Bibliometric Analysis of the Hundred Most-Cited Publications on Bone Metastases Research

Abstract

Background

Bone metastases (BM) represents a common complication of cancer, patients with BM may experience skeletal complications, such as pathological fractures, spinal cord compression, hypercalcemia, and persisting pain. Currently, there are a large number of publications available on this topic. The purpose of this study was to identify and analyze the 100 most-cited publications on BM research.

Method

All databases from the Web of Science were searched in a three-step approach. First, the 100 most-cited BM studies were identified using only one term “bone metastases” to allow for comprehensive keyword identification. Second, ten keywords identified from the results of the first search were used to conduct a second search of the databases to yield a separate list of the top 100 cited BM publications. Finally, the results of the two searches were overlapped and duplicated articles were removed. After overlapping, the top 100 most-cited articles on BM were selected for further analysis of title, authorship, source journal, publication year, geographic origin, research institution, number of citations, and subspecialty.

Results

The 100 most-cited articles were published from 1959 to 2014 in 44 different journals and were cited from 250 to 1707 times. The most influential period was from 2001–2010, which produced 50 out of the top 100 publications. A total of 12 countries contributed to the 100 articles, and the United States topped the list with 48 articles. The majority of publications were in Journal of Clinical Oncology, which published 16 articles. In terms of institutional support, a total of 13 institutions each supported at least 2 articles, and the first ranked institution was University of Texas M. D. Anderson Cancer Center (USA) with 8 articles. Regarding subspecialty of the studies, the most frequent studies were “clinical description” with 30 articles, followed by “clinical trial” with 20 articles.

Conclusion

In this comprehensive review, we identified and analyzed the 100-most-cited articles on BM research by measuring their citation number, and recognized some of the most important contributions by authors, institutions and countries. Furthermore, our study will help researchers and orthopedic surgeons understand the research trends for BM and as an efficient guide for future BM-related research. 

Introduction

Bone metastases (BM) represents a common complication in the most prevalent human cancers, whose incidence reaches 70–95% in multiple myeloma (MM), up to 65–90% in prostate cancer (PC), 65–75% in breast cancer (BC), 17–64% in lung cancer (LC), and 10% in colorectal cancer (CC) [1-4]. Patients with BM may experience skeletal complications including pathological fractures, hypercalcemia, spinal cord and nerve compression syndromes, and uncontrolled pain that require orthopedic surgery or/and radiotherapy, collectively referred to as skeletal-related events (SREs) [5,6]. These events seriously affect the quality of life (QoL) of patients and patient survival rates [7]. Therefore, the major treatment options for BM patients aim at improving the QoL and reducing SREs. Currently, BM treatments include loco-regional and systemic approaches. The former, mainly represented by focal excision and radiotherapy, are usually performed to relieve bone pain and to prevent pathological fractures. The latter mainly include anabolic agents, inhibitors of bone resorption and radiopharmaceuticals that aim at restoring severely impaired physiological bone turnover in metastatic bone disease patients [8].

In recent years, with the emergence of imaging techniques with improved sensitivity and specificity in the detection of bone injury, the early diagnosis of BM has significantly improved [9]. The diagnosis and management of BM has also gained much interest among surgeons, similarly, fundamental scientific research has also made major breakthroughs in understanding the mechanism involved in the development of BM. Concomitantly, a large number of studies regarding BM have been published.

Bibliometric analysis is a widely accepted approach for identifying high impact scientific studies on medicine and to quantitatively and qualitatively evaluate its academic impact [10,11] This analysis method has been widely performed in the field of orthopedic surgery [12-16]. To the best of our knowledge, there have been no reports on bibliometric analysis on BM to date. Therefore, our objective was to identify the top 100 most-cited studies on BM, and to analyze the characteristics and research trends of the most impactful publications. This bibliographic analysis will augment efforts in research consensus and will enable researchers to better align their research direction to address the issues that require additional research due to the lack of evidence and to tailor their future research on BM.

Materials And Methods

Inclusion Criteria

All available journals from the Web of Science database were searched to identify and analyze the 100 most-cited articles on BM between 1950 and 2020. To be considered for the top 100 list: (1) papers had to focus on the field of BM; (2) papers should be written in English; and (3) the publication date should be between the 1950 and 2020.

