Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

Contents lists available at ScienceDirect

Journal of Cranio-Maxillo-Facial Surgery

journal homepage: www.jcmfs.com

Review

Diagnostic accuracy of bone SPECT and SPECT/CT imaging in the diagnosis

of unilateral condylar hyperplasia: A systematic review and meta-analysis
L.H.E. Karssemakers a, b, *, L.M.P. Besseling a, L.J. Schoonmade c, N. Su a, d, J.W. Nolte a,
P.G. Raijmakers e, A.G. Becking a, f
a
Department of Oral and Maxillofacial Surgery, Amsterdam UMC/Emma Children’s Hospital, and Academic Centre for Dentistry Amsterdam (ACTA), University of
Amsterdam, Amsterdam, the Netherlands
b
Department of Head and Neck Surgery & Oncology, Netherlands Cancer Institute, Antoni Van Leeuwenhoek, Amsterdam, the Netherlands
c
Medical Library, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
d
Department of Oral Public Health, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the
Netherlands
e
Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
f
Department of Oral and Maxillofacial Surgery, MKA Kennemer & Meer, Haarlem, the Netherlands

A R T I C L E I N F O A B S T R A C T

Handling Editor: Prof. Emeka Nkenke Imaging with bone scans plays an important role in the diagnostic path of patients with unilateral condylar
hyperactivity or unilateral condylar hyperplasia (UCH). The aim of this study is to perform a systematic review of
Keywords: the diagnostic performance of the bone SPECT and SPECT/CT scan for the diagnosis of UCH.
MeSH keywords: mandible PubMed, SCOPUS and EMBASE were searched electronically to identify diagnostic accuracy studies that
Hyperplasia
assessed the diagnostic value of bone SPECT and SPECT/CT for the diagnosis of UCH, Meta-analyses were
Condyle
performed with Metadisc 1.4 and 2.0.
SPECT
Hyperactivity A total of 14 studies, with a total number of 887 patients, were included in the qualitative analysis and 11
Growth studies qualified for meta-analyses. The pooled sensitivity and specificity for the SPECT scan were 0.814 (95 %
SPECT/CT CI: 0.639-0.915) and 0.774 (95 % CI: 0.655-0.861), for the SPECT/CT scan these were 0.818 (95 % CI: 0.749-
0.874) and 0.901 (95 % CI: 0.840-0.945). The summary receiver operating characteristics of the SPECT scan
showed an area under the curve of 0.847 (95 % CI: 0.722-0.972) and that of the SPECT/CT scan was 0.928 (95 %
CI: 0.876-0.980).
Conclusion: Both bone SPECT scan and SPECT/CT scan provide a high diagnostic accuracy for UCH. The added
value of the SPECT/CT scan is questionable and given the potential disadvantages of the SPECT/CT scan,
including the increased radiation dose and costs, the diagnostic modality of first choice in patients with UCH
should be a SPECT scan.

1. Introduction and (serial) clinical and radiological examinations, this can guide the
clinician in the decision-making. If the mandibular asymmetry is pro­
Unilateral condylar hyperactivity is responsible for the diverse gressive and there is a unilateral condylar hyperactivity, the preferred
phenotypes in unilateral condylar hyperplasia (UCH). The misbalanced treatment to arrest the ongoing activity is a condylectomy. If there is a
bone activity in the mandibular condyles of patients with unilateral stable asymmetry with a balanced activity in the condyles, the aim of the
condylar hyperactivity causes facial asymmetry and subsequent treatment can be direct correction of the asymmetry, without the need to
disturbed dental occlusion. This potentially leads to unfavourable perform a condylectomy (Ghawsi et al., 2016).
function and aesthetics. An important factor in the diagnostic path of Bone scanning is the preferred diagnostic method to determine the
patients with suspected UCH is an accurate assessment of the bone ac­ condylar bone activity. It is performed by intravenous injection of
tivity in the mandibular condyles. Together with the patient’s history 99mTc-labeled (methyl- or hydroxy-) diphosphonate, which interacts

* Corresponding author. Department of Oral and Maxillofacial Surgery, Amsterdam UMC , University of Amsterdam Department of Head and Neck Surgery and
Oncology, The Netherlands Cancer Institute / Antoni van Leeuwenhoek Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
E-mail address: [email protected] (L.H.E. Karssemakers).

https://doi.org/10.1016/j.jcms.2024.01.013
Received 3 June 2023; Received in revised form 26 October 2023; Accepted 16 January 2024
Available online 24 January 2024
1010-5182/© 2024 The Authors. Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery. This is an open access article under
the CC BY license (http://creativecommons.org/licenses/by/4.0/).
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

