Research trends and hotspots of myositis ossificans: a bibliometric analysis from 1993 to 2022

in EFORT Open Reviews
Authors:
Bowen Lai Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Heng Jiang Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Yuan Gao Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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Xuhui Zhou Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China

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https://orcid.org/0000-0003-3198-8421

Correspondence should be addressed to X Zhou; Email: zhouxuhui@smmu.edu.cn

*(B Lai and H Jiang contributed equally to this work and are joint first authors)

DOI:
https://doi.org/10.1530/EOR-23-0207
Volume/Issue:
Volume 9: Issue 7
Page Range:
589–599
Article Type:
Review Article
Online Publication Date:
01 Jul 2024
Copyright:
© the author(s) 2024
Category:
General Orthopaedics
Open access

  • Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively.

  • Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022.

  • The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field.

  • Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP.

  • This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

Abstract

  • Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively.

  • Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022.

  • The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field.

  • Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP.

  • This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

Keywords: myositis ossificans; fibrodysplasia ossificans progressiva; heterotopic ossification; bibliometric analysis; research hotspot and trends

Introduction

Myositis ossificans (MO), characterized by benign heterotopic ossifications in soft tissues including muscles, tendons, ligaments, subcutaneous fat, and nerves, can be classified into two types: nonhereditary MO (the most common) and myositis ossificans progressiva (MOP) (1). Nonhereditary MO often occurs after traumatic injury in the parts of the thighs or arms. MOP, also known as fibrodysplasia ossificans progressiva (FOP, OMIM #135100), is a rare genetic disease (0.5 cases per million people (2)) with progressive whole-body ossification. It usually occurs after birth with malformed big toes and later leads to patients immobilized, deformed, or severely disabled, resembling a stone man (3).

Trauma can induce inflammation, release bone morphogenetic protein (BMP) and transforming growth factor (TGF), and promote the mesenchymal stem cells to differentiate into chondrocytes and osteoblasts, which at last participate in the process of bone formation and result in MO (4). FOP was identified as an autosomal dominant disease with the mutation of the ACVR1 (also known as ALK2) gene, which encodes the BMP type I receptor (5). It was reported that Activin A, a member of the TGFβ/BMP superfamily, induced SMAD1/5/8 activation through ACVR1 and enhanced endochondral ossification in FOP patients (6). However, the pathophysiology of MO was still unclear.

MO was usually misdiagnosed as soft tissue infection or tumors (7, 8). Elevated levels of serum alkaline phosphatase (SAP) may indicate the occurrence of MO (9). Ultrasound can depict calcification at the early stage of post injury and help diagnose MO timely (10). Moreover, radiography is the most important tool for diagnosis, while CT and MRI can help differentiate ossification from other diseases like osteosarcoma. It is worth noting that the misdiagnosis of FOP may result in the application of puncture or biopsy, which further aggravates the degree of ossification (11).

The prevention of MO for post-trauma patients should obey the Rest, Ice, Compression, Elevation method (RICE) (12). Once the disease is diagnosed, nonsurgical treatments including icing the bump, limiting the activity, taking non-steroidal anti-inflammatory drugs (NSAIDs), and physical therapy should be first considered. Surgery is only suitable for those who have severe pain and limited movement. However, the best operation timing reported by different studies is still controversial. No cure for FOP has been found till now, though more and more studies have focused on treatment in recent years. In 2023, the FDA approved the first drug Palovarotene (Sohonos™), a retinoic acid receptor γ (RARγ) agonist, for FOP treatment (13). Palovarotene can bind to RARγ, inhibit BMP/Smad signaling, and ultimately prevent heterotopic ossifications, as demonstrated by a phase 3 clinical trial (NCT03312634) (14). Other potential medicines include activin A antibodies (15), mTOR inhibitors (16), and ACVR1 inhibitors (17). Surgery for FOP patients should be prohibited because it will result in more bone formation.

The natural history and the endochondral osteogenesis process of FOP patients were first reported in 1993 and greatly contributed to the clinical diagnosis and treatment of the disease (11, 18). Over the course of 20 years, the number of studies focused on MO has grown rapidly, and the first drug for FOP was finally approved in 2023 (13). A large amount and various kinds of MO articles may cause information overload and filtering failure, making scholars difficult to grasp the research trends and newest hotspots. Bibliometrics is a quantitative method that extracts measurable data (like authors, countries, and institutions) from published articles, presents a thorough overview of a scientific area, and indicates how it has evolved over time, which can predict the future research trend of the specific field (19). To our knowledge, bibliometric analysis has been widely used in various research fields but has not been conducted for studies about MO. In this study, we conducted a bibliometric analysis of the 20-year period (from 1993 to 2022) literature related to MO, which provided a comprehensive review of the research characteristics and meaningful revelations for further studies to promote the development of MO research.

Materials and methods

Data source and selection

The literature related to MO was searched from the Web of Science Core Collection database (WoSCC) on October 16, 2023. The data source edition was limited to the Web of Science Citation Index Expanded (SCI-Expanded) to ensure the high quality and authority of the included studies. To explore the research trend of the disease, the 20-year time span ranged from January 1, 1993, to December 31, 2022. Medical Subject Headings (MeSH) term ‘Myositis Ossificans’ and other entry terms were identified through the MeSH database (https://www.ncbi.nlm.nih.gov/mesh/?term=myositis+ossificans). The search query with field tags and Booleans was ‘TS= ((Myositis Ossificans) OR (Fibrodysplasia Ossificans Progressiva) OR (Progressive Myositis Ossificans) OR (Progressive Ossifying Myositis) OR (Myositis Ossificans Progressiva))’.

Original articles and reviews written in English were included. The full record and cited references of each study were downloaded as plain text for evaluation. Two different authors (BL and HJ) reviewed the title and abstract of all records independently and selected studies related to the topic. In case of disputes, a third author (XZ) would evaluate again and discuss with all authors to reach a consensus.

