PATHOLOGY

Bibliometric Analysis of Medication-

Related Osteonecrosis of the Jaw: High
Citation Rates but Low Evidence
M
arcio Diniz-Freitas, DDS, PhD,* Maite Pena-Cristobal, DDS,y
opez, DDS,z Lucı́a Lago-M
endez, DDS, PhD,x
Daniel P
erez-L

andez-Feijoo, MD, DDS, PhD,k and Jacobo Limeres-Posse, DDS, PhD{
Javier Fern

Purpose: Citation analysis is one of the most commonly used bibliometric tools for measuring the
academic importance of a report in a specific area of knowledge. The objective of the present study
was to identify the 100 most cited reports on medication-related osteonecrosis of the jaw (MRONJ), deter-
mine their main bibliometric characteristics, and identify the bibliometric variables that affected the
citation rates.
Materials and Methods: We performed a data search in the Scopus database to determine the number
of MRONJ article citations up to September 30, 2018. We next selected the 100 most referenced studies and
recorded the following information: ranking according to the number of citations; citation density; number
and names of authors; language and year of publication; country and institution of origin; financial support;
journal name, impact factor, category, and quartile; type of research; evidence level; and area of study.
Results: The 100 most cited reports had a mean citation density of 21.7  20.7 (range, 6.2 to 99.4) and an
h-index of 96. The 100 most cited reports on MRONJ had been published in 42 scientific journals, classified
into 10 separate categories of the Journal Citation Reports; 56% of the articles were in the first quartile of
their category. Most of the studies had been classified with a level of evidence of 4 (n = 45) or 5 (n = 29). In
the bivariate analyses, only the conflict of interest (P = .002) was associated with citation density. After
adjusting for numerous variables, conflict of interest (r = 0.27; P = .020) and country of the first author
(r = 0.23; P = .043) were significantly associated with citation density.
Conclusions: The 100 most cited studies of MRONJ had a large number of citations and had been
reported in journals with a high impact factor; however, the studies had a generally low evidence level
and randomized clinical trials were lacking.
Ó 2019 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg -:1.e1-1.e17, 2019

*Assistant Professor, Special Care Dentistry Unit, School of
Medicine and Dentistry; and Researcher, Medical-Surgical Dentistry
Research Group (OMEQUI), Health Research Institute of Santiago
de Compostela (IDIS), University of Santiago de Compostela,
Santiago de Compostela, Spain.
yPhD Student, School of Medicine and Dentistry, University of
Santiago de Compostela, Santiago de Compostela, Spain.
zPhD Student, School of Medicine and Dentistry, University of
Santiago de Compostela, Santiago de Compostela, Spain.
xOral Health Unit, Galician Health Service (SERGAS), Ordenes, La
Coru~
na, Spain.
kAssistant Professor, Special Care Dentistry Unit, School of
Medicine and Dentistry; and Researcher, Medical-Surgical Dentistry
Research Group (OMEQUI), Health Research Institute of Santiago
de Compostela (IDIS), University of Santiago de Compostela,
Santiago de Compostela, Spain.
{Researcher, Medical-Surgical Dentistry Research Group
(OMEQUI), Health Research Institute of Santiago de Compostela
(IDIS); and Associate Professor, Special Care Dentistry Unit, School
of Medicine and Dentistry, University of Santiago de Compostela,
Santiago de Compostela, Spain.
Conflict of Interest Disclosures: None of the authors have any
relevant financial relationship(s) with a commercial interest.
Address correspondence and reprint requests to Dr Diniz-Freitas:
Special Care Dentistry Unit, School of Medicine and Dentistry,
University of Santiago de Compostela, Calle Entrerrı́os s/n, Santiago
de Compostela CP 15782, Spain; e-mail: marcio.diniz@usc.es
Received November 15 2018
Accepted April 10 2019
Ó 2019 American Association of Oral and Maxillofacial Surgeons
0278-2391/19/30446-X
https://doi.org/10.1016/j.joms.2019.04.015

