European Radiology (2023) 33:3178–3187

https://doi.org/10.1007/s00330-023-09485-4

MUSCULOSKELETAL

The value of different involvement patterns of the knee

“synovio‑entheseal complex” in the differential diagnosis
of spondyloarthritis, rheumatoid arthritis, and osteoarthritis:
an MRI‑based study
Boya Li1 · Zikang Guo1 · Jin Qu2 · Ying Zhan2 · Zhiwei Shen3 · Xinwei Lei2,4 

Received: 12 August 2022 / Revised: 25 December 2022 / Accepted: 25 January 2023 / Published online: 9 March 2023
© The Author(s), under exclusive licence to European Society of Radiology 2023

Abstract
Objectives  To explore the different involvement patterns of the knee “synovio-entheseal complex (SEC)” on MRI in patients
with spondyloarthritis (SPA), rheumatoid arthritis (RA), and osteoarthritis (OA).
Methods  This study retrospectively included 120 patients (male:female, 55:65) with a mean age of 39.20 years diagnosed
with SPA (n = 40), RA (n = 40), and OA (n = 40) at the First Central Hospital of Tianjin between January 2020 and May
2022. Six knee entheses were assessed by two musculoskeletal radiologists according to the SEC definition. Bone mar-
row lesions associated with entheses include bone marrow edema (BME) and bone erosion (BE), which were classified as
entheseal or peri-entheseal based on their relationship to the entheses. Three groups (OA, RA, and SPA) were established
to characterize the location of enthesitis and the different SEC involvement patterns. Inter-group and intra-group differ-
ences were analyzed using the ANOVA or chi-square tests, and the inter-class correlation coefficient (ICC) test was used
to determine inter-reader agreement.
Results  The study contained a total of 720 entheses. The SEC-based analysis revealed different involvement patterns in
three groups. The OA group had the most abnormal signals in tendons/ligaments (p = 0.002). The RA group had consider-
ably greater synovitis (p = 0.002). The majority of peri-entheseal BE was identified in the OA and RA groups (p = 0.003).
Furthermore, entheseal BME in the SPA group was significantly different from those in the other two groups (p < 0.001).
Conclusions  SEC involvement patterns differed in SPA, RA, and OA, which is important for differential diagnosis. SEC
should be used as a whole evaluation method in clinical practice.
Key Points 
• The “synovio-entheseal complex (SEC)” explained differences and characteristic alterations in the knee joint in patients
with spondyloarthritis (SPA), rheumatoid arthritis (RA), and osteoarthritis (OA).
• The various SEC involvement patterns are crucial for differentiating SPA, RA, and OA.
• When “knee pain” is the only symptom, a detailed identification of characteristic alterations in the knee joint of SPA
patients may help timely treatment and delay the structural damage.

Keywords  Spondyloarthritis · Rheumatoid arthritis · Osteoarthritis · Synovitis · MRI

Boya Li contributed to the manuscript as the first author.

* Boya Li 3
Clinical Science, Philips Healthcare, Beijing, China
* Xinwei Lei 4
Department of radiology, Tianjin First Central Hospital,
leixinwei66@163.com Tianjin Institute of Imaging Medicine, NO. 24 Fukang Road,
Nankai District, Tianjin 300192, China
1
First Central Clinical College, Tianjin Medical University,
Tianjin, China
2
Department of Radiology, Tianjin First Central Hospital,
Tianjin Institute of Imaging Medicine, Tianjin, China

