doi:10.1111/iej.

13030

Cholesterol crystals in periapical lesions of root

filled teeth

C. Plengwitthaya1, K. Dhanuthai2, S. Chantarangsu2 & C. Ratisoontorn1

1
Section of Endodontics, Department of Operative Dentistry, Chulalongkorn University; and 2Department of Oral Pathology,
Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

Abstract determine the association between independent vari-

ables and the presence of cholesterol crystals.
Plengwitthaya C, Dhanuthai K, Chantarangsu S,
Results The overall prevalence of cholesterol crystals
Ratisoontorn C. Cholesterol crystals in periapical lesions of
was 20.31%. The periapical biopsies >100 mm2 in size
root filled teeth. International Endodontic Journal, 52, 484–
on periapical films had a significantly greater preva-
490, 2019.
lence of cholesterol crystals than those <100 mm2
Aim To determine the prevalence of cholesterol crys- (P = 0.005). The biopsies diagnosed as radicular cysts
tals in periapical biopsies and to evaluate the correla- had a significantly greater prevalence of cholesterol
tion between cholesterol crystals in periapical biopsies crystals than the biopsies with other diagnoses
and age, gender, location of the periapical lesion, (P < 0.001). A pathological diagnosis of radicular cyst
pathologic diagnosis and lesion size. was the variable with the strongest association with
Methodology The biopsy report database (Faculty the presence of cholesterol crystals (P < 0.001;
of Dentistry, Chulalongkorn University, Bangkok, adjusted OR, 12.39).
Thailand) during 2005–2014 was reviewed. The Conclusions Presence of cholesterol crystals was
prevalence of cholesterol crystals in the periapical associated with periapical lesion diagnosed as a radic-
lesions of root filled teeth was determined. Pathologi- ular cyst and lesion >100 mm2 in area. Age, gender
cal diagnosis, patients’ age, gender and the location and location of the lesion did not influence the pres-
(maxilla or mandible) of the periapical lesion were ence of cholesterol crystals.
obtained from treatment records. The area of the
Keywords: age, cholesterol crystal, cyst, periapical
lesion from the periapical radiograph before surgery
lesion, size.
was calculated using ImageJ software. Univariate and
multivariate logistic regression analyses were used to Received 27 June 2018; accepted 15 October 2018

to treatment, new bone formation occurs, resulting in

Introduction
the initial reduction of the lesion size and its eventual
Periapical bone resorption, which can be seen as radi- healing (Seltzer et al. 1963, Storms 1969). On the
olucency in a radiograph, is an important sign of api- contrary, periapical lesions can persist or emerge as a
cal periodontitis. Intraradicular infection is the major consequence of the inability to adequately control the
cause of this condition (Kakehashi et al. 1965), and intraradicular infection. However, extraradicular
root canal treatment aims to eradicate it. Subsequent infection (Nair et al. 1990a), the presence of a foreign
body (Nair et al. 1990b), cyst (Nair et al. 1993) and
the formation of cholesterol crystal (Nair et al. 1998)
are also potential causes of post-treatment endodontic
Correspondence: Chootima Ratisoontorn, Section of disease, which need to be treated surgically.
Endodontics, Department of Operative Dentistry, Faculty of
Dentistry, Chulalongkorn University, 34 Henry-Dunant
Cholesterol is a steroid alcohol found in all tissue
Road, Bangkok 10330, Thailand (Tel.: 662-218-8795; types. It is the main component of cell membranes
fax: 662-218-8794; e-mail: [email protected]). and also a precursor of bile acids, steroid hormones