1.e1
1.e2
Bisphosphonate-related osteonecrosis of the jaw was
first described in 2003 and represents a complication
of antiresorptive therapy,1 which is especially preva-
lent in patients with cancer.2 The condition is
currently known as medication-related osteonecrosis
of the jaw (MRONJ) and has been defined as an area
of exposed bone or bone that can be probed through
an intraoral or extraoral fistula that has persisted for
longer than 8 weeks in patients who have taken antire-
sorptive or antiangiogenic agents and have not under-
gone radiotherapy or presented with evidence of
metastasis in the anatomic region.3
The effect of this disease in the setting of oral and
maxillofacial surgery has been demonstrated by the
considerable number of studies reported on this topic
in the previous 10 years in the leading journals of this
specialty. The scientific societies of oral and maxillofa-
cial surgery have actively participated in preparing di-
rectives and positioning documents on MRONJ3 and
have continued to include this topic in their con-
gresses’ programs (eg, the 101st Annual Meeting of
the American Association of Oral and Maxillofacial Sur-
geons, Boston, MA, 2019).
Since it was first reported, MRONJ has had consider-
able interest in the scientific community, to the point
at which 5 of the 10 most cited articles on maxillofacial
surgery have discussed MRONJ.4 Since the report of
the first bibliometric study by Garfield 5 in 1987,
several reviews have been reported on the most cited
articles in the various health science-related disci-
plines, including oral and maxillofacial surgery4 and
dentistry.6 However, the most cited studies in the field
of MRONJ have not yet been specifically analyzed.
Citation analysis (the study of how often other au-
thors have cited a publication) is one of the most
commonly used bibliometric tools to determine an ar-
ticle’s academic importance in a specific area of
knowledge. Citation analysis uses citation data to
quantify the effect of research as reflected by the num-
ber of references an article receives over time. A report
that has been highly cited has been read critically, has
been considered valuable, and has been used to pro-
mote and defend the findings from other
research studies.7
Using citation analysis and other quantitative
methods, bibliometric analysis can identify studies
with the greatest effect in a specific area of study. High-
ly cited reports can affect changes in clinical practice
and inspire controversy, discussion, and further
research. Therefore, identifying ‘‘classic’’ studies that
have contributed to the knowledge of MRONJ will
help to explain the history and development of
research and assist in designing future studies on this
medical issue. In the present study, we hypothesized
that we would find one or more identifiable factors
in the reports that were associated with the citation
BIBLIOMETRIC ANALYSIS OF MRONJ
rate. The specific aims of the present study were to
1) identify the 100 most cited reports on MRONJ since
it was first described in 2003; 2) determine the arti-
cles’ main bibliometric characteristics; and 3) identify
which of these bibliometric variables could be associ-
ated with the citation rate.
Materials and Methods
STUDY DESIGN AND SAMPLE
We designed and implemented a systematic search
of the Scopus database (from January 1, 2003 to
September 30, 2018) to identify reports eligible for in-
clusion in the study using the following combination
of MeSH terms and free text: TITLE-ABS-KEY (medica-
tion AND osteonecrosis OR avascular necrosis) OR
TITLE-ABS-KEY (bisphosphonates AND osteonecrosis
OR avascular necrosis) OR TITLE-ABS-KEY (drug
AND osteonecrosis OR avascular necrosis) OR TITLE-
ABS-KEY (antiresorptive AND osteonecrosis OR avas-
cular necrosis) OR TITLE-ABS-KEY (antiangiogenic
AND osteonecrosis OR avascular necrosis) OR TITLE-
ABS-KEY (angiogenesis AND inhibitors AND osteonec-
rosis OR avascular necrosis) OR TITLE-ABS-KEY
(alendronate AND osteonecrosis OR avascular necro-
sis) OR TITLE-ABS-KEY (risedronate AND osteonecro-
sis OR avascular necrosis) OR TITLE-ABS-KEY
(ibandronate AND osteonecrosis OR avascular necro-
sis) OR TITLE-ABS-KEY (pamidronate AND osteonec-
rosis OR avascular necrosis) OR TITLE-ABSKEY
(denosumab AND osteonecrosis OR avascular necro-
sis) OR TITLE-ABS-KEY (zoledronate AND osteonecro-
sis OR avascular necrosis) OR TITLE-ABS-KEY
(bevacizumab AND osteonecrosis OR avascular necro-
sis) OR TITLE-ABS-KEY (sunitinib AND osteonecrosis
OR avascular necrosis). We included studies that had
reported any type of study design and that had focused
on MRONJ. Because the present study was a bibliomet-
ric analysis, institutional review board approval was
not required.
BIBLIOMETRIC VARIABLES
We included the 100 most cited reports and ob-
tained their complete text. Two independent re-
viewers (M.P.C. and D.P.L.) analyzed each article and
recorded the following bibliometric variables: total
number of citations in Scopus, citation density (total
number of citations/time since the article’s publica-
tion),8 current citation index (number of citations in
2018), number and names of authors, language, publi-
cation date, country of origin, institution (based on the
first author), and the presence or absence of funding
and conflicts of interest.9 We also recorded the pub-
lishing journal’s name, factor, quartile, and category
according to the 2017 Journal Citation Reports
DINIZ-FREITAS ET AL
Science Edition (JCR) of Thomson Reuters (Eagan,
MN). The nature of each report was classified as pri-
mary (ie, basic science, clinical, epidemiological) or
secondary (ie, narrative review, systematic review,
meta-analysis) research.10 We analyzed the level of ev-
idence using the Oxford Centre for Evidence-Based
Medicine criteria.11
DATA ANALYSIS
We used VOSviewer mapping software (Centre for
Science and Technology Studies, University of Leiden,
Leiden, The Netherlands) to visualize the bibliometric
analysis of the recovered reports and created collabo-
ration maps and networks among the authors
and countries.
STATISTICAL ANALYSIS
We entered the data into a statistical database (SPSS,
version 24.0; IBM Inc, Armonk, NY) for analysis and
performed descriptive statistics on the 100 most cited
reports for all bibliometric variables analyzed. We used
bivariate analysis to identify the bibliometric variables
(predictor variables) associated with citation density
(outcome of interest). We also performed linear regres-
sion analysis to investigate the relationship between
citation density (dependent variable) and each article’s
characteristics. For all analyses, we considered P < .05
to indicate statistical significance.
Results
NUMBER AND DENSITY OF CITATIONS
Applying the search strategy to the Scopus database,
we obtained 7623 reports from which we selected the
100 most cited studies (Table 1). The number of cita-
tions per article ranged from 92 to 1591, with a total
of 24,276 citations and an h-index of 96 (96 of the
100 selected documents had $96 citations). The
mean citation density was 21.7  20.7 (range, 6.2
to 99.4).
The most cited article was the letter reported by
Marx1 in 2003 in the Journal of Oral Maxillofacial
Surgery, which described a series of 36 cases that
had progressed with painful bone exposure in the
jaw of patients with cancer treated with pamidronate
or zoledronate. Marx1 had emphasized the difficulty in
treating these lesions and their possible association
with dental extractions (77% of the cases). His report
had been cited 1591 times and had the greatest density
of citations (99 citations annually) and, therefore, the
greatest relative effect. The second most cited article,
with 1399 citations and also reported in Journal of
Oral Maxillofacial Surgery, was the series of 63 cases
by Ruggiero et al12 in 2004, which included 7 patients
who had undergone treatment of osteoporosis with
1.e3
oral bisphosphonates. With 1081 citations, the third
most cited study was that reported by Khosla et al13
in 2007 in the Journal of Bone and Mineral Research.
Their review had been prepared by the workgroup of
the American Society for Bone and Mineral Research
and presented its conclusions regarding the definition,
epidemiology, risk factors, imaging diagnosis, clinical
management, and future areas of research related to
this disease.
Of interest are the consensus documents of the
American Association of Oral and Maxillofacial Sur-
geons, in 7th, 8th, and 10th place in terms of citation
rank, with a combined total of 1820 citations. The
last update in 2014 had the second highest citation
density (90 citations annually year) and was the most
cited in the first 9 months of 2018, with 108 citations.
AUTHORS AND DATE AND LANGUAGE OF
PUBLICATION
A total of 528 investigators had participated in au-
thoring the 100 selected articles, with a mean of 7 au-
thors (range, 1 to 34) per article. Of these
investigators, 14 were noteworthy in quantitative
terms because they had participated in at least 4 of
the studies included in this ranking (Table 2). In terms
of the total number of citations, the most cited investi-
gators were Ruggiero et al (4605 citations), Marx
(4016 citations), and Woo (3039 citations). The co-
authorship results from the VOSviewer display are
shown in Figure 1. The largest number of reported
studies (20 of 100) was in 2008, and all 100 of the
selected studies had been reported in English.
COUNTRY AND INSTITUTION
The author affiliations for the most cited 100 articles
are listed in Table 3. The institution with the most
included articles was Adelaide Dental Hospital and
the University of Adelaide (Australia), with 5 articles
included in this ranking, followed by the Long Island
Jewish Medical Center (Brooklyn, NY) and the Stony
Brook School of Dental Medicine (Stony Brook, NY),
with 4 articles each. In addition, the American Associ-
ation of Oral and Maxillofacial Surgeons had 3
consensus articles included in the top 10 positions
of this list.
If we analyzed the country affiliation of the first
author, the 100 articles had originated from 14 coun-
tries. Stratified by the number of articles, the following
countries occupied the highest spots: United States
(n = 55), Greece (n = 7), Germany (n = 6), Italy
(n = 6), and Australia (n = 6; Table 4). When consid-
ering the country affiliation of the coauthors who
had contributed to the 100 most cited publications,
we found 24 countries. The coauthorship results for
these countries using the VOSviewer are shown in
1.e4 BIBLIOMETRIC ANALYSIS OF MRONJ

