Bibliometric Analysis of Global Research Productivity on Vitamin D and Bone Metabolism (2001–2020): Learn from the Past to Plan Future

Vitamin D has long been known for preserving bone and non-skeletal health. Despite its magnitude of impact, scarce literature has explored the evolution of the relevant published literature. This study aimed at evaluating the trends and performance of Vitamin D and bone metabolism-related publications (2001–2020). All pertinent English language 16,887 articles were searched and extracted from the Web of Science (WoS) database and “R-Bibliometrix” was used for comprehensive analysis. Around 60,149 authors contributed from 114 countries, showing the USA on top with >1/4th of all articles, followed by Japan, China, and the United Kingdom. For authors, Cooper C, Dawson-Hughes B, and Holick MF were found to have written the most articles, citations and highest h-index, respectively. Corresponding authors from the top 20 countries collectively were responsible for around 84% of the articles. Among 2735 sources, Osteoporosis International (632), Journal of Bone and Mineral Research (569), and Bone (448) were foremost. Most prominent sources showed recent declining contributions. The increasing trend of publications with a higher spike from 2008 to 2014, followed by a gradual increase till 2017, was observed. Leading countries, affiliations, and authors showed collaborative publications and were mostly from developed countries with limited contributions, particularly from low- and middle-income countries.


Introduction
Vitamin D (VD) is a lipid-soluble vitamin (a micronutrient) and an essential multifunction bioactive compound for human use [1]. It is not present abundantly in food supplies. It is produced by UV radiation in the skin and is extracted from foods derived from animals (vitamin D3) and plants (vitamin D2) [2,3]. Ultraviolet B (UVB) dermal synthesis exists as the primary means to receiving VD, containing 90% of a VD refill, whereas there are few natural sources of VD, such as various species of fish (salmon, sardines, tuna, mackerel), egg yolk, cod liver oil, organ meat [4]. Nevertheless, the rate of synthesis is impaired by a range of variables, including melanin pigment density; the usage of sunscreen and UV creams and apparel; VD dermal synthesis declines in aging populations due to aging or scarring of the skin; sun-exposure time; the month of the year; and sun-exposure period [5][6][7][8][9]. The VD receptor (VDR), a part of the steroid receptor clan,
King Abdul Aziz University (KAU) online library and digital resources were used to access information. The search strategy was planned after vigilantly selecting the appropriate search terms from literature and having opinions from relevant field experts for its reliability and validity. The topic (TS) field was selected as it comprises the title, abstract, author keywords, and keyword plus terms. Initially, the terms were identified for a) Vitamin D (Vitamin D OR Vit D OR Calcidiol OR Calcifediol OR Calciferol OR 25OHD OR Rickets), as shown in Figure 1 and b) Bone metabolism (Bone metabolism OR Bone OR osteo*). A later search was conducted by merging the abovementioned terms as shown in Figure 1b. In the year 2021, 5437 documents were published for Vitamin D with 3773 articles in English while Vitamin D and Bone metabolism showed 1176 documents with 839 articles. However, documents for the year 2021 were not included or extracted for further detailed analysis.
A total of 23,956 documents were found to be indexed in WoS (2001-2020) on the topic "Vitamin D and Bone metabolism" (Figure 1a,b). English was the most common language (n = 23,153, 96.6%) followed by German (n = 229, 1.3%). Articles were the leading type of document with n = 17,609 representing 73.5% of all documents followed by reviews (n = 3979, 16.6%) and meeting abstracts (n = 1579, 6.6%). Some information such as the type of documents, research areas, web of science categories (WC) were extracted using the intrinsic WoS data analyzer function.
For detailed analysis, all articles in the English Language (n = 16,887) were extracted in plain text files from WoS, as shown in Figure 1b. Two researchers (AAM and MB) independently searched and extracted articles to verify the process on the same day (1st October 2021). Later, for detailed analysis, the R-Bibliometrix package [44] was used. Among several tools used in scientometrics to evaluate research performance, R-Bibliometrix is considered to provide comprehensive analysis using an extensive range of indicators at documents, authors, and sources levels.