Data analysis and visualization

Various tools and software were used to conduct the bibliometric analysis. The R package ‘bibliometrix’ (20) described the basic information and publication trends of included studies, such as the number of documents, journals, authors, keywords, references, and the annual growth rate of studies. The results were exported into Microsoft Excel 365 sheets. VOSviewer (21) was used to analyze the co-occurrence and co-citation of authors, countries, institutions, journals, references, and keywords. The cluster analyses and network visualization were also performed by VOSviewer. Using CiteSpace (22), keywords burst in the timespan were identified. The line graphs and bar charts were also drawn by the R package ‘ggplot2’ (23).

Results

Overview of publications and time trends

The search in the WoSCC database (SCIE edition) resulted in 1907 publications. After screening studies and assessing eligibility according to the criteria (Fig. 1), a total of 1280 papers related to MO, written by 5080 authors from 1496 organizations in 68 countries, published in 568 journals, and cited 28 845 references from 4903 journals were included in the bibliometric analysis (Fig. 2A). From 1993 to 2022, the number of annual publications increased slightly with an annual growth rate of 2.76%. As shown in Fig. 2B, there was an obvious peak in 1998 (50 papers published). After 2008, there was a significant increase in the number of documents, and the largest number of articles was published in 2018 (n = 80) and stayed high afterward.

Figure 1
Figure 1

Flowchart of article inclusion for bibliometric analysis.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Figure 2
Figure 2

Descriptive analysis of the retrieved literature. (A) Main information of 1280 included articles related to MO. (B) Overall publication trends in the field from 1993 to 2022.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Analysis of research areas

The research areas of each publication over the past 20 years were obtained from the ‘SC’ field tags of the WOSCC database. Figure 3A shows a linear growth trend from ten research areas in 1993 to nearly 30 research areas in 2022. The top 20 most common research areas on MO are listed in Table 1, with 233 articles associated with ‘ORTHOPEDICS’, 183 with ‘SURGERY’, 163 with ‘RADIOLOGY’, ‘NUCLEAR MEDICINE & MEDICAL IMAGING’, 137 with ‘ENDOCRINOLOGY & METABOLISM’, and 93 with ‘CELL BIOLOGY’, respectively. The number of papers in the top ten research fields is 1004, accounting for 78.4375% of the total number of papers. In 1998, articles related to ‘ORTHOPEDICS’ and ‘SURGERY’ increased greatly and accounted for a great part of publications this year (Fig. 3B). The number of studies about ‘ENDOCRINOLOGY & METABOLISM’, which was the most popular area in a single year, reached 38 in 2018 (Fig. 3B).

Figure 3
Figure 3

Overall trend of research areas regarding MO. (A) The annual number of research areas and linear growth in 20 years. (B) The annual number of articles belonging to the top ten active research areas in 20 years.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Table 1

The top 20 research areas of publications on MO.
Research areas Number
ORTHOPEDICS 233
SURGERY 183
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING 163
ENDOCRINOLOGY & METABOLISM 137
CELL BIOLOGY 93
PEDIATRICS 92
PATHOLOGY 87
RESEARCH & EXPERIMENTAL MEDICINE 87
GENETICS & HEREDITY 84
GENERAL & INTERNAL MEDICINE 71
BIOCHEMISTRY & MOLECULAR BIOLOGY 65
DENTISTRY, ORAL SURGERY & MEDICINE 48
NEUROSCIENCES & NEUROLOGY 47
SPORT SCIENCES 43
PHARMACOLOGY & PHARMACY 41
RHEUMATOLOGY 40
ONCOLOGY 35
BIOTECHNOLOGY & APPLIED MICROBIOLOGY 28
VETERINARY SCIENCES 26
DEVELOPMENTAL BIOLOGY 24

Analysis of countries

About 68 countries in total contributed to studies on MO. Among them, 23 countries conducted more than 10 documents, with 11 of them publishing more than 30 studies. However, 23 countries contributed only to one article. As shown in Table 2, the USA contributed the most over 20 years with 545 articles (42.58% of all), followed by England, Japan, Germany, Italy, China, Netherlands, France, Turkey, and Canada were as follows. The USA also had the highest number of total citations (n = 26 596) and average citations per publication (n = 48.80), while studies from Turkey showed the lowest number of citations among the top ten countries, despite contributing 44 articles in total (Table 2). As shown in Fig. 4A, the USA published the most articles every year from 1993 to 2022, and it is worth noting that China performed the first studies in 2006 and has grown rapidly in recent years (ranked second in 2021 and 2022). The country collaboration map (Fig. 5) indicated that the USA, China, Japan, and various European countries communicated with each other more frequently, while countries in Africa and the Middle East seldom cooperated with other continents.

Figure 4
Figure 4

Overall publication trends in different countries and journals. (A) The annual number of articles written by the top five active countries in 20 years. (B) The cumulative number of articles published in the top six active journals in 20 years.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Figure 5
Figure 5

The visualization of cooperation relationships among countries. (A) The world map directly shows the cooperation relationships among countries. Countries with darker blue means more publications and the thicker line between countries represents closer cooperation. (B) The cooperation network of countries. Different colors represent the clusters calculated by VOSviewer.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Table 2

The top ten countries with the highest number of published articles regarding MO.
Rank Country Article counts Percentage (n/1280, %) Total number of citations Average number of citations
1 USA 545 42.58 26,596 48.80
2 England 129 10.08 5212 40.40
3 Japan 119 9.30 3995 33.57
4 Germany 76 5.94 2339 30.78
5 Italy 74 5.78 1605 21.69
6 China 70 5.47 1047 14.96
7 Netherlands 61 4.77 1699 27.85
8 France 58 4.53 1496 25.79
9 Turkey 44 3.44 352 8.00
10 Canada 39 3.05 1872 48.00