Table 1. LISTING OF 100 MOST CITED ARTICLES ON MEDICATION-RELATED OSTEONECROSIS OF THE JAW RANKED BY
CITATION DENSITY

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

1 Marx RE: Pamidronate (Aredia) and zoledronate (Zometa) induced 99.4 1591 56
avascular necrosis of the jaws: A growing epidemic. J Oral
Maxillofac Surg 61:1115, 2003
2 Ruggiero SL, Dodson TB, Fantasia J, et al: American Association of Oral 96 480 108
and Maxillofacial Surgeons position paper on medication-related
osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg
72:1938, 2014
3 Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL: Osteonecrosis of 93.3 1399 19
the jaws associated with the use of bisphosphonates: A review of 63
cases. J Oral Maxillofac Surg 62:527, 2004
4 Khosla S, Burr D, Cauley J, et al: Bisphosphonate-associated 90.1 1081 27
osteonecrosis of the jaw: Report of a Task Force of the American
Society for Bone and Mineral Research. J Bone Miner Res 22:1479,
2007
5 Marx RE, Sawatari Y, Fortin M, Broumand V: Bisphosphonate-induced 74.71 1046 37
exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk
factors, recognition, prevention, and treatment. J Oral Maxillofac
Surg 63:1567, 2005
6 Ruggiero SL, Dodson TB, Assael LA, et al: American Association of Oral 72.4 724 23
and Maxillofacial Surgeons position paper on bisphosphonate-
related osteonecrosis of the jaws—2009 update. J Oral Maxillofac
Surg 67:2, 2009
7 Woo S, Hellstein JW, Kalmar JR: Systematic review: Bisphosphonates 71.61 931 19
and osteonecrosis of the jaws. Ann Intern Med 144:753, 2006
8 Bamias A, Kastritis E, Bamia C, et al: Osteonecrosis of the jaw in cancer 59.5 833 24
after treatment with bisphosphonates: Incidence and risk factors.
J Clin Oncol 23:8580, 2005
9 Khan AA, Morrison A, Hanley DA, et al: Diagnosis and management of 59.5 238 55
osteonecrosis of the jaw: A systematic review and international
consensus. J Bone Miner Res 30:3, 2015
10 American Association of Oral and Maxillofacial Surgeons position 51.3 616 16
paper on bisphosphonate-related osteonecrosis of the jaws. J Oral
Maxillofac Surg 65:369, 2007
11 Durie BGM, Katz M, Crowley J, et al: Osteonecrosis of the jaw and 43 602 9
bisphosphonates (multiple letters). N Engl J Med 353:99, 2005
12 Drake MT, Clarke BL, Khosla S: Bisphosphonates: Mechanism of action 41.9 461 36
and role in clinical practice. Mayo Clin Proc 83:1032, 2008
13 Saad F, Brown JE, Van Poznak C, et al: Incidence, risk factors, and 41.7 292 32
outcomes of osteonecrosis of the jaw: Integrated analysis from three
blinded active-controlled phase III trials in cancer patients with
bone metastases. Ann Oncol 23:1341, 2012
14 Marx RE, Cillo JE Jr, Ulloa JJ: Oral bisphosphonate-induced 38.4 461 10
osteonecrosis: Risk factors, prediction of risk using serum CTX
testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397,
2007
15 Hoff AO, Toth BB, Altundag K, et al: Frequency and risk factors 37.9 417 10
associated with osteonecrosis of the jaw in cancer patients treated
with intravenous bisphosphonates. J Bone Miner Res 23:826, 2008
16 Mavrokokki T, Cheng A, Stein B, Goss A: Nature and frequency of 35 420 9
bisphosphonate-associated osteonecrosis of the jaws in Australia.
J Oral Maxillofac Surg 65:415, 2007
17 Badros A, Weikel D, Salama A, et al: Osteonecrosis of the jaw in 34 442 5
multiple myeloma patients: Clinical features and risk factors. J Clin
Oncol 24:945, 2006
DINIZ-FREITAS ET AL 1.e5

Table 1. Cont’d

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

18 Migliorati CA, Schubert MM, Peterson DE, Seneda LM: 29.1 407 3
Bisphosphonate-associated osteonecrosis of mandibular and
maxillary bone: An emerging oral complication of supportive
cancer therapy. Cancer 104:83, 2005
19 Ruggiero SL, Fantasia J, Carlson E: Bisphosphonate-related 26.2 341 6
osteonecrosis of the jaw: Background and guidelines for diagnosis,
staging and management. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 102:433, 2006
20 Lo JC, O’Ryan FS, Gordon NP, et al: Prevalence of osteonecrosis of the 26.1 235 17
jaw in patients with oral bisphosphonate exposure. J Oral
Maxillofac Surg 68:243, 2010
21 Allen MR, Burr DB: The pathogenesis of bisphosphonate-related 24.7 247 11
osteonecrosis of the jaw: So many hypotheses, so few data. J Oral
Maxillofac Surg 67:61, 2009
22 Ripamonti CI, Maniezzo M, Campa T, et al: Decreased occurrence of 24.3 243 9
osteonecrosis of the jaw after implementation of dental preventive
measures in solid tumour patients with bone metastases treated
with bisphosphonates: The experience of the National Cancer
Institute of Milan. Ann Oncol 20:137, 2009
23 Dimopoulos MA, Kastritis E, Bamia C, et al: Reduction of osteonecrosis 23.7 237 17
of the jaw (ONJ) after implementation of preventive measures in
patients with multiple myeloma treated with zoledronic acid. Ann
Oncol 20:117, 2009
24 Migliorati CA, Casiglia J, Epstein J, et al: Managing the care of patients 23 322 4
with bisphosphonate-associated osteonecrosis: An American
Academy of Oral Medicine position paper. J Am Dent Assoc
136:1658, 2005
25 Vahtsevanos K, Kyrgidis A, Verrou E, et al: Longitudinal cohort study of 21.5 215 14
risk factors in cancer patients of bisphosphonate-related
osteonecrosis of the jaw. J Clin Oncol 27:5356, 2009
26 Dimopoulos MA, Kastritis E, Anagnostopoulos A, et al: Osteonecrosis 20.5 267 9
of the jaw in patients with multiple myeloma treated with
bisphosphonates: Evidence of increased risk after treatment with
zoledronic acid. Haematologica 91:968, 2006
27 Hellstein JW, Adler RA, Edwards B, et al: Managing the care of patients 19.9 159 14
receiving antiresorptive therapy for prevention and treatment of
osteoporosis: Executive summary of recommendations from the
American Dental Association Council on Scientific Affairs. J Am
Dent Assoc 142:1243, 2011
28 Reid IR, Bolland MJ, Grey AB: Is bisphosphonate-associated 19.4 233 9
osteonecrosis of the jaw caused by soft tissue toxicity? Bone 41:318,
2007
29 Migliorati CA, Siegel MA, Elting LS: Bisphosphonate-associated 19.2 250 3
osteonecrosis: A long-term complication of bisphosphonate
treatment. Lancet Oncol 7:508, 2006
30 American Dental Association Council on Scientific Affairs: Dental 17.7 230 3
management of patients receiving oral bisphosphonate therapy:
Expert panel recommendations. J Am Dent Assoc 137:1144, 2006
31 Landesberg R, Cozin M, Cremers S, et al: Inhibition of oral mucosal cell 17.5 193 2
wound healing by bisphosphonates. J Oral Maxillofac Surg 66:839,
2008
32 Reid IR: Osteonecrosis of the jaw—Who gets it, and why? Bone 44:4, 17.5 175 5
2009
1.e6 BIBLIOMETRIC ANALYSIS OF MRONJ