Results
The search strategy yielded a total of 16,887 articles from 2735 sources on the topic of VD and bone metabolism, as shown in Table 1. The total number of authors was 60,149. The majority of the articles were multi-authored, while 4.5% (756) were single-authored articles contributed by <1% (577) of total authors. Open access articles were 44.5%. The collaborative index was 3.69. There were 8241 funding sources, supporting around 47% of total articles.

Results
The search strategy yielded a total of 16,887 articles from 2735 sources on the topic of VD and bone metabolism, as shown in Table 1. The total number of authors was 60,149. The majority of the articles were multi-authored, while 4.5% (756) were single-authored articles contributed by <1% (577) of total authors. Open access articles were 44.5%. The collaborative index was 3.69. There were 8241 funding sources, supporting around 47% of total articles.
The annual evolution of scientific production is displayed in Figure 2. The number of articles was generally increasing with a maximum in 2017 (1150). A spike with increased production was observed from 2008 to 2013, followed by a gradual increase until 2017. The annual publication growth rate in the last two decades was 4.5%. Higher mean total citations per article and year were observed for the previous decade (2001-2010) with a maximum in 2004. The annual evolution of scientific production is displayed in Figure 2. The nu of articles was generally increasing with a maximum in 2017 (1150). A spike wit creased production was observed from 2008 to 2013, followed by a gradual increase 2017. The annual publication growth rate in the last two decades was 4.5%. Higher total citations per article and year were observed for the previous decade      Table 2 shows the top 20 contributing countries in terms of articles and correspond ing authors. There were 61,095 country appearances from 115 countries while 94 countrie were found to have corresponding authors. Among those, the most productive countr was the USA (n = 15,838, 26.30% as CA) followed by Japan, China, the United Kingdom and Italy. Corresponding authors from the top 5, 10, and 20 countries were collectivel responsible for 49%, 65.7%, and 85.2% of total articles, respectively. Most of the article were found to be from single country representation (81%) and led by the USA whil Switzerland showed relatively more multiple country publication (MCP) ratio followed by Netherland and the United Kingdom. High Income countries contribution was 81.3% (n = 49,693) followed by upper middle income, lower middle income & low income with 13.78% (n = 8418), 4.74% (n = 2894) & 0.15% (n = 90), respectively (table with countrie contribution along with their socioeconomic status shared in supplementary files).
This study found that most of the multi-country publications were between author from two countries. Among those, USA/Canada showed to have maximum (315) collabo rations followed by USA/UK, USA/China, USA/Japan, and USA/Germany, with 214, 206 150, and 143 collaborations, respectively.   Table 2 shows the top 20 contributing countries in terms of articles and corresponding authors. There were 61,095 country appearances from 115 countries while 94 countries were found to have corresponding authors. Among those, the most productive country was the USA (n = 15,838, 26.30% as CA) followed by Japan, China, the United Kingdom, and Italy. Corresponding authors from the top 5, 10, and 20 countries were collectively responsible for 49%, 65.7%, and 85.2% of total articles, respectively. Most of the articles were found to be from single country representation (81%) and led by the USA while Switzerland showed relatively more multiple country publication (MCP) ratio followed by Netherland and the United Kingdom. High Income countries contribution was 81.3% (n = 49,693) followed by upper middle income, lower middle income & low income with 13.78% (n = 8418), 4.74% (n = 2894) & 0.15% (n = 90), respectively (table with countries contribution along with their socioeconomic status shared in supplementary files). This study found that most of the multi-country publications were between authors from two countries. Among those, USA/Canada showed to have maximum (315) collaborations followed by USA/UK, USA/China, USA/Japan, and USA/Germany, with 214, 206, 150, and 143 collaborations, respectively. Table 3 shows the top 10 most frequent affiliations and funding sources. Harvard University and McGill University were leading affiliations. The leading funding organizations were the United States Department of Health Human Services and the National Institutes of Health (NIH). Figure 4 shows a Sankey diagram for the top 20 most productive