Odontoclastic Resorptive Lesions Research Articles

Elevated pro-inflammatory cytokines and chemokines in saliva of cats with feline odontoclastic resorptive lesion

Feline odontoclastic resorptive lesion (FORL) is an inflammatory oral disease of unknown aetiopathogenesis that affects between 20% to 75% of cats. Twenty immune-associated molecules were measured in saliva of 25 healthy and 40 cats with FORL using a multiplex assay. No statistically significant differences were observed in the levels of these proteins between the healthy group and the diseased group of cats. A two-step cluster analysis of the oral microbiome and salivary cytokine data identified two subgroups of cats with FORL: FORL-1 (subset of cats with a less diverse oral microbiome) and FORL-2 (diseased cats with a microbiome similar to that of healthy animals). The level of some key proinflammatory cytokines (IL-1β, IL-12p40) and chemokines (IL-8, RANTES, KC) were significantly higher in the FORL-1 subgroup than in the FORL-2 subgroup and the healthy group. In addition, TNF-α levels were greater in the FORL-1 subgroup than in the FORL-2 subgroup. These increases in pro-inflammatory cytokines and chemokines indicate active ongoing inflammation that may promote the osteoclastic/odontoclastic activity associated with FORL.

Feline Tooth Resorption: A Description of the Severity of the Disease in Regard to Animal's Age, Sex, Breed and Clinical Presentation.

Feline tooth resorption (odontoclastic resorptive lesion) is a common and important issue in veterinary dentistry. This study aimed to analyse the disease's severity and correlation with clinical information in the population of feline patients in Poland in the area of Lower Silesia. An analysis of the clinical charts of 174 cats with dental problems, which were diagnosed as tooth resorption, was conducted. The gender and breed had no influence on the disease severity, but the disease progressed with age. The lesions were mostly encountered within the third and fourth maxillary premolars (107, 108, 207, 208) and mandibular molars (309, 409). No direct correlation was found between the presence or severity of the disease and the clinical signs of affected cats. The study shows that feline tooth resorption is a common issue in feline dentistry and should be taken into account in all cases of animals with any signs of oral disease, including gingivitis and/or dental plaque with preserved appetite. A careful intraoral radiographic examination is essential to avoid false negative results in ambiguous cases.

Expression of Toll-like receptor and cytokine mRNAs in feline odontoclastic resorptive lesion (FORL) and feline oral health

Feline odontoclastic resorptive lesion (FORL) is a common chronic inflammatory condition whose aetiopathogenesis remains unclear. FORL affects 20–75% of cats and causes excruciating pain and tooth loss. The purpose of this study was to evaluate chronic inflammation in FORL by assessing differences in Toll-like receptor (TLR) and cytokine transcripts in gingival tissues between diseased and healthy cats. Gingival tissue samples were collected from 14 healthy cats with no known clinical signs of oral disease and 41 cats with FORL. Levels of mRNA encoding TLR2, TLR3, TLR4, TLR7, TLR9 and the cytokines interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-12, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) was evaluated using quantitative real-time PCR. Statistical significance of the results was assessed using non-parametric tests. Levels of TLR and cytokine transcripts were upregulated in gingival tissue from cats with FORL as compared with healthy gingival tissue: TLR2, TLR3 and TLR9, p ≤ 0.001; TLR4 and TLR7, p ≤ 0.01; IFN-γ, IL-4, IL-6, IL-10, IL-12, IL-1β and TNF-α, p ≤ 0.001). In conclusion, expression of TLR and both pro- and anti-inflammatory cytokines were significantly increased, confirming an ongoing chronic inflammatory response to the microbiome in FORL. It is likely that dysbiosis of the oral microbiota in cats with FORL activates the innate immune response, leading to active inflammation that results in tooth resorption.

Equine Incisor Lesions: Histologic Confirmation of Radiographic, Macroscopic, and Micro-Computed Tomographic Findings.