with the crystalline hydroxyapatite in the mineral phase of the bone and Two reviewers (L.B. and L.K.) independently screened all potential
therefore reflects the osteogenic activity (Adams and Banks 2022). The relevant titles and abstracts for eligibility. The first selection process was
technique to visualize this activity has evolved within the past decades. done using www.rayyan.ai. After the first selection, the selected articles
From planar scanning in the late 1970s and early 1980s to the more were full-text reviewed by the same reviewers independently. Reference
recently introduced single photon emission computed tomography lists of the included articles were checked for any additional studies.
(SPECT)/computed tomography (CT) scanning. In 1978, Donoff intro­ Any discrepancies were resolved by consensus. After the first selec­
duced qualitative assessment of bone scintigraphy to evaluate facial tion, the full text was obtained for further review. Studies with over­
asymmetry (Donoff et al., 1978). Cisneros and Kaban modified the lapping study population were only included once.
technique and used planar scanning and quantitative assessment (Kaban
et al., 1982; Cisneros and Kaban 1984). The scintigraphic activity of the
condyles was evaluated as a ratio in relation to the fourth lumbar 2.3. Methodological quality assessment
vertebra. With SPECT, a tomographic reconstructed image can be pro­
duced. In 1995, Pogrel et al. was the first to publish the SPECT technique The included studies were assessed for risk of bias using the revised
in a population of UCH patients (Pogrel et al., 1995). In a systematic Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool (Whiting
review by Saridin et al., the diagnostic value of the planar scan tech­ et al. 2011). All studies were assessed by summarizing the primary study
nique and the SPECT scan technique in patients with UCH was assessed in a flow diagram and by rating the risk of bias of the study by answering
(Saridin et al., 2011). They concluded that, due to the superior sensi­ the signal questions on four key domains; patient selection, index test,
tivity of the SPECT in comparison with planar bone scanning, quanti­ reference standard, and flow and timing. Quality assessment was done
tative assessment of the SPECT scan is the preferred diagnostic method independently by two reviewers (L.B. and L.K.). Any discrepancies be­
for patient with UCH. After this review, the three-dimensional imaging tween the two reviewers were resolved by consensus.
technique SPECT with computed X-ray tomography (CT) gained popu­ If the signal questions of one domain were all answered the same, the
larity. The diagnostic performance of the SPECT/CT in patients with risk of bias of that domain was ranked in the corresponding category. If
UCH seems promising, yet the benefit of the SPECT/CT scan compared there were any inconsistencies within the answers to the signal ques­
to the SPECT is questionable (Karssemakers et al., 2022). tions, the following downgrading was applied: if one of the answers to
The aim of this study is to perform a systematic review of the diag­ the signal questions was “no", both in combination with an answer “yes"
nostic performance of the SPECT and SPECT/CT scan for the diagnosis of or “unclear", the risk of bias of that domain was considered high. The
UCH. risk of bias of a domain was found to be unclear if the answers to the
signal questions were both “yes" and “unclear".

2. Materials and methods

2.4. Data extraction and data analysis
2.1. Search strategy
The following relevant data were extracted from the included arti­
This systematic review was conducted in accordance with the cles: 1) study design; 2) diagnostic scans used; 3) number of people in
Preferred Reporting Items for Systematic Reviews and Meta-Analyses test groups; 4) number of people in control groups; 5) mean age of test
(PRISMA) statement (www.prisma-statement.org) (Page et al., 2021). population; 6) mean age of control population; 7) index test; 8) methods
A comprehensive search was performed in the bibliographic databases of quantification; 9) quantitative assessment; 10) reference standards;
PubMed, Embase.com and Scopus from inception to September 8, 2022, 11) sensitivity SPECT/SPECT/CT; 12) specificity SPECT/SPECT/CT; 13)
in collaboration with a medical librarian (L.S.). Search terms included positive predictive value (PPV) SPECT/SPECT/CT; 14) negative pre­
controlled terms (MeSH in PubMed and Emtree in Embase) as well as dictive value (NPV) SPECT/SPECT/CT.
free text terms. The following terms were used (including synonyms and
closely related words) as index terms or free-text words: ‘condylar hy­
perplasia’ and ‘radionuclide imaging’ or similar diagnostic tools. A 2.5. Data analysis
search filter was applied to exclude animal studies. The search was
performed without date or language restrictions. Duplicate articles were The data analysis was conducted using Meta-DiSc 1.4 and Meta-DiSc
excluded. The full search strategies for all databases can be found in the version 2.0 (Meta-Disc, Clinical Biostatistics Unit, Ramon y Cajal Hos­
Supplementary Information. pital, Madrid, Spain). A random-effect model was used to calculate the
overall pooled estimates of sensitivity, specificity, positive likelihood
ratio (LR+), negative likelihood ratio (LR− ), and diagnostic odds ratio
2.2. Selection process (DOR) with 95 % confidence intervals (CIs). The forest plot and sum­
mary receiver operating characteristic (sROC) curve were generated to
Studies were included if they met the following inclusion criteria: graphically present the interaction between sensitivity and specificity.
The overall test performance was quantified using the area under the
• Study reporting on unilateral condylar hyperactivity/hyperplasia sROC curve (sAUC) and Q* (the point where sensitivity equals speci­
• SPECT and/or SPECT/CT was part of the diagnostic workup ficity on the sROC curve). The sAUC measures the overall capacity of the
• Article published between 1960 and 2022, test to discriminate between participants with the disease and those
• Clinical patient study without it. A sAUC of 0.5 or lower indicates no discriminative ability.
• Study focusses on diagnostic methods The higher a sAUC is, the higher the diagnostic accuracy is.
• Minimum of 10 patients included and/or 10 diagnostic scans per­
formed (control group not included). 3. Results

Studies were excluded if they met the following exclusion criteria: 3.1. Search results

• The language of the article was other than English, Dutch or German, After removing duplicate studies, 1672 studies were assessed for
• The article was a non-clinical study (oral presentation, poster pre­ their eligibility based on the title and abstract. A total of 76 articles were
sentation, correspondence, laboratory study, systematic review) or eligible for full text screening. Ultimately, 14 articles met the inclusion
case studie. criteria. Reasons for exclusions are shown in the flow chart (Fig. 1).

