Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that outputs in a pulsed wave mode, with energy intensity significantly lower than traditional ultrasound (1). LIPUS is considered a promising technology and has been widely applied in various clinical treatments and basic research (2). Its low frequency, low energy, and non-thermal effects have attracted the attention of numerous scholars (3). Increasing evidence shows that LIPUS can effectively stimulate osteoblasts, promote bone formation, and activate other stem/progenitor cells (4). LIPUS can enhance the vitality, proliferation, and multi-directional differentiation of various postnatal mesenchymal stem cells (MSCs) (2). Moreover, it can reduce the expression of pro-inflammatory cytokines, limit the infiltration of inflammatory cells, and regulate the phenotype of inflammatory cells (5). These beneficial changes may be related to increased blood flow, activated mitochondrial biogenesis, and anti-oxidative stress to promote muscle healing (6–8). Currently, LIPUS has been extensively used in tissue repair and regeneration, fracture healing, and inhibition of inflammatory responses. Additionally, it has significant potential therapeutic value in the field of urology, including chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (9), erectile dysfunction (ED) (10, 11), stress urinary incontinence (SUI) (12), as well as gynecology, including premature ovarian insufficiency (13) and incomplete uterine involution (14).

Bibliometrics is a method of literature analysis that utilizes quantitative and qualitative perspectives to quantify and visualize published literature, thereby facilitating the evaluation of intrinsic connections and distribution patterns within research literature (15, 16). It offers a comprehensive and systematic assessment of the present research status, while also identifying potential avenues for future research within targeted fields. Bibliometrics effectively integrates information throughout the research process, enhances understanding, and assists in the deepening of knowledge regarding specific research areas (17, 18). It has been noted that there is currently a lack of bibliometric analysis focusing on the recent cooperation and research trends of LIPUS, with a focus on endocrinology and metabolism. Therefore, we conducted a systematic search of LIPUS-related literature in the Web of Science Core Collection (WoSCC) database and performed a comprehensive bibliometric analysis to clarify its current research status. We also combined with the latest published literature to analyze the research hotspots of LIPUS in the field of endocrinology and metabolic diseases to gain insights into future research directions in this field.

In this global study, we conducted bibliometric analysis to summarize the collaboration network, research trends and hotspots, as well as future directions of LIPUS research. A total of 655 records were retrieved and published in 292 journals by 2973 authors from 794 institutions in 46 countries/regions. This is the first systematic study using bibliometric methods to analyze the development patterns of LIPUS over the past decade and analyze its research in the field of endocrine and metabolic diseases, which will guide its future development direction.

The results of this study indicate that China has the highest number of publications (n=295), followed by the United States (n=125), Japan (n=112), Canada (n=55), and South Korea (n=25), suggesting that LIPUS-related research is still relatively dominated by developed countries, which also reflects the correlation between scientific research, economic investment, and national social economy. The citation frequency of published articles can represent the academic influence of the results to a certain extent. Currently, China (n=4531), the US (n=2332), Japan (n=1555), and Canada (n=1024) have the highest total citation frequencies, consistent with the publication ranking. However, in terms of the average citation frequency of published articles, the top five countries are the Netherlands, France, Italy, the UK, and Germany, indicating that these countries may have higher academic influence in this field.

Regarding the distribution of patterns of institutions publishing relevant research and their national origins, the overall trend is consistent. In terms of the number of publications, four of the top five institutions are from China, namely Chongqing Medical University (n=52), Chinese Academy of Sciences (n=28), China Medical University (n=19), and Nanjing Medical University (n=17), while the other is the University of Alberta in Canada (n=34). Moreover, Chongqing Medical University has the highest total citation frequency of published articles (n=698) worldwide. Scholars planning to conduct LIPUS-related research should pay close attention to the academic achievements of this institution in the future.

In terms of author distribution, Tarek El-Bialy ranks first with 21 publications, focusing on the application of LIPUS in oral medicine-related areas such as the maxilla, mandible, alveolar bone, and orthodontics (19–24). Feng-Yi Yang and Yan Wang follow closely with 17 publications each. Feng-Yi Yang has the highest total citation frequency and primarily focuses on combining LIPUS to treat neurological disorders. He proved that LIPUS stimulation can be a potential therapeutic method by accelerating myelin regeneration through weakening glial cell activation, enhancing mature oligodendrocyte density, and increasing the production of BDNF (25). Abdominal LIPUS stimulation can combat neuroinflammation by enhancing tight junction protein levels and inhibiting colonic inflammation (26). LIPUS stimulation can serve as a potential therapeutic tool against Parkinson’s disease, possibly combined with its neural regenerative and protective effects (27, 28), and has therapeutic effects on erectile dysfunction caused by cavernous nerve injury (29). The scholar with the highest average citation frequency is Professor Andrew Harrison from The Chinese University of Hong Kong. His main academic contributions include exploring the effects of different therapeutic ultrasound intensities on rat fracture healing (30), demonstrating the positive effect of far-field LIPUS on stimulating bone cells and promoting mechanical transmission between bone and osteoblasts (31), summarizing the patterns and mechanisms of LIPUS in repairing fractures and conducting clinical trials of LIPUS in patients with non-healing chronic fractures (32–35). Scholars planning to study relevant research on LIPUS in orthopedics should pay attention to the research progress of Professor Andrew Harrison in the future.