countries, affiliations, and authors showing dominant contributions by institutes from the USA, followed by Canada and Australia. The Sankey diagram displays how quantities are distributed among items (countries, affiliations, and authors). Thickness of the links (connections) shows high volume of flow between set of values. Among countries, the USA, Japan, and the United Kingdom showed maximum citations with 208,165, 32,834, and 32,007 citations, respectively. As shown in Table 4, the author Holick MF (USA) was the leading contributor with 5 highly cited articles. In terms of sources, "The Journal of Clinical Endocrinology & Metabolism" and "The American Journal of Clinical Nutrition" were the leading contributors with 4 articles. In terms of study types, mostly were research articles (10, including 4 animal studies) followed by clinical trials and reviews, 4 in each category, respectively. Three (3) and 10 articles showed ≥500 internal (within study selected articles) and ≥1000 global citations, respectively. Among countries, the USA, Japan, and the United Kingdom showed maximum citations with 208,165, 32,834, and 32,007 citations, respectively. As shown in Table 4, the author Holick MF (USA) was the leading contributor with 5 highly cited articles. In terms of sources, "The Journal of Clinical Endocrinology & Metabolism" and "The American Journal of Clinical Nutrition" were the leading contributors with 4 articles. In terms of study types, mostly were research articles (10, including 4 animal studies) followed by clinical trials and reviews, 4 in each category, respectively. Three (3) and 10 articles showed ≥ 500 internal (within study selected articles) and ≥1000 global citations, respectively.     Figure 5a shows the year-wise growth of the 10 most productive sources over the last 2 decades. Osteoporosis International, Journal of Bone and Mineral Research, and Bone were the leading sources with 632, 569, and 448 articles, respectively. Among research areas and web of science categories (WC), Endocrinology Metabolism was the leading contributor. Figure 5b shows the distribution of the most frequent (top 3) keywords trends (2001-2020). In total, 16,775 author keywords were used. The 20 most frequently used keywords occurred from a minimum of 245 to a maximum of 3468 times. Vitamin D (n = 3468), osteoporosis (n = 2499), bone mineral density (n = 1474), calcium (n = 891) and vitamin D deficiency (n = 636), were the most frequently used keywords. A relatively increased frequency of leading keywords was observed between 2012 to 2015.

Discussion
Vitamin D is a vitamin cum steroid hormone. It was originally recognized as a biomolecule used in the body for calcium and phosphate homeostasis. However, now VD has multiple non-skeletal preventive and therapeutic applications for maintenance and improvement of health. Thus, extensive research over this prohormone seemed imperative. Quality research work in healthcare generates critical evidence to fill the gaps in our knowledge of health and disease.
This study found that since the year 1900, >2/3rd of VD-related research articles in English have been published in the last two decades (2001-2020). When explored for VD and bone metabolism, >80% (16,887) of total articles in English were published in the same timeframe. This study summarizes patterns and results over the last two decades (2001-2020) to provide a clearer understanding of the overall productivity of VD and bone metabolism research. Besides, it offers a connection to examine developments in science study on the use of the podium for bibliometrics. Only 1% of articles were single authored with a dominant majority of multi-authored articles in the last 2 decades. The annual growth rate for publications was found to be 4.5%. The trend showed a steady rise in the number of publications with maximum publications in 2017 (1150). Nearly two-thirds of the articles were published over the last 10 years (2011-2020). A spike of maximum productivity was seen from the year 2008 to 2013, producing around 31% of total articles (5218), followed by a gradual increase until 2017. During 2 months in the summer of 2011, more than 500 publications were made on VD mostly about its non-skeletal functions [15]. A similar declining trend of VD and musculoskeletal research output was also observed in a study on VD with co-word analysis [45]. The following decline in publication trend after 2014 could presumably be due to the several factors such as researchers diverted toward other aspects of VD like its role in reproduction [46], diabetes mellitus [19], gestational diabetes [47], CVD and obesity [22], asthma [48], autoimmune diseases [49], depression, hypertension, cancers [50], and many other aspects [45].