Simple SummaryIncisor diseases are a common problem in equine medicine. However, Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) and other lesions are often only diagnosed in advanced stages. In this study, the incisors of 20 horses were examined. The findings of X-rays, macroscopical inspection, and micro-computed tomography (µCT) were compared. Five categories from healthy to severely affected teeth were formed and selected teeth from each category were additionally examined by means of histology. Odontoclastic resorption of dental hard substances, infiltration of inflammatory cells, areas of irregular dental cementum, and formation of granulation tissue were observed. Resorptive lesions previously detected by µCT were confirmed by microscopical imaging, however, not all resorptive lesions were regarded as a pathological condition like EOTRH. Detailed microscopical inspection revealed the presence of so-called surface resorptions which represent repaired resorptive lesions without any pathological consequence for the horse. Nevertheless, some incisors which appeared healthy on the X-rays featured histological findings related to EOTRH. Therefore, the detection of early incisor lesions in equine medicine remains challenging.Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) and other incisor lesions are often diagnosed only in advanced stages. The incisors of 20 horses were examined radiographically, macroscopically, and via micro-computed tomography (µCT) to discriminate EORTH-affected teeth. Five categories from healthy to severely affected teeth were formed and teeth from each category were examined histologically to evaluate the opportunity of earlier radiographic diagnosis. Histologically, odontoclastic resorptive lesions, leukocytic infiltrations, and areas of irregular cementum and granulation tissue were observed. The extent and severity of histological findings were correlated to the µCT data. Micro-CT imaging was suitable to detect subtle irregularities in the dental substances which were referred to as resorptive lesions. Although histological examinations confirmed the presence of resorptive lesions, not all of them were classified as pathological conditions. Instead, repaired surface lesions were documented which were regarded as a physiological condition. Nevertheless, incisors which were radiographically regarded as healthy can also feature histological signs of EOTRH. Therefore, due to the possibility of misinterpreting radiographic findings combined with superimpositions on intraoral radiographs, the detection of early resorptive lesions remains challenging.

Microbiome analysis of feline odontoclastic resorptive lesion (FORL) and feline oral health.

IntroductionFeline odontoclastic resorptive lesion (FORL) is one of the most common and painful oral diseases of the cat. It is characterised by tooth resorption due to destructive activity of odontoclasts. FORL can result in tooth loss. While the aetiology of FORL is not clearly understood, it is thought to be multifactorial and bacteria are likely to play a major role.HypothesisDysbiosis of the normal feline oral microbiota leads to an alteration in commensal bacteria populations, which results in the development of FORL.AimThe purpose of the current study was to determine the composition of the microbiomes associated with feline oral health and FORL.MethodologySupragingival plaque was collected from 25 cats with a healthy oral cavity and 40 cats with FORL. DNA was extracted from each sample, the V4 region of the 16S rRNA gene amplified by polymerase chain reaction and amplicons sequenced. Diversity and species richness analyses were performed, principal component analysis was used to explore differences between the oral microbiomes of healthy cats and those with FORL, and linear discriminant analysis effect size was used to assess differences between the groups.ResultsThe six most abundant bacterial genera identified were Bergeyella , Capnocytophaga, Lampropedia, Morexella, Porphyromonas and Treponema . Two-step cluster analysis of the data identified two FORL sub-groups (FORL-1, FORL-2). The FORL-2 sub-group was very similar to the healthy group, whilst the FORL-1 sub-group was clearly different from both the FORL-2 sub-group and the healthy groups. In this analysis, Capnocytophaga (P <0.001) and Lampropedia (P <0.01) were found at significantly lower levels and Porphyromonas at a slightly higher level in the FORL-1 sub-group compared to the healthy and FORL-2 sub-groups. Microbial diversity was found to be less in the FORL-1 sub-group than in the healthy group. Lampropedia sp., a phosphate-accumulating oral commensal species, was significantly lower in the FORL-1 sub-group.ConclusionThe oral microbiota associated with the FORL-1 sub-group is distinct from that found in the healthy group and FORL-2 sub-group. Lampropedia species may influence the local calcium-phosphate ratio, which could be a factor in tooth and bone resorption observed in FORL.