LIPUS has significant clinical value in the treatment of various diseases and has been recognized by numerous high-level journals and editors. Nearly 300 journals have published reports related to LIPUS, with the top three journals in terms of number of published studies being ULTRASOUND IN MEDICINE AND BIOLOGY, ULTRASONICS, and SCIENTIFIC REPORTS, which also have the highest total citation frequencies. The top three journals in terms of average citation frequency are BRAIN STIMULATION, PLOS ONE, and JOURNAL OF ORTHOPAEDIC SCIENCE.

High-frequency keywords and burst words help scholars clarify future research directions in related fields. After keyword network and burst word analysis, we found that LIPUS-related research has gradually progressed from previous growth factors (36, 37), fracture healing (38–41), and integrins (42–44) to fields such as oxidative stress (45), regeneration (46, 47), and tumors (48–50). This suggests that the exploration of molecular biological mechanisms for LIPUS is gradually deepening, and its application areas are gradually expanding to major diseases such as cancer, proving once again the broad application prospects and clinical value of LIPUS.

The value of LIPUS in endocrine and metabolic diseases has attracted increasing attention. Han et al. found that LIPUS could increase testosterone levels in animal models and alleviate Leydig cell aging in vitro ( 51). Furthermore, combining LIPUS with tadalafil effectively treats erectile dysfunction in patients with type 2 diabetes (52), and promotes nerve regeneration and improves erectile function by enhancing Schwann cell proliferation, migration, and expression of neurotrophic factors such as nerve growth factor (53). In terms of bone metabolism, Wu et al. have demonstrated that LIPUS can accelerate osteoblast differentiation and promote bone formation in a rat model of osteoporosis (54), and its ultrasound intensity is closely related to its therapeutic effect on osteoporosis (55, 56). Diabetes is a typical disease caused by glucose metabolism disorder, with a long course and many complications. LIPUS has unique effects in regulating glucose metabolism, and has been extensively studied. It has been shown to prevent muscle atrophy in rats with type 1 diabetes (57), and lower blood pressure in hypertensive patients with type 2 diabetes (58). LIPUS shows potential as a new therapy for type 2 diabetes (59). Our study stands at the forefront of summarizing the role and mechanisms of LIPUS from the perspective of endocrine and metabolic diseases, which will facilitate further research in this field by scholars in the future. However, our search has also revealed that, although research on LIPUS in this field is gradually gaining momentum, there is still significant room for further exploration, particularly in relation to specific diseases. The search results indicate that the most well-established application of LIPUS is in the study of osteoporosis. It has progressed from preliminary research on cellular and molecular mechanisms to practical clinical applications, and has shown promising therapeutic effects. There are also relevant studies on diabetes-related osteoporosis, muscle atrophy, erectile dysfunction, among others. However, research on specific diseases such as thyroid disorders and gout remains limited, with most studies focusing on the cellular and molecular levels, still some distance away from clinical application. However, it is well known that many endocrine and metabolic diseases are influenced by hormonal actions or metabolic disruptions. The specific regulatory mechanisms of LIPUS on substances such as glucose, lipids, hormones, and bone have been extensively documented, providing a foundation for its future clinical applications and driving advancements in the field.

Undoubtedly, this study, like other bibliometric studies, has certain limitations. Firstly, the data source mainly comes from the core dataset of WoSCC and lacks other databases, which may result in some omissions in the data we included. Secondly, the language type set for this study is only limited to English, which may cause relevant research in other languages to be missed. In addition, some newly published research results may be missed due to lack of inclusion in the database. Therefore, in the future, we will continue to update the data, pay attention to other non-English literature reports, and the latest published research.

Through comprehensive bibliometric analysis, we systematically analyzed global research on LIPUS over the past decade. Overall, the number of publications showed a fluctuating upward trend and the annual publication volume has now stabilized at a high level. In recent years, China and the United States have made the greatest contributions to LIPUS research, and their cooperation and exchanges have been the closest. The research interest in LIPUS for endocrine and metabolic diseases is steadily increasing, with a particular focus on areas such as regulation of glucose metabolism, lipid metabolism, and bone metabolism. Furthermore, LIPUS has shown promising applications in various diseases, with osteoporosis serving as a notable example. Based on the current development trend, it is expected that research on LIPUS will continue to increase globally, and exploring the related molecular mechanisms of LIPUS and expanding its clinical applications will be the future direction of research, especially in the field of endocrine and metabolic diseases.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

GC designed the whole study, analyzed the data and drafted the manuscript. HN revised the manuscript. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version.