Exclusion Criteria

The exclusion criteria included: (1) papers that focused on broad areas with no emphasis on BM; and (2) papers focused on primary bone/spinal tumor.

Search strategy and study selection

As of 5 July 2020, we identified the 100 most-cited BM research studies published between 1950 and 2020, excluding non-English language studies. In order to achieve a higher comprehensiveness and accurateness of the study, a three-step approach was adopted to search the databases of the Web of Science, as shown in the flow chart in Figure 1.

First, the Web of Science databases was searched using the keyword “bone metastases.” The search produced 85,957 results, which were then ranked in descending order of the total number of citations. In the initial 1200 studies identified, the 100 most-cited papers on BM were selected based on titles and abstracts. The aim was to provide a more comprehensive study of BM, and the title and abstract of the identified 100 studies were systematically analyzed for possible keywords. Combined with other keywords known to be relevant to the field of BM research, a search query composed of a group of 10 keywords was established and used for a second database search by topic. The 10 keywords identified were “bone metastases,” “bone metastasis,” “metastatic bone disease,” “skeletal metastases,” “spinal metastases,” “spinal metastasis,” “metastatic spine disease,” “osseous metastases,” “osteolytic metastases,” and “osteoblastic metastases.”

Second, every search word or phrase was delimited by an OR term, by this means, additional search results were obtained. The second search showed 105,159 results, again were ranked these in descending order of the total number of citations. Of the top 1000 preliminary studies, 100 articles related to BM were selected based on titles and abstracts.

Third, the studies of the two selections were compared, and duplicate studies were removed and the 100 most-cited BM studies were selected for finally analysis.

To ensure consistency of data extraction, two independent authors evaluated the articles for their relevance to BM and the 100 most-cited articles on BM were finial determined. Finally, the 100 most-cited articles were then extracted with regard to basic information including: title, authorship, source journal, publication year, geographic origin, research institution, number of citations, and subspecialty.

Statistical Methods

All data were manually extracted from the Web of Science database and recorded in Microsoft Excel 2016 or further analysis or visualization. VOSviewer (Leiden University, Leiden, the Netherlands) is a commonly used software tool for creating maps for network analysis and visualization. In this study, this software was used to visualize the relationships and the time distribution between the most frequently occurring concepts and keywords.

Results

Overview of publications

The 100 most-cited articles involving BM research were cited from 250 to 1707 times in 44 different journals and the mean citation number was 467.5 (Table 1). “A multigenic program mediating breast cancer metastasis to bone,” published by Kang et al., was the most-cited article (cited 1707 times). The earliest published article was “Experiences with metastatic neoplasms involving the spinal cord,” which was published in 1959 by Barron et al. (cited 312 times). The most recent article was “Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: Results from a phase 3, double-blind, randomised trial,” published by Sartor et al. in 2017 (cited 312 times).

Country of publications

The top 100 articles originated from 12 different countries. Authors from the United States contributed 48 articles. European centers from ten countries published 34 articles in total. Among these, 10 articles were from the United Kingdom, 8 articles were from France, 3 articles were from Italy, Sweden, and The Netherlands, 2 articles were from Switzerland and Belgium, and 1 article was from Austria, Denmark and Germany. Authors from Asia and Africa published relatively fewer articles compared to the United States and Europe. Authors from Japan published 5 articles, and Israel 1 articles, respectively. Besides, authors from Canada and Australia published 10 and 1 articles, respectively.

Year of publication

The publishing period responsible for the largest number of studies was 2001 to 2010 with 50 articles, followed by 1991 to 2000 with 24 articles, 1981 to 1990 with 11 articles, 2011 to 2014 with 10 articles, and the period 1971 to 1980 with 3 articles (Figure 3). Notably, only 2 articles were published before 1970.

Journals of publications

Overall, 44 different journals were represented on the list of the 100 most-cited studies (Table 2). The Journal of Clinical Oncology was the most popular journal, which was responsible for 16 articles and 7218 total citations. This was followed by Cancer with 10 articles with 4888 total citations. Cancer Research, Spine, Journal of Neurosurgery, Journal of the National Cancer Institute, and Cancer Cell each with 4, 4, 3, 3 and 3 articles, respectively. Although there were only 2 articles on the list which were published in Lancet, their mean citations per article was the highest (1106 times per article).