АНАЛИЗ ЭТИОЛОГИИ И РЕНТГЕНОДИАГНОСТИКА ОДОНТОКЛАСТИЧЕСКОГО РЕЗОРБЦИОННОГО ПОРАЖЕНИЯ ЗУБОВ У КОШЕК

In veterinary medicine, one of the most relevant area is dentistry of small pets. Of all dentistry diseases - 80% of cases are due to Feline odontoclastic resorptive lesion (FORL), which is more often diagnosed in cats. 35 cats have been diagnosed with den-tal disorders in vet-clinic "Altervet" for the period from November 2018 to April 2019. The analysis of the statistical information was carried out: 86 % of cats, that is 30 heads, were diagnosed FORL. The assess-ment was carried out according to the degree of tooth damage from x-rays images, and there are 2 types of resorption today: type 1 and type 2. Moreover, one of the examined cats simultaneously detected both types of FORL. Various degrees of tooth damage have been studied. Lesions of various parts of the tooth (crowns, necks, aboral and ros-tral roots of the teeth) were found, which were marked on radiographs. A statistical analysis of the incidence by breed, age, sex of animals and types of feed was conducted. The middle animal age of the disease inci-dence is 10 years. It was found that animals with pathology were nourished different types of food: mixed, dry, wet and natural. However, a greater number of cats with FORL were fed mixed (14 heads) and dry (8 heads) feed, 47 and 27%, respectively. It was found that in male this pathology is di-agnosed more often, in our case it is 73%, than in female- 27%.The disease was more common in mongrel cats – 18 heads, than in thoroughbred animals -12 heads, it turned out 60 and 40% of the number of affected animals. Reliable data on the influence of sex and breed on the occurrence of FORL has not been established.

Oral Disease and Microbiota in Free-Roaming Cats

Oral health status was evaluated in 34 free-roaming cats that were submitted to a Trap-Neuter-Return program. Only 38.2% of individual cats showed oral disease. Periodontal disease (PD) was present in 6 cats ( 17.6%). Four cats (11.8%) showed feline gingivostomatitis, and clinical evidence of feline odontoclastic resorptive lesions was detected in only 3 animals (8.8%) by probing, but radiological studies would be necessary for reliable detection. Signs of PD occurred in 31.6% of teeth; only the less severe stages of PD were present. No retention of deciduous teeth, malocclusion, tumors, or dental fractures were found. Calicivirus was detected in 50% of the cats. The most frequent bacteria found were α-hemolytic Streptococcus (23.5%), Staphylococcus (17.6%), Neisseria (15.7%), and Pasteurella (11.8%). A significant association between age and oral disease was found (P = .001). The mean of bacterial strains/genus was higher in healthy mouths than in diseased mouths (4.5 vs. 2.1). In diseased mouths, Staphylococcus was the most frequently isolated genus (23.1%), whereas α-hemolytic Streptococcus was most prevalent in healthy mouths (33.3%). A significant association was detected between Porphyromonas and fungal isolation, with a fear concordance coefficient (κ = .334; P = .016).

Prevalence of feline calicivirus in cats with odontoclastic resorptive lesions and chronic gingivostomatitis

Feline odontoclastic resorptive lesion (FORL) and feline chronic gingivostomatitis (FCGS) are two of the most common diseases of the feline oral cavity. While evidence is emerging that FCGS is caused by gingival inflammation initiated and perpetuated by the oral microbiota, little is known in this regard for FORL. Feline calicivirus (FCV) has been associated with the presence of FCGS and is thought to play a role in the initiation of this disease. In this study, the incidence of FCV was investigated in cats with FORL and FCGS, and compared to unaffected controls. FCV was detected by viral culture. The incidence of FCV was as follows: 6 (24.0%) of 24 control cats, 9 (22.5%) of 40 cats with FORL and 15 (60.0%) of 25 cats with FCGS were positive for FCV. There was a significant difference in FCV incidence between all the groups (p=0.003) but none between the control group and the FORL group. However, significant differences were observed in the incidence of FCV between control and FCGS (p=0.010) and between FORL and FCGS (p=0.006). It is concluded that although FCV may be associated with FCGS, it appears unlikely to play a role in FORL.