484 International Endodontic Journal, 52, 484–490, 2019 © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd
 Plengwitthaya et al. Cholesterol crystals of root canal treated teeth

and vitamin D (Harvey & Champe 2005). Cholesterol Chulalongkorn University were reviewed. The proto-
is absorbed in the small intestine (Carr & Jesch col was approved by the Human Research Ethics
2006), synthesized in the liver and transported to tis- Committee of the Faculty of Dentistry, Chulalongkorn
sues and organs through blood by binding to proteins University. The periapical biopsies were obtained dur-
in the form of lipoprotein. Many dietary and genetic ing surgical retreatment of teeth with apical pathosis
factors regulate plasma cholesterol levels (Lecerf & de at the Postgraduate Endodontic clinic and the Oral
Lorgeril 2011). A notorious cholesterol crystal-related and Maxillofacial Surgery clinic. Inclusion criteria
disease is atherosclerosis, an accumulation of choles- were as follows:
terol in the blood vessel walls. Cholesterol crystal can 1. Teeth with history of previous root canal treat-
also be found in other tissues and causes inflamma- ment before periapical surgery.
tion of the organ, such as otitis media, or the choles- 2. Periapical radiographs (include the entire periapi-
terol granuloma in the thorax (Ross 1999). cal lesion) taking before the periapical surgery
Cholesterol crystals can be found in odontogenic were available.
cysts, especially radicular cysts. The cystic fluid with 3. Periapical radiolucencies were observed on the
cholesterol crystals is gold- or straw-coloured clini- radiographs.
cally (Browne 1971) and is crystalline diamond The pathological diagnosis was previously reported
(rhomboid) in shape when viewed under a micro- by oral pathologists on duty at the time of surgery.
scope. If a tissue with cholesterol crystal is stained The formalin-fixed paraffin-embedded tissues were
with H & E, needle-shaped clefts, also called choles- stained with haematoxylin-eosin (H&E) and examined
terol clefts, are revealed. The prevalence of cholesterol under a light microscope at the magnifications from
crystals was reported in the range of 18%–44% (Nair 409 to 2009. The pathological diagnosis was classi-
et al. 1998) being higher in inflammatory odonto- fied as follows:
genic cysts and lower in non-inflammatory cysts such 1. Radicular cyst: Cavity partially or completely
as odontogenic keratocyst (keratocystic tumour). The lined by non-keratinized stratified squamous
inflammatory process is likely to have an important epithelium with inflammatory cells in the centre
role in the formation of cholesterol crystal (Browne or lumen.
1971). Cholesterol crystals are also surrounded by 2. Periapical granuloma: Granulation lesion at the
multinucleated giant cells (Shear 1963). In apical area of the tooth infiltrated by lympho-
atherosclerosis, cholesterol deposition and crystalliza- cytes, plasma cells and macrophages with well-
tion on inflammatory responses has been described developed fibrous capsule.
(Grebe & Latz 2013). 3. Scar tissues: A dense, collagenous connective tis-
Recently, Slutzky-Goldberg et al. (2013) reported sue with wavy collagen fibres and a lack of
the relationship between cholesterol crystals and age inflammatory cells.
in tissues from apical surgery cases. They reported 4. Abscess: A collection of PMNs, pus cells and cell
that elderly patients had a significantly greater preva- debris in the tissue.
lence of cholesterol crystals than adolescent patients. To determine the prevalence of cholesterol crystals,
However, factors such as gender, location of the peri- one researcher (CP) examined the histopathological
apical lesion, pathologic diagnosis and lesion size sections for the presence of cholesterol clefts and
have not been evaluated for the correlation with the foamy cells. In paraffin sections processed for H&E
prevalence of cholesterol crystals in periapical lesions. staining, the cholesterol was dissolved by the fat sol-
Therefore, this study aimed to determine the preva- vents used in dehydration and infiltration, and
lence of cholesterol crystals in periapical biopsies and appeared as needle-shaped space (cholesterol clefts)
evaluate the correlation between cholesterol crystals within the tissues. In case of doubt, CP consulted the
in periapical biopsies and age, gender, location of board-certified oral pathologist (KD). Foamy cells are
the periapical lesion, pathologic diagnosis and lesion known to form by the unregulated uptake of oxidized
size. low-density lipoprotein (LDL), thus showing massive
lipid droplets in macrophage cytoplasm.
Variables including patients’ age, gender and the
Materials and methods
location of the periapical lesion were searched from
In this retrospective study, the biopsy reports during treatment records. For the size of the lesion, the peri-
2005–2014 from the Department of Oral Pathology, apical radiographs before surgery were obtained from

© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 52, 484–490, 2019 485
 Cholesterol crystals of root canal treated teeth Plengwitthaya et al.

treatment records and digitized with an optical scan- Table 1 Case distribution according to pathological diag-
ning process for digital files (JPEG) with 800 dpi reso- noses
lution. The images were transferred to the ImageJ Radicular Scar
software (version 1.48v, National Institutes of Health, Cyst Granuloma tissue Abscess
Washington, DC, USA) for lesion area measurement.
Maxilla 51 57 3 1
Delineation was performed on the radiographic image Mandible 11 5 0 0
to exclude tooth structure, but include the area of Total 62 62 3 1
bone rarefaction.