448
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

Fig. 1. PRISMA 2009 flow diagram.

3.2. QUADAS-2 2022), the SPECT/CT scan in three studies (Hamed et al., 2017; Mostafa
et al., 2021; Karssemakers et al., 2022) and another three studies
Overall, the risk of bias regarding the domain ‘flow and timing’ was examined both SPECT and SPECT/CT (Theerakulpisut et al., 2016;
considered high. In most studies, there was an undefined interval be­ Agarwal et al., 2017; Liu and Shi 2019). All studies, except for Mostafa
tween the index test and the reference standard, not all test subjects et al. (2020), used clinical examination (Hodder et al., 2000; Pripatna­
were included in the analysis (sometimes due to lack of follow-up) or the nont et al., 2005; Saridin et al., 2008; AlSharif et al., 2014; Wen et al.,
test subjects did not receive the same reference standard. 2014; Rushinek et al., 2016; Theerakulpisut et al., 2016; Agarwal et al.,
The complete risk of bias assessment is shown in Table 1. 2017; Hamed et al., 2017; Chan and Leung 2018; Liu and Shi 2019;
Karssemakers et al., 2022) and/or radiological examination (Hodder
et al., 2000; Pripatnanont et al., 2005; Saridin et al., 2008; AlSharif
3.3. Summary of the general characteristics of the included studies et al., 2014; Wen et al., 2014; Agarwal et al., 2017; Hamed et al., 2017;
Chan and Leung 2018; Liu and Shi 2019; Karssemakers et al., 2022; Xiao
The study size of the 14 included studies ranged from 18 to 200 et al., 2022) as the reference standard. Seven studies (Pripatnanont
patients; a total of 887 patients were included (Table 2). In all studies, et al., 2005; Saridin et al., 2008; Agarwal et al., 2017; Hamed et al.,
the majority of the patients in the test group were female. The average 2017; Chan and Leung 2018; Karssemakers et al., 2022; Xiao et al.,
percentage of female patients was 62.6 % ± 8.52 % (range 52.4 %-77.8 2022) explicitly mentioned that serial clinical or radiological assessment
%). The age of the test population in the studies ranged between 8 and during follow-up was part of the reference standard, and five studies
66 years, with a mean age of 21.1 ± 1.3 years. (Wen et al., 2014; Agarwal et al., 2017; Hamed et al., 2017; Mostafa
Of the included studies, six studies were performed prospectively et al., 2021; Karssemakers et al., 2022) used histopathological exami­
(Pripatnanont et al., 2005; Saridin et al., 2008; Wen et al., 2014; nation as part of the reference standard (Table 2).
Rushinek et al., 2016; Mostafa et al., 2021; Karssemakers et al., 2022).
The SPECT scan was examined in eight studies (Hodder et al., 2000;
Pripatnanont et al., 2005; Saridin et al., 2008; AlSharif et al., 2014; Wen
et al., 2014; Rushinek et al., 2016; Chan and Leung 2018; Xiao et al.,