Analysis of institutions

With the development of the internet and rapid transportation, interinstitutional cooperation has been growing quickly in recent years and is crucial for the execution of high-quality research. The top 50 institutions that published the most documents related to MO were divided into eight clusters and had close cooperation with each other (Fig. 6A). As shown in Fig. 6B, the University of Pennsylvania, Harvard University, Children's Hospital of Philadelphia, University of California Davis, and Massachusetts General Hospital focused on MO earlier, while other organizations including Mayo Clinic, Harvard Medical School, and Hospital Italiano de Buenos Aires started concentrating on MO research in recent years. Table 3 lists the top ten institutions with the most publications over 20 years, and seven of them were institutions in the USA. The University of Pennsylvania published the most papers (n = 176) with 8731 citations, followed by Mayo Clinic (n = 47), University of California San Francisco (n = 45), Children's Hospital of Philadelphia (n = 31), and University of Oxford (n = 29). It is worth noting that the average number of citations at Harvard University is 139.25, the highest among all institutions.

Figure 6
Figure 6

The visualization of cooperation relationships among institutions. (A) The cooperation network of institutions. Different colors represent the clusters calculated by VOSviewer. (B) The time trend of cooperative relationships among institutions. Different colors represent the annual period of the publications, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2020.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Table 3

The top ten institutions with the highest number of published articles regarding MO.
Rank Institution Country Article counts Total number of citations Average number of citations
1 University of Pennsylvania USA 176 8731 49.61
2 Mayo Clinic USA 47 600 12.77
3 University of California, San Francisco USA 45 1762 39.16
4 Children's Hospital of Philadelphia USA 31 1692 54.58
5 University of Oxford England 29 1593 54.94
6 Saitama Medical University Japan 29 1588 54.76
7 University of California, Davis USA 26 1216 46.77
8 University of Tokyo Japan 24 856 35.67
9 Harvard University USA 24 3342 139.25
10 University of Michigan USA 21 924 44.00

Analysis of journals

Articles on MO were published in 569 journals, and the top ten most published journals with the Impact Factor (IF), H-index, and Quartile in category are listed in Table 4. Bone published the most articles (n = 71), while Journal of Bone and Joint Surgery-American Volume had the largest number of citations (n = 2258) and average citations (n = 132.82). Among the ten journals, half of them were mainly related to Orthopedics and Surgery, three of them (Skeletal Radiology, Pediatrics Radiology, and European Radiology) focused on Medical Imaging, and the rest (Orphanet Journal of Rare Diseases and American Journal of Medical Genetics Part A) were associated with genetics and heredity. Figure 4B shows the total number of articles in the top six most published journals as time goes by. Articles published on Clinical Orthopedics and Related Research grew fast before 2003 but soon reached its peak. After 2011, the number of publications on Bone grew exponentially till now, and Bone became the most-published journal in 2018.

Table 4

The top ten journals with the highest number of published articles regarding MO.
Rank Journal title Article counts Percentage (n/1280, %) IF 2022 H-index Quartile in category Total number of citations Average number of citations
1 Bone 71 5.55 4.1 183 Q2 1807 25.45
2 Skeletal Radiology 38 2.97 2.1 81 Q3 1029 27.08
3 Clinical Orthopaedics and Related Research 37 2.89 4.2 185 Q1 1163 31.43
4 Journal of Bone and Mineral Research 27 2.11 6.2 223 Q1 1707 63.22
5 Journal of Bone and Joint Surgery-American Volume 17 1.33 5.3 235 Q1 2258 132.82
6 Orphanet Journal of Rare Diseases 17 1.33 3.7 87 Q2 459 27.00
7 American Journal of Medical Genetics Part A 16 1.25 2.0 79 Q3 449 28.06
8 Pediatric Radiology 15 1.17 2.3 77 Q2 221 14.73
9 Journal of Oral and Maxillofacial Surgery 13 1.02 1.9 109 Q4 152 11.69
10 European Radiology 11 0.86 5.9 134 Q1 652 59.27

Analysis of authors and co-cited authors

The 1280 articles were published by 5080 authors in total from 1993 to 2022. Only 58 articles were written by a single author, and the average number of co-authors per study was 5.48, while 16.17% of all documents were international co-authorship, indicating a high level of cooperation (Fig. 2). The author clusters were visualized by VOSviewer (Fig. 7A), and the top ten authors are listed in Table 5. Kaplan FS, Shore EM, and Pignolo RJ published the most articles (far more than others) about MO and had close cooperation with each other. Other core authors included Katagiri T, Yu PB, Hsiao EC, and Bullock AN. Among all authors, the total number of citations (n = 8428), H-index (n = 50), and G-index (n = 89) of Kaplan FS were the highest, indicating that he was a pivotal figure in the field of MO. Moreover, though Yu PB and Xu MQ published only 21 and 18 articles, respectively, the average number of citations per article was 82.10 and 83.94, demonstrating the impact of their research. Kaplan FS, Shore EM, and Xu MQ conducted their studies before 2000 as pioneers and continue to contribute much till now, while the other seven authors listed in the top ten published their first articles after 2007, representing new forces in this field (Fig. 7B).

Figure 7
Figure 7

Analysis and visualization of authors, co-cited authors, and co-cited references. (A) The cooperation network of authors. (B) Top ten active authors’ production over time in papers regarding MO. The number of publications was visualized by the size of the circle. (C) Co-cited network of the top 50 active authors. (D) Visualization network of co-cited references regarding MO articles. Different colors represent the clusters calculated by VOSviewer.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

Table 5

The top ten most active authors with the highest number of published articles regarding MO.
Rank Author Article counts Total number of citations Average number of citations H-index G-index
1 Kaplan, FS 145 8428 58.12 50 89
2 Shore, EM 109 6965 63.90 45 82
3 Pignolo, RJ 60 1844 30.73 23 42
4 Katagiri, T 29 1590 54.83 17 29
5 Hsiao, EC 26 429 16.50 12 20
6 Yu, PB 21 1724 82.10 13 21
7 Bullock, AN 19 1280 67.37 15 19
8 Eekhoff, EMW 19 331 17.42 9 18
9 Haga, N 18 318 17.67 11 17
10 Xu, MQ 18 1511 83.94 12 18

A total of 21 947 authors were included in the co-citation analysis. Figure 7C shows the top 50 authors who had more than 60 citations overall. The top five co-cited authors included Kaplan FS (1709 citations), Shore EM (663 citations), Pignolo RJ (424 citations), Connor JM (373 citations), and Fukuda T (216 citations).