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European Radiology (2023) 33:3178–3187
Abbreviations
ASAS Assessment of Spondyloarthritis interna-
tional Society
BE Bone erosion
BME Bone marrow edema
BML Bone marrow lesions
CL Collateral ligament
ESSG European Spondyloarthropathy Study
Group
GTi Gastrocnemius tendon insertion
HIS Hospital information system
HLA-B27 Human leukocyte antigen B27
ICC Inter-class correlation coefficient
LCL-PT Lateral collateral ligament + popliteal
tendon (femoral attachment)
MCP Metacarpophalangeal
OA Osteoarthritis
PCL Posterior cruciate ligament (tibial
attachment)
PDW-SPAIR Proton density–weighted-spectral attenu-
ated inversion recovery
PsA Psoriatic arthritis
PTi Patellar tendon insertion
PTo Patellar tendon origin
QTi Quadriceps tendon insertion
RA Rheumatoid arthritis
SEC Synovio-entheseal complex
SPA Spondyloarthritis
T1W-TSE T1-weighted turbo spin echo
T2W-FFE T2-weighted fast field echo
Introduction
“Enthesitis” is defined as inflammation at the insertion into
the bone of a tendon, ligament, or joint capsule [1]. It is cen-
tral to spondyloarthritis (SPA) pathophysiology [2] with high
prevalence at axial and several peripheral locations. Enthesi-
tis was included in the European Spondyloarthropathy Study
Group (ESSG) SPA diagnostic criteria [2, 3]. It has been asso-
ciated with immune, metabolic, and degenerative diseases [4,
5]. Due to the highly overlapping clinical and imaging features
of SPA, rheumatoid arthritis (RA), and osteoarthritis (OA)
in the knee joint [6], it is particularly challenging to make an
accurate differential diagnosis, especially when specific sero-
logical markers and laboratory indicators are negative [7, 8].
According to a recent study, peripheral enthesitis was the most
prevalent peripheral musculoskeletal manifestation in SPA, with
39% of patients having lower extremity involvement, especially
in the knee [9]. In psoriatic arthritis (PsA), peripheral enthesitis
was assumed to develop before peripheral joint symptoms [10,
11]. Enthesitis has also been reported in RA patients ranging
from none to 60% [12–14] and occurs in OA patients due to
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recurring micro-injuries to the bone [15]. Only using enthesitis
to differentiate SPA from RA and OA seems unreliable.
Magnetic resonance imaging (MRI) is always used to
detect early inflammatory and destructive changes because of
its excellent resolution and sensitivity in assessing soft tissue,
cartilage, and bone alterations [16–19]. MRI-based studies
revealed that enthesitis was more than just a localized inser-
tion site abnormality [20]. It forms the “enthesis organ,” a
complex functional anatomical unit, together with tendons/
ligaments, joint capsules, and neighboring soft tissues [21].
This explained the injury pattern and why specific enthesitis
leads to diffuse pathological changes [22]. Although the syn-
ovium does not form part of the enthesis organ, most tendons/
ligaments attach to the bones near the synovial joints. Entheses
and the adjacent fibrocartilage are the same as the synovial
and articular cartilage, both receiving nutrients and lubrication
from the adjacent synovial. The “synovio-entheseal complex
(SEC)” refers to the interdependent anatomical, physiological,
and functional relationship between synovial and enthesis [15].
The core is that primary enthesitis triggers secondary synovi-
tis [15]. This concept offers a more comprehensive interpreta-
tion of MRI data in patients with SPA, RA, and OA involving
the knee, as well as novel differential diagnosis options.
Firstly, most prior research focused on the foot and ankle
joints [15, 23–26]. The SEC, directly associated to the syno-
vial cavity in synovial joints such as the knee, offers a better
understanding of the anatomical basis of entheseal-related
disorders. Nevertheless, research is still lacking [22]. Sec-
ondly, the SEC produced by the posterior cruciate ligament
(PCL) was associated with entheseal damages in OA [27]
and briefly described in SPA [21, 22]. However, the other
knee entheses have not been fully characterized. Moreover,
the SEC was established based on histopathology, and it is
uncertain whether it can be used to interpret MRI data.
Therefore, to provide new clinical ideas for differential
diagnosis to achieve precise identification and treatment to
delay structural damage, the aim of this study was to explore
the different involvement patterns of the knee SEC on MRI
in patients with SPA, RA, and OA.
Materials and methods
Patients and inclusion criteria
This retrospective study was approved by the Institutional
Review Board of Tianjin First Central Hospital Medical
Ethics Committee (No. 2022N143KY). Patients, with con-
firmed clinical diagnoses of SPA, RA, or OA by rheumatolo-
gists, underwent an MRI for knee pain with suspected knee
involvement between January 2020 and May 2022.
Patients with the ages ranged from 18 to 45 years in each
group met the diagnostic criteria. The SPA group consisted
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of forty patients who met the Assessment of Spondyloarthri-
tis international Society (ASAS) criteria [28]. Forty RA and
OA patients from the same time period were matched. All
RA patients fulfilled the criteria of the American College of
Rheumatology [29]. The inclusion of OA patients was based
on the 2009 EULAR evidence-based recommendations for
the diagnosis of knee OA [30], including the three recom-
mended symptoms (persistent knee pain, morning stiffness
less than 30 min, and impaired function) as well as the three
most relevant indicators (crepitus, restricted movement, and
bone enlargement). Exclusion criteria were as follows: meta-
bolic bone disease, abnormal knee development, knee sur-
gery, bone tumors or trauma, septic arthritis, and infectious
lesions. The clinical data including sex, age, and HLA-B27
was acquired through the hospital information system (HIS).
MRI protocol
All MRI scans were performed using a 3.0 T MRI system
(Ingenia, Philips Healthcare). Using a dedicated extremity
coil, the patient was positioned supine with the knee joint in
the center of the scanning field. The scan parameters of the
complete MRI sequences are illustrated in Table 1.
MRI sign interpretation and evaluation
All MRI scans were evaluated by two musculoskeletal radi-
ologists (readers 1 [L.B.Y.] and 2 [Q.J.], junior radiologists
with 2 and 12 years of experience in knee joint reading)
who were blinded to the diagnosis and the patient informa-
tion. The disagreement images were determined by reader
3 [Z.Y.] (a senior radiologist with 20 years of image inter-
pretation experience, specialized in musculoskeletal imag-
ing). The sites and criteria have been standardized to avoid
overinterpretation or misinterpretation.
Six knee entheses, histopathologically confirmed the
presence of enthesis organs, were chosen for evaluation [22].
Referring to Binks DA et al’s method for assessing the SEC
Table 1  Detailed MRI Sequence Imaging modality
sequences and imaging