449
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

Table 1 Theerakulpisut et al., 2016; Agarwal et al., 2017; Hamed et al., 2017;
Risk of bias according to QUADAS-2 (Hodder et al., 2000; Pripatnanont et al., Chan and Leung 2018; Liu and Shi 2019). Saridin et al. and Rushinek
2005; Saridin et al., 2008; AlSharif et al., 2014; Wen et al., 2014; Rushinek et al., et al. used a cut-off value of 56.0 % and 56.1 %, respectively (Saridin
2016; Theerakulpisut et al., 2016; Agarwal et al., 2017; Hamed et al., 2017; et al., 2008; Rushinek et al., 2016). Karssemakers et al. also used a
Chan and Leung 2018; Liu and Shi 2019; Mostafa et al., 2021; Karssemakers cut-off value of >55.0 %; however, they found that for the SPECT/CT a
et al., 2022).
cut-off of >54.0 % resulted in the best diagnostic accuracy (Karsse­
Study Patient Index Reference Flow & makers et al., 2022). The study by Hamed et al. was the only one that
selection test standard timing
used a combined quantification method to diagnose UCH. In their study,
1 Agarwal et al. ☺ ☺ ☺ ? a patient was considered to have UCH when the affected condyle showed
(2017) a relative activity uptake of ≥55 %, an absolute condylar uptake of >10
2 Alsharif et al. ?
%, a radiotracer count ratio of >1.10, a condyle-to-clivus ratio of >1.44
☹ ☺ ☺
(2014)
3 Chan and Leung ☹ ☺ ☺ ☺ and an enlarged condyle with sclerosis and ground glass haziness on the
(2018) CT scan (Hamed et al., 2017).
4 Hamed (2017) ☺ ☺ ☺ ☹
5 Hodder et al. (2000) ☹ ? ? ?
6 Karssemakers et al. ☺ ☺ ☺ ☺ 3.5. Qualitative analysis
(2022)
7 Liu and Shi (2019) ☺ ☺ ☺ ? Due to the increased heterogeneity, three studies were included only
8 Mostafa (2020) ☹ ☺ ☹ ☹
in the qualitative analysis (Hodder et al., 2000; Pripatnanont et al.,
9 Pripatnanont et al. ☹ ? ☺ ☹
(2005) 2005; Theerakulpisut et al., 2016). Hodder et al. were the first to indi­
10 Rushinek et al. ☹ ☺ ☺ ? cate that the condylar difference of more than 10 % is indicative for
(2016) UCH; they reported a sensitivity and specificity of 100 % (Hodder et al.,
11 Saridin et al. (2009) ☺ ☺ ☺ ☹ 2000). Pripatnanont et al. confirmed this 10 % cut off in their population
12 Theerakulpisut ☹ ☺ ☹ ☹
et al. (2016)
of 21 patients. However, both studies lack sufficient data to calculate
13 Wen et al. (2014) ☹ ? ? ☹ reliable accuracy of their index test. Theerakulpisut et al. focused on the
14 Xiao et al. (2022) ☺ ☺ ☺ ☹ agreement between the SPECT and SPECT/CT and did not correlate the
diagnostic findings with the gold standard. Therefore, diagnostic accu­
racy with sensitivity and specificity outcomes could not be obtained
3.4. Quantification method
(Theerakulpisut et al., 2016).

Studies differed in their analytical method to determine the activity

of the mandibular condyles. In the SPECT/CT group, all studies used the 3.6. Quantitative analysis
CT scan to orientate and align the SPECT scan and to apply attenuation
correction. Liu et al. drew an anatomical volume of interest around the The pooled sensitivity for the SPECT scan and SPECT/CT scan was
mandibular condyle on the CT scan and determined the activity within 0.814 (95 %CI: 0.639-0.915) and 0.818 (95 %CI: 0.749-0.874)
this volume. Most other studies centred the region of interest on the (Table 3a+3c and Fig. 2a +b). For the SPECT scan the pooled speci­
hyperactive part of the ipsilateral condyle and copied it to the contra­ ficity was 0.774 (95 %CI: 0.655-0.861), for the SPECT/CT the pooled
lateral side. The condylar activity was calculated using the absolute specificity was 0.901 (95 %CI: 0.840-0.945) (Table 3a+3ctbl3a and
condylar uptake difference between the right and left condyle or as a Fig. 3a +b). For the SPECT, the pooled LR-was 0.24 (95 %CI: 0.11-0.53)
relative uptake difference by dividing the ipsilateral condylar uptake and the LR+ was 3.60 (95 %CI: 2.13-6.10), for the SPECT/CT the LR-was
with the total condylar uptake of the right and left condyle. The cut-off 0.22 (95 %CI: 0.16-0.30) and the LR+ was 7.13 (95 %CI: 4.40-11.56)
values used for the relative uptake difference were mostly >55 % (Table 3a + 3c). The χ2 between-study heterogeneity for the sensi­
(AlSharif et al., 2014; Mostafa et al., 2021; Karssemakers et al., 2022; tivity and specificity of the SPECT studies was 56.23 and 25.82, with an
Xiao et al., 2022) or ≥55 % (Hodder et al., 2000; Wen et al., 2014; I2 of 87.60 and 72.90. For the SPECT/CT the χ2 between-study hetero­
geneity was 2.43 and 4.69, with an I2 of 0.00 and 14.6. When removing

Table 2
General characteristics of the included studies. NR: not reported, CE: clinical examination, RE: radiological examination, HPE: histopathological examination.
STUDY (FIRST YEAR OF DESIGN INDEX TEST TEST GROUP SIZE AGE, YR, MEAN ± SD FOLLOW-UP, MO, MEAN REFERENCE
AUTHOR) PUB. (FEMALES) (RANGE) ± SD (RANGE) STANDARD