Table 1. Cont’d

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

33 Hansen T, Kunkel M, Weber A, James Kirkpatrick C. Osteonecrosis of 17.3 225 4

the jaws in patients treated with bisphosphonates—
Histomorphologic analysis in comparison with infected
osteoradionecrosis. J Oral Pathol Med 35:155, 2006
34 Zervas K, Verrou E, Teleioudis Z, et al. Incidence, risk factors and 17.2 223 6
management of osteonecrosis of the jaw in patients with multiple
myeloma: A single-centre experience in 303 patients. Br J Haematol
134:620, 2006
35 Pazianas M, Miller P, Blumentals WA, et al: A review of the literature on 17 204 3
osteonecrosis of the jaw in patients with osteoporosis treated with
oral bisphosphonates: Prevalence, risk factors, and clinical
characteristics. Clin Ther 29:1548, 2007
36 Boonyapakorn T, Schirmer I, Reichart PA, et al: Bisphosphonate- 16.8 185 5
induced osteonecrosis of the jaws: Prospective study of 80 patients
with multiple myeloma and other malignancies. Oral Oncol 44:857,
2008
37 Aghaloo TL, Felsenfeld AL, Tetradis S: Osteonecrosis of the jaw in a 16.4 148 8
patient on denosumab. J Oral Maxillofac Surg 68:959, 2010
38 Filleul O, Crompot E, Saussez S: Bisphosphonate-induced 16.3 147 8
osteonecrosis of the jaw: A review of 2,400 patient cases. J Cancer
Res Clin Oncol 136:1117, 2010
39 Bilezikian JP: Osteonecrosis of the jaw—Do bisphosphonates pose a 16.1 209 1
risk? N Engl J Med 355:2278, 2006
40 Tanvetyanon T, Stiff PJ: Management of the adverse effects associated 15.8 206 5
with intravenous bisphosphonates. Ann Oncol 17:897, 2006
41 Bagan JV, Murillo J, Jimenez Y, et al: Avascular jaw osteonecrosis in 15.7 220 2
association with cancer chemotherapy: Series of 10 cases. J Oral
Pathol Med 34:120, 2005
42 Carlson ER, Basile JD: The role of surgical resection in the management 15.7 157 7
of bisphosphonate-related osteonecrosis of the jaws. J Oral
Maxillofac Surg 67:85, 2009
43 Hellstein JW, Marek CL: Bisphosphonate osteochemonecrosis (bis- 15.2 213 2
phossy jaw): Is this phossy jaw of the 21st century? J Oral Maxillofac
Surg 63:682, 2005
44 Otto S, Schreyer C, Hafner S, et al: Bisphosphonate-related 14.7 103 11
osteonecrosis of the jaws—Characteristics, risk factors, clinical
features, localization and impact on oncological treatment.
J Craniomaxillofac Surg 40:303, 2012
45 Ruggiero SL, Dodson TB, Assael LA, et al: American Association of Oral 14.3 143 6
and Maxillofacial Surgeons position paper on bisphosphonate-
related osteonecrosis of the jaw—2009 update. Aust Endod J
35:119, 2009
46 Abu-Id MH, Warnke PH, Gottschalk J, et al: ‘‘Bis-phossy jaws’’—High 14 154 3
and low risk factors for bisphosphonate-induced osteonecrosis of
the jaw. J Craniomaxillofac Surg 36:95, 2008
47 Christodoulou C, Pervena A, Klouvas G, et al: Combination of 14 140 4
bisphosphonates and antiangiogenic factors induces osteonecrosis
of the jaw more frequently than bisphosphonates alone. Oncology
76:209, 2009
48 Yoneda T, Hagino H, Sugimoto T, et al: Bisphosphonate-related 14 126 4
osteonecrosis of the jaw: Position paper from the Allied Task Force
Committee of Japanese Society for Bone and Mineral Research,
Japan Osteoporosis Society, Japanese Society of Periodontology,
Japanese Society for Oral and Maxillofacial Radiology, and Japanese
Society of Oral and Maxillofacial Surgeons. J Bone Miner Metab
28:365, 2010
DINIZ-FREITAS ET AL 1.e7

Table 1. Cont’d

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

49 Rizzoli R, Burlet N, Cahall D, et al: Osteonecrosis of the jaw and 13.5 149 2
bisphosphonate treatment for osteoporosis. Bone 42:841, 2008
50 Grant B, Amenedo C, Freeman K, Kraut RA: Outcomes of placing 13.5 149 1
dental implants in patients taking oral bisphosphonates: A review of
115 cases. J Oral Maxillofac Surg 66:223, 2008
51 Sarasquete ME, Garcı́a-Sanz R, Marı́n L, et al: Bisphosphonate-related 13.5 148 5
osteonecrosis of the jaw is associated with polymorphisms of the
cytochrome P450 CYP2C8 in multiple myeloma: A genome-wide
single nucleotide polymorphism analysis. Blood 112:2709, 2008
52 Yarom N, Yahalom R, Shoshani Y, et al: Osteonecrosis of the jaw 13.4 161 5
induced by orally administered bisphosphonates: Incidence, clinical
features, predisposing factors and treatment outcome. Osteoporosis
Int 18:1363, 2007
53 Taylor KH, Middlefell LS, Mizen KD: Osteonecrosis of the jaws induced 13.3 120 2
by anti-RANK ligand therapy. Br J Oral Maxillofac Surg 48:221, 2010
54 Khan AA, S
andor GKB, Dore E, et al: Canadian consensus practice 13 143 6
guidelines for bisphosphonate associated osteonecrosis of the jaw.
J Rheumatol 35:1391, 2008
55 Sedghizadeh PP, Stanley K, Caligluri M, et al: Oral bisphosphonate use 12.7 127 1
and the prevalence of osteonecrosis of the jaw: An institutional
inquiry. J Am Dent Assoc 140:61, 2009
56 Guarneri V, Miles D, Robert N, et al: Bevacizumab and osteonecrosis of 12.7 114 11
the jaw: Incidence and association with bisphosphonate therapy in
three large prospective trials in advanced breast cancer. Breast
Cancer Res Treat 122:181, 2010
57 Sonis ST, Watkins BA, Lyng GD, et al: Bony changes in the jaws of rats 12.6 126 3
treated with zoledronic acid and dexamethasone before dental
extractions mimic bisphosphonate-related osteonecrosis in cancer
patients. Oral Oncol 45:164, 2009
58 Barasch A, Cunha-Cruz J, Curro FA, et al: Risk factors for osteonecrosis 12.4 99 8
of the jaws: A case-control study from the CONDOR dental PBRN.
J Dent Res 90:439, 2011
59 Allen MR, Burr DB: Mandible matrix necrosis in beagle dogs after 12.4 136 5
3 years of daily oral bisphosphonate treatment. J Oral Maxillofac
Surg 66:987, 2008
60 Weitzman R, Sauter N, Eriksen EF, et al: Critical review: Updated 12.3 148 3
recommendations for the prevention, diagnosis, and treatment of
osteonecrosis of the jaw in cancer patients. Crit Rev Oncol Hematol
62:148, 2007
61 Fedele S, Porter SR, D’Aiuto F, et al: Nonexposed variant of 12.2 110 6
bisphosphonate-associated osteonecrosis of the jaw: A case series.
Am J Med 123:1060, 2010
62 Sedghizadeh PP, Kumar SKS, Gorur A, et al: Identification of microbial 12.2 134 3
biofilms in osteonecrosis of the jaws secondary to bisphosphonate
therapy. J Oral Maxillofac Surg 66:767, 2008
63 Silverman SL, Landesberg R: Osteonecrosis of the jaw and the role of 11.7 117 4
bisphosphonates: A critical review. Am J Med 122:33, 2009
64 Bedogni A, Blandamura S, Lokmic Z, et al: Bisphosphonate-associated 11.5 127 3
jawbone osteonecrosis: A correlation between imaging techniques
and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 105:358, 2008
65 Lesclous P, Abi Najm S, Carrel J, et al: Bisphosphonate-associated 11.5 115 4
osteonecrosis of the jaw: A key role of inflammation? Bone 45:843,
2009
1.e8 BIBLIOMETRIC ANALYSIS OF MRONJ