Bivariate associations between investigated vari-

Statistical analysis
ables and the presence or absence of cholesterol crys-
Independent variables were included as follows: (i) age tals are presented in Table 2. The periapical biopsies
(<60, ≥60); (ii) gender; (iii) location (maxilla, mand- from lesions ≥100 mm2 on the periapical films or the
ible); (iv) area (<100, ≥100 mm2) and (v) pathological pathological diagnosis as radicular cyst were associ-
diagnosis (cyst, others). The association between the ated with significantly higher occurrence of choles-
presence of cholesterol crystals and each independent terol crystals than the periapical biopsies from lesions
variable was calculated using the Pearson chi-square <100 mm2 or other diagnoses (P = 0.005 and
test. Univariate and multivariate logistic regression <0.001, respectively). The age <60, male gender and
analyses were used to determine the degree of associa- mandibular location were associated with higher fre-
tion between independent variables and the presence quency of cholesterol crystals, but the differences were
of cholesterol crystals. In the multivariate model, those not significant.
independent variables were included in the model Logistic regression analyses were performed to fur-
regardless of their significance in univariate model. ther determine the degree of association between the
Crude and adjusted odds ratios (ORs) and correspond- independent variables and the presence of cholesterol
ing 95% confidence intervals (CIs) were calculated for crystals (Table 3). In the univariate analysis, the peri-
each independent variable. Statistical analyses were apical lesion size ≥100 mm2 and the pathological
performed using SPSS Statistics for Windows, version diagnosis as radicular cyst significantly increased the
19.0 (IBM, Armonk, NY, USA), and a P value <0.05 likelihood for the presence of cholesterol crystals, with
was considered statistically significant. an OR of 3.51 (95% CI: 1.41–8.76) and 12.39 (95%
CI: 3.49–43.99), respectively. However, no significant
association was observed between age <60 or male
Results
gender or mandibular location and the presence of
From 401 periapical biopsies of apical surgery cases cholesterol crystals (P > 0.05). When the independent
in the database during 2005–2014, 128 biopsies variables were regressed multivariately, the
were included. The reasons for exclusion of cases
were unavailable periapical films (171 biopsies), teeth
were not previously root filled (85 biopsies) and large
lesions were not included fully in the periapical films
(19 biopsies). Amongst the 128 biopsies analysed, the
majority of biopsies were in the <60 years old age
group (116 of 128, 90.6%), female patients (73 of
128, 57.0%), located in the maxilla (111 of 128,
86.7%), <100 mm2 in size on periapical films (96 of
128, 75.0%) and were diagnosed as radicular cyst
(62 of 128, 48.4%) and periapical granuloma (62 of
128, 48.4%) (Table 1).
Cholesterol crystals were detected as needle-shaped
space in sections of periapical tissues. The overall
prevalence of cholesterol crystals was 20% (26 of Figure 1 Photomicrograph showing radicular cyst with
128). Foam cells were concertedly observed in sec- cholesterol crystals and foam cells in the lumen. (Haema-
tions with cholesterol crystals (Fig. 1). toxylin & eosin stain, original magnification 2009).