AGARWAL 2017 Retrospective SPECT, 21 (11) 21.9 ± 5.3 (14–35) NR follow-up CE, RE,
SPECT/CT HPE
Al-sHARIF 2014 Retrospective SPECT 33 (25) 22.1 ± 6.4 (15-42) 44.1 ± 19.4 (8-75) CE, RE
CHAN 2018 Retrospective SPECT 200 (118) 21.0 ± 4.3 (NR) 12.0 ± NR (NR) CE, RE, serial
assessment
HAMED 2017 Retrospective SPECT/CT 20 (14) 23.0 ± 6.4 (12-36) NR follow-up CE, RE,
HPE
HODDER 2000 Retrospective SPECT 18 (14) 20.0 ± NR (13–34) 2.8 ± NR (1-5) CE, RE
KARSSEMAKERS 2022 Prospective SPECT/CT 156 (84) 19.7 ± 7.6 (11–54) 26.4 ± 15.6 (4-78) follow-up CE, RE,
HPE
LIU 2019 Retrospective SPECT, 56 (32) 19.8 ± NR (15-28) NR CE, RE
SPECT/CT
MOSTAFA 2020 Prospective SPECT/CT 24 (13) 23.0 ± 7.0 (NR) 12.0 ± NR (NR) HPE
PRIPATNANONT 2005 Prospective SPECT 21 (14) NR ± NR (12-46) NR ± NR (1-4) follow-up CE, RE
RUSHINEK 2016 Prospective SPECT 51 (27) 21.5 ± NR (8-66) NR CE, questionnaires
SARIDIN 2008 Prospective SPECT 56 (34) 21.3 ± NR (12-43) 9.0 ± NR (1.8-16.2) follow-up CE, RE
THEERAKULPISUT 2016 Retrospective SPECT, 51 (36) 21.6 ± 3.4 (NR) NR CE
SPECT/CT
WEN 2014 Prospective SPECT 105 (63) 21.5 ± NR (13-33) NR CE, RE, HPE
XIAO 2022 Retrospective SPECT 75 (49) 18.9 ± 5.7 (NR) NR RE

450
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

Table 3 the study of Chan et al., (2018 (Chan and Leung 2018) and Xiao et al.,
a and 3bDiagnostic accuracy of the included studies for the SPECT scan in UCH 2022 (Xiao et al., 2022), the χ2 between-study heterogeneity for the
with (3a) and without the study of Chan and Leung, 2018; Xiao et al., (2022) SPECT changed to 4.29 for the sensitivity and 11.15 for the specificity,
(3b). TP: true positive, FP: false positive, FN: false negative, TN: true negative, with an I2 of 0.00 and 55.2, respectively (Table 3b). The diagnostic odds
Se: sensitivity, Sp: specificity, PPV: positive predictive value, NPV: negative ratio of the SPECT was 20.456 (95 %CI: 7.439-56.25) and of the
predictive value, LR-: negative likelihood ratio, LR+: positive likelihood ratio.
SPECT/CT was 34.20 (95 %CI: 17.31-67.58) (40.985 (20.703-81.138)
TP FP FN TN Se Sp LR- LR+ with a χ2 between-study heterogeneity of 31.39 for the SPECT and 3.58
Agarwal et al. 12 2 3 4 0.80 0.67 0.30 2.40 for the SPECT/CT and an I2 of 80.9 and 0.00, respectively.
(2017) Fig. 4a and b shows the summary receiver operating characteristic
Alsharif et al. 15 2 2 14 0.88 0.88 0.13 7.06 (sROC) curve for both the SPECT scan and SPECT/CT scan. The area
(2014)
under the curve (AUC) of the SPECT scan was 0.847 (95 % CI: 0.722-
Chan and Leung 11 36 23 130 0.32 0.78 0.86 1.49
(2018) 0.972) and the AUC of the SPECT/CT scan was 0.928 (95 % CI: 0.876-
Liu and Shi (2019) 25 5 5 21 0.83 0.81 0.21 4.33 0.980).
Rushinek et al. 7 10 1 33 0.88 0.77 0.16 3.76
(2016)
4. Discussion
Saridin et al. 27 1 2 26 0.93 0.96 0.07 25.14
(2008)
Wen et al. (2014) 38 7 2 11 0.95 0.61 0.08 2.44 The results of this systematic review indicate that the diagnostic
Xiao et al. (2022) 21 19 17 18 0.55 0.48 1.08 accuracy of both the SPECT and the SPECT/CT scan for diagnosing UCH
is good; there is no significant advantage of the SPECT-CT scan when
compared to the SPECT scan regarding the diagnosing hyperactivity.
Pooled 0.81 0.77 0.24 3.60
Heterogeneity (chi- 56.23 25.82 59.7 31.02
Establishing ongoing hyperactivity in the mandibular condyle is one
squared) of the main goals in the diagnostic path of patients with a suspected
Inconsistency (I-square) 87.60 72.90 88.3 77.4 UCH. This can be assessed indirectly by monitoring the patients’ clinical
TP FP FN TN Se Sp LR- LR+ situation in time on multiple moments (e.g. with dental casts, cone-beam
CT scanning or clinical photographs) or instantly by nuclear bone
Agarwal et al. (2017) 12 2 3 4 0,80 0,67 0,30 2,40
Alsharif et al. (2014) 15 2 2 14 0,88 0,88 0,13 7,06
scanning. The drawback of the indirect approach is that patients may
Liu and Shi (2019) 25 5 5 21 0,83 0,81 0,21 4,33 develop severe asymmetry during the follow-up time and have a delay in
Rushinek et al. 7 10 1 33 0,88 0,77 0,16 3,76 treating hyperactivity or correcting the asymmetric sequalae of UCH.
(2016) The severity of the asymmetry is related to the final outcome of the
Saridin et al. (2008) 27 1 2 26 0,93 0,96 0,07 25,14
patients. Patients treated in the early active phase of UCH tend to have a
Wen et al. (2014) 38 7 2 11 0,95 0,61 0,08 2,44
more symmetric final outcome after corrective osteotomy compared to
patients with more advanced asymmetry (Maniskas et al., 2020). This
Pooled 0.89 0.80 0.16 3.88 emphasizes the importance of adequately establishing the diagnosis of
Heterogeneity (chi- 4.29 11.15 4.12 8.86 hyperactivity in the condyles. SPECT scanning has shown to be an
squared)
excellent diagnostic modality for establishing condylar hyperactivity
Inconsistency (I-square) 0.00 55.2 0.00 43.6
(Saridin et al., 2011). However, with technological developments and
the introduction of hybrid scanning techniques, the SPECT/CT scan is
increasingly used in patients with UCH. The potential advantages of
Table 3c
combining functional imaging (SPECT) with anatomical orientation
Diagnostic accuracy of the included studies for the SPECT/CT scan in UCH.
(CT) are promising. With the use of the CT scan, the mandibular condyle
TP FP FN TN Se Sp LR- LR+ can be more easily located, and therefore the drawing a region of in­
Agarwal et al. (2017) 12 0 3 6 0.80 1.00 0.24 10.94 terest may be more accurate. In theory, the CT scan can also be used to
Hamed (2017) 12 0 2 6 0.86 1.00 0.18 11.67 rule out other bone pathology disorders, and it can be used for attenu­
Karssemakers et al. 62 9 15 70 0.81 0.89 0.22 7.07 ation correction (Patton and Turkington 2008). The most important
(2022)
Liu and Shi (2019) 23 4 7 22 0.77 0.85 0,28 4.98
disadvantage of the SPECT/CT is the increased radiation dose to the
Mostafa (2020) 21 1 2 24 0.91 0.96 0,09 22.83 patients (between 0.1 and 0.2 mSv), especially since the majority of UCH
patients are adolescents (Karssemakers et al., 2022). Furthermore,
addition of the CT scan leads to increase costs, and a mismatch of the CT
Pooled 0.82 0.90 0.22 7.13 and SPECT scan can potentially lead to errors in the interpretation.
Heterogeneity (chi- 2.43 4.69 2.42 2.36
Given these disadvantages and the already good diagnostic perfor­
squared)
Inconsistency (I-square) 0.00 14.6 0.00 0.00 mance of the SPECT scan, the added value of the SPECT/CT scan is
questionable. In the present study, the difference of the pooled sensi­
tivity of the SPECT and SPECT/CT is of non-significant clinical or