Table 1. Cont’d

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

66 Khan AA, S
andor GKB, Dore E, et al: Bisphosphonate associated 11.3 113 6
osteonecrosis of the jaw. J Rheumatol 36:478, 2009
67 Cartsos VM, Zhu S, Zavras AI: Bisphosphonate use and the risk of 11.3 124 1
adverse jaw outcomes: A medical claims study of 714,217 people.
J Am Dent Assoc 139:23, 2008
68 Lazarovici TS, Yahalom R, Taicher S, et al: Bisphosphonate-related 11.2 112 6
osteonecrosis of the jaws: A single-center study of 101 patients.
J Oral Maxillofac Surg 67:850, 2009
69 Jeffcoat MK: Safety of oral bisphosphonates: Controlled studies on 11.2 145 1
alveolar bone. Int J Oral Maxillofac Implants 21:349, 2006
70 Farrugia MC, Summerlin DJ, Krowiak E, et al: Osteonecrosis of the 11 143 0
mandible or maxilla associated with the use of new generation
bisphosphonates. Laryngoscope 116:115, 2006
71 Wessel JH, Dodson TB, Zavras AI: Zoledronate, smoking, and obesity 10.9 120 2
are strong risk factors for osteonecrosis of the jaw: A case-control
study. J Oral Maxillofac Surg 66:625, 2008
72 Kikuiri T, Kim I, Yamaza T, et al: Cell-based immunotherapy with 10.7 96 3
mesenchymal stem cells cures bisphosphonate-related
osteonecrosis of the jaw-like disease in mice. J Bone Miner Res
25:1668, 2010
73 Wang EP, Kaban LB, Strewler GJ, et al: Incidence of osteonecrosis of 10.6 127 1
the jaw in patients with multiple myeloma and breast or prostate
cancer on intravenous bisphosphonate therapy. J Oral Maxillofac
Surg 65:1328, 2007
74 Chiandussi S, Biasotto M, Dore F, et al: Clinical and diagnostic imaging 10.4 135 3
of bisphosphonate-associated osteonecrosis of the jaws.
Dentomaxillofac Radiol 35:236, 2006
75 Grbic JT, Landesberg R, Lin S, et al: Incidence of osteonecrosis of the 10.3 113 1
jaw in women with postmenopausal osteoporosis in the health
outcomes and reduced incidence with zoledronic acid once yearly
pivotal fracture trial. J Am Dent Assoc 139:32, 2008
76 Ficarra G, Beninati F, Rubino I, et al: Osteonecrosis of the jaws in 10.2 143 1
periodontal patients with a history of bisphosphonates treatment.
J Clin Periodontol 32:1123, 2005
77 Badros A, Terpos E, Katodritou E, et al: Natural history of osteonecrosis 10.2 112 6
of the jaw in patients with multiple myeloma. J Clin Oncol 26:5904,
2008
78 Bagan JV, Jimenez Y, Murillo J, et al: Jaw osteonecrosis associated with 10.2 132 3
bisphosphonates: Multiple exposed areas and its relationship to
teeth extractions—Study of 20 cases. Oral Oncol 42:327, 2006
79 Walter C, Al-Nawas B, Gr€ otz KA, et al: Prevalence and risk factors of 10 110 1
bisphosphonate-associated osteonecrosis of the jaw in prostate
cancer patients with advanced disease treated with zoledronate. Eur
Urol 54:1066, 2008
80 Sedghizadeh PP, Kumar SKS, Gorur A, et al: Microbial biofilms in 10 100 1
osteomyelitis of the jaw and osteonecrosis of the jaw secondary to
bisphosphonate therapy. J Am Dent Assoc 140:1259, 2009
81 Hansen T, Kunkel M, Springer E, et al: Actinomycosis of the jaws— 9.91 119 3
Histopathological study of 45 patients shows significant
involvement in bisphosphonate-associated osteonecrosis and
infected osteoradionecrosis. Virchows Arch 451:1009, 2007
82 Edwards BJ, Hellstein JW, Jacobsen PL, et al: Updated 9.91 109 0
recommendations for managing the care of patients receiving oral
bisphosphonate therapy: An advisory statement from the American
Dental Association Council on Scientific Affairs. J Am Dent Assoc
139:1674, 2008
DINIZ-FREITAS ET AL 1.e9

Table 1. Cont’d

Citation Scopus 2018

Rank Study Density Citations (n) Citations (n)

83 Arce K, Assael LA, Weissman JL, Markiewicz MR: Imaging findings in 9.9 99 6
bisphosphonate-related osteonecrosis of jaws. J Oral Maxillofac Surg
67:75, 2009
84 Kyrgidis A, Vahtsevanos K, Koloutsos G, et al: Bisphosphonate-related 9.82 108 4
osteonecrosis of the jaws: A case-control study of risk factors in
breast cancer patients. J Clin Oncol 26:4634, 2008
85 Khamaisi M, Regev E, Yarom N, et al: Possible association between 9.66 116 2
diabetes and bisphosphonate-related jaw osteonecrosis. J Clin
Endocrinol Metab 92:1172, 2007
86 Kunchur R, Need A, Hughes T, Goss A: Clinical investigation of 9.6 96 0
C-terminal cross-linking telopeptide test in prevention and
management of bisphosphonate-associated osteonecrosis of the
jaws. J Oral Maxillofac Surg 67:1167, 2009
87 Purcell PM, Boyd IW: Bisphosphonates and osteonecrosis of the jaw. 9.5 133 1
Med J Aust 182:417, 2005
88 Carter G, Goss AN, Doecke C: Bisphosphonates and avascular necrosis 9.14 128 1
of the jaw: A possible association. Med J Aust 182:413, 2005
89 Tarassoff P, Csermak K: Avascular necrosis of the jaws: Risk factors in 9.12 146 1
metastatic cancer patients. J Oral Maxillofac Surg 61:1238, 2003
90 Raje N, Woo SB, Hande K, et al: Clinical, radiographic, and biochemical 9 99 5
characterization of multiple myeloma patients with osteonecrosis of
the jaw. Clin Cancer Res 14:2387, 2008
91 Melo MD, Obeid G: Osteonecrosis of the jaws in patients with a history 8.71 122 1
of receiving bisphosphonate therapy: Strategies for prevention and
early recognition. J Am Dent Assoc 136:1675, 2005
92 Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS: Intravenous 8.66 104 0
bisphosphonate therapy and inflammatory conditions or surgery of
the jaw: A population-based analysis. J Natl Cancer Inst 99:1016,
2007
93 Ruggiero SL, Drew SJ: Osteonecrosis of the jaws and bisphosphonate 8.58 103 1
therapy. J Dent Res 86:1013, 2007
94 Harper RP, Fung E: Resolution of bisphosphonate-associated 8.25 99 1
osteonecrosis of the mandible: Possible application for intermittent
low-dose parathyroid hormone [rhPTH(1-34)]. J Oral Maxillofac
Surg 65:573, 2007
95 Bianchi SD, Scoletta M, Cassione FB, et al: Computerized tomographic 7.91 95 3
findings in bisphosphonate-associated osteonecrosis of the jaw in
patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 104:249, 2007
96 Van den Wyngaert T, Huizing MT, Vermorken JB: Bisphosphonates and 7.84 102 0
osteonecrosis of the jaw: Cause and effect or a post hoc fallacy? Ann
Oncol 17:1197, 2006
97 Wang HL, Weber D, McCauley LK: Effect of long-term oral 7.66 92 0
bisphosphonates on implant wound healing: Literature review and a
case report. J Periodontol 78:584, 2007
98 Cheng A, Mavrokokki A, Carter G, et al: The dental implications of 6.71 94 0
bisphosphonates and bone disease. Aust Dent J 50:4, 2005
99 Carter GD, Goss AN: Bisphosphonates and avascular necrosis of the 6.86 103 2
jaws. Aust Dent J 48:268, 2003
100 Greenberg MS: Intravenous bisphosphonates and osteonecrosis. Oral 6.26 94 1
Surg Oral Med Oral Pathol Oral Radiol Endod 98:259, 2004
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillofac Surg 2019.
1.e10 BIBLIOMETRIC ANALYSIS OF MRONJ