The retrieved articles were geographically distributed through 114 countries and among those, 32 contributed with ≥100 articles on the study topic. The United States, with 1/4th of the total articles, was the most productive country, followed by Japan, China, and the UK. Study findings point towards major contributions and better scientific output quality from developed countries, primarily the USA, UK, Canada, and European countries. Approximately >3/4 of the published articles related to this topic were published from the western world, especially from the USA. Study findings showed some similarities with other studies conducted on global VD [27] and osteoporosis [51] research productivity showing major contributions by western and developed countries led by the USA but a bit in a different order. Besides the western world, Japan, China, Turkey and Korea also showed decent contributions. Notably, among the top 20 contributing countries, India and Iran were the only 2 from LMICs.
Osteoporosis is the most common bone metabolic problem, and its prevalence is worldwide. In the Eastern Mediterranean Region, the overall pooled osteoporosis prevalence was 24.4% [52]. Research reports from various South and Southeast Asia countries have shown, with few exceptions, a common prevalence of hypovitaminosis D (VD deficiency/insufficiency) in both genders and all age groups of the populace [8]. The Middle East and Africa register the highest rates of rickets worldwide, amid abundant sunlight, and low VD levels are prevalent in the region [53]. VD is synthesized with sunlight. Surprisingly, despite abundant sunlight in several Asian countries, osteoporosis and osteopenia have a high incidence [53][54][55][56]. With the common prevalence of hypovitaminosis D and the high incidence of osteoporosis, one can expect high productivity in research; however, the present study results indicate that the VD and bone metabolism research publication and quality are significantly lower than the western world.
Though, VD deficiency and relevant issues are considered global affecting most parts of the world. It has been reported commonly in the developed world and growing in the Americas and Europe [13,27,57], yet the situation is worst in less developed countries. Study findings also found marginal contributions from many affected regions and lowand middle-income countries. It can also be attributed to another study which found that around 31% of funded articles were also written in the USA and other developed countries. Furthermore, open access articles made up 39.5%, indicating the limitation in terms of access for stakeholders in less developed regions. There could be multiple reasons, such as lack of available resources in terms of funding, unavailability of stateof-the-art research laboratories, lack of qualified and skilled workforce required, fewer quality journals produced from these countries, etc. Most open-access journals charge article processing charges (APC) ranging from 1500-5000 dollars per article. Such a huge APC amount may be one of the hurdles in publishing good quality research in high-impact factor journals. One of the reasons for low research output from middle-income and lowermiddle-income countries could be that we conducted a search on the Web of Science only and many journals published from such countries are not indexed on the Web of Science.
Most of the top 20 prolific authors were from the USA, Europe, UK, and Canada. Among those, 19 authors contributed with ≥50 articles. Authors: Dawson Hughes B (USA), Mosekilde L (Denmark), Lips P (Netherlands), and Cooper C (UK), were found to be the most productive. In terms of impact, one author, Holick MF (USA) had the most citations, followed by Reginster JY (Belgium) and Dawson-Hughes B (USA). Seven (7)  These findings suggest that some of the authors are potentially established senior researchers in the field due to their consistent contributions throughout 2 decades, such as Holick MF and Dawson-Hughes B, among others. For corresponding authors, the most productive country was again the USA, with >1/4th of the total articles, followed by Japan, China, the United Kingdom, and Italy. Corresponding authors from the top 20 countries collectively were responsible for 84.3% of the total articles. Interestingly, among these top 20 prolific authors, all had started publication year from 2000 to 2002 in the study timeframe and mostly showed notable productivity with impact. Most of the articles were found to be from single country representation and led by the USA, while Switzerland and Netherlands showed relatively more multiple country publication (MCP) ratio, followed by Canada, Germany, and the United Kingdom. This finding showed a relatively increased trend of multi-country contributions from European countries. Leading countries, affiliations, and authors have produced collaborative publications, mainly from the USA, Europe, Canada, and the UK, with small contributions from low-and middle-income nations. Despite having the highest single country contribution, the USA seemed to be the hub of collaborations and affiliations dominating two of the three clusters found among leading affiliations. Similar trends were observed for countries with maximum total citations. Fourteen institutes contributed with >200 articles, and among them, four (4) showed >300 articles-namely, Harvard University, Mcgill University, University of Wisconsin, and the University of Toronto. Like leading affiliations, the leading funding organizations were also from the USA with two; United States Department of Health Human Services and National Institutes of Health NIH, as the leading funding sources with >2000 contributions. These findings are also aligned with the finding of a relevant study, which is that the USA also had the lead in funding sources and affiliations [27]. Perhaps, it aligns with the higher publication power of the USA, UK, and other resourceful and developed countries with established platforms [27,58].