Analysis of co-cited references and journals

There were 29 021 co-cited references in total. The number of cited references that had more than 50 and 100 citations were 66 and 11, respectively. The visualization network of co-cited references regarding MO demonstrated the close relationship among those studies (Fig. 7D). The details of the top ten highly cited papers in the field within 20 years showed the development and understanding of research topics (Table 6). The most cited article published in Nature Genetics, titled ‘A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva’, was written by Kaplan FS in 2006 with a total of 410 citations. It could be noted that early articles mainly focused on clinical diagnosis and treatment, while publications after 2006 began to explore the molecular and genetic mechanisms of the disease. Half of the top ten articles were about the role of BMP type I receptor ACVR1 on FOP, indicating the most cutting-edge research hotspots. Though the article ‘ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A’ from Science Translational Medicine written by Economides AN was just published in 2015, it had acquired 153 citations and was the No. 5 highly cited paper in the field, which showed that activin A may be an important research direction in the future.

Table 6

The top ten highest cited literature related to MO.
Rank Title Journal Corresponding author Publication year Total number of citations
1 A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva Nature Genetics Kaplan, FS 2006 410
2 Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1 Human Mutation Shore, EM 2009 192
3 The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients Journal of Bone and Joint Surgery-American Volume Kaplan, FS 1993 185
4 Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients Journal of Bone and Joint Surgery-British Volume Connor, JM 1982 173
5 ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A Science Translational Medicine Economides, AN 2015 153
6 Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva New England Journal of Medicine Kaplan, FS 1996 147
7 BMP type I receptor inhibition reduces heterotopic ossification Nature Medicine Yu, PB 2008 142
8 Fibrodysplasia ossificans progressiva Best Practice & Research Clinical Rheumatology Kaplan, FS 2008 142
9 The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. Journal of Bone and Joint Surgery-American Volume Kaplan FS 1993 131
10 The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization Journal of Clinical Investigation Shore, EM 2009 111

Analysis of keywords

From 1993 to 2022, 4092 keywords were identified from the studies, and 1217 of them occurred more than once. The cluster network divided the keywords into four clusters (Fig. 8A), and the word cloud word plot showed the important keywords (Fig. 8B). The keywords with the top ten occurrences were ‘fibrodysplasia ossificans progressiva’ (n = 378), ‘myositis ossificans’ (n = 370), ‘heterotopic ossification’ (n = 332), ‘acvr1’ (n = 107), ‘bone’ (n = 106), ‘fop’ (n = 98), ‘mutation’ (n = 91), ‘natural history’ (n = 90), ‘differentiation’ (n = 86), and ‘expression’ (n = 86). The time trend of keywords in the included studies is shown in Fig. 8C. It is worth noting that keywords with dark colors, including ‘myositis ossificans’, ‘diagnosis’, ‘features’, ‘therapy’, ‘calcification’, ‘prevention’, ‘appearance’, and ‘mri’, were all associated with the clinical management of the disease. However, as time went on, studies have become focused on the pathogenesis and mechanism of FOP, and the recent light-colored keywords contain ‘acvr1’, ‘alk2’, ‘activin a’, ‘inhibition’, ‘activation’, ‘usp6’, ‘bmp’, ‘tgf-beta’, ‘nflammation’, ‘osteoblast’, ‘chondrogenesis’, and ‘progenitor cells’.

Figure 8
Figure 8

Visualization of keywords occurring in publications related to MO. (A) The visualization network of keywords. Different colors represent the clusters calculated by VOSviewer. (B) Cloud word plot showing the important keywords. A bigger font size represents a higher importance degree. (C) The time trend of cooperative relationships among keywords. Different colors represent the annual period of the keywords, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2016. (D) The top 25 with the strongest citation bursts in MO research. The red bar indicates the hot time of keywords.

Citation: EFORT Open Reviews 9, 7; 10.1530/EOR-23-0207

The top 25 keywords with the strongest citation bursts were analyzed by CiteSpace (Fig. 8D). The results can show the emerging trends of studies in the field. ‘Clinical feature’ occurred early in 1993 but ended soon in 2004. ‘TGF beta receptor’ and ‘signaling pathway’ burst from 2007, while ‘gene’ and ‘progenitor cells’ were seen after 2012. Most importantly, various keywords burst in recent years, including ‘osteogenic differentiation’, ‘activin a’, ‘inflammation’, ‘acvr1’, ‘usp6’, and ‘alk2’, which may indicate further research direction.

Discussion

In this study, we conducted a bibliometric analysis of the literature regarding MO in the past 20 years. The term MO was first defined in 1868 by Von Dusch and contained a wide range of disease spectrum regardless of etiology from solitary ossification to progressive congenital syndromes in many later studies. In 1905, Morgan found the formation of osseous in muscle after injury and named the phenotype as traumatic MO (24). In 1982, FOP and its characteristic imaging manifestations were reported, and then the number of case reports and studies concentrating on FOP began to grow rapidly (25). In 1993, Kaplan FS reviewed the nature history of 44 FOP patients and analyzed their histopathological specimens, indicating the endochondral osteogenesis process of the disease and providing a basis for finding candidate FOP-related genes (11, 18).