classified according to the JCR category as dentistry,

Table 2. AUTHORS WITH AT LEAST 4 PUBLICATIONS oral surgery, and medicine (n = 54), oncology
IN THE 100 MOST CITED STUDIES OF MEDICATION-
RELATED OSTEONECROSIS OF THE JAW (n = 16), endocrinology and metabolism (n = 11), med-
icine, general and internal (n = 8), hematology (n = 4),
First Author Coauthor Last Total rheumatology (n = 2), otorhinolaryngology (n = 1), pa-
Author (n) (n) Author (n) (n) thology (n = 1), pharmacology and pharmacy (n = 1),
and urology (n = 1). According to the impact level, 25
Ruggiero SL 6 2 0 8 of the 42 scientific journals were in the first quartile of
Landesberg R 0 6 0 6 their category, 12 were in the second, and 5 were in
Marx RE 3 2 0 5
the third. The journal with the most reports included
Migliorati CA 3 1 2 6
in this ranking was the Journal of Oral and Maxillofa-
Terpos E 0 4 1 5
Woo SB 1 3 1 5 cial Surgery with 24 articles, followed by the Journal
Dimopoulos MA 2 0 2 4 of the American Dental Association with 9, the
Dodson TB 0 4 0 4 Annals of Oncology with 5, and the Journal of Clin-
Hellstein JW 2 2 0 4 ical Oncology, also with 5 reports; 26 were open ac-
Kastritis E 0 4 0 4 cess. The journal with the highest impact factor
Khosla S 1 2 1 4 (79,258) was the New England Journal of Medicine,
Mehrotra B 0 2 2 4 with 2 articles included in the ranking, in 9th and
Reid IR 2 2 0 4 34th place, with 602 and 209 citations, respectively.
Yarom N 1 1 2 4
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillo-
fac Surg 2019. TYPES OF RESEARCH, LEVEL OF EVIDENCE, AND
STUDY AREA

Figure 2. The top 3 countries with the greatest link
strength were the United States (total link strength,
72), the United Kingdom (total link strength, 48),
and Canada (total link strength, 41).
JOURNALS, IMPACT FACTOR, QUARTILE, AND
CATEGORY
The journals with the most articles included in the
list, with their impact factor, quartile, and category,
are listed in Table 5. The 100 most cited studies of
MRONJ had been reported in 42 scientific journals,
Most of the studies were classified as primary
research (n = 64), with a predominance of clinical
research (n = 38) but also epidemiological (n = 17)
and basic research (n = 9). In terms of secondary
research (n = 36), most were narrative reviews
(n = 31), with 5 systematic reviews.
Most of the studies were classified with a level of ev-
idence of 4 (n = 45) and 5 (n = 29), followed by those
with a level of evidence of 3 (n = 10) and 2 (n = 7).
None of the studies had a level of evidence of 1. The
level of evidence could not be classified for 9 basic
research articles.
The most commonly researched areas were those
regarding the clinicopathologic characteristics of
MRONJ and its treatment (n = 35), its etiopathogenesis
(n = 24), and its epidemiology (n = 11). Many of the
selected studies had jointly addressed different aspects
of the disease (global overview; n = 25).

CONFLICTS OF INTEREST AND FUNDING FOR THE

FIGURE 1. Coauthor analysis among the 100 most cited studies of
medication-related osteonecrosis of the jaw. The size of the points
represents the frequency of coauthorship. The line between 2 points
represents the collaboration between authors. The thicker the line,
the closer the collaboration between 2 authors.
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillo-
fac Surg 2019.
100 MOST CITED STUDIES
Of the 100 most cited reports, 28% had reported
conflicts of interest, and 24% had been conducted
with some type of funding.
The bivariate associations between the predictor
variables and citation density are presented in
Table 5. In the bivariate analysis, only conflicts of inter-
est (P = .002) were associated with citation density.
The results of the multiple linear regression model
for citations are listed in Table 6. After adjusting for
several variables, the conflicts of interest (r = 0.27;
P = .020) and first author’s country (r = 0.23;
DINIZ-FREITAS ET AL 1.e11

Table 3. INSTITUTIONS AND DEPARTMENTS WITH GREATEST REPRESENTATION IN RANKING ACCORDING TO FIRST
AUTHOR’S AFFILIATION

Institution Country Studies (n)

Oral and Maxillofacial Surgery Unit, Adelaide Dental Hospital and University of Adelaide Australia 5
Division of Oral and Maxillofacial Surgery, Long Island Jewish Medical Center USA 4
Division of Oral and Maxillofacial Surgery, Stony Brook School of Dental Medicine USA 4
Division of Oral and Maxillofacial Surgery, University of Miami Miller School of Medicine USA 3
Division of Diagnostic Sciences and Center for Craniofacial Molecular Biology, School of USA 3
Dentistry, University of Southern California
Institute of Pathology, Johannes Gutenberg University, University of Mainz Germany 3
Departments of Oral and Maxillofacial Surgery, Haematology and Oncology, Greece 3
Theagenio Cancer Hospital
Divisions of Endocrinology and Geriatrics, Department of Medicine, McMaster University Canada 3
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillofac Surg 2019.

P = .043) were significantly associated with cita-
tion density.
Discussion
The objective of the present study was to identify
the 100 most cited articles on MRONJ, to determine
their main bibliometric characteristics, and to identify
which of these bibliometric variables were associated
with citation density. To the best of our knowledge,
the present study is the first to identify and analyze
the bibliometric characteristics of the 100 most cited
studies on MRONJ 15 years since it was first described.
The findings of the present study have allowed us to
gain a historical perspective on the scientific progress
in studying MRONJ and highlight areas that require
further research and development. However, the pre-
sent study was unable to identify the bibliometric char-
acteristics associated with a higher citation density.
As discussed, bibliometric and scientometric ana-
lyses are relevant in various disciplines for monitoring
research, using various tools that help analyze the
quantity and quality of the reports.14 For example,
the frequency with which an article has been cited
could indicate other investigators’ interest in using
the data for their own research. Highly cited studies
could indicate a tendency in clinical practice and
can, therefore, be considered to generate greater clin-
ical and research interest on the reported topics.15
Although MRONJ is a recently described disease, the
increasing number of cases of MRONJ and the drugs
involved in its etiopathogenesis have resulted in
considerable interest in the scientific community,
which would explain the large number of reports
within just 15 years. A recent bibliometric study found
that 5 of the 10 most cited studies in the area of oral and
maxillofacial surgery were related to MRONJ.4 Also, 7
of the 10 most cited reports in the Journal of Oral
and Maxillofacial Surgery since the start of its publica-
tion were related to MRONJ, occupying the top 3 pla-
ces among the most cited articles in the Journal.
The considerable effect of this disease reflected in
the scientific data might be explained by the multidis-
ciplinary interest in this condition and its various indi-
cations for antiresorptive and antiangiogenic agents.
This interest is reflected by the distribution of the re-
ports among the 10 categories of the JCR, including
dentistry, oral surgery, and medicine; oncology; and
endocrinology and metabolism.
Although MRONJ can occur spontaneously
(without identification of a precipitating factor),
most reported cases occurred after invasive dental
procedures (mainly tooth extractions,16 which, in
many healthcare contexts, represent the most com-
mon dental procedure). Given the dramatic course
these injuries can follow, dentists and oral and maxillo-
facial surgeons involved in the dental management of
patients undergoing treatment with antiresorptive
and antiangiogenic agents should seek validated and
updated treatment protocols to minimize the risk of
their procedures.17 The 100 most cited reports also
included 12 consensus documents from various scien-
tific societies, although the documents’ recommenda-
tions were somewhat conflicting18 and lacked solid
evidence,19 as shown by the ongoing controversy on
issues such as the usefulness of the C-terminal telopep-
tide for identifying individuals at risk, discontinuing
the ‘‘drug holiday’’ before starting dental manipula-
tions, and the use of antibiotic prophylaxis.14
Another interesting finding was the lack of random-
ized clinical trials (RCTs) among the 100 most cited
studies. This lack of high-quality scientific evidence
has been identified in both the prevention and the
treatment of MRONJ. Karna et al20 conducted a
systematic review and meta-analysis of the risk reduc-
tion strategies for MRONJ and concluded that,
although dental preventive measures decreased the
incidence rate of MRONJ by 77.3% for patients with
1.e12 BIBLIOMETRIC ANALYSIS OF MRONJ