Human and Feline Invasive Cervical Resorptions: The Missing Link?—Presentation of Four Cases

This report describes 4 patients presenting with multiple teeth affected by invasive cervical resorption (ICR). The cases came to our attention between 2006 and 2008; previously, no cases of multiple ICR (mICR) had been reported in Switzerland. Characteristics common to all 4 cases included progression of disease over time, similar clinical and radiographic appearance of lesions, and obscure etiology. The histologically assessed teeth showed a similar pattern of tooth destruction, with resorptive lesions being confined to the cervical region. Howship's lacunae and multinucleated, tartrate-resistant acid phosphatase–positive odontoclasts were detected. None of the teeth presented with internal resorption. The positive pulp sensitivity corresponded to the histologic findings, indicating that the pulp tissue resisted degradation even in advanced stages of resorptive lesions. Although mICR is rare in humans, a similar disease known as feline odontoclastic resorptive lesions (FORL) is common in domestic, captive, and wild cats. The etiology of FORL, like that of mICR, remains largely unknown. Because FORL has been associated with feline viruses, we asked our mICR patients whether they had had contact with cats, and interestingly, all patients reported having had direct (2 cases) or indirect (2 cases) contact. In addition, blood samples were taken from all patients for neutralization testing of feline herpes virus type 1 (FeHV-1). Indeed, the sera obtained were able to neutralize (2 cases) or partly inhibit (2 cases) replication of FeHV-1, indicating transmission of feline viruses to humans. Future studies on mICR (and FORL) should evaluate the possible role of a (feline) virus as an etiologic (co-)factor in this disease.

奇形歯に破歯細胞性吸収病巣が併発した下顎内歯瘻の犬の1例

奇形歯に破歯細胞性吸収病巣が併発した下顎内歯瘻の犬の1例

Editorship: Something like “Pulling Teeth!”

Whole tooth extraction is generally considered to be the treatment of choice for teeth with advanced feline external odontoclastic resorptive lesions. These teeth often have both a weakened, brittle crown and radicalar ankylosis. These two factors cause frustration and sometimes complications during attempts at extraction. This study investigated the alternative of intentionally leaving part or all of non-pathologic tooth roots in situ to prevent iatrogenic trauma to the patient, loss of alveolar bone, and prolonged healing of surgical defects. Fifty one roots from 23 teeth were radiographed 5–36 months following elective root retention; continued resorption without surrounding bony reaction was seen in almost all cases. In one cat, the roots retained normal periodontal ligament one year later; and in another cat that developed severe stomatitis, the intentionally retained roots were extracted at the same time that the remaining molar teeth were extracted.

Odontoclastic Resorptive Lesions in a Dog

We found odontoclastic resorptive lesions on premolars and molars in a 4- year-old miniature dachshund. The teeth had been extracted because the dentin was resorbed. In some teeth, the roots had been replaced by hard tissue, and so we amputated the crowns and curetted roots and alveolar bone. Histopathological examination revealed that the dentin was resorbed by odontoclasts and was replaced with bony tissue. Ten months later we found resorptive lesions in other teeth, and we treated them along with the first treatment. At the time of writing, since this is the first report of a dog with the same lesion in other teeth after the first treatment, we hope to establish better treatment and prevention methods.

An NMR- and MS-based metabonomic investigation of saliva metabolic changes in feline odontoclastic resorptive lesions (FORL)-diseased cats

