Radiol Oncol 2025; 59(1): 54-62. doi: 10.2478/raon-2025-0008
54
research article
Prevalence of diffuse idiopathic skeletal 
hyperostosis and association with coronary 
artery calcifications in Slovenia
Vesna Lesjak1, Timea Hebar1, Maja Pirnat1,2
1 Radiology Department, University Medical Centre Maribor, Maribor, Slovenia
2 Medical Faculty, University of Maribor, Maribor, Slovenia
Radiol Oncol 2025; 59(1): 54-62.
Received 4 August 2024 
Accepted 19 November 2024
Correspondence to: Vesna Lesjak, M.D., Radiology Department, University Medical Centre Maribor, Ljubljanska 5, SI-2000 Maribor, Slovenia. 
E-mail: vesna.lesjak@ukc-mb.si
Disclosure: No potential conflicts of interest were disclosed. 
This is an open access article distributed under the terms of the CC-BY license (https://creativecommons.org/licenses/by/4.0/).
Background. The aim of this study was to analyze the epidemiological aspects of diffuse idiopathic skeletal hyper-
ostosis (DISH) patients in Slovenia, to evaluate the relationship between coronary CT angiography (CCTA)-derived 
epicardial adipose tissue (EAT) density and coronary artery calcifications (CAC) in patients with and without DISH, and 
study influencing factors of these parameters.
Patients and methods. The research comprised patients referred for CCTA due to a clinical suspicion of coronary 
artery disease. DISH, CAC score and EAT attenuation were quantified using non-contrast imaging. Diagnosis of DISH 
was based on Resnick criteria. The CCTA was assessed for the presence of obstructive coronary artery disease (CAD). 
The association between DISH and the extent of CAC was explored, using correlation analysis and multivariate regres-
sion. 
Results. The study cohort included 219 participants. The prevalence of DISH was 7.8%. In univariate logistic regression, 
body mass index (BMI) (odds ratio [OR] 1.133, p = 0,005), age (OR 1.055, p = 0,032) and diabetes (OR 3.840, p = 0,015) 
were significantly associated with the condition. However, this association did not persist on multinomial multivariate 
analysis, but gender, age, hypertension and EAT attenuation were found to be significantly associated with the in-
creasing CAC strata.
Conclusions. The prevalence of DISH found is comparable with prior literature. There was no independent relation-
ship between the prevalence of DISH and CAC. Our data point to a more nuanced and perhaps non-causal link 
between coronary artery disease and DISH.
Key words: diffuse idiopathic skeletal hyperostosis; coronary artery calcification; epicardial adipose tissue; metabolic 
syndrome; body mass index; coronary artery disease
Introduction
Diffuse idiopathic skeletal hyperostosis (DISH) is 
a systemic condition, originally described in 1950 
by Forestier and Querol.1 In 1976 most commonly 
used criteria to diagnose DISH were introduced 
by Resnick and Niwayama.2 New bone formation, 
partially in entheses, is the condition’s defining 
feature.3 It is known that DISH affects more men 
than women, and its incidence rises with age.4 
Prevalence in Asian countries varies between 3.8% 
and 27.0%, in the USA between 7.7% and 13.2%, 
and in Italy 12.8%.5,6 The etiology of DISH is not 
utterly understood. The disorder is linked to meta-
bolic syndrome and its components, including 
diabetes, obesity, and hypertension7,8, associations 
were reported with large waist circumference, 
cardiomegaly, hyperinsulinaemia, dyslipidaemia 
and hyperuricaemia.3 DISH is associated with in-
creased calcifications in coronary arteries3, and 
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis 55
also in thoracic9 and abdominal aorta.10 The risk 
of myocardial infarction is considerably higher in 
DISH patients.11
Between the myocardium and the visceral peri-
cardium is a visceral fat deposit called epicardial 
adipose tissue (EAT).12 It surrounds the heart and 
coronary arteries, being vascularized by branches 
of the coronary arteries.12,13 EAT is metabolically 
active, has a thermogenic role, secretes cytokines 
with pro- and anti-atherosclerotic qualities, and is 
hypothesized to defend against mechanical inju-
ries to the heart and coronary vessels.14 It is thought 
to have a role in the onset of atherosclerosis, al-
though it is unclear whether systemic processes 
or paracrine effects of EAT directly contribute to 
the development of atherosclerosis.15 The research 
has shown abundant evidence of the correlation 
between EAT volume and cardiovascular risk 
factors, coronary artery calcification and major 
adverse cardiac events.16 There has been recently 
increased interest in EAT attenuation as a marker 
of risk.17 In some studies a lower EAT attenuation 
on non-contrast enhanced cardiac CT scans has 
been linked to the risk of future events18, whereas 
in other studies a higher EAT attenuation has been 
linked to an increased risk.19 
Up until recently, vascular calcification was 
thought to be an inevitable result of aging, and 
the development of coronary artery calcification 
(CAC) was thought to be a passive process. The de-
velopment of CAC is now recognized as an active 
pathogenic process.