486 International Endodontic Journal, 52, 484–490, 2019 © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd
 Plengwitthaya et al. Cholesterol crystals of root canal treated teeth

Table 2 Bivariate associations between investigated variables et al. 2013). The limitation of the present study is
and the presence or absence of CC in periapical biopsies of that the whole lesion was not always available for
root canal treated teeth histopathological examination. As a result, the cases
Variables Total n CC n (%) No CC n (%) P-value* in which cholesterol crystals were not observed, may
actually contain cholesterol crystals in parts of the tis-
Age
<60 116 24 (20.7) 92 (79.3) 0.742
sue that were not examined. However, all cases were
≥60 12 2 (16.7) 10 (83.3) subject to the same criteria, examining the whole
Gender histopathological slides for the presence of cholesterol
Male 55 14 (25.5) 41 (74.5) 0.209 crystals. A highly significant prevalence of cholesterol
Female 73 12 (16.4) 61 (83.6)
deposit in periapical biopsies amongst elderly patients
Location
Upper 111 22 (19.8) 89 (80.2) 0.723
(>60 years old) has been reported (Slutzky-Goldberg
Lower 17 4 (23.5) 13 (76.5) et al. 2013). The authors reported that the prevalence
Size of cholesterol crystals was significantly higher in male
<100 mm2 96 14 (14.6) 82 (85.4) 0.005 biopsies than female biopsies in the elderly. However,
≥100 mm2 32 12 (37.5) 20 (62.5)
no correlation between age or gender and the preva-
Pathological diagnosis
Cyst 62 23 (37.1) 39 (62.9) <0.001
lence of cholesterol crystals was found in the present
Others 66 3 (4.5) 63 (95.5) study. One major contrast between the present study
and that of Slutzky-Goldberg et al. (2013) was the
*Association between the presence of CC and each indepen-
dent variable was analysed using the Pearson chi-square test. age groups. They grouped the specimens as elderly
A significant association (P < 0.05) was indicated in bold. (over 60 years old) and adolescent (13–21 years old),
whilst the present study compared <60 to ≥60 years
pathological diagnosis of radicular cyst remained sig- old. Besides the aforementioned age grouping, the dif-
nificant, with adjusted OR of 10.90 (95% CI: 2.81– ference in genetic backgrounds could also contribute
42.34). to the disagreement between the two studies.
The two variables that had an association with the
presence of cholesterol crystal in the persisting peri-
Discussion
apical lesion of the root filled teeth were the patholog-
Cholesterol crystals have been related to inflammatory ical diagnosis of radicular cyst and lesion size larger
diseases including chronic apical periodontitis (Grebe than 100 mm2. According to Grossman (1950), one
& Latz 2013). Accumulation of cholesterol crystals in of the preliminary clinical diagnostic signs of a peri-
the periapical area is one of the histopathological fea- radicular cysts is a periapical lesion greater than
tures of persistent chronic apical periodontitis and 200 mm2 (Grossman 1950). In addition, Natkin et al.
implicated as an aetiologic factor in non-resolving (1984) analysed the data of various studies and
chronic inflammation (Nair et al. 1998). In this study, related the radiographic lesion size to histology. They
the prevalence of cholesterol crystals in periapical reported that with a radiographic lesion area of
biopsies of root filled teeth that had undergone peri- 200 mm2 or larger, the prevalence of cysts was
apical surgery (20%) falls within the range of previ- almost 100%. In this study, the largest granuloma
ous studies that reported a range from 18% to 44% size was 199.32 mm2, and lesions larger than
(Sanchis et al. 1998, Nair 2006, Slutzky-Goldberg 200 mm2 were pathologically diagnosed as cysts in

Table 3 Crude and adjusted odds

Univariate logistic Multivariate logistic
ratios (OR) and 95% confidence inter-
regression regression
vals (CI) for the association between
independent variables and the presence Crude OR Adjusted OR
of CC in periapical biopsies of root filled Variables (95% CI) P-value (95% CI) P-value
teeth Age <60 1.30 (0.27–6.35) 0.742 1.31 (0.23–7.64) 0.764
Male 1.74 (0.73–4.13) 0.212 1.18 (0.45–.3.08) 0.739
Lower jaw 1.25 (0.37–4.19) 0.724 0.92 (0.24–3.56) 0.909
Size ≥100 mm2 3.51 (1.41–8.76) 0.007 1.28 (0.46–3.59) 0.641
Cyst 12.39 (3.49–43.99) <0.001 10.90 (2.81–42.34) 0.001

A significant association (P < 0.05) is indicated in bold.

© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 52, 484–490, 2019 487
 Cholesterol crystals of root canal treated teeth Plengwitthaya et al.

agreement with previous reports. The biopsies were ones (Slutzky-Goldberg et al. 2013). Foam cells are a
grouped into <100 and >100 mm2 in size, and the hallmark of early-stage atherosclerotic lesions, gener-
cholesterol crystals were more prevalent in the peri- ated in association with imbalance of cholesterol
apical lesion of the larger lesions. In the past, choles- influx, esterification and efflux (Yu et al. 2013). Crys-
terol crystals from cystic fluid were used for the talline cholesterol found in early atherosclerotic
diagnosis of radicular cyst or other inflammatory lesions induces NLRP3 inflammasome activation driv-
odontogenic cysts. However, in some radicular cysts, ing atherosclerosis development and progression (Due-
cholesterol crystals cannot be detected from the cystic well et al. 2010). Multimolecular protein complexes,
fluid. Therefore, cholesterol crystals are no longer NLRP3 inflammasome, which regulate the activity of
used as a diagnostic aid for the diagnosis of radicular caspase-1 and the maturation and release of inter-
cysts (Shear & Speight 2007). Recently, different leukin-1beta (IL-1b), can contribute to atherosclerosis.
‘grayscale value’ readings of a CBCT image were pro- Cholesterol-exposed macrophage also increases the
posed for determining the presence of a cyst or a secretion of IL-1 and stimulates bone resorption by
granuloma; however, this method was reported to be ogren et al.
increasing the activity of the osteoclasts (Sj€
unreliable (Rosenberg et al. 2010), and surgical 2002). Elevated asymmetrical dimethylarginine
biopsy and histopathological evaluation remain the (ADMA) plasma level is also implicated in endothelial
gold standard for the diagnosis of radicular cyst dysfunction and the pathogenesis and progression of
(Trope et al. 1989, Simon et al. 2006). atherosclerosis (Notsu et al. 2015). Likewise, apical
How cholesterol crystals are generated in chronic periodontitis is also associated with increased serum
apical periodontitis has not been elucidated clearly. In levels of inflammatory markers, C-reactive protein,
a study of 535 teeth with odontogenic cysts, and 402 interleukin (IL)-1, IL-2, IL-6, IgA, IgG, IgM and
with radicular cysts, cholesterol crystals were found ADMA (Gomes et al. 2013). Due to the similar serum
in lesions with hemosiderin pigment (Browne 1971); inflammatory marker profile between apical periodon-
hence, it is believed that cholesterol crystals are titis and atherosclerosis, patients with risk factors of
derived from the cell membrane decomposition of ery- atherosclerosis, in particular smoking hypertensive
throcytes. Cholesterol crystals evidently play an patients, were also found to have the increased preva-
important role in atherosclerosis. Cholesterol crystals lence of apical periodontitis and root canal treatment
found in the pathologic intimal thickening (American (Segura-Egea et al. 2011). However, under the limita-
Heart Association Type III lesion), the earliest sign of tions of this retrospective study, the association
progressive lesion of atherosclerosis, were assumed to between the risk factors of atherosclerotic cardiovas-
be derived from dead and dying smooth muscle cells cular disease, such as tobacco exposure, hyperlipi-
(Sakakura et al. 2013). However, it has been reported daemia, hypertension, inactivity, overweight and
that endothelial cells were active in processing LDL diabetes and the presence of cholesterol crystal in the
by taking up and metabolizing LDL. Ultimately, when persisted periapical lesion of the root canal treated
overburdened with intracellular cholesterol, it gener- teeth has not been examined.
ated cholesterol crystals (Baumer et al. 2017). Physi- The connection between low-grade inflammation of
cal factors including temperature, pH, cholesterol apical periodontitis and early endothelial impairment,
hydration and saturation influenced rate and volume a predictor for future development of cardiovascular
of cholesterol crystallization (Vedre et al. 2009). disease, has been demonstrated. Young adult patients
Whether the pathogenesis of chronic apical periodon- with apical periodontitis (age 20–40 years old) free
titis with cholesterol crystals is a reflection of from periodontal disease, cardiovascular disease and
atherosclerosis plaque formation remains to be cardiovascular risk factors had reduced endothelial
explored. flow reverse, suggesting the existence of an early
The role of cholesterol crystals in mediating chronic endothelial dysfunction (Cotti et al. 2011, Cotti &
apical periodontitis could be regarded as the inflam- Mercuro 2015). These patients with apical periodonti-
matory response against the crystalline material (Nair tis had significantly greater blood concentrations of
et al. 1998) and the bone resorbing activity of the IL-1, IL-2, IL-6 and ADMA and a significant reduction
cytokine (IL-1a) released from macrophages exposed of endothelial flow reverse (Cotti & Mercuro 2015).
to crystalline cholesterol (Sj€ogren et al. 2002). Foam Relationship between the presence of cholesterol crys-
cells were observed in the periapical lesions with tal in persistent periapical lesions and cardiovascular
cholesterol crystals in this study as well as in previous function remains to be clarified.