The feline odontoclastic resorptive lesion (FORL) is a common oral problem in cats. The disease has increased steadily since the domestication of cats and etiology of this disease has not been fully determined although several theories have been proposed. Feeding practices, vaccination, and neutering programs have all been suspected to be associated with FORL. The aim of the current study is to assess the feasibility of metabonomics to detect at an early stage the onset of the disease. The diagnostic biomarkers could then be used as “efficacy markers” for nutritional intervention in preventing and/or slowing the progression of FORL. 1H-NMR- and LC/MS-based metabonomic analysis of saliva samples obtained from a group of 21 cats (11 healthy and 10 FORL diseased) showed clear differences in the metabolic composition of saliva from healthy and FORL-diseased cats. To identify biomarkers, the spectroscopic data was processed using partial least-squares discriminant analysis (PLS-DA) and validated by leave-one-subject-out cross validation. The PLS-DA model predicted FORL- diseased cats with over 60% accuracy. The maximum value of Q2 of the random permutation sets was less than 0.3. The diseased cats showed increased levels of many organic and amino acids, such as acetate, lactate, propionate, isovalerate, tryptamine, and phenylalanine suggesting changes in oral microflora in the disease situation. This study is preliminary and a larger study with more samples to further validate the biomarker profile predictive of an early FORL pathophysiological status is in progress.

Analysis of the surface characteristics and mineralization status of feline teeth using scanning electron microscopy

External resorption of teeth by odontoclasts is a common condition of unknown origin affecting domestic cats. Odontoclastic resorptive lesions involve the enamel cementum junction (ECJ, cervix) and root surface, leading to extensive loss of enamel, dentine and cementum. This study was undertaken in order to determine whether features of the surface anatomy and mineralization of feline teeth could explain why odontoclastic resorptive lesions are so prevalent in this species. Backscattered electron scanning electron microscopy was used to study enamel, cementum and dentine in non-resorbed, undemineralized teeth from adult cats. Analysis of the ECJ revealed thin enamel and cementum and exposed dentine at this site. Furthermore, enamel mineralization decreased from the crown tip to the ECJ, and dentine mineralization was lowest at the ECJ and cervical root. Analysis of cementum revealed variations in the organization and composition of fibres between the cervical, mid- and apical root although no significant differences in mineralization of cementum were detected between different regions of the root. Reparative patches associated with resorption of cementum by odontoclasts and repair by cementoblasts were present on the root surface. In conclusion, results suggest that the ECJ and cervical dentine could be at a greater risk of destruction by odontoclasts compared with other regions of the tooth. The relationship of these features to the development and progression of resorption now requires further examination.

Hypoxia Induces Giant Osteoclast Formation and Extensive Bone Resorption in the Cat

Dental disease due to osteoclast (OC) overactivity reaches epidemic proportions in older domestic cats and has also been reported in wild cats. Feline odontoclastic resorptive lesions (FORL) involve extensive resorption of the tooth, leaving it liable to root fracture and subsequent loss. The etiopathogenesis of FORL remains unclear. Here, we explore the hypothesis that FORL is associated with hypoxia in the oral microenvironment, leading to increased OC activity. To investigate this, we developed a method of generating OCs from cat blood. Reducing O2 from 20% to 2% increased the mean area of OC eightfold from 0.01 to 0.08 mm2. In hypoxic cultures, very large OCs containing several hundred nuclei were evident (reaching a maximum size of approximately 14 mm2). Cultures exposed to 2% O2 exhibited an increase of approximately 13-fold in the area of bone slices covered by resorption lacunae. In line with this finding, there was a significant increase in cells differentiating under hypoxic conditions, reflected in increased expression of cathepsin K and proton pump enzymes. In conclusion, these results demonstrate that oxygen tension is a major regulator of OC formation in the cat. However, in this species, hypoxia induces the formation of "giant" OCs, which can be so large as to be visible with the naked eye and yet also actively resorb. This suggests that local hypoxia is likely to play a key role in the pathogenesis of FORL and other inflammatory conditions that are associated with bone resorption in cats.