The common feature of atherosclerosis - ectopic 
bone production is known as the cause of coronary 
artery calcification, and new bone formation being 
the defining feature of DISH led us to hypothesize 
that arterial calcification and the occurrence of 
DISH are strongly correlated. 
To our knowledge, the prevalence of DISH in 
the Slovenian population has not been evaluated. 
Based on this framework, the objective of our 
study is to analyze the epidemiological aspects of 
DISH patients in Slovenia, to evaluate the relation-
ship between coronary CT angiography (CCTA)-
derived EAT density and CAC in patients with 
and without DISH, and study influencing factors 
of these parameters.
Patients and methods
This cross-sectional study was conducted at the 
Department of Radiology, University Medical 
Centre Maribor. This study was conducted with 
approval of local ethics committee (UKC-MB-
KME-24/21) and performed accordingly to the 
Declaration of Helsinki. All participants gave writ-
ten informed consent.
Study protocol
Between January 2022 and January 2024, adult pa-
tients referred for CCTA were included in the study. 
Participants responded to questionnaires assess-
ing socio-demographic information, lifestyle and 
health-related factors, which contains self-reported 
information on age, gender, weight status, chronic 
diseases, smoking and physical activity.  Exclusion 
criteria were age < 18 years, known malignancy 
and prior coronary artery bypass surgery. A total 
of 219 cases were included in the study. 
Body mass index (BMI)
We calculated the BMI by using self-reported 
height and weight following the formula: weight 
(kg) divided by height (m) squared. According to 
WHO standards, BMI was categorized into un-
derweight (BMI < 18.5), normal (18,5–24.99), over-
weight (BMI ≥ 25) and obese (BMI ≥ 30).20
CT acquisition protocol
All examinations were performed on Somatom 
Drive CT scanner (Siemens Medical Solutions, 
Erlengen, Germany). Noncontrast, non-gated 
CT scan was performed to measure the Agatson 
coronary artery calcification score (CACS), as de-
scribed previously.21 The sum of the individual le-
sion scores from the four vessels; left main (LM), 
left anterior descending (LAD), circumflex (LCX), 
and right coronary artery (RCA) produced the 
total coronary calcium score. The Agatson Units 
were classified into four categories: 0, > 0 and < 
100, 100−400, and > 400. These categories repre-
sent no, mild/minimal, moderate, and substantial 
plaque burden. In the same way the calcium score 
(Agatson) was measured for proximal thoracic aor-
ta (from aortic root to the first branch of the aortic 
arch), aortic root and ascending aorta.
The EAT attenuation was measured on the same 
axial images used for CACS. Epicardial adipose 
tissue Hounsfield units (HU) were measured us-
ing regions of interest (ROI) near the proximal part 
of RCA, between the right atrium and right ven-
tricular outflow tract, as previously described.15
Hepatic and splenic HU attenuation values 
were quantified by placing two ROI in the liver 
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis56
and one in spleen, in the same axial slice. Liver to 
spleen ratio was calculated by dividing the mean 
liver attenuation by the splenic HU. Nonalcoholic 
fatty liver disease (NAFLD) was defined as liver 
to spleen ratio < 1 and/or mean liver attenuation < 
40 HU.22
A retrospective ECG-gated CCTA examination 
was done in all participants, to assess coronary 
artery disease (CAD). CCTA datasets were trans-
ferred to a workstation (Syngo.via VB10. Siemens 
Healthcare, Forchheim, Germany), and coronary 
arteries were evaluated for the presence of obstruc-
tive CAD (defined as at least one lesion causing the 
stenosis of lumen ≥ 50%). CCTA images were re-
constructed with a slice thickness of 0.6 mm. The 
CT studies were evaluated by radiologists having 
more than five years of experience in cardiac imag-
ing.
Diffuse idiopathic skeletal hyperostosis 
(DISH)
Resnick classification criteria were used to define 
DISH: the presence of flowing bridging ossifica-
tion of at least four contiguous vertebrae, (relative) 
preservation of the intervertebral disc height and 
the absence of apophyseal joint bony ankylosis, as 
described. The prevalence of DISH was diagnosed 
by a single musculoskeletal radiologist evaluating 
CT images. 
Metabolic syndrome
The metabolic syndrome (MetS) was defined ac-
cording to the International Diabetes Federation 
(IDF) definition23: BMI greater than 30 kg/m2 (in 
this case the central obesity can be assumed and 
waist circumference measure is not necessary) 
plus any two of the four factors: 1 raised triglyc-
erides (≥ 1.7 mmol/l) or specific treatment for this 
abnormality, 2 reduced HDL cholesterol (< 1.03 
mmol/l in males or < 1.29 mmol/l in females) or 
specific treatment, 3 raised blood pressure (systolic 
BP ≥ 130 or diastolic ≥ 85 mmHg) or treatment for 
diagnosed hypertension, and 4 raised fasting plas-
ma glucose (≥ 5.6 mmol/l) or previously diagnosed 
diabetes type 2. 