For the top 20 most cited documents, 12 (60%) documents were published between 2001 and 2006. The top-cited articles cover a diverse range of topics. The author Holick MF (USA) was the leading contributor with 5 highly cited articles (25%), followed by Shimada T (Japan) with 3 articles. In terms of sources, "The Journal of Clinical Endocrinology & Metabolism" was the leading contributor with 4 articles (20%), followed by "The New England Journal of Medicine (NEJM)" and "The American Journal of Clinical Nutrition". Six (6) and 8 articles showed ≥200 internal (within study selected articles) and ≥1000 global citations, respectively. Holick MF was also the author of the most cited article (>4000 citations), which was published by "The Journal of Clinical Endocrinology & Metabolism" in 2011.
Among 2617 sources, 14 journals contributed with ≥100 articles in the study timeframe. Most of the top 20 journals were in Q1 and/or Q2 category of JCR quartiles. Journals: Osteoporosis International, Journal of Bone and Mineral Research, and Bone were the leading contributors. Most of the relevant productive journals were consistent contributors over the last two decades with relatively increased productivity from 2008 to 2016, followed by declining contributory trends. Among research areas and web of science categories (WC), Endocrinology Metabolism was the leading contributor, followed by Nutrition Dietetics, Urology Nephrology, Medicine General Internal, and Biochemistry Molecular Biology. A study showed that endocrine and metabolism, musculoskeletal, cancers, and neuropsychological issues were the major contributors to VD research [45]. Mainly similar trends were also observed in a relevant studies study on VD where the shift towards more extra skeletal aspects showed relatively increasing trends compared to the recent decline in bone-related issues [27,45]. A total of 16,775 keywords were used. Vitamin D, osteoporosis, bone mineral density, calcium, and vitamin D deficiency were the most frequently used ones. However, if we analyze the keywords, it is seen that the keywords cover multidisciplinary topics concerning vitamin D and bone metabolism. Besides, a relatively increased frequency of leading keywords between 2008 to 2014 also aligned with the earlier finding of increased productivity around the same period.
This study had a few limitations such as data was based on the Web of Science database only. Though data standardization might be a hindrance, adding or comparing it with other databases can potentially provide a more comprehensive picture. Secondly, this study included articles in English only that limit the contributions from certain regions. Furthermore, the lack of similar studies on the issue also limits the margin of discussion with comparisons.

Conclusions
This study provides a missing analysis of global research trends and performance on VD and bone metabolism and found the last two decades (2001-2020) to be the most productive. Analysis of all articles published in English showed a generally increasing trend with a higher spike from 2008 to 2013. Though most articles were published in the last decade, leading sources showed a recent decline in relevant productivity and suggested the shifting trend towards non-skeletal aspects related to VD. Major contributions were from western and developed countries led by the USA, with marginal contributions from affected regions like the Middle East, South Asia, and other less resourceful settings. Leading authors, affiliations, funding sources, and collaborations were also found to be mainly from the developed regions showing the limitation in collective global research and contributions. These findings from the past not only provide directions for relevant stakeholders, but also require consideration and suggest exploring feasible options in the future to promote research culture and support for settings with limited resources.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu14030542/s1, Table S1: Countries contribution along with their socioeconomic status. Data Availability Statement: The data file used for this study will be shared or uploaded in supplementary files when required and further inquiries can be directed to the corresponding author.