Authors of publications

Regarding the authors, A Lipton was the most productive author with 11 articles in total, followed by R. E. Coleman with 11 articles. J. E. Brown, G. N. Hortobagyi, F. Saad, J. J. Seaman, J. J. Body, and L. S. Rosen, with 5 articles each (Table 3).

Institutions of publications

In terms of institutional support, a total of 13 institutions each supported at least 2 articles (Table 4). The first ranked institution was the University of Texas M. D. Anderson Cancer Center (USA) with 8 articles. The second top ranked institution was Weston Park Hospital with 5 articles. The Memorial Sloan-Kettering Cancer Center (USA), and the University of Toronto (Canada) were tied for third with 4 articles each.

Subspecialty of publications

Regarding the subspecialty of the studies, the most frequent studies were “clinical description” (n=30), followed by “clinical trial” (n=20), “mechanism” (n=16), “drug efficacy” (n=11) “radiotherapy” (n=7), “evaluation” (n=5), “surgery treatment” (n=4), “detection” (n=3), “murine model” (n=2), and “prediction” (n=2) (Figure 4).

Keyword analysis of publications

As shown in Figure 5, the 28 terms (defined as being used more than 6 times within titles and abstracts in all of the articles) were classified into 3 clusters: “clinical trial”, “clinical features”, and “basic research”. Among the “clinical trial” cluster, keywords used in the top articles were listed as follows: trial (30 items), time (26 items), event (23 items), week (22 items), and spinal cord compression (20 items). For the cluster of “clinical features”, the primary keywords were as follows: treatment (61 items), survival (29 items), pain (29 items), year (27 items), and site (21 items). In the “basic research” cluster, the primary keywords were as follows: cell (35 items), factor (25 items), breast cancer (25 items), effect (24 items), and therapy (22 items).

As shown in Figure 6, VOSViewer assigned colors to keywords according to the average year in which they appeared in the article. In the early stage of BM research, both the biological and clinical fields were the main hotspots. In the early stage of BM research, treatment of BM was the main hotspot. Recent trends showed that the words “SRE”, “zoledronic acid”, “hazard rate”, “denosumab”, and “intension” appeared as keywords articles after 2006. There was most of the key words appear in the “clinical trial” cluster.

Discussion

The present bibliometric analysis determined and characterized the 100 most-cited publications in the Web of Science databases. After identifying the most-cited research articles, we obtained insight into the historic developmental trends in BM research that reflected the great importance and academic concern placed on the study of BM.

Undoubtedly the publishing date will affect citation numbers, the longer periods after the article is published allows for a greater opportunity to be cited. In our study, the most productive period was from 2001 to 2010 with 50 articles. However, only 2 articles were published before 1970. This indicates that the improvement of BM research quality and efficiency promoted an increase in papers and citations in recent years. Notably, no top-cited articles were published after 2015 in our current analysis. We speculated the following possible reasons for this: firstly, because BM has always been a hot research field for researchers and orthopedic surgeons, numerous high-quality articles have already been published, although, we have only included the top 100 most-cited articles, therefore, articles with relatively fewer citations are not included. Secondly, more recently published articles need time to be cited widely.

In total, 44 different journals published the top 100 most-cited studies, with the Journal of Clinical Oncology contributing most studies, followed by Cancer. It has been reported that major journals can attract high-quality research articles in their fields, maintaining high the impact factors of these journals [17]. Compared with other similar bibliometric studies, top 100 articles have been published in a greater number of journals, while, the most contributive journals have published fewer articles [18,19]. We speculated that this may be related to more high-quality journals in the field of cancer.

Overall, 12 different countries contributed to the top 100 articles, and the most productive country of article origin was the United States, followed by European centers. In contrast, Asia (Japan, Israel) made a relatively small contribution to the 100 most-cited articles, which indicated that there is still a large gap of scientific studies published between Asian countries and western developed areas. Thus, various countries, especially in developing regions, have to endeavor make greater contributions to be integrated into the world scientific processes.

VOSviewer software was used to analyze the keywords of the main subjects of these 100 articles. The 100 most-cited articles extracted from all database of the Web of Science were classified into 3 clusters: “clinical trial,” “clinical features,” and “basic research.” In the clinical trial cluster, “trial” and “time” were the most frequently appearing keywords on the network map. This finding demonstrated that randomized controlled trials investigating drug therapy are a major research direction in the field of BM. In the clinical features cluster, the most frequently occurring keywords included “treatment,” “survival,” and “pain” meaning that the clinical efficacy and prognosis of BM patients have been widely studied. Further, in the basic research cluster, “cell,” “factor,” and “breast cancer” were the most frequently keywords, which illustrated that the research interest was mainly focused on the molecular biology of BM. Generally, molecular mechanisms, treatment, and prognosis were hot topics in the research of BM.

Keyword analysis is an indispensable approach to evaluate the evolution of research hotspots in this field. To the best of our knowledge, this study is the first to visually summarize the evolution of global research trends on BM. Among the 3 keyword clusters “clinical trial,” “clinical features,” and “basic research,” the former is of great interest because of the obvious changes in the research hotspots over the last 20 years. From simple attention to pain control to a series of clinical problems caused by SREs, researchers and surgeons are focusing increasingly on improving prognosis and prolonging the survival of patients with BM [20,21]. In-depth study of the molecular mechanisms, targeted therapies, and immunotherapy have attracted increasing attention, and some studies have led to agents being recommended as first-line drugs by the guidelines, such as denosumab [22]. In addition, in recent years, with the rapid progress of radiotherapy research, especially the emergence of stereotactic body radiation therapy (SBRT), radiotherapy has also received strong research interest from doctors and patients [23,24]. Even so, surgery and chemotherapy still play an irreplaceable role. Thus, it is necessary to review the highly quality articles to understand milestones during the study of BM.

Although this current analysis was relatively comprehensive and objective, it had several limitations. First, the date for literature search was 5 July 2020, theoretically, which could limit the citation numbers by time. Second, besides the Web of Science, Google Scholar and SCOPUS databases could also provide citation data, these databases may display a different number of citations and therefore may provide different analysis results [25].Third, since the top 100 articles selected are limited to English, we might have overlooked high-impact articles in other languages. Finally, some recently published high-quality articles were not included in this analysis due to their low citation frequency.

In summary, despite its limitations, bibliometric analysis remains one of the best methods to quantify the impact of scientific studies and to quantify the contributions of researchers [26,27]. We believe that this study highlights a series of intellectual milestones in BM research. The present study identified influential authors, institutions, countries, and journals that have made outstanding contributions to BM research. Undoubtedly, this study will provide a catalogue of valuable articles for young researchers and will help scientists to master research hotspots and to determined future academic pursuits.

Conclusion

The BM literature has grown continuously over the years. The 100 most-cited publications in BM research were searched and analyzed, and the contribution of the authors and their origins were identified. This article provides insight into the development of BM research, and should contribute to help scientists to grasp the international research hotspots on BM research.

Abbreviations

BM: bone metastases

MM: multiple myeloma

PC: prostate cancer

BC: breast cancer

LC: lung cancer

CC: colorectal cancer

SREs: skeletal-related events

QoL: quality of life

SBRT: stereotactic body radiation therapy

Declarations

Acknowledgements

Not applicable.

Author’s contributions

Conceived and designed the study: Yao Kang and Jun Zhang. Revised the protocol: Tingxiao Zhao and Yuan Zhang. Extracted the data: Jun Lv, Meng Ge and Yazeng Huang. Performed the statistical analysis: Zhanqiu Dai, Haiyu Shao, and Xiaoyan Ding. Wrote the manuscript: Tingxiao Zhao and Yuan Zhang. All authors contributed constructive comments on the paper. The authors read and approved the final manuscript.

Funding

This study was supported by grants from The Graduate Research and Innovation Program of Bengbu Medical College (Byycx1906 to Dr. Tingxiao Zhao ).

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Ethics approval is not required due to this work is carried out on open data.

Consent for publication

Not applicable.

Competing Interests:

The authors declare that they have no competing interests.

Device Status/Drug Statement:

The manuscript submitted does not contain information about medical devices

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