modality TR/TE (ms)
PDW-SPAIR sag 3548/30
T1W-TSE sag 573/20
PDW-SPAIR cor 3291/30
PDW-SPAIR tra 3284/30
T2W-FFE sag 357/9.2
MRI, magnetic resonance imaging; T1W-TSE, T1-weighted turbo spin echo; PDW-SPAIR, proton density–
weighted-spectral attenuated inversion recovery; T2W-FFE, T2-weighted fast field echo; sag, sagittal imag-
ing; cor, coronal imaging; tra, transverse imaging; TR, repetition time; TE, echo time; FOV, field of view
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European Radiology (2023) 33:3178–3187
formed by the posterior cruciate ligament (PCL) [31], the
following entheses were assessed: PCL (tibial attachment),
quadriceps tendon insertion (QTi), patellar tendon origin
(PTo), patellar tendon insertion (PTi), gastrocnemius tendon
insertion (GTi), and lateral collateral ligament + popliteal
tendon (femoral attachment) (LCL-PT).
The assessment items include as follows: tendon/ligament
abnormalities, bone marrow lesions (BML) associated with
entheses, synovitis, adjacent soft tissue edema, related fat
pad edema, medial meniscus injury, and enthesophytes.
Tendon/ligament abnormalitie  In all sequences, normal ten-
dons and ligaments exhibited uniformly low signal. Normal
tendons/ligaments have a high signal on T1-weighted turbo
spin echo (T1W-TSE) and proton density–weighted-spectral
attenuated inversion recovery (PDW-SPAIR) but normal on
T2-weighted fast field echo (T2W-FFE) if their course is at
an angle of approximately 55° to the main magnetic field
direction. In order to exclude the “magic angle effect,” it was
regarded abnormal when there were high signals on T1W-
TSE, PDW-SPAIR, and T2W-FFE simultaneously.
BML associated with entheses  Bone marrow edema (BME)
and bone erosion (BE) were included. BME was defined as
a patchy slightly low signal on T1W-TSE in comparison to
the normal yellow marrow high-signal background and no
definite cortical defects, and a high signal on PDW-SPAIR.
BE was a defect in subchondral bone associated with full-
thickness loss of the dark appearance of the subchondral
cortex, with loss of signal on T1W-TSE compared with the
normal bright appearance of adjacent bone marrow. Bone
cysts shown a rounded bright fluid signal with well-defined
borders on PDW-SPAIR. According to the relationship to
the entheses, the evaluation sites were classified as entheseal
(direct insertion of tendon/ligament into the bone) and peri-
entheseal (immediately adjacent to the entheses, tendon/liga-
ment compression on the bone but not direct insertion site)
(Fig. 1). Except for the above-mentioned conditions, BME
and BE were not evaluated at any additional sites.
Matrix size Slices (mm) Slice thick- FOV (mm)
ness (mm)
212 × 156 26 3 160 × 160 × 86
292 × 218 26 3 180 × 163 × 86
228 × 194 28 3 160 × 160 × 92
240 × 175 28 3 180 × 180 × 123
232 × 186 24 3 160 × 160 × 79
European Radiology (2023) 33:3178–3187
Fig. 1  The “synovio-entheseal complex (SEC)” in the knee joint; it
illustrates the difference between the entheseal site (black star) and
peri-entheseal site (black asterisk). The entheseal site is the area where
the tendon/ligament is directly inserted into the bone. Conversely, the
peri-entheseal site is the bone compressed by the tendon/ligament but
not directly inserted site. BML associated with entheses includes BME
and BE. B, bone; E, enthesis; TL, tendons/ligaments; C, capsule; SM,
synovial membrane; CL, cartilage; M, meniscus; BML, bone marrow
lesions; BME, bone marrow edema; BE, bone erosion
Synovitis  It included synovial thickening, bursitis, and vari-
ous degrees of joint capsule effusion. Synovial thickness can-
not be accurately measured with conventional MRI scans.
Adjacent soft tissue and related fat pad edema Subcuta-
neous soft tissues and muscles were included. The PDW-
SPAIR signal was elevated compared to normal muscle
signal during edema.
Medial meniscus injury  It was assessed as normal or injured.
On PDW-SPAIR, an abnormal linear or lamellar high signal
in the posterior horn of the medial meniscus was considered
an injury.
Enthesophytes  An enthesophyte is a bony spur that arises at
an enthesis, and extends in the direction of pull of the liga-
ment/tendon and evaluated on T1W-TSE [32]. Care should
be taken to distinguish enthesophytes from osteophytes.
Statistical analysis
All data were statistically analyzed using the SPSS 25.0
software. The mean and standard deviation (SD) were
used to describe the quantitative data, which was then ana-
lyzed using the ANOVA test. Frequencies (%) were used to
describe categorical data, which was analyzed using chi-
square tests. The influence relationship between the synovitis
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in GTi with peri-entheseal BE of the GTi and the increased
abnormal signal in PCL with medial meniscal injury was
examined using the binary logistic regression analysis. A
p-value < 0.05 was considered statistically significant. The
inter-observer variability of the MRI signs was evaluated
by the inter-class correlation coefficient (ICC) test. An ICC
above 0.80 was considered of good reproducibility.
Results
Patient characteristics
This study included 120 patients (male:female, 55:65;
age: 39.20 ± 10.25  years) and 720 entheses. The
age of patients in the OA, RA, and SPA groups was
39.35 ± 5.86, 43.05 ± 10.50, and 35.80 ± 12.34, respec-
tively, with statistically significant differences between
the RA group and OA and SPA groups (p < 0.001). RA
patients were predominantly female (n = 36/40, 90%),
in contrast to the OA (n = 17/40, 42.5%) and SPA
(n = 12/40, 30%) groups (p < 0.001). Twenty-seven
SPA patients were HLA-B27 positive. Detailed clini-
cal characteristics of the patients are shown in Table 2.
Frequency and location of knee enthesitis
in patients with OA, RA, and SPA
The incidence of knee enthesitis was similar (p = 0.368)
in the OA (n = 192/240, 80%), RA (n = 204/240, 85%),
and SPA (n = 183/240, 76%) groups (p = 0.368) (Table 2).
However, the locations of the three groups were clearly
different. Enthesitis at the PTo was detected in all 40
OA patients. The GTi (n = 36/40, 90%) and LCL-PT
(n = 36/40, 90%) were the most common sites in the RA
group, while the LCL-PT was the most frequent site in the
SPA group (n = 36/40, 90%).
Different SEC involvement patterns in patients
with OA, RA, and SPA
First, patient-level intergroup comparisons revealed a differ-
ent SEC involvement pattern in the OA, RA, and SPA groups
(Fig. 2). In the OA group, tendon/ligament abnormalities
(n = 155/240, 63%, p = 0.002) and adjacent soft tissue edema
(n = 106/240, 44%, p = 0.002) dominated SEC involvement
(Fig. 3I–L). In the RA group, synovitis was significantly more
common than in the OA and SPA groups (n = 153/240, 64%,
p = 0.002). Interestingly, peri-entheseal BE was significantly
higher in the OA (n = 15/240, 6%) and RA groups (n = 24/240,
10%) than in the SPA group (n = 3/240, 1%) (p = 0.003). Sig-
nificantly different from the other two groups (p < 0.001), SEC
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Table 2  Clinical characteristics, Group p-value