Table 4. SCIENTIFIC JOURNALS IN WHICH 100 MOST CITED STUDIES ON MEDICATION-RELATED OSTEONECROSIS OF
THE JAW WERE REPORTED

Studies Impact Factor

Journal (n) (JCR 2017) Quartile JCR Category

Journal of Oral and Maxillofacial Surgery 24 1.779 Q2 Dentistry, oral surgery, and medicine
Journal of the American Dental Association 9 2.486 Q1 Dentistry, oral surgery, and medicine
Annals of Oncology 5 13.926 Q1 Oncology
Journal of Bone and Mineral Research 4 6.314 Q1 Endocrinology and metabolism
Journal of Clinical Oncology 5 26.303 Q1 Oncology
Bone 4 4.455 Q1 Endocrinology and metabolism
Oral Surgery, Oral Medicine, Oral Pathology, 4 1.718 Q2 Dentistry, oral surgery, and medicine
Oral Radiology
Oral Oncology 3 4.636 Q1 Dentistry, oral surgery, and
medicine/oncology
Australian Dental Journal 2 1.494 Q3 Dentistry, oral surgery, and medicine
Journal of Cranio-Maxillofacial Surgery 2 1.960 Q2 Dentistry, oral surgery, and
medicine/surgery
Journal of Dental Research 2 5.380 Q1 Dentistry, oral surgery, and medicine
Journal of Oral Pathology and Medicine 2 2.237 Q1 Dentistry, oral surgery, and medicine
New England Journal of Medicine 2 79.258 Q1 Medicine, general and internal
American Journal of Medicine 2 5.117 Q1 Medicine, general and internal
Journal of Rheumatology 2 3.470 Q2 Rheumatology
Medical Journal of Australia 2 4.227 Q1 Medicine, general and internal
Annals of Internal Medicine 1 19.384 Q1 Medicine, general and internal
Australian Endodontic Journal 1 1.371 Q3 Dentistry, oral surgery, and medicine
Blood 1 15.132 Q1 Hematology
Breast Cancer Research and Treatment 1 3.605 Q2 Oncology
British Journal of Haematology 1 5.128 Q1 Hematology
British Journal of Oral and Maxillofacial 1 1.260 Q3 Dentistry, oral surgery, and
Surgery medicine/surgery
Cancer 1 6.537 Q1 Oncology
Clinical Cancer Research 1 10.199 Q1 Oncology
Clinical Therapeutics 1 3.185 Q2 Pharmacology and pharmacy
Critical Reviews in Oncology/Hematology 1 4.495 Q1 Hematology
Dentomaxillofacial Radiology 1 1.848 Q2 Dentistry, oral surgery, and medicine
European Urology 1 17.581 Q1 Urology and nephrology
Haematologica 1 9.090 Q1 Hematology
International Journal of Oral and 1 1.699 Q2 Dentistry, oral surgery, and medicine
Maxillofacial Implants
Journal of Bone and Mineral Metabolism 1 2.472 Q3 Endocrinology and metabolism/medicine,
research, and experimental
Journal of Cancer Research and Clinical 1 3.282 Q2 Oncology
Oncology
Journal of Clinical Periodontology 1 4.046 Q1 Dentistry, oral surgery, and medicine
Journal of Periodontology 1 3.392 Q1 Dentistry, oral surgery, and medicine
Journal of the National Cancer Institute 1 11.238 Q1 Oncology
Laryngoscope 1 2.442 Q2 Otorhinolaryngology
Mayo Clinical Proceedings 1 7.199 Q1 Medicine, general and internal
Oncology 1 Not available in JCR 2017
Osteoporosis International 1 3.856 Q2 Endocrinology and metabolism
Journal of Clinical Endocrinology 1 5.789 Q1 Endocrinology and metabolism
and Metabolism
Lancet Oncology 1 36.418 Q1 Oncology
Virchows Archiv 1 2.936 Q2 Pathology
Abbreviations: JCR, Journal Citation Reports Science Edition; Q, quartile.
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillofac Surg 2019.
DINIZ-FREITAS ET AL
FIGURE 2. Coauthor analysis mapping among the 24 countries. The size of the points represents the frequency of coauthorship. The line be-
tween 2 points represents the collaboration between authors from different countries. The thicker the line, the closer the collaboration between 2
authors.
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillofac Surg 2019.
cancer, the quality of the evidence was low owing to
the high risk of bias and the observational nature of
most of the included studies. Despite research efforts,
MRONJ remains a difficult-to-treat disease. El-Rabbany
et al21 conducted a systematic review of the effective-
ness of various treatment modalities used for MRONJ.
The results suggested that surgery for MRONJ can
result in greater rates of complete resolution than
medical treatment, although the available evidence
for supporting these conclusions was based on studies
of low to medium quality. It has been suggested that
the disease’s undetermined pathogenesis and low inci-
dence rate have impeded the design and implementa-
tion of well-controlled studies with adequate
statistical power.22
In general terms, it has been suggested that the
scarcity of RCTs in the setting of maxillofacial surgery
could have resulted from factors such as the center in
which the treatment is performed (academic vs.
nonacademic), the resources required to implement
an RCT, and the immediacy of increasing the curricu-
lum vitae (prioritizing the number of reports over their
quality).23
Although efforts have been made in recent years to
improve the quality of research, the vast majority of
the most cited studies of MRONJ had a low evidence
level, confirming that the most cited reports were
not necessarily those of greater quality in terms of
research method.24,25 The results of the present
1.e13
study are consistent with those from previous
studies, which have reported a low level of evidence
in dentistry6 and craniomaxillofacial surgery data.23
However, although case series and narrative reviews
have a low level of evidence, in many situations they
will represent the best available evidence in clinical
practice, and, in some situations, it could be difficult
to conduct a randomized or cohort study.26
The 100 selected studies had been reported in scien-
tific journals with high impact factors and were mostly
included in the first quartile of their category. It has
been shown that studies reported in journals with
high impact factors will be cited more frequently
than those reported in less prominent journals.27
However, this could simply reflect the ability of the
best journals to attract better articles.
All the studies included in the present analysis had
been reported in English. Also, the country affiliation
for most of the first authors had been the United States,
both very common situations in this type of
review.28,29
We also noted a scarce presence of nonbisphospho-
nate antiresorptive agents and antiangiogenic agents in
use among the most cited reports. This finding could
have been because this association has been reported
more consistently after 2010. Also, it was not until
2014 that these agents had been included in the diag-
nostic criteria for MRONJ.3 Therefore, studies that had
addressed these drugs have had a shorter time to be
1.e14 BIBLIOMETRIC ANALYSIS OF MRONJ

Table 5. DESCRIPTIVE STATISTICS AND BIVARIATE ANALYSIS TO IDENTIFY BIBLIOMETRIC VARIABLES ASSOCIATED
WITH CITATION DENSITY