Fig. 2. a and 2b. Forest plot of sensitivity of the SPECT (a) and SPECT/CT scan (b).

451
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

Fig. 3. a and 3b. Forest plot of specificity of the SPECT (a) and SPECT/CT scan (b).

Fig. 4. a and 4bsROC curves of SPECT (a) and SPECT/CT scan (b).

statistical meaning (0.81 and 0.82, respectively). Albeit not statistically rule out other bone pathology (Saridin et al., 2010; Espinosa et al.,
significant, the pooled specificity of the SPECT/CT was 13 % higher than 2021). However, the potential bias regarding the reference standard
the pooled specificity of the SPECT (0.90 and 0.77, respectively). When applies for both the SPECT and SPECT/CT studies; therefore, the com­
relying completely on bone imaging when making a decision to perform parison of the diagnostic performance may still be valid.
a condylectomy, this difference could very well be of clinical relevance. Second, there was considerable variability among the studies
For example, 13 % more patients are falsely identified by the SPECT scan included in the SPECT scan analysis. The subanalysis (Tables 3a and 3b)
as UCH and possibly undergo an unnecessary condylectomy. However, showed that this was due mainly to the studies by Chan and Leung and
the majority of the literature states that the bone scan is used as a tool Xiao et al. (Chan and Leung 2018; Xiao et al., 2022). The study by Chan
supportive of the clinical situation and that the decision to perform a and Leung compared the results of the SPECT scan with serial radio­
condylectomy is certainly not solely made based on the SPECT scan graphic two-dimensional (2D) tracings during the follow-up time. None
results (Pripatnanont et al., 2005; Saridin et al., 2009; Agarwal et al., of the patients underwent operation during the follow-up time, and only
2017; Hamed et al., 2017; Karssemakers et al., 2022). The clinical 17 % of the patients were found to have active growth during follow-up.
relevance of this difference in the pooled specificity is therefore un­ The study by Xiao et al. compared the SPECT scan with serial 3D
known. When looking at the relationship of the sensitivity and speci­ assessment of the CBCT scan. They used a more than 5 % growth on
ficity at various thresholds, the SPECT/CT scan outperforms the SPECT multiple CBCT landmarks as evidence of active UCH. This interpretation
scan, with an AUC of 0.928 and 0.847, respectively. Again, the clinical of this gold standard of UCH is not demonstrated in other reports, and it
relevance of this difference is probably limited, and the disadvantages is questionable as to whether the sole use of the serial CBCT imaging
associated with SPECT/CT imaging are probably not justified by the with a cutoff of 5 % is valid. For these reasons, the significantly different
higher diagnostic performance of SPECT/CT. results of the Chan and Leung and the Xiao et al. studies should be
In interpreting the results of the present systematic review, there are interpret with caution; however, the studies did fulfill the criteria of the
some limitations. First, there is considerable bias in most of the studies, research question of this systematic review. Therefore, these studies
especially in the way in which h the reference standard was used. There were included in the definitive analysis; however, with a significantly
is no consensus as to what the gold standard definition for UCH is. In the lower sensitivity of 32 % and 55 % and a different research design
present review, most studies used a combination of serial clinical follow- compared to the other studies, they were outliers. The effect of these
up and histopathological examination as the gold standard (Agarwal studies on the pooled results were interpreted as of minor clinical value.
et al., 2017; Hamed et al., 2017; Karssemakers et al., 2022). Other
studies used only serial clinical or radiological examination (Pripatna­ 5. Conclusion
nont et al., 2005; Saridin et al., 2008; Chan and Leung 2018; Xiao et al.,
2022) or only histopathological examination (Wen et al., 2014; Mostafa Both bone SPECT scan and SPECT/CT scan provide a high diagnostic
et al., 2021). Although several common histopathological features of accuracy for UCH. The added diagnostic value of the SPECT/CT scan
UCH are mentioned in the literature, UCH remains a non-specific his­ above SPECT scanning is non-significant and given the potential dis­
topathology, and the histopathological examination is used mainly to advantages of the SPECT/CT scan, including the increased radiation