Our study showed that though the number of MO studies increased gradually in the past 20 years, a clear cut-off year was 2009. The literature numbers stood on a new level after 2009 probably because the two highest-cited articles published in 2006 (5) and 2009 (26) first found a common heterozygous mutation (c.617G>A; p.R206H) of ACVR1, a type of BMP receptor, both in the classical and atypical FOP patients, which greatly promoted research into the pathophysiologic mechanisms and therapeutic approaches to FOP.

The changes in research areas on MO were also worth noting. From 1993 to 2022, ‘SURGERY’ and ‘RADIOLOGY’ were the most frequently focused, just less than ‘ORTHOPEDICS’, indicating the importance of radiology in diagnosing MO and surgery in treating MO. Moreover, the number of studies regarding ‘CELL BIOLOGY’ and ‘ENDOCRINOLOGY & METABOLISM’ grew rapidly after 2010, which showed the changes in research focus. In 2018, more than 30 MO literature were about metabolism, most of them concentrated on the role of activin A (27) and TGF-β/BMP (28) signaling pathways in the pathogenesis of FOP. Some potential therapeutic approaches, like mast cell inhibition (29) and the usage of retinoid agonists (30), were also explored in mouse models.

The collaborations between countries were close and mainly occurred between the USA, Europe, China, and Japan. It is worth noting that the USA published the most articles in the field and had the greatest impact in the past 20 years because of the huge budget and famous research centers. Kaplan FS and Shore EM, the two most influential authors in MO research, were both American from the University of Pennsylvania and had conducted a series of important studies together. They directed the Center for Research in FOP and Related Disorders, the only center in the world devoted entirely to the disease. Pignolo RJ, who also graduated from UPenn and now works at the Mayo Clinic, was a principal investigator of the clinical trial of the RARγ agonist palovarotene for the treatment of FOP. Yu PB was the director of the Cardiovascular Research Center of Massachusetts General Hospital. Though he was not a doctor of orthopedics, his research focused on the TGF-β/BMP signaling in the pathogenesis of bone biology, heterotopic ossifications, and FOP. In 2016, he demonstrated that a muscle-resident interstitial Mx1+ population and a Scx+ tendon-derived progenitor mediate heterotopic ossification with or without injury, respectively (31), which contributed to the development of therapies specific for traumatic MO and FOP targeting cells of different lineage origins.

Keywords of MO studies were mainly divided into three types: (1) the clinical features, diagnostic methods, and surgery techniques of MO, especially about traumatic MO; (2) the natural history, radiology characteristics, and case reports of FOP; (3) genetic etiology and related molecules of FOP, including ACVR1 (ALK2), activin A, TGF-β, and BMP. Research containing keywords from the first type was mainly published before 2010. As time went by, studies began to concentrate on FOP and type three included the most popular research keywords in recent years. These large numbers of studies have also spawned drug development on FOP. Palovarotene (Sohonos™) is an RARγ agonist that has been validated in a phase 3 clinical trial (NCT03312634 (14)) and approved by the FDA in 2023. Investigation of activin-A antibody Garetosmab in FOP is still ongoing (NCT03188666 (32)) and may provide more therapeutic strategies for FOP patients.

This bibliometric study has some limitations. Though SCIE was one of the largest and most authoritative databases, literature published in non-index journals was not included in our study. Moreover, articles written in non-English were not included. It is possible that some data loss resulted from the title search's use of keywords to ensure the accuracy of included studies.

ICMJE Conflict of Interest Statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.

Funding Statement

This work was supported by grants from the National Natural Science Foundation of China (82302084).

Author contribution statement

BL and HJ contributed equally to this work. BL, HJ, and XZ conceived and designed the study. HJ takes responsibility for the acquisition of the data and the analysis of the data. BL and YG drafted the manuscript. HJ and XZ revised critically the manuscript for important intellectual content. All authors approved the final version to be published.

References

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    Walczak BE, Johnson CN, & Howe BM. Myositis ossificans. Journal of the American Academy of Orthopaedic Surgeons 2015 23 612–622. (https://doi.org/10.5435/JAAOS-D-14-00269)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2↑

    Martelli A, & Santos AR. Cellular and morphological aspects of fibrodysplasia ossificans progressiva. Lessons of formation, repair, and bone bioengineering. Organogenesis 2014 10 303–311. (https://doi.org/10.4161/org.29206)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3↑

    Kaplan FS, Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, Groppe J, & Shore EM. Fibrodysplasia ossificans progressiva. Best Practice and Research. Clinical Rheumatology 2008 22 191–205. (https://doi.org/10.1016/j.berh.2007.11.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4↑

    Kan L, Liu Y, McGuire TL, Berger DMP, Awatramani RB, Dymecki SM, & Kessler JA. Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells 2009 27 150–156. (https://doi.org/10.1634/stemcells.2008-0576)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5↑

    Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, et al.A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics 2006 38 525–527. (https://doi.org/10.1038/ng1783)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6↑

    Barruet E, Morales BM, Lwin W, White MP, Theodoris CV, Kim H, Urrutia A, Wong SA, Srivastava D, & Hsiao EC. The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling. Stem Cell Research and Therapy 2016 7 115. (https://doi.org/10.1186/s13287-016-0372-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7↑

    Cortellazzo Wiel L, Trevisan M, Murru FM, Rabusin M, & Barbi E. Myositis ossificans mimicking sarcoma: a not so rare bioptic diagnostic pitfall. Italian Journal of Pediatrics 2020 46 110. (https://doi.org/10.1186/s13052-020-00874-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8↑

    Yamaga K, Kobayashi E, Kubota D, Setsu N, Tanaka Y, Minami Y, Tanzawa Y, Nakatani F, Kawai A, & Chuman H. Pediatric myositis ossificans mimicking osteosarcoma. Pediatrics International 2015 57 996–999. (https://doi.org/10.1111/ped.12672)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9↑

    Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clinical Orthopaedics and Related Research 1991 263 13–29. (https://doi.org/10.1097/00003086-199102000-00003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10↑

    Bauer AH, Bonham J, Gutierrez L, Hsiao EC, & Motamedi D. Fibrodysplasia ossificans progressiva: a current review of imaging findings. Skeletal Radiology 2018 47 1043–1050. (https://doi.org/10.1007/s00256-018-2889-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11↑

    Kaplan FS, Tabas JA, Gannon FH, Finkel G, Hahn GV, & Zasloff MA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. Journal of Bone and Joint Surgery. American Volume 1993 75 220–230. (https://doi.org/10.2106/00004623-199302000-00009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12↑

    Järvinen TAH, Järvinen TLN, Kääriäinen M, Aärimaa V, Vaittinen S, Kalimo H, & Järvinen M. Muscle injuries: optimising recovery. Best Practice and Research. Clinical Rheumatology 2007 21 317–331. (https://doi.org/10.1016/j.berh.2006.12.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13↑

    Hoy SM. Palovarotene: first approval. Drugs 2022 82 711–716. (https://doi.org/10.1007/s40265-022-01709-z)

  • 14↑

    Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, et al.Reduction of new heterotopic ossification (HO) in the open-label, Phase 3 MOVE trial of palovarotene for fibrodysplasia ossificans progressiva (FOP). Journal of Bone and Mineral Research 2023 38 381–394. (https://doi.org/10.1002/jbmr.4762)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15↑

    Vanhoutte F, Liang S, Ruddy M, Zhao A, Drewery T, Wang Y, DelGizzi R, Forleo-Neto E, Rajadhyaksha M, Herman G, et al.Pharmacokinetics and pharmacodynamics of Garetosmab (anti-activin A): results from a first-in-human Phase 1 study. Journal of Clinical Pharmacology 2020 60 1424–1431. (https://doi.org/10.1002/jcph.1638)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16↑

    Maekawa H, Kawai S, Nishio M, Nagata S, Jin Y, Yoshitomi H, Matsuda S, & Toguchida J. Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1. Orphanet Journal of Rare Diseases 2020 15 122. (https://doi.org/10.1186/s13023-020-01406-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17↑

    Williams E, Bagarova J, Kerr G, Xia DD, Place ES, Dey D, Shen Y, Bocobo GA, Mohedas AH, Huang X, et al.Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva. JCI Insight 2021 6. (https://doi.org/10.1172/jci.insight.95042)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18↑

    Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, Sando N, Zasloff M, & Kaplan FS. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. Journal of Bone and Joint Surgery. American Volume 1993 75 215–219. (https://doi.org/10.2106/00004623-199302000-00008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19↑

    Thompson DF, & Walker CK. A descriptive and historical review of bibliometrics with applications to medical sciences. Pharmacotherapy 2015 35 551–559. (https://doi.org/10.1002/phar.1586)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20↑

    Aria M, & Cuccurullo C. bibliometrix: an R-tool for comprehensive science mapping analysis. Journal of Informetrics 2017 11 959–975. (https://doi.org/10.1016/j.joi.2017.08.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21↑

    Van Eck NJ, & Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 2010 84 523–538. (https://doi.org/10.1007/s11192-009-0146-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22↑

    Chen C. Searching for intellectual turning points: progressive knowledge domain visualization. PNAS 2004 101(Supplement 1) 5303–5310. (https://doi.org/10.1073/pnas.0307513100)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23↑

    Wickham H. ggplot2. WIREs 2011 3 180–185. (https://doi.org/10.1002/wics.147)

  • 24↑

    Jones R, & Morgan D. Medical radiology: on osseous formations in muscles due to injury (traumatic myositis ossificans). Archives of the Roentgen Ray 1905 9 245–249. (https://doi.org/10.1259/arr.1905.0141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25↑

    Connor JM, & Evans DA. Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. Journal of Bone and Joint Surgery. British Volume 1982 64 76–83. (https://doi.org/10.1302/0301-620X.64B1.7068725)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26↑

    Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, et al.Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Human Mutation 2009 30 379–390. (https://doi.org/10.1002/humu.20868)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27↑

    Lees-Shepard JB, Yamamoto M, Biswas AA, Stoessel SJ, Nicholas S-AE, Cogswell CA, Devarakonda PM, Schneider MJ, Cummins SM, Legendre NP, et al.Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva. Nature Communications 2018 9 471. (https://doi.org/10.1038/s41467-018-02872-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28↑

    Wang X, Li F, Xie L, Crane J, Zhen G, Mishina Y, Deng R, Gao B, Chen H, Liu S, et al.Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice. Nature Communications 2018 9 551. (https://doi.org/10.1038/s41467-018-02988-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29↑

    Brennan TA, Lindborg CM, Bergbauer CR, Wang H, Kaplan FS, & Pignolo RJ. Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP). Bone 2018 109 259–266. (https://doi.org/10.1016/j.bone.2017.08.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30↑

    Pacifici M. Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial. Bone 2018 109 267–275. (https://doi.org/10.1016/j.bone.2017.08.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31↑

    Dey D, Bagarova J, Hatsell SJ, Armstrong KA, Huang L, Ermann J, Vonner AJ, Shen Y, Mohedas AH, Lee A, et al.Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Science Translational Medicine 2016 8 366ra163–366ra163. (https://doi.org/10.1126/scitranslmed.aaf1090)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32↑

    Di Rocco M, Forleo-Neto E, Pignolo RJ, Keen R, Orcel P, Funck-Brentano T, Roux C, Kolta S, Madeo A, Bubbear JS, et al.Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial. Nature Medicine 2023 29 2615–2624. (https://doi.org/10.1038/s41591-023-02561-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

EFORT Open Reviews is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

As an open-access journal, EFORT Open Reviews articles are immediately available to read on publication, without restriction. The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Dec 2021 onwards Past Year Past 30 Days
Full Text Views 1480 1480 86
PDF Downloads 592 592 79

 

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Online ISSN:
2058-5241
Copyright:
© the author(s) 2024
Article Type:
Review Article
Page Range:
589–599
Published Online:
01 Jul 2024
Keywords:
myositis ossificans; fibrodysplasia ossificans progressiva; heterotopic ossification; bibliometric analysis; research hotspot and trends
  • Figure 1
    View in gallery
    Figure 1

    Flowchart of article inclusion for bibliometric analysis.