488 International Endodontic Journal, 52, 484–490, 2019 © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd
 Plengwitthaya et al. Cholesterol crystals of root canal treated teeth

Conclusion asymptomatic human teeth with therapy-resistant periapi-

cal lesions: a long-term light and electron microscopic fol-
The presence of cholesterol crystals in periapical low-up study. Journal of Endodontics 16, 580–8.
lesions of root filled teeth was associated with radicu- Nair PN, Sj€ ogren U, Krey G, Sundqvist G (1990b) Therapy-
lar cysts and lesions >100 mm2 in area. Age, gender resistant foreign body giant cell granuloma at the periapex
and location of the lesion were not associated with of a root-filled human tooth. Journal of Endodontics 16,
the presence of cholesterol crystals. 589–95.
Nair PN, Sj€ ogren U, Schumacher E, Sundqvist G (1993)
Radicular cyst affecting a root-filled human tooth: a long-
Conflict of interest term post-treatment follow-up. International Endodontic
Journal 26, 225–33.
The authors have stated explicitly that there are no Nair PN, Sj€ ogren U, Sundqvist G (1998) Cholesterol crystals
conflict of interests in connection with this article. as an etiological factor in non-resolving chronic inflamma-
tion: an experimental study in guinea pigs. European Jour-
nal of Oral Sciences 106, 644–50.
References
Natkin E, Oswald RJ, Carnes LI (1984) The relationship of
Baumer Y, McCurdy S, Weatherby TM et al. (2017) Hyper- lesion size to diagnosis, incidence, and treatment of peri-
lipidemia-induced cholesterol crystal production by apical cysts and granulomas. Oral Surgery, Oral Medicine,
endothelial cells promotes atherogenesis. Nature Communi- Oral Pathology 57, 82–94.
cations 8, 1129. Notsu Y, Yano S, Shibata H, Nagai A, Nabika T (2015)
Browne RM (1971) The origin of cholesterol in odontogenic Plasma arginine/ADMA ratio as a sensitive risk marker for
cysts in man. Archives of Oral Biology 16, 107–13. atherosclerosis: Shimane CoHRE study. Atherosclerosis
Carr TP, Jesch ED (2006) Food components that reduce 239, 61–6.
cholesterol absorption. Advances in Food and Nutrition Rosenberg PA, Frisbie J, Lee J et al. (2010) Evaluation of
Research 51, 165–204. pathologists (histopathology) and radiologists (cone beam
Cotti E, Mercuro G (2015) Apical periodontitis and cardio- computed tomography) differentiating radicular cysts from
vascular diseases: previous findings and ongoing research. granulomas. Journal of Endodontics 36, 423–8.
International Endodontic Journal 48, 926–32. Ross R (1999) Atherosclerosis is an inflammatory disease.
Cotti E, Dessi C, Piras A et al. (2011) Association of endodontic American Heart Journal 138, S419–20.
infection with detection of an initial lesion to the cardiovas- Sakakura K, Nakano M, Otsuka F, Ladich E, Kolodgie FD,
cular system. Journal of Endodontics 37, 1624–9. Virmani R (2013) Pathophysiology of atherosclerosis pla-
Duewell P, Kono H, Rayner KJ et al. (2010) NLRP3 inflam- que progression. Heart, Lung and Circulation 22, 399–411.
masomes are required for atherogenesis and activated by Sanchis JM, Penarrocha M, Bagan JV, Guarinos J, Vera F
cholesterol crystals. Nature 464, 1357–61. (1998) Incidence of radicular cysts in a series of 125 chronic