Covariates
Additional data were collected: age in years, sex 
(male, female), smoking behavior (current smoker 
yes/no) and physical activity (days per week). The 
presence of hypertension, diabetes mellitus type 2 
and hypercholesterolemia was established by the 
question ‘Have you had these condition?’ and/or 
the self-reported usage of antihypertensive drugs, 
glucose lowering and lipid lowering drugs. Other 
chronic health conditions included angina pecto-
ris, and previous myocardial infarction. 
Statistical analysis
All continuous variables were tested for normal 
distribution (Shapiro-Wilk test). Normally distrib-
uted variables are given as means and standard de-
viations (SD), non-normally distributed variables 
are given as median (interquartile range [Q1−Q3]) 
and categorical variables are presented as numbers 
and percentages (%). Comparisons of demographic 
characteristics and potential covariates between 
the DISH and no DISH groups were conducted us-
ing Mann-Whitney U test and independent sample 
t-test for continuous variables, and Chi-square test 
for categorical variables. Group-wise compari-
sons were performed with the Kruskal-Wallis test. 
Independent sample t-test, Pearson or Spearman 
rank correlations were calculated to determine the 
relationships between EAT attenuation and risk 
factors. We also evaluated the relationship between 
EAT attenuation and CT parameters using multi-
variable linear regression analyses. To determine 
the association between the presence of DISH, EAT 
and CAC, univariate and multivariate logistic re-
gression analyses were performed. The models in-
cluded DISH status (present or absent) as depend-
ent factor and age, gender, BMI, eight, smoking 
status, diabetes, hypertension and hypercholes-
terolemia as independent variables. A multivari-
FIGURE 1. A 68-year old male with diffuse idiopathic skeletal hyperostosis (DISH) 
coronary artery calcification score (CACS) > 400. (A) Typical appearance of 
DISH in thoracic spine, sagittal plane. (B) Calcifications in LAD = left anterior 
descending artery
A B
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis 57
ate multinomial logistic regression was performed 
with CAC categories (> 0 and < 100, 100−400, > 
400) as independent factor and CACS = 0 as refer-
ence category and DISH status as dependent fac-
tor. Multivariate analyses were done in a stepwise 
backward elimination based on a p-value < 0,10. 
We analyzed the prevalence of DISH and CACS in 
the relation to the amount of risk factors (diabetes, 
BMI > 30, hypertension, hypercholesterolemia) pre-
sent. Comparisons between the DISH and no DISH 
groups were conducted using Chi-square test. All 
statistical analyses were performed using the SPSS 
29.0 software package (IBM, Armonk, NY, USA). 
All tests were 2-sided and a ‘P’ value of less than 
0.05 was considered statistically significant.
Results
A total of 219 participants were included in the 
study. The overall prevalence of DISH was 7.8%. 
The prevalence of DISH was about twice as high 
in males than in females (10.4% vs. 4.8%). The char-
acteristics of the demographics and cardiovascu-
lar risk factors of participants with and without 
DISH are shown in Table 1. Compared to patients 
without DISH, those with DISH were significantly 
older (67.3 vs. 60.5 years). 42.6% of subjects were 
obese (45.5% men and 39.4% women). Among 
subjects with DISH, 68.8% were obese, compared 
to 40.4% of patients without DISH. NAFLD was 
present in 26.3% of participants; in 29.4 % of pa-
tients with DISH and in 26.0% of patients without 
DISH. Metabolic syndrome was present in 15.4% of 
participants, in subjects with DISH in 43.8%, com-
pared to 13.0% of subjects without DISH.
Additionally, in subjects with DISH a signifi-
cantly higher BMI was noted (32.8 vs. 28.9) and 
more diabetes (35.3% vs. 12.4%). Figure 1 shows an 
example of a male patient with DISH and abun-
dant calcifications in left anterior descending coro-
nary artery.
Subjects without DISH were about three times 
more likely to not have coronary artery calcifica-
TABLE 1. Characteristics of the cohort 
DISH no DISH p-value
Age (years), mean (SD) 67.3 ± 10.1 60.5 ± 12.2 0.029
Gender (f/m), N 5/12 99/103 0.120
Weight (kg), mean (SD) 96.6 ± 20.3 84.5 ± 17.5 0.008
Height (cm), mean (SD) 170.9 ± 6.5 171.0 ± 9.7 0.980
BMI (kg/m2), mean (SD) 32.8 ± 7.2 28.9 ± 5.3 0.011
Family history of cardiovascular disease, N (%) 11 (64.7%) 119 (59.2%) 0.657
Diabetes, N (%) 6 (35.3%) 25 (12.4%) 0.010
Hypercholesterolemia, N (%) 6 (35.3%) 51 (25.4%) 0.371
Hypertension, N (%) 12 (70.6%) 110 (54.7%) 0.206
Current smoker, N (%) 2 (11.8%) 38 (18.9%) 0.465
Angina pectoris, N (%) 4 (23.5%) 92 (44%) 0.076
Metabolic syndrome, N (%) 7 (43.8%) 25 (13.0%) 0.001
EAT attenuation  (HU), mean (SD) -98.5 ± 11.8 -101.7 ± 13.0 0.347
NAFLD 5 (29.4%) 52 (26.0%) 0.759
CACS (au) = 0 2 (11.8%) 68 (33.8%) 0.063
CACS (au), median (IQR) 101.0 (4.7-569.0) 27.3 (0-391.8) 0.241
Calcifications in proximal thoracic aorta, median 
(IQR) 196.4 (12.3-759.5) 14.3 (0-244.6) 0.023
Calcifications in aortic root, median (IQR) 146.8 (8.3-758.0) 1.8 (0-175.0) 0.013
Calcifications in ascending aorta, median (IQR) 2.1 (0-35.2) 0.0 (0-3.9) 0.109
Myocardial infarction, N (%) 1 (6.0%) 12 (6.0%) 0.988
BMI = body mass index; CACS (au) = Agatson coronary artery calcification score; DISH = diffuse idiopathic skeletal hyperostosis (DISH); EAT = epicardial adipose tissue; 
f/m = female/male; IQR = interquartile range; N = number, NAFLD = nonalcoholic fatty liver disease; SD = standard deviation
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis58
tions compared to subjects with DISH (33.8% vs. 