452
L.H.E. Karssemakers et al. Journal of Cranio-Maxillo-Facial Surgery 52 (2024) 447–453

dose and costs, the diagnostic modality of first choice in patients with MAG, Hamed, Alazzazy, M.Z., MAA, Basha, 2017. The validity of SPECT/CT in diagnosis
of condylar hyperplasia. The Egyptian Journal of Radiology and Nuclear Medicine
UCH should be a SPECT scan.
48 (2), 451–459, 12.
Maniskas, S., Ly, C.L., Parsaei, Y., Bruckman, K.C., Steinbacher, D.M., 2020. Facial
Funding asymmetry in unilateral condylar hyperplasia: comparing treatment for active versus
burnt-out disease. Plast. Reconstr. Surg. 146 (4), 439e–445e, 32.
Mostafa, N.M., Moustafa, S., Hussien, M.T., Ali, W.A., Osman, M.H., Shahine, M.S.,
None. Abdelhafez, Y.G., 2021. Utility of single-photon emission computed tomography/
computed tomography in suspected unilateral condylar hyperplasia: a
Declaration of competing interest histopathologic validation study. J. Oral Maxillofac. Surg. 79 (5), 1083.e1081-1083.
e1010.10.
Page, M.J., Mckenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D.,
None. Shamseer, L., Tetzlaff, J.M., Akl, E.A., Brennan, S.E., Chou, R., Glanville, J.,
Grimshaw, J.M., Hróbjartsson, A., Lalu, M.M., Li, T., Loder, E.W., Mayo-Wilson, E.,
Mcdonald, S., Mcguinness, L.A., Stewart, L.A., Thomas, J., Tricco, A.C., Welch, V.A.,
Appendix A. Supplementary data Whiting, P., Moher, D., 2021. The PRISMA 2020 statement: an updated guideline for
reporting systematic reviews. BMJ 372 n71.n72.
Supplementary data to this article can be found online at https://doi. Patton, J.A., Turkington, T.G., 2008. SPECT/CT physical principles and attenuation
correction. J. Nucl. Med. Technol. 36 (1), 1–10, 35.
org/10.1016/j.jcms.2024.01.013. Pogrel, M.A., Kopf, J., Dodson, T.B., Hattner, R., Kaban, L.B., 1995. A comparison of
single-photon emission computed tomography and planar imaging for quantitative
References skeletal scintigraphy of the mandibular condyle. Oral Surg. Oral Med. Oral Pathol.
Oral Radiol. Endod. 80 (2), 226–231, 26.
Pripatnanont, P., Vittayakittipong, P., Markmanee, U., Thongmak, S., Yipintsoi, T., 2005.
Adams, C., Banks, K.P., 2022. Bone Scan. StatPearls. Treasure Island (FL). StatPearls
The use of SPECT to evaluate growth cessation of the mandible in unilateral condylar
Publishing Copyright © 2022, StatPearls Publishing LLC.
hyperplasia. Int. J. Oral Maxillofac. Surg. 34 (4), 364–368, 15.
Agarwal, K.K., Mukherjee, A., St, A., Tripathi, M., Bal, C., 2017. Incremental value of
Rushinek, H., Tabib, R., Fleissig, Y., Klein, M., Tshori, S., 2016. Evaluation of three
single-photon emission computed tomography/computed tomography in the
analysis methods for (99m)Tc MDP SPECT scintigraphy in the diagnosis of unilateral
diagnosis of active condylar hyperplasia. Nucl. Med. Commun. 38 (1), 29–34, 7.
condylar hyperplasia. Int. J. Oral Maxillofac. Surg. 45 (12), 1607–1613, 16.
Alsharif, A.A., Tarawneh, E.S., Alkawaleet, Y.I., Abukaraky, A.E., Alahmad, H.T.,
Saridin, C.P., Raijmakers, P.G., Tuinzing, D.B., Becking, A.G., 2008. Comparison of
Malkawi, Z.A., Juweid, M.E., 2014. Standardization of quantitative single photon
planar bone scintigraphy and single photon emission computed tomography in
emission computed tomography in control individuals and in patients with condylar
patients suspected of having unilateral condylar hyperactivity. Oral Surg. Oral Med.
hyperplasia. Nucl. Med. Commun. 35 (12), 1268–1276, 8.