Gomes MS, Blattner TC, Sant’Ana Filho M et al. (2013) Can periapical lesions. Histopathologic study. Revue de Stomatolo-
apical periodontitis modify systemic levels of inflammatory gie et de Chirurgie Maxillo-Faciale (Paris) 98, 354–8.
markers? A systematic review and meta-analysis. Journal Segura-Egea JJ, Castellanos-Cosano L, Velasco-Ortega E et al.
of Endodontics 39, 1205–17. (2011) Relationship between smoking and endodontic
Grebe A, Latz E (2013) Cholesterol crystals and inflamma- variables in hypertensive patients. Journal of Endodontics
tion. Current Rheumatology Reports 15, 313. 37, 764–7.
Grossman LI (1950) Root Canal Therapy, 3rd edn. Philadel- Seltzer S, Bender IB, Turkenkopf S (1963) Factors affecting
phia, PA, USA: Lea & Febiger. successful repair after root canal therapy. The Journal of
Harvey RA, Champe PC (2005) Biochemistry, 3rd edn. Balti- the American Dental Association 67, 651–62.
more, MD, USA: Lippincott Wiliams and Wilkins. Shear M (1963) Cholesterol in dental cysts. Oral Surgery,
Kakehashi S, Stanley HR, Fitzgerald RJ (1965) The effects of Oral Medicine, Oral Pathology 16, 1465–73.
surgical exposures of dental pulps in germ-free and con- Shear M, Speight P (2007) Cysts of the Oral and Maxillofacial
ventional laboratory rats. Oral Surgery, Oral Medicine, Oral Regions, 4th edn. Oxford, UK: Blackwell Munksgaard.
Pathology 20, 340–9. Simon JH, Enciso R, Malfaz JM, Roges R, Bailey-Perry M,
Lecerf JM, de Lorgeril M (2011) Dietary cholesterol: from Patel A (2006) Differential diagnosis of large periapical
physiology to cardiovascular risk. British Journal of Nutri- lesions using cone-beam computed tomography measure-
tion 106, 6–14. ments and biopsy. Journal of Endodontics 32, 833–7.
Nair PN (2006) On the causes of persistent apical periodonti- Sj€
ogren U, Mukohyama H, Roth C, Sundqvist G, Lerner UH
tis: a review. International Endodontic Journal 39, 249–81. (2002) Bone-resorbing activity from cholesterol-exposed
Nair PN, Sj€ ogren U, Krey G, Kahnberg KE, Sundqvist G macrophages due to enhanced expression of interleukin-
(1990a) Intraradicular bacteria and fungi in root-filled, 1alpha. Journal of Dental Research 81, 11–6.

© 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd International Endodontic Journal, 52, 484–490, 2019 489
 Cholesterol crystals of root canal treated teeth Plengwitthaya et al.

Slutzky-Goldberg I, Baev V, Volkov A, Zini A, Tsesis I (2013) computerized tomography. Endodontics & Dental Traumatol-
Incidence of cholesterol in periapical biopsies among ado- ogy 5, 69–72.
lescent and elderly patients. Journal of Endodontics 39, Vedre A, Pathak DR, Crimp M, Lum C, Koochesfahani M,
1477–80. Abela GS (2009) Physical factors that trigger cholesterol
Storms JL (1969) Factors that influence the success of crystallization leading to plaque rupture. Atherosclerosis
endodontic treatment. Journal of the Canadian Dental Associ- 203, 89–96.
ation 35, 83–97. Yu XH, Fu YC, Zhang DW, Yin K, Tang CK (2013) Foam
Trope M, Pettigrew J, Petras J, Barnett F, Tronstad L (1989) cells in atherosclerosis. Clinica Chimica Acta 424, 245–52.
Differentiation of radicular cyst and granulomas using

490 International Endodontic Journal, 52, 484–490, 2019 © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd