-citation relationships. For a detailed examination of these interconnections, refer to Table 4 and Figure 7 . Top 10 cited studies of PMOP-related hormones. PMOP = postmenopausal osteoporosis. Co-cited references of related hormone studies in PMOP. The color of the nodes in the figure represents the year. The nodes represent the cited literature, and the node text represents the first author (publication time) of the cited literature. The larger the nodes, the greater the co-occurrence frequency of the cited literature. The lines between the nodes represent the co-citation relationships between the 2 cited studies. Emergence analysis is a critical approach that scrutinizes the notable fluctuations in citation patterns of specific scientific literature over time, thereby reflecting the prevailing interests and focal points of researchers within the realm of hormone-related research in PMOP during particular periods. Utilizing CiteSpace, we identified 25 scientific studies exhibiting pronounced citation emergence and compiled their titles for in-depth analysis. [ 10 - 14 , 19 - 34 ] As illustrated in Figure 8 , the surge in citations for this body of scientific literature spans from as early as 2004 to as recently as 2020. A study with a particularly high citation frequency is Rossouw JE’s ““Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial,” which registered an intensity of 138.22. This study was cited earlier, between 2004 and 2007, and with greater frequency than other works, suggesting its significant impact and authoritative status among researchers in this field. The second most frequently cited study pertains to the impact of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis, with an intensity of 85.71, and its period of citation emergence was also relatively early, extending from 2004 to 2006. Based on the data presented in Figure 8 and Table 5 , the average citation intensity for these 25 highly emergent scientific studies is approximately 46.95, with the duration of this intensity typically ranging from 3 to 6 years. For further details, refer to Figure 8 and Table 5 . Topics of 25 scientific studies that strongly emerged in PMOP-related hormone studies. PMOP = postmenopausal osteoporosis. Top 25 scientific papers with the highest citation frequency of related hormone studies in PMOP. In the figure, “Reference” stands for scientific literature, “Year” stands for the year when the keyword first appeared, “Strength” stands for emergence strength, “Begin” and “End” stand for the start and end years of the literature as the research frontier, respectively, and the lines in the figure represent the time span from 2004 to 2024. The light blue line represents the time period when the literature was not cited, the dark blue line represents the time period when the literature was cited, and the red line represents the time period when the literature was a research hotspot. PMOP = postmenopausal osteoporosis. In scholarly literature, keywords serve as pivotal descriptors. They encapsulate the essence of the research content and act as a conduit between the literature, its readers, researchers, and database retrieval systems. Keyword co-occurrence analysis is a valuable tool for swiftly identifying the focal points of research within a specific domain. From the corpus of research on hormones related to PMOP spanning the past 2 decades, a total of 7252 keywords were extracted. A background network visualization analysis was conducted on keywords with a co-occurrence frequency of at least 300, as depicted in Figure 9 . The prominence of certain keywords, such as “vertebrate alfacts,” suggests a broad scope of investigation in the field of PMOP-related hormones, attracting considerable research attention. The compilation of the top 10 keywords by frequency and centrality reveals that “postmenopausal women” (n = 3664) is the most prevalent, followed by “bone mineral density” (n = 2581) and “mineral density” (n = 1805). In terms of centrality, the leading terms are “postmenopausal” (0.2), “isoflavones” (0.17), and “eralpha” and “hotflushes” (0.13). By considering both the co-occurrence frequency and centrality of keywords and excluding those directly related to the overarching theme, the core keywords for PMOP-related hormones were identified as “alendronate,” “oxidative stress,” and “D deficiency.” For a detailed visualization and breakdown, refer to Figure 9 and Table 6 . Top 10 keywords in terms of the frequency and centrality of related hormone studies in PMOP. The centrality values are rounded to 2 decimal places. A value of 0 indicates that the original centrality degree of the node is <0.01. PMOP = postmenopausal osteoporosis. Co-occurrence of keywords in related hormone studies in PMOP. Nodes in the figure represent keywords, and the more keywords that appear, the larger the node; the color of the node represents the year; the lines between nodes represent the co-occurrence relationship between keywords, and the more lines represent the more times that the keyword and other keywords appear in the same literature. PMOP = postmenopausal osteoporosis. Keyword emergence analysis is a critical method for tracking the temporal shifts in citation frequencies of specific keywords, thereby providing insights into the evolving research foci within a field over time. In this study, we identified the top 25 keywords demonstrating the most pronounced emergence patterns. As illustrated in Figure 10 , the keyword “estrogen plus progestin” emerged early, with citations rapidly increasing from 2004 and peaking in 2008. This trend suggests that these hormones were among the first to garner substantial research interest in the domain of PMOP-related hormonal research. Research on strontium ranelate, while initiated in 2004, truly emerged as a significant keyword between 2009 and 2014, potentially indicating substantial progress or breakthroughs in this area during those periods, drawing considerable researcher attention. Denosumab, which entered the field in 2009, began to show significant emergence from 2016 through 2024, suggesting its potential to play a substantial role in PMOP-related hormonal studies post-2016, with an anticipated continued increase in future research. The keyword “oxidative stress,” introduced in 2005, did not peak until 2020, when it was cited en masse, indicating a possible major breakthrough in oxidative stress research in 2020 that captured the interest of the research community. Lastly, “romosozumab” and “gut microbiota” were the most recent keywords to gain attention in 2019 and 2020, respectively, with their emergence continuing to the present, suggesting their recent recognition as relevant topics in this field and highlighting the need for ongoing research expansion in these areas. For a visual representation of these trends, see Figure 10 . Top 25 outburst charts of literature keywords in related hormone research fields in PMOP. Keywords in the figure represent the year when the keyword first appeared. Strength represents the emergence strength. Begin and End represent the start and end years, respectively, when the keyword was used as the research frontier. Lines in the figure represent the time span from 2004 to 2024. The dark and light blue lines represent the periods when the keyword does not appear and the periods when it appears, and the red lines represent the periods when the keyword appears as a research hotspot. PMOP = postmenopausal osteoporosis.

In this investigation, we employed bibliometric methodology to perform both qualitative and quantitative analyses of the scientific literature pertaining to hormone research in PMOP. Utilizing CiteSpace as our analytical software, we reviewed the research milestones and advancements within this domain. Our analysis encompassed a quantitative and visual examination of annual publication volumes, contributing countries and institutions, publishing venues, authorships, as well as associated literature and keywords. From 2004 onwards, a total of 7253 papers have been published in this field. A notable surge in publication numbers was observed between 2017 and 2018, potentially signifying significant breakthroughs in PMOP-related hormone research that heightened scholarly interest. Over the past 2 decades, however, the annual average of published papers has remained consistently around 340, suggesting a sustained level of research engagement in this area. Among the nations engaged in PMOP-related hormone research, the United States and China hold dominant positions, with the United States leading globally in scientific literature output, nearly doubling the publication count of China, which ranks second. Furthermore, the United States tops the world in terms of the quality of its published scientific literature, indicating a relative advancement in the field of PMOP-related hormones. Interestingly, the UK’s published scientific literature quality is on par with that of the US, despite a considerably lower publication volume, suggesting that while PMOP-related hormone research in the UK may have had a later start, its progress has been rapid. As China’s investment in scientific research funding grows, so too does the quality of its research output, gradually aligning with international standards in PMOP research. The slight lag in China’s research may be attributed to differences in population structure among countries. European and American countries, compared to Asian nations, have encountered the challenges of an aging society more swiftly, which has indirectly spurred the development of PMOP-related hormone research. Representing a significant demographic shift, developing countries like China are also progressively facing the implications of an aging population. Consequently, since 2017, research on PMOP-related hormones in developing countries has garnered increased attention, emerging as a formidable force in this research arena. In comparison to the Institut National de la Santé et de la Recherche Médicale (Inserm) and Harvard University, the collaboration between scientific research institutions is instrumental for the sustained advancement of academic inquiry. Despite the existence of inter-agency partnerships, the extent of collaboration remains suboptimal. For instance, the limited cooperation between US and Chinese institutions partially impedes the swift progression of this field. Consequently, we advocate strongly for enhanced cooperation and exchange among all research institutions to collectively foster the development and advancement of PMOP-related hormone research. This study’s publication in the Journal of Osteoporosis International (IF = 4.0) underscores its standing as a prominent journal within the current landscape of this field. The Journal of Bone and Mineral Research (IF = 6.2) exerts the most significant impact, complemented by its highest citation frequency and the second-highest number of citations, attesting to its esteemed position in PMOP-related hormone research, favored by a broad spectrum of researchers. The preponderance of high-impact, JCR Region 1 and 2 journals among the co-cited publications signifies their international quality and substantial support for research on PMOP-related hormones. Furthermore, the clustering of PMOP-related hormone studies in journals spanning cytology, molecular biology, histology, endocrinology, and medical and clinical domains indicates that the field has reached a mature phase of development, encompassing both foundational experimental research and clinical treatment applications. Prominent authors in the realm of PMOP-related hormone research include John Bilezikian, Sundeep Khosla, and Richardson Eastell, each contributing over 30 articles to the scientific discourse. Cummings stands out among co-cited authors, with an impressive 1581 citations, reflecting his significant impact on the field. A search of the WoSCC database reveals that Cummings has published a total of 635 scientific papers, primarily focusing on the influence of endocrine and metabolic mechanisms on osteoporosis. This body of work has laid the theoretical and experimental groundwork for the study of PMOP-related hormones, earning widespread attention and citation among researchers. Co-cited literature, which refers to scientific documents that are concurrently cited by multiple studies, is indicative of foundational research within a specific domain. In this study, we identified the top 10 most frequently cited scientific studies to establish a benchmark for the field of PMOP-related hormone research. Notably, Rossouw et al’s 2002 publication, “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial,” cited 327 times, significantly outstripping other literature. This study revealed that long-term estrogen and