  • Figure 2
    View in gallery
    Figure 2

    Descriptive analysis of the retrieved literature. (A) Main information of 1280 included articles related to MO. (B) Overall publication trends in the field from 1993 to 2022.

  • Figure 3
    View in gallery
    Figure 3

    Overall trend of research areas regarding MO. (A) The annual number of research areas and linear growth in 20 years. (B) The annual number of articles belonging to the top ten active research areas in 20 years.

  • Figure 4
    View in gallery
    Figure 4

    Overall publication trends in different countries and journals. (A) The annual number of articles written by the top five active countries in 20 years. (B) The cumulative number of articles published in the top six active journals in 20 years.

  • Figure 5
    View in gallery
    Figure 5

    The visualization of cooperation relationships among countries. (A) The world map directly shows the cooperation relationships among countries. Countries with darker blue means more publications and the thicker line between countries represents closer cooperation. (B) The cooperation network of countries. Different colors represent the clusters calculated by VOSviewer.

  • Figure 6
    View in gallery
    Figure 6

    The visualization of cooperation relationships among institutions. (A) The cooperation network of institutions. Different colors represent the clusters calculated by VOSviewer. (B) The time trend of cooperative relationships among institutions. Different colors represent the annual period of the publications, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2020.

  • Figure 7
    View in gallery
    Figure 7

    Analysis and visualization of authors, co-cited authors, and co-cited references. (A) The cooperation network of authors. (B) Top ten active authors’ production over time in papers regarding MO. The number of publications was visualized by the size of the circle. (C) Co-cited network of the top 50 active authors. (D) Visualization network of co-cited references regarding MO articles. Different colors represent the clusters calculated by VOSviewer.

  • Figure 8
    View in gallery
    Figure 8

    Visualization of keywords occurring in publications related to MO. (A) The visualization network of keywords. Different colors represent the clusters calculated by VOSviewer. (B) Cloud word plot showing the important keywords. A bigger font size represents a higher importance degree. (C) The time trend of cooperative relationships among keywords. Different colors represent the annual period of the keywords, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2016. (D) The top 25 with the strongest citation bursts in MO research. The red bar indicates the hot time of keywords.

Figure 1

Flowchart of article inclusion for bibliometric analysis.
Figure 2

Descriptive analysis of the retrieved literature. (A) Main information of 1280 included articles related to MO. (B) Overall publication trends in the field from 1993 to 2022.
Figure 3

Overall trend of research areas regarding MO. (A) The annual number of research areas and linear growth in 20 years. (B) The annual number of articles belonging to the top ten active research areas in 20 years.
Figure 4

Overall publication trends in different countries and journals. (A) The annual number of articles written by the top five active countries in 20 years. (B) The cumulative number of articles published in the top six active journals in 20 years.
Figure 5

The visualization of cooperation relationships among countries. (A) The world map directly shows the cooperation relationships among countries. Countries with darker blue means more publications and the thicker line between countries represents closer cooperation. (B) The cooperation network of countries. Different colors represent the clusters calculated by VOSviewer.
Figure 6

The visualization of cooperation relationships among institutions. (A) The cooperation network of institutions. Different colors represent the clusters calculated by VOSviewer. (B) The time trend of cooperative relationships among institutions. Different colors represent the annual period of the publications, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2020.
Figure 7

Analysis and visualization of authors, co-cited authors, and co-cited references. (A) The cooperation network of authors. (B) Top ten active authors’ production over time in papers regarding MO. The number of publications was visualized by the size of the circle. (C) Co-cited network of the top 50 active authors. (D) Visualization network of co-cited references regarding MO articles. Different colors represent the clusters calculated by VOSviewer.
Figure 8

Visualization of keywords occurring in publications related to MO. (A) The visualization network of keywords. Different colors represent the clusters calculated by VOSviewer. (B) Cloud word plot showing the important keywords. A bigger font size represents a higher importance degree. (C) The time trend of cooperative relationships among keywords. Different colors represent the annual period of the keywords, in which the color from blue to yellow represents the annual occurrence time from 2010 to 2016. (D) The top 25 with the strongest citation bursts in MO research. The red bar indicates the hot time of keywords.
  • 1