enthesitis, and the components
of SEC OA (n = 40) RA (n = 40) SPA (n = 40)
a b
Sex (F/M) 17/23 36/4 12/28a  < 0.001
Age* 39.35 ± 5.86 43.05 ± 10.50 35.80 ± 12.34 0.006
HLA-B27( +) - - 27/40 (67.50) -
Enthesitis
  PCL 37/40 (92.50)a 34/40 (85.00)a 35/40 (87.50)a 0.568
  QTi 35/40 (87.50)a 30/40 (75.00)a 27/40 (67.50)a 0.102
  PTo 40/40 (100.00)a 33/40 (82.50)b 34/40 (85.00)b 0.024
  PTi 37/40 (92.50)a 35/40 (87.50)a 27/40 (67.50)b 0.008
  GTi 17/40 (42.50)a 36/40 (90.00)b 24/40 (60.00)a  < 0.001
  LCL-PT 26/40 (65.00)a 36/40 (90.00)b 36/40 (90.00)b 0.004
No. of total ­enthesitis† 192/240 (80.00)a 204/240 (85.00)a 183/240 (76.25)a 0.368
SEC†
  Tendon/ligament abnormalities 155/240 (63.33)a 104/240 (43.33)b 128/240 (53.33)b 0.002
  Entheseal BME 5/240 (2.08)a 7/240 (2.92)a 25/240 (10.42)b  < 0.001
  Entheseal BE 6/240 (2.50)a 6/240 (2.50)a 12/240 (5.00)a 0.153
  Peri-entheseal BME 2/240 (0.83)a 8/240 (3.33)a 4/240 (1.67)a 0.104
  Peri-entheseal BE 15/240 (6.25)a 24/240 (10.00)a 3/240 (1.25)b 0.003
  Synovitis 103/240 (42.92)a 153/240 (63.75)b 112/240 (46.67)a 0.002
  Adjacent soft tissue edema 106/240 (44.17)a 90/240 (37.50)b 81/240 (33.75)b 0.002
  Related fat pad edema 58/240 (24.17)a 51/240 (21.25)a 48/240 (20.00)a 0.673
  Enthesophytes 0/240 (0.00)a 1/240 (0.42)a 2/240 (0.83)a 0.44
  Medial meniscus injury 25/240 (10.42)a 17/240 (7.08)a 15/240 (6.25)a 0.06
*
 Data are mean ± standard deviation. All other data are n (%)
†
 Data indicates the number of entheses involved and represented as n (%)
a, b
 If the marked letters are the same between any two groups, the difference between the two groups is not
statistically significant. On the contrary, a different marker letter indicates a statistically significant differ-
ence between the two groups. A p-value < 0.05 was considered statistically different
OA, osteoarthritis; RA, rheumatoid arthritis; SPA, spondyloarthritis; HLA-B27, human leukocyte antigen
B27; PCL, posterior cruciate ligament (tibial attachment); QTi, quadriceps tendon insertion; PTo, patellar
tendon origin; PTi, patellar tendon insertion; GTi, gastrocnemius tendon insertion; LCL-PT, lateral collat-
eral ligament + popliteal tendon (femoral attachment); SEC, synovio-entheseal complex; BME, bone mar-
row edema; BE, bone erosion
Bold values represent p < 0.05