Oral Pathol. Oral Radiol. Endod. 106 (3), 426–432, 17.
Chan, B.H., Leung, Y.Y., 2018. SPECT bone scintigraphy for the assessment of condylar
Saridin, C.P., Raijmakers, P.G., Al Shamma, S., Tuinzing, D.B., Becking, A.G., 2009.
growth activity in mandibular asymmetry: is it accurate? Int. J. Oral Maxillofac.
Comparison of different analytical methods used for analyzing SPECT scans of
Surg. 47 (4), 470–479, 9.
patients with unilateral condylar hyperactivity. Int. J. Oral Maxillofac. Surg. 38 (9),
Cisneros, G.J., Kaban, L.B., 1984. Computerized skeletal scintigraphy for assessment of
942–946, 19.
mandibular asymmetry. J. Oral Maxillofac. Surg. 42 (8), 513–520, 25.
Saridin, C.P., Raijmakers, P.G., Slootweg, P.J., Tuinzing, D.B., Becking, A.G., Van Der
Donoff, R.B., Jeffcoat, M.K., Kaplan, M.L., 1978. Use of a miniaturized detector in facial
Waal, I., 2010. Unilateral condylar hyperactivity: a histopathologic analysis of 47
bone scanning. Int. J. Oral Surg. 7 (5), 482–487, 22.
patients. J. Oral Maxillofac. Surg. 68 (1), 47–53, 37.
Espinosa, S., Covarrubias, E., Díaz, R., Díaz, K.T., Cafferata, E.A., 2021. Histologic
Saridin, C.P., Raijmakers, P.G., Tuinzing, D.B., Becking, A.G., 2011. Bone scintigraphy as
findings and related diagnostic methods in condylar hyperactivity. Int. J. Oral
a diagnostic method in unilateral hyperactivity of the mandibular condyles: a review
Maxillofac. Surg. 50 (1), 54–63, 36.
and meta-analysis of the literature. Int. J. Oral Maxillofac. Surg. 40 (1), 11–17, 27.
Ghawsi, S., Aagaard, E., Thygesen, T.H., 2016. High condylectomy for the treatment of
Theerakulpisut, D., Somboonporn, C., Wongsurawat, N., 2016. Single photon emission
mandibular condylar hyperplasia: a systematic review of the literature. Int. J. Oral
computed tomography without and with hybrid computed tomography in
Maxillofac. Surg. 45 (1), 60–71, 28.
mandibular condylar hyperplasia. J. Med. Assoc. Thai. 99 (Suppl. 5), S65–S73, 20.
Hodder, S.C., Rees, J.I., Oliver, T.B., Facey, P.E., Sugar, A.W., 2000. SPECT bone
Wen, B., Shen, Y., Wang, C.Y., 2014. Clinical value of 99Tcm-MDP SPECT bone
scintigraphy in the diagnosis and management of mandibular condylar hyperplasia.
scintigraphy in the diagnosis of unilateral condylar hyperplasia. Sci. World J. 2014.
Br. J. Oral Maxillofac. Surg. 38 (2), 87–93, 11.
ID 256256.21.
Kaban, L.B., Cisneros, G.J., Heyman, S., Treves, S., 1982. Assessment of mandibular
Whiting, P.F., Rutjes, A.W., Westwood, M.E., Mallett, S., Deeks, J.J., Reitsma, J.B.,
growth by skeletal scintigraphy. J. Oral Maxillofac. Surg. 40 (1), 18–22, 24.
Leeflang, M.M., Sterne, J.A., Bossuyt, P.M., Group, Q.-, 2011. QUADAS-2: a revised
Karssemakers, L.H.E., Nolte, J.W., Rehmann, C., Raijmakers, P.G., Becking, A.G., 2022.
tool for the quality assessment of diagnostic accuracy studies. Ann. Intern. Med. 155
Diagnostic performance of SPECT-CT imaging in unilateral condylar hyperplasia. Int.
(8), 529–536, 1673.
J. Oral Maxillofac. Surg. 13.
Xiao, J., Wu, Z., Ye, W., 2022. Using 3D medical modeling to evaluate the accuracy of
Liu, P., Shi, J., 2019. Is single-photon emission computed tomography/computed
single-photon emission computed tomography (SPECT) bone scintigraphy in
tomography superior to single-photon emission computed tomography in assessing
diagnosing condylar hyperplasia. J. Oral Maxillofac. Surg. 80 (2), 285.e281-285.
unilateral condylar hyperplasia? J. Oral Maxillofac. Surg. 77 (6), 1279.e1271-1279.
e289.39.
e1277.14.

453