progestogen therapy substantially increases the risk of cardiovascular disease, thereby enriching the research foundation for the use of hormones in the prevention and treatment of PMOP and stimulating further advancements in the field. Subsequent influential topics in the scientific literature encompass the therapeutic relationship between parathyroid hormone (1–34) and PMOP, the interplay between the parathyroid gland and alendronate sodium and their therapeutic effects on PMOP, the fracture risk reduction associated with estrogen therapy, the therapeutic efficacy of abaloparatide on PMOP, the significant treatment effects of denosumab combined with alendronate on PMOP, the substantial improvement in fracture risk conferred by romosozumab, the enhancement of PMOP outcomes by romosozumab in combination with alendronate, the capacity of zoledronic acid to improve bone mineral density in PMOP patients, and the inhibitory effect of alendronate sodium on parathyroid therapy. These highly cited scientific studies have undoubtedly provided a new foundation and reference point for the study of PMOP-related hormones. By integrating citation analysis, keyword analysis, and literature review, we have identified treatment as the paramount direction in the field of PMOP-related hormone research, with oxidative stress, vitamin D deficiency, and romosozumab emerging as key research foci within this therapeutic paradigm. Building upon these findings, our study delves into the intricate mechanisms and potential avenues of investigation concerning the interplay between hormones and PMOP. Estrogen, progesterone, parathyroid hormone, and other hormonal agents are known to facilitate early osteoblast differentiation, enhance collagen activity, and suppress osteoclast activity within the human body. [ 35 ] The onset and progression of PMOP are attributed to rapid fluctuations in hormone levels, leading to an imbalance between bone resorption and bone formation. [ 36 ] Numerous studies have corroborated the close correlation between hormone levels and the development of PMOP. [ 37 , 38 ] Oxidative stress, characterized by an imbalance between oxidative and antioxidant processes, has been widely recognized as a significant pathogenic factor in bone metabolic diseases. [ 39 ] The accumulation of reactive oxygen species triggers oxidative stress, leading to cellular senescence, aberrant differentiation, and apoptosis, thereby adversely affecting bone cells and compromising bone homeostasis. [ 40 ] Notably, our bibliometric analysis revealed that “oxidative stress” emerged as a prominent research hotspot around 2020, with a burst strength of 19.24 (Fig. 10 ), indicating a sharp increase in scholarly attention and reflecting its growing importance in PMOP-related hormone research. Evidence suggests that hormones can modulate redox homeostasis by regulating reactive oxygen species production, with oxidative stress often occurring in response to fluctuations in hormonal levels. [ 41 ] The strong co-occurrence of keywords such as “estrogen deficiency” and “oxidative stress” in our cluster analysis (e.g., cluster #8) further supports the interrelationship between hormonal dysregulation and oxidative damage in PMOP pathogenesis. However, a review of the literature [ 42 , 43 ] indicates that there remains a relative paucity of studies exploring the prevention and treatment of PMOP through the targeted modulation of oxidative stress by hormonal interventions – particularly beyond the scope of estrogen. The recent surge in related publications, as captured by our emergence analysis, highlights an accelerating research effort to fill this gap. Our findings suggest that hormonal levels may influence the systemic redox state, thereby contributing to PMOP progression – a hypothesis that warrants further experimental validation. Elucidating the specific mechanisms by which hormones affect PMOP through oxidative stress regulation thus represents a critical and timely direction for future research. Vitamin D, a micronutrient metabolized into a multifunctional steroid hormone, plays a broad role in biological functions within the body. [ 44 ] Studies indicate that changes in hormonal levels can impact vitamin D absorption. [ 45 ] Vitamin D is intricately linked to calcium and phosphorus metabolism, with the majority stored in the body as 25-hydroxyvitamin D (25(OH)D). [ 46 ] In cases of vitamin D deficiency, insufficient 25(OH)D levels can diminish the body’s efficiency in inducing calcium synthesis, reduce calcium ion absorption in the small intestine, impede the renewal of calcium salts and new bone formation, inhibit phosphorus absorption and the renal tubular reabsorption of calcium and phosphorus, thereby lowering blood calcium and phosphorus levels, which is detrimental to new bone formation and calcification. [ 47 ] Similar to oxidative stress research, there is a dearth of studies on the prevention and treatment of PMOP by modulating hormonal levels to ameliorate vitamin D deficiency. Unveiling the molecular mechanisms underlying these interactions will constitute a significant avenue for future investigative efforts. Romosozumab, a humanized monoclonal antibody and the most advanced sclerostin inhibitor, antagonizes the negative regulatory function of sclerostin on bone metabolism, thereby promoting osteoblastic bone formation and suppressing osteoclastic bone resorption. [ 48 ] Our bibliometric analysis highlights romosozumab as a key emerging research focus, with the keyword demonstrating a strong citation burst (strength:23.59) since 2019, reflecting its growing importance in PMOP therapeutics. As a class, sclerostin antibodies are known to positively regulate bone metabolic balance and stimulate bone formation. [ 49 ] At the genetic level, these antibodies reduce DNA double-strand breaks and facilitate DNA repair mechanisms through upregulation of KU70 protein expression, thereby attenuating osteoblast apoptosis. [ 50 ] Previous studies have demonstrated that sclerostin antibodies enhance osteoblast proliferation and differentiation while inhibiting apoptosis, which indirectly leads to reduced osteoclast activity. [ 51 ] Mechanistically, sclerostin antibodies block the binding of sclerostin to LRP5/6 co-receptors, thereby mitigating its inhibitory effect on the Wnt signaling pathway. [ 52 ] As a specific sclerostin-neutralizing antibody, romosozumab selectively binds sclerostin, prevents its interaction with LRP5/6, and exerts a dual-acting regulatory effect on PMOP, combining both bone-forming and antiresorptive properties. [ 53 ] This is further supported by several landmark clinical trials, such as those by Cosman et al and Saag et al, which are among the most frequently co-cited references in our analysis, underscoring the foundational role of these studies in shaping current research directions. At present, this agent has not received regulatory approval in China, and there remains a notable scarcity of domestic clinical studies and evidence-based reports. Consequently, investigating the mechanisms through which romosozumab influences PMOP progression via hormonal pathway modulation may become a central research focus for future therapeutic strategies and prevention of PMOP. Employing CiteSpace software, this study conducted a visual analysis of the scientific literature on PMOP-related hormones within the WoSCC database. A comprehensive examination was performed, encompassing the number of publications, contributing countries and institutions, publishing journals, journal co-citations and clustering, authorships, co-citations, literature co-citations, literature emergence, keyword co-occurrence, and keyword emergence. This analysis spanned the global research landscape on PMOP-related hormones over the past 2 decades. The study revealed complex interrelations between hormones and PMOP, involving multiple facets such as mechanisms, therapeutic products, and molecular targets. It is imperative to delve into the specific preventative and treatment strategies for PMOP, as well as the pathogenesis of related hormones. The impact of modulating hormone levels to mitigate oxidative stress and vitamin D deficiency on the onset and progression of PMOP warrants further investigation. Additionally, the manner in which romosozumab regulates related hormones to enhance the therapeutic efficacy of PMOP is a potential area of exploration. Investigating the mechanisms underlying clinical applications may represent a future research direction and trend in this field. As research intensifies and technology advances, it is anticipated that more groundbreaking findings will emerge, leading to significant contributions to human health. Although this study utilized bibliometric methods to reveal the macroscopic picture of hormone research in PMOP, it still has some inherent limitations. The data used in this study were solely sourced from the WoSCC, which is an authoritative database in this field. However, it does not cover all the journals in PubMed, Scopus, Embase, etc, and some regionally important journals may be omitted. Additionally, we only included English-language literature, which may have overlooked valuable research results published in other languages, resulting in a certain deviation in the portrayal of global research activities. Moreover, bibliometric analysis heavily relies on data accuracy. Although we have tried our best to clean and merge author names and institution names, we still cannot completely avoid errors caused by variations in author name spellings and differences in institution abbreviations, which may have a slight impact on the precise measurement of the output of specific authors or institutions. The cornerstone of this study’s methodological analysis is citation data, but citation behavior is influenced by various factors and is not solely an embodiment of academic influence. There is a “citation lag” phenomenon, where some foundational classic studies will remain in high citation positions for a long time, which may cause certain emerging frontier trends to be relatively weakened in the co-cited network. Moreover, non-quality factors such as journal prestige and author popularity also affect citation rates. Future research can consider incorporating data from multiple languages and multiple databases, combined with content analysis for a more in-depth qualitative interpretation, to make up for the shortcomings of pure quantitative analysis, thereby obtaining a more comprehensive and 3-dimensional understanding.

Thanks to the corresponding author for guidance and to all the providers in the study data.