Mean Citation Minumum Maximum

Variable Authors (n) Density Citation Density Citation Density r* P Value

Authors 0.124 .221

Country (first author) 0.641 .813
United States 56 25.7  25.1 6.2 99.4
Greece 7 23.7  16.4 9.8 59.5
Germany 6 13.7  3.2 9.9 17.3
Australia 6 12.8  10.9 6.7 35.0
Italy 6 12.8  5.8 7.9 24.3
Canada 4 31.3  23.7 11.3 59.5
Israel 3 11.42  1.9 9.6 13.4
Spain 3 13.1  2.8 10.1 15.7
Belgium 2 12.1  6 7.8 16.3
United Kingdom 2 12.7  0.7 12.2 13.3
New Zealand 2 18.4  1.3 17.5 19.4
France 1 11.5
Switzerland 1 13.5
Japan 1 14.0
JCR category 0.285 .983
Dentistry, oral surgery, and medicine 54 21.5  23 6.2 99.4
Oncology 16 21.5  14.1 7.8 59.5
Endocrinology and metabolism 11 27  25.7 9.6 90.1
Medicine, general and internal 8 26.9  22.9 9.1 71.6
Hematology 4 15.8  3.7 12.3 20.5
Rheumatology 2 12.1  1.2 11.3 13.0
Otorhinolaryngology 1 11
Pathology 1 9.9
Pharmacology and pharmacy 1 17.0
Urology 1 10.0
Impact factor 0.085 .401
Quartile 1.181 .311
Q1 54 20.5  17.1 7.6 90.1
Q2 40 24.7  25.8 6.2 99.4
Q3 5 11  3.9 6.7 14.3
Type of research 2.269 .135
Primary 64 19.3  18.5 7.6 99.4
Secondary 36 25.8  24.0 6.2 96.0
Study design 1.042 .411
Case series 31 25.8  24.7 7.9 99.4
Narrative review 30 23.8  23.5 6.2 96.0
Retrospective/prospective cohort 15 16.4  8.7 8.6 41.7
Case control 10 12.6  4.8 9 24
Systematic review 5 34.5  28.7 11.3 71.6
Case report 4 11.42  4.2 7.6 16.4
Animal study 3 11.8  1.0 10.6 12.6
Cross sectional 1 10.0
In vitro study 17.5
Level of evidence 0.859 .465
II 7 32.2  25.4 11.1 71.6
III 10 15.1  6.2 8.6 26.1
IV 45 22.7  23.6 6.7 99.4
V 29 22.5  20.5 6.2 96.0
Funding 1.048 .309
Yes 24 17.9  17.6 7.6 90.1
No 76 22.8  21.6 6.2 99.4
DINIZ-FREITAS ET AL 1.e15

Table 5. Cont’d

Mean Citation Minumum Maximum

Variable Authors (n) Density Citation Density Citation Density r* P Value

Conflicts of interest
Yes 28 31.9  25.4 9.9 96 10.423 .002y
No 72 17.9  17.2 6.2 99.4
Open access 0.65 .799
Yes 16 22.9  20.8 6.7 90.1
No 84 21.4  20.8 6.2 99.4

Abbreviations: JCR, Journal Citation Reports Science Edition; Q, quartile.

* Bivariate correlations were computed using the Pearson correlation coefficient for continuous and ordinal measurements
and Student’s t test and analysis of variance for categorical measurements.
y Statistically significant associations (P < .05).
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillofac Surg 2019.

cited. The broadening of indications for the use of the absolute number of citations in the Scopus data-
antiresorptive and antiangiogenic drugs and the use base. It is, therefore, possible that other studies with
of other biologic agents such as tyrosine kinase inhib- a greater number of citations among databases such
itors, mammalian target of rapamycin inhibitors, and as WOS and Google Scholar were not included in
cytotoxic chemotherapy could increase the risk of this ranking. The time factor would also have a clear
MRONJ30,31 and, thus, become the subject of effect on this aspect. Recently reported studies could
relevant studies in the near future. be at a disadvantage and undervalued in terms of their
In the present series, we found a predominance of scientific effect because they would have had less time
studies with clinical content compared with those re- to accumulate citations.32 This can be partially reme-
porting basic research. This finding was also observed died by analyzing the mean number of annual citations
when analyzing the most cited studies in other medical (citation density).33 Furthermore, the true effect of a
disciplines.6 study cannot be adequately assessed for at least
The present study had certain limitations that 20 years after its publication.34
should be considered. Although we conducted a thor- The 2 most widely used methods for measuring the
ough search in the Scopus database, some studies quality of a scientific study have been the number of
could have been omitted. The present study used a citations received and the impact factor of the journal
cross-sectional design, and we had recorded the data in which the article was reported. Despite a number of
at a single moment in time. Our primary objective disadvantages in assessing the quality of articles based
was to identify the most cited studies according to solely on quantifying the number of citations, it is
currently the most accepted method for judging an
article’s or journal’s merits, and its use has been
Table 6. MULTIPLE LINEAR REGRESSION MODEL TO
INVESTIGATE RELATIONSHIP BETWEEN SELECTED reported in several medical disciplines.35
ARTICLE CHARACTERISTICS AND CITATION DENSITY A number of investigators have reported that the
impact factor is not useful for analyzing an article’s
Predictor Variable r t P Value scientific quality owing to the impact factor’s limita-
tions, which include that the impact factor is not
Conflicts of interest 0.27 2.38 .020*
comparable between different areas of research.35 In
Country (first author) 0.23 2.06 .043*
Funding 0.22 1.94 .056
the field of odontology, only 2 journals, at present,
Impact factor 0.10 0.81 .421 have had an impact factor greater than 5. The present
JCR category 0.19 1.42 .159 analysis, therefore, used a distribution by quartile
JCR quartile 0.04 0.33 .739 within each JCR category to assess the various scienti-
Level of evidence 0.14 0.98 .330 fic journals.
Number of authors 0.16 1.31 .195 The 100 most cited studies on MRONJ are consid-
Open access 0.11 0.98 .329 ered important in the field of oral and maxillofacial
Type of study 0.04 0.36 .723 disease and in other areas of biomedical research.
Abbreviation: JCR, Journal Citation Reports Science Edition. These studies can indicate how research on MRONJ
* Statistically significant association (P < .05). has evolved, the future direction of research, the
Diniz-Freitas et al. Bibliometric Analysis of MRONJ. J Oral Maxillo- most active areas in this field, and the most studied
fac Surg 2019. topics. The present study also identified the
1.e16
investigators who have reported the essential findings
and the journals in which the findings were reported.
This approach is also interesting from an educa-
tional and economic point of view. First, the most cited
reports could be included in study programs (in this
case, for MRONJ), given that the clinicians and
researchers involved with this disease should be
knowledgeable about these studies.36 In addition,
citation analysis is a tool that quantitatively analyzes
a researcher’s or research group’s scientific produc-
tion, which has been increasingly considered when
obtaining financing.37
The role of the lay press in general terms consists of
identifying findings of considerable interest and
communicating them to the general population,
mainly to individuals with limited education regarding
understanding academic data. Paradoxically, the media
have preferentially covered methodologically weak
medical research (preferring observational studies to
clinical trials).38 It has been suggested that most
studies selected by newspapers and other popular me-
dia outlets have received more citations.39 However,
the studies covered have been extracted from a very
small number of journals, mostly Nature and
Science.39 The main reason for the high number of
citations these studies will receive is likely the strict
selection criteria for studies reported in these journals
and not the dissemination of these articles in the lay
press. Of the 100 selected articles on MRONJ with
the most citations in Scopus, we found that only 2
had achieved an Altmetric Attention Score greater
than 10 points (available at: www.altmetrics.com).
In conclusion, the 100 most cited articles on MRONJ
had a large number of citations, had all been reported
in English, and most had been generated in the United
States. Most of the studies had been reported in
journals with a high impact factor; however, their evi-
dence level was generally low, and RCTs were lacking.
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