involvement in the SPA group was mainly entheseal BME
(Fig. 4). Detailed frequency and percentages of other detected
MRI signs are shown in Table 2. The differences remained
significant after correcting for sex and age. The inter-observer
agreement for MRI indicators of SEC is shown in Table 3.
Next, the specific conditions of the enthesis level were
analyzed (Fig. 5). In the SEC formed by the PTo, all OA
patients (n = 40/40, 100%) showed high signals in the patellar
tendon. In the GTi-formed SEC, the RA group detected sig-
nificantly more synovitis than the OA and SPA groups (both
p < 0.001) (Fig. 3E–H). Moreover, the incidence of entheseal
BME was higher in the SPA and RA groups compared to that
in the OA group (p = 0.011 and 0.021, respectively).
In addition, the binary logistic regression analysis
revealed a significant positive effect relationship between
the synovitis and peri-entheseal BE of the GTi (z = 1.993,
p = 0.046 < 0.05, OR = 4.907). Moreover, the increased
abnormal signal in the PCL had a statistically signifi-
cant positive effect on medial meniscal injury (z = 3.971,
p = 0.000 < 0.01, OR = 4.870).
Discussion
This study aimed to interpret the knee MRI images using
the SEC definition, and BML were evaluated separately into
entheseal BML and peri-entheseal BML. The results indi-
cated that the incidence of knee enthesitis was similar in
patients with SPA, RA, and OA, but the location and knee
SEC involvement patterns were significantly different.
Enthesitis has long been regarded as an important MRI
marker in the diagnosis of SPA [33]. Two main peripheral joint