11.0%). In subjects with a CACS > 400, DISH was 
present in 13.3%, while in subjects with CACS = 0 
DISH was present in 2.8% (Table 2).
Associations between EAT attenuation, cardio-
vascular risk factors and CT parameters are de-
picted in Table 3. There is a significant correlation 
between EAT attenuation and BMI (rho = 0.243, p 
< 0.001), CACS (rho = 0.256, p < 0.001) and calcifi-
cations in ascending aorta (rho = 0.052, p = 0.011), 
as well as significant association between EAT at-
tenuation and gender (p < 0.001) and NAFLD (p = 
0.022). 
Figure 2A shows EAT attenuation for patients 
with different Agatson score CACS category. Mean 
EAT attenuation was lower in patients with CACS 
= 0 than in patients with CACS > 400 (-103.7 ± 13.8 
HU vs. -95.9 ± 11.3 HU [p < 0.001]), also in patients 
with CACS > 0 and < 100 the mean EAT attenuation 
was lower than in patients with CACS > 400 (-104.5 
± 12.2 HU vs. -95.9 ± 11.3 HU (p < 0.001)).
Group-wise comparisons between BMI catego-
ries showed significant differences in EAT attenu-
ation (p = 0.007), as shown in Figure 2B. In patients 
with BMI < 18.5 EAT attenuation was -96.0 ± 9.9 
HU (there were only two patients in this group). In 
patients with BMI 18.5−24.9 -107.1 ± 13.9 HU, with 
BMI between 25 and 29.9 -102.1 ± 13.2 HU and in 
patients with BMI > 30 -98.4 ± 11.6 HU.
On univariate analysis, it was observed that age 
(p = 0.032), BMI (p = 0.005) and diabetes (p = 0.015) 
were found to be significantly associated with the 
presence of DISH (Table 4). In multiple logistic 
regression model age and BMI were found to be 
significantly associated with the presence of DISH, 
odds ratio (OR) 1.060, p = 0.029 and OR 1.132, p = 
0.009.
In the multinomial multivariate logistic regres-
sion analysis with the different CACS categories as 
outcome and those without coronary artery calcifi-
cations (CACS = 0) as a reference category, gender, 
age, hypertension and epicardial fat attenuation 
were found to be significantly associated with the 
increasing CAC strata (Table 5). Male gender has a 
16.786 time greater odds of having CACS > 400 than 
female gender, compared to subjects with CACS = 0 
(p < 0.001). Subjects with hypertension have a 5.423 
times greater odds of having CACS > 400 than sub-
jects without hypertension, compared to subjects 
with CACS = 0 (p < 0.001). There is a 1.227-fold in-
crease in the likelihood of having CACS > 400 with 
every additional year of age, compared to subjects 
with CACS = 0 (p < 0.001). Every additional unit of 
EAT attenuation (HU) increases the odds of hav-
TABLE 2. Prevalence of diffuse idiopathic skeletal hyperostosis (DISH) among Agatson coronary artery calcification score (CACS) categories
CACS = 0 
(N = 70)
CACS > 0 and < 100
(N = 62)
CACS = 100−400
(N = 33)
CACS > 400
(N = 53)
DISH 2.8% 10.3% 6.6% 13.3%
No DISH 97.2% 89.7% 93.4% 86.7%
TABLE 3. Association of epicardial adipose tissue (EAT) attenuation with 
conventional coronary artery disease (CAD) risk factors and CT parameters
Variable EAT attenuation (HU) p-value
Gender
M     - 98.3 ± 11.3
< 0.001
F      - 105.4 ± 13.6
NAFLD
Y      - 98.3 ± 12.8
0.022
N      - 102.7 ± 12.8
Family history of cardiovascular disease
Y     - 100.1 ± 12.8
0.261
N     - 104.5 ± 14.1
Diabetes
Y     - 104.2 ± 14.3 
0.883
N     - 101.3 ± 13.3
Hypercholesterolemia
Y     - 99.4 ± 13.5
0.402
N     - 102.6 ± 13.3 
Hypertension
Y     - 99.2 ± 12.4
0.129
N     - 105.2 ± 14.1
Smoking
Y     - 97.8 ± 13.3
0.361
N     - 102.9 ± 13.3
Regular physical activity
Y     - 101.6 ± 12.8
0.653
N     - 101.9 ± 14.4 
Correlation 
coefficient
CACS (Agatson) 0.306 < 0.001
CACS per vessel
   LM 0.159 0.018
   LAD 0.247 < 0.001
   LCX 0.269 < 0.001
   RCA 0.289 < 0.001
Calcifications in proximal thoracic aorta 0.110 0.103
Calcifications in aortic root 0.082 0.226
Calcifications in ascending aorta 0.172 0.011
Age 0.006 0.834
BMI 0.243 < 0.001
BMI = body mass index; CACS = coronary artery calcification score; f = female; HU = Hounsfield 
units; LAD = left anterior descending artery; LCX = left circumflex artery; m = male; LM = left 
main coronary artery; NAFLD = nonalcoholic fatty liver disease; RCA = right coronary artery
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Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis 59
ing CACS > 400 by 1.052 times when compared to 
subjects with CACS = 0 (p = 0.022). DISH, smoking 
status, diabetes, hypercholesterolemia and meta-
bolic syndrome were excluded from the model, 
since they did not meet the criteria (p < 0.1).