Evaluation of calciotropic hormones in cats with odontoclastic resorptive lesions

To assess associations between epidemiologic and laboratory variables and calciotropic hormones in cats with odontoclastic resorptive lesions (ORLs). 182 client-owned cats older than 1 year of age with oral disease. Information on medical history, behavior, living environment, and feeding management was assessed by use of a questionnaire. After induction of general anesthesia, oral examination was performed following standardized protocols and included dental probing and full-mouth radiography. Laboratory analyses included evaluation of FeLV-FIV status, serum biochemical analyses, CBC, urinalysis, and serum concentrations of intact parathyroid hormone (iPTH), parathyroid hormone-related peptide (PTHrP), 25-hydroxyvitamin D (25-OHD), free thyroxine (fT4), and ionized calcium (iCa). ORLs were identified in 72.5% of cats. Mandibular third premolars were the most commonly affected teeth. Cats with ORLs were significantly older (mean, 9.2 years) than cats without ORLs (mean, 6.6 years). Multivariate logistic regression analysis revealed that 25-OHD, urine specific gravity, jaw-opening reflex on probing, and missing teeth were significant variables, even after accounting for age. Cats with ORLs had significantly higher mean serum concentration of 25-OHD (112.4 nmol/L) and significantly lower mean urine specific gravity (1.0263), compared with cats without ORLs (89.8 nmol/L and 1.0366, respectively). Results did not indicate associations between iPTH, PTHrP, or fT4 and development of ORLs. In affected cats, the importance of high serum 25-OHD and low urine specific gravity has not been determined.

A rapid screening technique for feline odontoclastic resorptive lesions

The feline odontoclastic resorptive lesion (FORL) status (presence or absence of odontoclastic resorptive lesions) of 423 clinically healthy cats was determined based on radiographic findings in a series of full mouth radiographs (eight views). This status was compared with the FORL status based on evaluation of only two views, namely the right and left mandibular premolar and molar views. Using the FORL status of the right and left third mandibular premolars (307 and 407) alone correctly predicted overall FORL status in 93.4 per cent of cats. The sensitivity of the new technique (FORL cases correctly diagnosed as positive by the test) was 78.5 per cent, while the negative predictive value (negative FORL cases correctly diagnosed by the test) was 91.3 per cent. Overall FORL status can therefore be confidently diagnosed in nine out of 10 cats by assessing FORL status in just two teeth (307 and 407) using two films, which has benefits for the cat (less anaesthetic time and reduced exposure to radiation) and the owner (reduced cost of screening).

Feline odontoclastic resorptive lesions: unveiling the early lesion.

The purpose of this study was to increase understanding of the factors initiating feline odontoclastic resorptive lesions (FORLs). Fifty-six teeth (clinically and radiographically unaffected by ORLs) were harvested. Of these, 43 were from cats that had ORLs in other teeth (group A) and 13 were from cats with no clinical or radiographic evidence of ORLs in any teeth (group B). Twenty-six teeth in group A and one tooth in group B showed histological evidence of external root resorption (surface resorption and replacement resorption resulting in ankylosis). Some teeth in group B showed healed cementum resorption. It has previously been assumed that FORLs were similar to lesions associated with peripheral inflammatory root resorption, and were associated with periodontal disease. These histological findings suggest instead that a FORL is a non-inflammatory replacement resorption, resulting in ankylosis. The periodontal ligament of resorbing teeth lacked normal fibrous architecture, but was not inflamed. Resorption was not identified in cervical cementum. However, the histological appearance of the cervical cementum differed between the two groups. Several aetiopathogenetic explanatory models which arise from these observations are discussed.

Abstract

Odontoclastic resorptive lesions in healthy cats Ingham, K. E., Gorrel, C., Blackburn, J. & Farnsworth, W. (2001) Prevalence of odontoclastic resorptive lesions in a population of clinically healthy cats. Journal...

Prevalence of odontoclastic resorptive lesions in a population of clinically healthy cats.

The prevalence of odontoclastic resorptive lesions (ORLs) was determined in a clinically healthy cat population (228 cats) using both clinical (oral examination) and radiographic (full-mouth series with intraorally positioned dental film) methods. The overall prevalence rate was 29 per cent (mean age of the cat population 4.9 years). The mandibular third premolars (307, 407) were the most commonly affected tooth and the pattern of ORL development was symmetrical in most cats. The risk of having ORLs was found to increase with increasing age and cats with clinically and radiographically missing teeth were more likely to have the condition. Neutering, gender, age at neutering or mean whole mouth gingivitis index did not affect the prevalence of ORLs.