    Walczak BE, Johnson CN, & Howe BM. Myositis ossificans. Journal of the American Academy of Orthopaedic Surgeons 2015 23 612–622. (https://doi.org/10.5435/JAAOS-D-14-00269)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Martelli A, & Santos AR. Cellular and morphological aspects of fibrodysplasia ossificans progressiva. Lessons of formation, repair, and bone bioengineering. Organogenesis 2014 10 303–311. (https://doi.org/10.4161/org.29206)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Kaplan FS, Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, Groppe J, & Shore EM. Fibrodysplasia ossificans progressiva. Best Practice and Research. Clinical Rheumatology 2008 22 191–205. (https://doi.org/10.1016/j.berh.2007.11.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Kan L, Liu Y, McGuire TL, Berger DMP, Awatramani RB, Dymecki SM, & Kessler JA. Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells 2009 27 150–156. (https://doi.org/10.1634/stemcells.2008-0576)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, et al.A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics 2006 38 525–527. (https://doi.org/10.1038/ng1783)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Barruet E, Morales BM, Lwin W, White MP, Theodoris CV, Kim H, Urrutia A, Wong SA, Srivastava D, & Hsiao EC. The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling. Stem Cell Research and Therapy 2016 7 115. (https://doi.org/10.1186/s13287-016-0372-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Cortellazzo Wiel L, Trevisan M, Murru FM, Rabusin M, & Barbi E. Myositis ossificans mimicking sarcoma: a not so rare bioptic diagnostic pitfall. Italian Journal of Pediatrics 2020 46 110. (https://doi.org/10.1186/s13052-020-00874-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Yamaga K, Kobayashi E, Kubota D, Setsu N, Tanaka Y, Minami Y, Tanzawa Y, Nakatani F, Kawai A, & Chuman H. Pediatric myositis ossificans mimicking osteosarcoma. Pediatrics International 2015 57 996–999. (https://doi.org/10.1111/ped.12672)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clinical Orthopaedics and Related Research 1991 263 13–29. (https://doi.org/10.1097/00003086-199102000-00003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bauer AH, Bonham J, Gutierrez L, Hsiao EC, & Motamedi D. Fibrodysplasia ossificans progressiva: a current review of imaging findings. Skeletal Radiology 2018 47 1043–1050. (https://doi.org/10.1007/s00256-018-2889-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Kaplan FS, Tabas JA, Gannon FH, Finkel G, Hahn GV, & Zasloff MA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. Journal of Bone and Joint Surgery. American Volume 1993 75 220–230. (https://doi.org/10.2106/00004623-199302000-00009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Järvinen TAH, Järvinen TLN, Kääriäinen M, Aärimaa V, Vaittinen S, Kalimo H, & Järvinen M. Muscle injuries: optimising recovery. Best Practice and Research. Clinical Rheumatology 2007 21 317–331. (https://doi.org/10.1016/j.berh.2006.12.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Hoy SM. Palovarotene: first approval. Drugs 2022 82 711–716. (https://doi.org/10.1007/s40265-022-01709-z)

  • 14

    Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, et al.Reduction of new heterotopic ossification (HO) in the open-label, Phase 3 MOVE trial of palovarotene for fibrodysplasia ossificans progressiva (FOP). Journal of Bone and Mineral Research 2023 38 381–394. (https://doi.org/10.1002/jbmr.4762)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Vanhoutte F, Liang S, Ruddy M, Zhao A, Drewery T, Wang Y, DelGizzi R, Forleo-Neto E, Rajadhyaksha M, Herman G, et al.Pharmacokinetics and pharmacodynamics of Garetosmab (anti-activin A): results from a first-in-human Phase 1 study. Journal of Clinical Pharmacology 2020 60 1424–1431. (https://doi.org/10.1002/jcph.1638)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Maekawa H, Kawai S, Nishio M, Nagata S, Jin Y, Yoshitomi H, Matsuda S, & Toguchida J. Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1. Orphanet Journal of Rare Diseases 2020 15 122. (https://doi.org/10.1186/s13023-020-01406-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Williams E, Bagarova J, Kerr G, Xia DD, Place ES, Dey D, Shen Y, Bocobo GA, Mohedas AH, Huang X, et al.Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva. JCI Insight 2021 6. (https://doi.org/10.1172/jci.insight.95042)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, Sando N, Zasloff M, & Kaplan FS. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. Journal of Bone and Joint Surgery. American Volume 1993 75 215–219. (https://doi.org/10.2106/00004623-199302000-00008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Thompson DF, & Walker CK. A descriptive and historical review of bibliometrics with applications to medical sciences. Pharmacotherapy 2015 35 551–559. (https://doi.org/10.1002/phar.1586)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Aria M, & Cuccurullo C. bibliometrix: an R-tool for comprehensive science mapping analysis. Journal of Informetrics 2017 11 959–975. (https://doi.org/10.1016/j.joi.2017.08.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Van Eck NJ, & Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 2010 84 523–538. (https://doi.org/10.1007/s11192-009-0146-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Chen C. Searching for intellectual turning points: progressive knowledge domain visualization. PNAS 2004 101(Supplement 1) 5303–5310. (https://doi.org/10.1073/pnas.0307513100)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Wickham H. ggplot2. WIREs 2011 3 180–185. (https://doi.org/10.1002/wics.147)

  • 24

    Jones R, & Morgan D. Medical radiology: on osseous formations in muscles due to injury (traumatic myositis ossificans). Archives of the Roentgen Ray 1905 9 245–249. (https://doi.org/10.1259/arr.1905.0141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Connor JM, & Evans DA. Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. Journal of Bone and Joint Surgery. British Volume 1982 64 76–83. (https://doi.org/10.1302/0301-620X.64B1.7068725)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, et al.Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Human Mutation 2009 30 379–390. (https://doi.org/10.1002/humu.20868)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Lees-Shepard JB, Yamamoto M, Biswas AA, Stoessel SJ, Nicholas S-AE, Cogswell CA, Devarakonda PM, Schneider MJ, Cummins SM, Legendre NP, et al.Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva. Nature Communications 2018 9 471. (https://doi.org/10.1038/s41467-018-02872-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Wang X, Li F, Xie L, Crane J, Zhen G, Mishina Y, Deng R, Gao B, Chen H, Liu S, et al.Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice. Nature Communications 2018 9 551. (https://doi.org/10.1038/s41467-018-02988-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Brennan TA, Lindborg CM, Bergbauer CR, Wang H, Kaplan FS, & Pignolo RJ. Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP). Bone 2018 109 259–266. (https://doi.org/10.1016/j.bone.2017.08.023)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Pacifici M. Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial. Bone 2018 109 267–275. (https://doi.org/10.1016/j.bone.2017.08.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Dey D, Bagarova J, Hatsell SJ, Armstrong KA, Huang L, Ermann J, Vonner AJ, Shen Y, Mohedas AH, Lee A, et al.Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Science Translational Medicine 2016 8 366ra163–366ra163. (https://doi.org/10.1126/scitranslmed.aaf1090)

    • PubMed
    • Search Google Scholar
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