Discussion
Despite the fact that DISH is a common condition, 
epidemiology of the disease in Slovenia is un-
known. The overall prevalence of DISH in our co-
hort was 7.8% (10.4% in men and 4.8% in women). 
Our results are consistent with the literature, var-
ying from 3.8% in China24 to 30.8% in Pakistan25, 
7.8% in Iceland26 and 12.8% in Italy.5 The differ-
ences can to some extent be explained by the dif-
ferences in study population, diagnostic criteria 
and variety of imaging methods used – chest x-ray 
or CT scan, whole- spine scans or partial (chest) 
scans.26 Prevalence of DISH increases with age and 
male to female prevalence ratio is 2:1.27 In the cur-
rent study, subjects with DISH were significantly 
older than patients without DISH, however, the lo-
gistic analysis confirmed ageing to influence the 
prevalence of DISH significantly.
Previous studies reported higher BMI in pa-
tients with DISH than in those without DISH.26-28 
Also, various metabolic variables are associated 
with DISH, in particular obesity and type 2 dia-
betes mellitus.29,30 Several paleopathological stud-
ies showed that the prevalence of DISH varied 
significantly between groups of different social 
standing, with speculation that the upper socioec-
onomic status groups were excessively nourished, 
with likely increased incidence of obesity, in com-
parison with the individuals with lower social 
status.29 In the present study, diabetes and BMI 
significantly affected the prevalence of DISH in 
logistic regression analysis. Insulin, a peptide that 
promotes bone development, is raised in diabetes. 
It is speculated, that in patients with diabetes, in-
sulin can promote the new bone growth and there-
by excess bone formation.31 Chondrocytes and 
periosteal mesenchymal cells inside the enthesis 
can proliferate under the impact of several factors 
(i.e. insulin, transforming growth factor-β1,…) 
to form osteoblasts, fibroblasts and myoblasts. 
Furthermore, different metabolic agents (i.e. insu-
lin, insulin-like growth factor 1,…) have the po-
tential to induce bone formation by stimulating 
the proliferation of chondrocytes, fibroblasts and 
osteoblasts.29 Increased rates of obesity in DISH 
patients may indicate that certain adipokines have 
TABLE 4. Univariate logistic regression analysis with diffuse idiopathic skeletal 
hyperostosis (DISH) status as the dependent factor
Variable units OR p-value
Age + 1 year 1.055 0.032
Gender Male vs. female 2.307 0.129
BMI + 1 kg/m2 1.133 0.005
Diabetes Present vs. absent 3.840 0.015
Hypertension Present vs. absent 1.985 0.213
Hypercholesterolemia Present vs. absent 0.623 0.375
Smoking Present vs. absent 1.748 0.470
BMI = body mass index; OR = odds ratio
A
B
FIGURE 2. Epicardial fat attenuation in subjects with (A) different coronary artery 
calcium score and (B) different body mass index (BMI) categories. Data are 
presented as box plots, where boxes represent the interquartile range (IQR), 
the lines within the box represent the median, and the lines outside the boxes 
represent the upper quartile plus 1.5 times IQR or the lower quartile minus 1.5 
times the IQR.
CACS = coronary artery calcification score
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Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis60
a role in the disorder’s development. Several of 
these fat-derived hormones (i.e. leptin) have an as-
sociation with bone metabolism growth.3 Obesity-
related chronic inflammation with proinflamma-
tory cytokines such as IL-6, TNF-α etc. could con-
tribute to the formation of calcifications, as discs 
and ligaments of the spine may have receptors for 
them. Leptin causes chondrocytes to release more 
chondrocyte degradation mediators and promotes 
the proliferation of intervertebral disc cells. Leptin 
stimulates the inflammatory response by raising 
IL-6, which causes ligamentum flavum hyper-
trophy and fibrosis.32 In this study, subjects with 
DISH had a higher prevalence of metabolic syn-
drome and NAFLD than those without DISH. The 
prevalence of NAFLD and metabolic syndrome 
rises with obesity; and NAFLD is considered as 
both, a cause and a result of metabolic syndrome. 