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Fig. 2  Different involvement
patterns of the “synovio-enthe-
seal complex (SEC)” in OA,
RA, and SPA groups. In the OA
group, the changes in the SEC
were dominated by the “tendon/
ligament abnormalities.” In
the RA group, inflammation of
the synovial component was
dominant among the SEC. In
the SPA group, entheseal BME
was significantly different from
that in the other two groups.
Peri-entheseal BE was mostly
found in the OA and RA groups
and significantly different from
that in the SPA group. OA, oste-
oarthritis; RA, rheumatoid
arthritis; SPA, spondyloarthri-
tis; BME, bone marrow edema;
BE, bone erosion

Table 3  Inter-observer agreement for MRI signs of SEC early diagnosis of SPA. However, inconsistent with previ-
ICC 95% CI
ous studies, various degrees of enthesitis and synovitis were
detected in all three groups, and the frequency of enthesitis
Tendon/ligament abnormalities 0.816 0.747–0.868 was similar. One possible interpretation is that the introduc-
Entheseal BME 0.821 0.721–0.854 tion and development of the SEC led to a new criterion for the
Entheseal BE 0.914 0.879–0.939 enthesitis evaluation, allowing us to identify more enthesitis-
Peri-entheseal BME 0.888 0.843–0.921 related lesions that had been missed in previous studies.
Peri-entheseal BE 0.886 0.841–0.919 In contrast, a study of 41 individuals with early knee
Synovitis 0.827 0.761–0.876 arthritis showed that the prevalence, severity, and location
Adjacent soft tissue edema 0.9 0.960–0.929 of knee enthesitis were similar in patients with SPA and
Related fat pad edema 0.718 0.619–0.795 RA and that synovitis was prominent in both conditions
Enthesophytes 0.947 0.925–0.963 [34]. Enthesitis on MRI was not useful for distinguishing
Medial meniscus injury 0.924 0.892–0.946 SPA from RA. Yet, the average age of the patients in this
MRI, magnetic resonance imaging; SEC, synovio-entheseal complex;
study was greater than 45, which is not a common age
ICC, inter-class correlation coefficient; 95% CI, confidence interval; for SPA. Enthesitis was also observed with degeneration,
BME, bone marrow edema; BE, bone erosion and its prevalence increased with age [35]. The differ-
ence between the two groups may be underestimated. In
involvement patterns were proposed: the “RA,” dominated by the current study, 120 patients aged less than 45 were
“synovitis”; and the “SPA,” primarily enthesitis followed by included, validating and further expanding upon prior
synovitis [1]. Moreover, OA may also show degenerative- research. The results indicated substantial differences
related entheseal changes. When patients only have “knee in the knee enthesitis site. In the OA group, all patients
pain” as their primary symptom, accurately identifying the observed involvement in PTo, whereas the RA group was
three diseases becomes a difficult challenge in clinical practice. most frequently involved in GTi (n = 36/40, 90%). In addi-
Previous researches on the use of knee enthesitis in distin- tion to the reported PTo, PTi, and QTi [34], thirty-six
guishing SPA from RA and OA remain highly controversial. SPA patients developed enthesitis in LCL-PT. The LCL-
The knee MRI study investigation by Emad [14] showed PT is less affected by degeneration than the PTo, and
that all SPA patients had enthesitis, although none of the RA further research is required to determine how important
patients did. Enthesitis may be clinically significant for the this difference in location is for differential diagnosis.

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3184 European Radiology (2023) 33:3178–3187

Fig. 3  Different involvement patterns of SEC in patients with SPA,
RA and OA. A–D Male, 20 years old, with a history of SPA. PDW-
SPAIR showed a high signal in the medial head of the gastrocnemius
muscle at the insertion site posterior to the femoral condyle (white
arrow). T1W-TSE showed no significant bone loss in the correspond-
ing area, suggesting BME. E–H Female, 19 years old, with a history
of RA. F–H PDW-SPAIR showed a high signal at the site that the
medial head of the gastrocnemius muscle compresses the bone poste-
rior to the femoral condyle (white arrow), but not the insertion site. E
T1W-TSE showed a low-signal area of bone loss at the correspond-
ing site, suggesting BE at the non-attachment site (black arrow). The
tendon signal is normal, but synovial significantly thickening ( ). I–L
Male, 42 years old, with a history of OA. J–L PDW-SPAIR showed a
high signal at the site that the lateral head of the gastrocnemius muscle
compresses the bone posterior to the femoral condyle and small cystic
lesions with well-defined borders (white arrow). Also, the tendon
showed a high signal (not shown in the figure). I T1W-TSE showed
a low-signal area of bone loss at the corresponding site, suggesting
BE at the non-attachment site (black arrow). T1W-TSE, T1-weighted
turbo spin echo imaging; PDW-SPAIR, proton density–weighted-spec-
tral attenuated inversion recovery; sag, sagittal imaging; cor, coronal
imaging; tra, transverse imaging; SPA, spondyloarthritis; RA, rheu-
matoid arthritis; OA, osteoarthritis; SEC, synovio-entheseal complex;
BME, bone marrow edema; BE, bone erosion

Fig. 4  Male, 45 years old, with

a history of SPA. A T1W-TSE
showed no significant bone loss.
B The increased signal at the
PTo (small white arrow) with
BME at the attachment site
(large white arrow) on PDW-
SPAIR. Peripheral soft tissue
edema. PTo, patellar tendon
origin; T1W-TSE, T1-weighted
turbo spin echo imaging;
PDW-SPAIR, proton density–
weighted-spectral attenuated
inversion recovery; BME, bone
marrow edema