It is widely documented that NAFLD increases 
the risk of development of atherosclerosis and 
cardiac events. Studies showed that NAFLD diag-
nosed on non-contrast CT to be a strong predictor 
of MACE (major adverse cardiovascular events) at 
14-year follow-up.22 We found no correlation be-
tween NAFLD and DISH, however there is a sig-
nificant association between EAT attenuation and 
NAFLD. 
Our study’s findings support earlier research 
suggesting that DISH is linked to a greater extent 
of calcifications in blood vessels.3,9,33 Indeed, we 
observed an increase of DISH prevalence across 
CACS categories. CACS was higher in subjects 
with DISH compared to the non-DISH group, but 
the association did not perseverate on multivariate 
analysis, similar as in previous studies.34 It is hy-
pothesized that subjects with DISH may be prone 
to form calcifications in arteries and in aortic 
valve, amongst other locations, however, our data 
point to a more nuanced, maybe non-causal link 
between CAD and DISH.  
The relationship between EAT volume and 
attenuation, coronary artery plaque load, and 
coronary artery disease is widely recognized in 
the literature. In our study EAT attenuation was 
significantly higher in subjects with CACS > 400 
compared to subjects with CACS = 0. Higher EAT 
attenuation might reflect inflammation in epi-
cardial fat, which was described in patients with 
acute coronary syndrome.35 EAT also increases 
with vascularization and higher amount of mito-
chondria and decreases with fatty acids overload.19 
Statins also decrease EAT attenuation over time, 
via reducing metabolic activity within the EAT 
by reducing vascularity, cellularity and inflam-
mation15, therefore, an influence of therapy with 
statins might have influenced the observed EAT 
attenuation. Among patients with coronary artery 
disease having open heart surgery, an increase in 
pro-inflammatory mediators and cytokines in the 
EAT was reported, as EAT regulates local inflam-
mation in the immediate vicinity of the coronar-
ies.36 In our study, chronic, low-grade inflamma-
tion might be a significant pathophysiologic con-
nection between DISH, NAFLD, EAT, and CAC. 
However, to further understand the underlying 
processes, more research should be conducted 
correlating EAT attenuation to local and systemic 
metabolic and inflammatory mechanisms.
The limitations of the current study include its 
small sample size, the possibility of selection bi-
as due to the inclusion of many individuals with 
medical disorders, and a cross-sectional design of 
the study, as a result of which, the possible impact 
of DISH on mortality cannot be assessed. 
To understand the mechanism connecting DISH 
and coronary artery calcification a multidiscipli-
nary approach that investigates inflammatory, 
metabolic, genetic, molecular, and environmental 
factors is required. Future research needs to focus 
on elucidating common signaling pathways and 
TABLE 5. Multinomial multivariate logistic regression analysis on the association of diffuse idiopathic skeletal hyperostosis (DISH) and coronary 
artery calcification score (CACS) category
CACS category
gender age hypertension EAT attenuation
OR p-value OR p-value OR p-value OR p-value
>0 and <100 3.515 0.008 1.087 <0.001 3.956 0.001 0.980 0.225
100-400 7.583 <0.001 1.156 <0.001 5.023 0.003 1.005 0.804
> 400 16.786 <0.001 1.227 <0.001 5.423 0.001 1.052 0.022
OR = odds ratio
Coronary artery calcifications (CAC) category is the outcome compared to the subjects without CAC (CACS = 0) as reference category
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis 61
risk factors that underlie both conditions, employ-
ing a combination of molecular, imaging, genetic, 
and clinical methodologies, with prospective stud-
ies and clinical trials, to enhance our comprehen-
sion of the fundamental mechanisms.
Conclusions
There was no independent relationship identified 
between the prevalence of DISH and CACS. The 
specific processes that lead to new bone develop-
ment in DISH patients, particularly in entheses, 
still remain unclear.
Acknowledgements 
The authors would like to thank Laura Kocet for 
her assistance with statistical processing. The pro-
ject described was funded by University Medical 
Centre Maribor, internal research grant number 
IRP-2021/01-11.
References
1. Forestier J, Rotes-Querol J. Senile ankylosing hyperostosis of the spine. Ann 
Rheum Dis 1950; 9: 321-30. doi: 10.1136/ard.9.4.321
2. Resnick D, Niwayama G. Radiographic and pathologic features of spinal in-
volvement in diffuse idiopathic skeletal hyperostosis (DISH) Radiology 1976; 
119: 559-68. doi: 10.1148/119.3.559
3. Oudkerk SF, Mohamed Hoesein FAA, W PTM, Öner FC, Verlaan JJ, de 
Jong PA, et al. Subjects with diffuse idiopathic skeletal hyperostosis have 
an increased burden of coronary artery disease: an evaluation in the 
COPDGene cohort. Atherosclerosis 2019; 287: 24-9. doi: 10.1016/j.athero-
sclerosis.2019.05.030
4. Weinfeld RM, Olson PN, Maki DD, Griffiths HJ. The prevalence of diffuse 
idiopathic skeletal hyperostosis (DISH) in two large American Midwest met-
ropolitan hospital populations. Skelet Radiol 1997; 26: 222-5. doi: 10.1007/
s002560050225
5. Ciaffi J, Borlandelli E, Visani G, Facchini G, Miceli M, Ruscitti P, et al. F. 
Prevalence and characteristics of diffuse idiopathic skeletal hyperostosis 
(DISH) in Italy. Radiol Med 2022; 127: 1159-69. doi: 10.1007/s11547-022-
01545-x
6. Yoshihara H, Nadarajah V, Horowitz E. Prevalence and characteristics of 
thoracic diffuse idiopathic skeletal hyperostosis in 3299 black patients. Sci 
Rep 2021; 11: 22181. doi: 10.1038/s41598-021-01092-x
7. Mader R, Novofestovski I, Adawi M, Lavi I. Metabolic syndrome and cardio-
vascular risk in patients with diffuse idiopathic skeletal hyperostosis. Semin 
Arthritis Rheum 2009; 38: 361-5. doi: 10.1016/j.semarthrit.2008.01.010
8. Mattera M, Reginelli A, Bartollino S, Russo C, Barile A, Albano D, et al. 
Imaging of metabolic bone disease. Acta Biomed 2018; 89(1-S): 197-207. 
doi: 10.23750/abm.v89i1-S.7023
9. Harlianto NI, Westerink J, Hol ME, Wittenberg R, Foppen W, van der Veen 
PH, et al. Patients with diffuse idiopathic skeletal hyperostosis have an in-
creased burden of thoracic aortic calcifications. Rheumatol Adv Pract 2022; 
6: rkac060. doi: 10.1093/rap/rkac060
10. Pariente-Rodrigo E, Sgaramella GA, Olmos-Martínez JM, Pini-Valdivieso SF, 
Landeras-Alvaro R, Hernández-Hernández JL. Relationship between diffuse 
idiopathic skeletal hyperostosis, abdominal aortic calcification and associ-
ated metabolic disorders: data from the Camargo cohort. Med Clin 2017; 
149: 196-202. doi: 10.1016/j.medcli.2017.01.030
11. Glick K, Novofastovski I, Schwartz N, Mader R. Cardiovascular disease in 
diffuse idiopathic skeletal hyperostosis (DISH): from theory to reality-a 
10-year follow-up study. Arthritis Res Ther 2020; 22: 190. doi: 10.1186/
s13075-020-02278-w
12. Wu Y, Zhang A, Hamilton DJ, Deng T. Epicardial fat in the maintenance of 
cardiovascular health. Methodist Debakey Cardiovasc J 2017; 13: 20-4. doi: 
10.14797/mdcj-13-1-20
13. Bertaso AG, Bertol D, Duncan BB, Foppa M. Epicardial fat: definition, meas-
urements and systematic review of main outcomes. Arq Bras Cardiol 2013; 
101: e18-28. doi: 10.5935/abc.20130138
14. Iacobellis G. Aging effects on epicardial adipose tissue. Front Aging 2021; 2: 
666260. doi: 10.3389/fragi.2021.666260
15. Raggi P, Gadiyaram V, Zhang C, Chen Z, Lopaschuk G, Stillman AE. Statins 
reduce epicardial adipose tissue attenuation independent of lipid lower-
ing: a potential pleiotropic effect. J Am Heart Assoc 2019; 8: e013104. doi: 
10.1161/JAHA.119.013104
16. Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan 
RS, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease 
risk factors, and vascular calcification in a community-based sample the 
Framingham heart study. Circulation 2008; 117: 605-13. doi: 10.1161/
CIRCULATIONAHA.107.743062
17. Archer JM, Raggi P, Amin SB, Zhang C, Gadiyaram V, Stillman AE. Season and 
clinical factors influence epicardial adipose tissue attenuation measurement 
on computed tomography and may hamper its utilization as a risk marker. 
Atherosclerosis 2021; 321: 8-13. doi: 10.1016/j.atherosclerosis.2021.01.025
18. Goeller M, Achenbach S, Marwan M, Doris MK, Cadet S, Commandeur 
F, et al. Epicardial adipose tissue density and volume are related to sub-
clinical atherosclerosis, inflammation and major adverse cardiac events in 
asymptomatic subjects, J Cardiovasc Comput Tomogr 2018; 12: 67-73. doi: 
10.1016/j.jcct.2017.11.007
19. Mahabadi AA, Balcer B, Dykun I, Forsting M, Schlosser T, Heusch G, et al. 
Cardiac computed tomography-derived epicardial fat volume and attenua-
tion independently distinguish patients with and without myocardial infarc-
tion. PLoS One 2017; 12: e0183514. doi: 10.1371/journal.pone.0183514
20. World Health Organization. Obesity and overweight. [internet]. [cited 2024 
Mar 13]. Available at: https://www.who.int/news-room/fact-sheets/detail/
obesity-and-overweight 
21. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano 
R. Quantification of coronary artery calcium using ultrafast computed 
tomography. J Am Coll Cardiol 1990; 15: 827-32. doi: 10.1016/0735-
1097(90)90282-t
22. Lin A, Wong ND, Razipour A, McElhinney PA, Commandeur F, Cadet SJ, et 
al. Metabolic syndrome, fatty liver, and artificial intelligence-based epicar-
dial adipose tissue measures predict long-term risk of cardiac events: a 
prospective study. Cardiovasc Diabetol 2021; 20: 27. doi: 10.1186/s12933-
021-01220-x
23. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome − a new world-wide defi-
nition. A Consensus Statement from the International Diabetes Federation. 
Diabet Med 2006; 23: 469-80. doi: 10.1111/j.1464-5491.2006.01858.x
24. Liang H, Liu G, Lu S, Chen S, Jiang D, Shi H, et al. Epidemiology of ossification 
of the spinal ligaments and associated factors in the Chinese population: a 
cross-sectional study of 2000 consecutive individuals. BMC Musculoskelet 
Disord 2019; 20: 253. doi: 10.1186/s12891-019-2569-1
25. Adel H, Khan SA, Adil SO, Huda F, Khanzada U, Manohar M, et al. CT-based 
evaluation of diffuse idiopathic skeletal hyperostosis in adult population; 
prevalence, associations and interobserver agreement. J Clin Densitom 
2020; 23: 44-52. doi: 10.1016/j.jocd.2018.12.001
26. Auðunsson AB, Elíasson GJ, Steingrímsson E, Aspelund T, Sigurdsson S, 
Launer L, et al. Diffuse idiopathic skeletal hyperostosis in elderly Icelanders 
and its association with the metabolic syndrome: the AGES-Reykjavik Study. 
Scand J Rheumatol 2021; 50: 314-8. doi: 10.1080/03009742.2020.1846779
Radiol Oncol 2025; 59(1): 54-62.
Lesjak V et al. / Epidemiological aspects of diffuse idiopathic skeletal hyperostosis62
27. Harlianto NI, Oosterhof N, Foppen W, Hol ME, Wittenberg R, van der Veen 
PH, van Ginneken B, et al. Diffuse idiopathic skeletal hyperostosis is as-
sociated with incident stroke in patients with increased cardiovascular risk. 
Rheumatology 2022; 61: 2867-74. doi: 10.1093/rheumatology/keab835
28. Ishimura D, Morino T, Murakami Y, Yamaoka S, Kinoshita T, Takao M. 
Examining the association between the extent of anterior longitudinal 
ligament ossification progression and comorbidities in diffuse idiopathic 
skeletal hyperostosis. Cureus 2023; 15: e51357. doi: 10.7759/cureus.51357 
29. Pillai S, Littlejohn G. Metabolic factors in diffuse idiopathic skeletal hyper-
ostosis-a review of clinical data. Open Rheumatol J 2014; 8: 116-28. doi: 
10.2174/1874312901408010116
30. Okada E, Ishihara S, Azuma K, Michikawa T, Suzuki S, Tsuji O, et al. Metabolic 
syndrome is a predisposing factor for diffuse idiopathic skeletal hyperosto-
sis. Neurospine 2021; 18: 109-16. doi: 10.14245/ns.2040350.175
31. Sencan D, Elden H, Nacitarhan V, Sencan M, Kaptanoglu E. The prevalence 
of diffuse idiopathic skeletal hyperostosis in patients with diabetes mellitus. 
Rheumatol Int 2005; 25: 518-21. doi: 10.1007/s00296-004-0474-9
32. Chaput CD, Siddiqui M, Rahm MD. Obesity and calcification of the liga-
ments of the spine: a comprehensive CT analysis of the entire spine in 
a random trauma population. Spine J 2019; 19: 1346-53. doi: 10.1016/j.
spinee.2019.03.003
33. Orden AO, David JM, Díaz RP, Nardi NN, Ejarque AC, Yöchler AB. Association 
of diffuse idiopathic skeletal hyperostosis and aortic valve sclerosis. 
Medicina (B Aires) 2014; 74: 205-9. PMID: 24918668
34. Lantsman CD, Brodov Y, Matetzky S, Beigel R, Lidar M, Eshed I, et al. No 
correlation between diffuse idiopathic skeletal hyperostosis and coronary 
artery disease on computed tomography using two different scoring sys-
tems. Acta Radiol 2023; 64: 508-14. doi: 10.1177/02841851221090890
35. Konishi M, Sugiyama S, Sato Y, Oshima S, Sugamura K, Nozaki T, et 
al. Pericardial fat inflammation correlates with coronary artery dis-
ease. Atherosclerosis 2010; 213: 649-55. doi: 10.1016/j.atherosclero-
sis.2010.10.007
36. Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, et al. Human 
epicardial adipose tissue expresses a pathogenic profile of adipocytokines 
in patients with cardiovascular disease. Cardiovasc Diabetol 2006; 5: 1. doi: 
10.1186/1475-2840-5-1.