13
European Radiology (2023) 33:3178–3187
Fig. 5  Detailed MRI signs of SEC at each enthesis for patients in the
OA, RA, and SPA groups. OA, osteoarthritis; RA, rheumatoid arthri-
tis; SPA, spondyloarthritis; PCL, posterior cruciate ligament (tibial
attachment); QTi, quadriceps tendon insertion; PTo, patellar tendon
All previous studies have focused on the diagnostic
efficacy of differential enthesitis and synovitis. Latest
histopathological studies indicate that enthesitis and
synovitis should be evaluated as a whole, the SEC [15,
31]. Enthesis and synovial were two main components.
Without blood vessels and macrophages, the enthesis
is susceptible to micro-structural damage. Notably, the
incidence of entheseal BME was significantly higher
in the SPA group than in the other two groups in the
current study. The possible explanation is that the ten-
dons in the enthesis organs are continuous with the
articular cartilage. When mechanical stress are applied
to the enthesis, micro-damage can occur, then lead to
BME where the tendon/ligament is directly attached to
the bone [36]. In contrast, the synovial is rich in mac-
rophages and is vascularized. It is composed of loose
connective and fatty tissue that is sensitive to inflam-
mation [15]. The enthesis organs can be classified into
joint-related and extra-articular according to their rela-
tionship to the joint capsule. Within the SEC, these two
types of enthesis organs are formed by the synovial com-
position within the joint capsule and the subtendinous
bursa, respectively [21, 22].
In the metacarpophalangeal (MCP) joints in RA
patients, erosion formation occurs adjacent to the ori-
gins of the collateral ligament (CL), which are also
sites of bone compression [36]. In the current knee
MRI study, peri-entheseal BE was most common in
patients with RA and synovitis had a significant posi-
tive effect on peri-entheseal BE in the GTi (z = 1.993,
p = 0.046 < 0.05, OR = 4.907). Possibly as a result of
the “bare zone,” the synovium is in direct contact with
the bone, allowing osteoclast activation and promot-
ing BE formation [37]. Although we observed a ten-
dency to micro-injury and the presence of BE at the
bone compression site, we were only able to determine
a positive relationship between synovitis and BE at the
3185
origin; PTi, patellar tendon insertion; GTi, gastrocnemius tendon inser-
tion; LCL-PT, lateral collateral ligament + popliteal tendon (femoral
attachment); BME, bone marrow edema; BE, bone erosion
same location. The correlation between bone compres-
sion and erosion formation is unclear. Peri-entheseal BE
was equally prevalent in OA patients and thought to be
associated with abnormal adaptive immune responses
due to synovial fibroblast dysfunction and osteoclast
activation [23].
In the RA group, the SEC was dominated by inflam-
matory changes in the synovial component. The prolif-
eration of synovial tissue and blood vessels, the accu-
mulation of inflammatory cells and chemokines, and
the production of degradative enzymes can infiltrate and
destroy adjacent structures [38–40]. Enthesis is subject
to micro-damage while simultaneously lowering physi-
ologic stress at the bone interface [41, 42]. This may
facilitate the conditions for the infiltration of inflam-
matory cells into the synovium, resulting in secondary
synovitis [43, 44]. This perspective was reflected by the
OA and SPA groups. Compared to RA, patients with
SPA have fatty deposits and enthesophytes as a result
of tissue repair in the later stages of bone destruction.
Only one patient with RA and two patients with SPA had
enthesophytes in the QTi in the current study. Perhaps
the majority of RA patients enrolled were at a late stage
due to delayed diagnosis. Meanwhile, are enthesophytes
unique to SPA patients?
The study still has some limitations. The enrolled
patients all had at least one enthesitis, which may contrib-
ute to some selection bias. However, this study focused on
the different involvement patterns of SEC in different disor-
ders; bias is not expected to have an impact on the results.
Although contrast-enhanced MRI of the knee joint may aid
in the visualization of enthesitis and synovitis [13, 31], it
is seldom used in daily clinical practice, and its additional
benefit in diagnosing SPA has been demonstrated be neg-
ligible [45, 46]. Future research should use MRI surface
micro-coils to improve the accuracy of minor structure
identification of the knee joint.
13
3186
Conclusion
Enthesitis and synovitis have a significant overlap in differ-
ent diseases and separate evaluation is of limited value for
differential diagnosis. However, SEC has different involve-
ment patterns in various diseases and is critical for the dif-
ferential diagnosis of SPA, RA, and OA. When patients pre-
sent with entheseal BME with or without tendon/ligament
abnormalities may be suggestive for the clinical diagnosis
of SPA. SEC should be utilized as a whole assessment unit
in clinical practice.
Acknowledgements  Thanks to all colleagues in the radiology depart-
ment of Tianjin First Central Hospital for their support. In addition, we
thank Dr. Huang Shan (Philips Healthcare, Shanghai) for her linguistic
assistance in this study.
Funding  Funded by Tianjin Key Medical Discipline (Specialty) Con-
struction Project (TJYXZDXK-041A).
Declarations  7(1):e001450
10. Kaeley GS, Kaler JK (2020) Peripheral enthesitis in spondyloar-
Guarantor  The scientific guarantor of this publication is Xinwei Lei.
Conflict of interest  One of the authors (Zhiwei Shen) is an employee
of Philips Healthcare. The remaining authors declare no relationships
with any companies whose products or services may be related to the
subject matter of the article.
Statistics and biometry  No complex statistical methods were neces-
sary for this paper.
Informed consent  Written informed consent was omitted by the Insti-
tutional Review Board of Tianjin First Central Hospital Medical Ethics
Committee because the study was performed in a retrospective manner.
Ethical approval  This study was approved by the Institutional Review
Board of Tianjin First Central Hospital Medical Ethics Committee
(No.2022N143KY).
Methodology 
• retrospective
• cross-sectional study
• performed at one institution
References
1. McGonagle D, Gibbon W, Emery P (1998) Classifi-
cation of inf lammatory arthritis by enthesitis. Lancet
352(9134):1137–1140
2. McGonagle D, Aydin SZ, Marzo-Ortega H, Eder L, Ciurtin C
(2021) Hidden in plain sight: is there a crucial role for enthesitis
assessment in the treatment and monitoring of axial spondyloar-
thritis? Semin Arthritis Rheum 51(6):1147–1161
3. Dougados M, van der Linden S, Juhlin R et al (1991) The Euro-
pean Spondylarthropathy Study Group preliminary criteria
for the classification of spondylarthropathy. Arthritis Rheum
34(10):1218–1227
13
European Radiology (2023) 33:3178–3187
4. Resnick D, Niwayama G (1983) Entheses and enthesopathy. Ana-
tomical, pathological, and radiological correlation. Radiology.
146(1):1–9
5. Eshed I (2019) SP0096 MRI of large joints in arthritis: how to
do and how they are different from small joints? Ann Rheum Dis
78(Suppl 2):28.2-28. https://​doi.​org/​10.​1136/​annrh​eumdis-​2019-​
eular.​8471
6. Mease P, Bhutani M, Hass S, Yi E, Hur P, Kim N (2022) Com-
parison of clinical manifestations in rheumatoid arthritis vs.
spondyloarthritis: a systematic literature review. Rheumatol Ther
9(2):331–378
7. Yasser R, Yasser E, Hanan D, Rasker JJ (2010) Enthesitis in
seronegative spondyloarthropathies with special attention to the
knee joint by MRI: a step forward toward understanding disease
pathogenesis. Clin Rheumatol 30(3):313–322
8. Emad Y, Ragab Y, Bassyouni IH et al (2010) Enthesitis and related
changes in the knees in seronegative spondyloarthropathies and
skin psoriasis: magnetic resonance imaging case-control study. J
Rheumatol 37(8):1709–1717
9. López-Medina C, Molto A, Sieper J et al (2021) Prevalence
and distribution of peripheral musculoskeletal manifestations
in spondyloarthritis including psoriatic arthritis: results of the
worldwide, cross-sectional ASAS-PerSpA study. RMD Open
thritis: lessons from targeted treatments. Drugs 80(14):1419–1441
11. Schett G, Lories RJ, D’Agostino MA et  al (2017) Enthesi-
tis: from pathophysiology to treatment. Nat Rev Rheumatol
13(12):731–741
12. D’Agostino MA, Said-Nahal R, Hacquard-Bouder C, Brasseur JL,
Dougados M, Breban M (2003) Assessment of peripheral enthesi-
tis in the spondylarthropathies by ultrasonography combined
with power Doppler: a cross-sectional study. Arthritis Rheum
48(2):523–533
13. Narváez J, Narváez JA, de Albert M, Gómez-Vaquero C, Nolla
JM (2012) Can magnetic resonance imaging of the hand and
wrist differentiate between rheumatoid arthritis and psoriatic
arthritis in the early stages of the disease? Semin Arthritis Rheum
42(3):234–245
14. Emad Y, Ragab Y, Shaarawy A et al (2009) Can magnetic reso-
nance imaging differentiate undifferentiated arthritis based on
knee imaging? J Rheumatol 36(9):1963–1970
15. McGonagle D, Lories RJ, Tan AL, Benjamin M (2007) The con-
cept of a “synovio-entheseal complex” and its implications for
understanding joint inflammation and damage in psoriatic arthritis
and beyond. Arthritis Rheum 56(8):2482–2491
16. Erdem C, Sarikaya S, Erdem L, Ozdolap S, Gundogdu S (2005)
MR imaging features of foot involvement in ankylosing spondy-
litis. Eur J Radiol 53(1):110–119
17. Momeni M, Brindle K (2009) MRI for assessing erosion and joint
space narrowing in inflammatory arthropathies. Ann N Y Acad
Sci 1154:41–51
18. Mathew AJ, Krabbe S, Kirubakaran R et al (2019) Utility of mag-
netic resonance imaging in diagnosis and monitoring enthesitis in
patients with spondyloarthritis: an OMERACT systematic litera-
ture review. J Rheumatol 46(9):1207–1214
19. Mathew AJ, Østergaard M (2020) Magnetic resonance imaging of
enthesitis in spondyloarthritis, including psoriatic arthritis—status
and recent advances. Front Med 7:296
20. Watad A, Cuthbert RJ, Amital H, McGonagle D (2018) Enthesitis:
much more than focal insertion point inflammation. Curr Rheu-
matol Rep 20(7):41
21. Benjamin M, McGonagle D (2009) The enthesis organ concept
and its relevance to the spondyloarthropathies. Adv Exp Med Biol
649:57–70
European Radiology (2023) 33:3178–3187
22. Benjamin M, Moriggl B, Brenner E, Emery P, McGonagle D,
Redman S (2004) The “enthesis organ” concept: why enthesopa-
thies may not present as focal insertional disorders. Arthritis
Rheum 50(10):3306–3313
23. Schett G (2007) Joint remodelling in inflammatory disease. Ann
Rheum Dis 66(Suppl 3):iii42-44
24. Harman H, Süleyman E (2018) Features of the Achilles tendon,
paratenon, and enthesis in inflammatory rheumatic diseases: a
clinical and ultrasonographic study. Z Rheumatol 77(6):511–521
25. Baraliakos X, Sewerin P, de Miguel E et al (2020) Achilles tendon
enthesitis evaluated by MRI assessments in patients with axial
spondyloarthritis and psoriatic arthritis: a report of the methodol-
ogy of the ACHILLES trial. BMC Musculoskelet Disord 21(1):767
26. Baraliakos X, Sewerin P, de Miguel E et al (2022) Magnetic reso-
nance imaging characteristics in patients with spondyloarthritis
and clinical diagnosis of heel enthesitis: post hoc analysis from
the phase 3 ACHILLES trial. Arthritis Res Ther 24(1):111
27. Wetterslev M, Maksymowych WP, Lambert RGW et al (2021) Joint
and entheseal inflammation in the knee region in spondyloarthritis -
reliability and responsiveness of two OMERACT whole-body MRI
scores. Semin Arthritis Rheum 51(4):933–939
28. Rudwaleit M, van der Heijde D, Landewé R et al (2009) The
development of Assessment of SpondyloArthritis international
Society classification criteria for axial spondyloarthritis (part II):
validation and final selection. Ann Rheum Dis 68(6):777–783
29. Aletaha D, Neogi T, Silman AJ et al (2010) 2010 Rheumatoid
arthritis classification criteria: an American College of Rheuma-
tology/European League Against Rheumatism collaborative initia-
tive. Arthritis Rheum 62(9):2569–2581
30. Zhang W, Doherty M, Peat G et al (2010) EULAR evidence-based
recommendations for the diagnosis of knee osteoarthritis. Ann
Rheum Dis 69(3):483–489
31. Binks DA, Bergin D, Freemont AJ et al (2014) Potential role of
the posterior cruciate ligament synovio-entheseal complex in joint
effusion in early osteoarthritis: a magnetic resonance imaging
and histological evaluation of cadaveric tissue and data from the
Osteoarthritis Initiative. Osteoarthritis Cartilage 22(9):1310–1317
32. Hardcastle SA, Dieppe P, Gregson CL et al (2014) Osteophytes,
enthesophytes, and high bone mass: a bone-forming triad
with potential relevance in osteoarthritis. Arthritis Rheumatol
66(9):2429–2439
33. Robinson PC, van der Linden S, Khan MA, Taylor WJ (2021)
Axial spondyloarthritis: concept, construct, classification and
implications for therapy. Nat Rev Rheumatol 17(2):109–118
34. Paramarta JE, van der Leij C, Gofita I et al (2014) Peripheral joint
inflammation in early onset spondyloarthritis is not specifically
related to enthesitis. Ann Rheum Dis 73(4):735–740
35. Bakirci S, Solmaz D, Stephenson W, Eder L, Roth J, Aydin SZ
(2020) Entheseal changes in response to age, body mass index,
and physical activity: an ultrasound study in healthy people. J
Rheumatol 47(7):968–972
3187
36. Tan AL, Tanner SF, Conaghan PG et al (2003) Role of metacar-
pophalangeal joint anatomic factors in the distribution of synovitis
and bone erosion in early rheumatoid arthritis. Arthritis Rheum
48(5):1214–1222
37. McGonagle D, Tan AL, Møller Døhn U, Ostergaard M, Benjamin
M (2009) Microanatomic studies to define predictive factors for
the topography of periarticular erosion formation in inflammatory
arthritis. Arthritis Rheum 60(4):1042–1051
38. Meng XH, Wang Z, Zhang XN, Xu J, Hu YC (2018) Rheumatoid
arthritis of knee joints: MRI-pathological correlation. Orthop Surg
10(3):247–254
39. Mundinger A, Ioannidou M, Meske S, Dinkel E, Beck A, Sigmund
G (1991) MRI of knee arthritis in rheumatoid arthritis and spon-
dylarthropathies. Rheumatol Int 11(4–5):183–186
40. Gylys-Morin VM, Graham TB, Blebea JS et al (2001) Knee in
early juvenile rheumatoid arthritis: MR imaging findings. Radiol-
ogy 220(3):696–706
41. Myers SL, Flusser D, Brandt KD, Heck DA (1992) Prevalence of
cartilage shards in synovium and their association with synovitis
in patients with early and endstage osteoarthritis. J Rheumatol
19(8):1247–1251
42. Mathiessen A, Conaghan PG (2017) Synovitis in osteoarthritis:
current understanding with therapeutic implications. Arthritis Res
Ther 19(1):18
43. Eshed I, Bollow M, McGonagle D et al (2007) MRI of enthesitis
of the appendicular skeleton in spondyloarthritis. Ann Rheum Dis
66(12):1553–1559
44. McGonagle D, Gibbon W, O’Connor P, Green M, Pease C, Emery
P (1998) Characteristic magnetic resonance imaging entheseal
changes of knee synovitis in spondylarthropathy. Arthritis Rheum
41(4):694–700
45. Hermann KG, Landewé RB, Braun J, van der Heijde DM (2005)
Magnetic resonance imaging of inflammatory lesions in the spine
in ankylosing spondylitis clinical trials: is paramagnetic contrast
medium necessary? J Rheumatol 32(10):2056–2060
46. de Hooge M, van den Berg R, Navarro-Compán V et al (2013)
Magnetic resonance imaging of the sacroiliac joints in the early
detection of spondyloarthritis: no added value of gadolinium com-
pared with short tau inversion recovery sequence. Rheumatology
(Oxford) 52(7):1220–1224
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