Association between Estrogen Levels and Temporomandibular Disorders: An Updated Systematic Review.

The aim of this systematic review is to evaluate the impact of estrogen levels on the occurrence of temporomandibular disorders (TMDs) in humans. Searches were conducted in the same databases as follows: PubMed, the Cochrane Collaboration database, and the Scopus database. In accordance with the MeSH database and previous work, the following keywords were used: 'estrogens' and 'temporomandibular joint disorders'. Twelve studies were included in the review and were assessed for the quality of evidence. Estrogen levels are associated with pain modulation in the temporomandibular joint and the entire orofacial region. There is insufficient evidence to either confirm or refute the influence of estrogen on the occurrence of TMDs. The study was registered under the identifier: 10.17605/OSF.IO/BC7QF.

Animal models of temporomandibular joint heterotopic ossification: a scoping review.

There are few animal models for heterotopic ossification of the temporomandibular joint (TMJ-HO). This scoping review provides an overview of current knowledge on the induction methods and specific conditions required to produce TMJ-HO in various animal models. Two independent reviewers selected papers from the PubMed, Web of Science, and Cochrane Library databases. The inclusion criteria were articles in English, in vivo studies, and a TMJ-HO induction method. Observational, in vitro, human studies, reviews, and book chapters were excluded. Twenty-four publications were included. HO was surgically, genetically, or chemically induced through single or combined defects in the condyle, articular disc, and temporal bone in animal models (sheep=9 studies, mouse=5, rat=4, rabbit=2, pig=2, goat=1, dog=1, monkey=1) specific for traumatic TMJ-HO (n=4), ankylosis (n=9), osteoarthritis (n=8), experimental disc perforation (n=1), status post-TMJ replacement (n=1), and status post bilateral sagittal split osteotomy (n=1). TMJ-HO remains challenging to study due to its multifactorial etiology and largely unknown pathogenesis, which varies between species. There is a need for more accurate, reproducible animal models that can be extrapolated to human TMJ-HO and a consolidated clinical classification system to allow for meaningful future research.

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. CASE PRESENTATION: This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. CONCLUSIONS: These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study.

Background: The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs. Methods: Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren's syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality. Results: Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including "CD25++ CD8+ T cell % CD8+ T cell" (mediation proportion: 6.2%) and "CD3 on activated CD4 regulatory T cell" (5.4%). Additionally, "CD127 on granulocyte" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05). Conclusion: This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.

Congenital Infiltrating Lipomatosis of Face-Induced Temporomandibular Joint Ankylosis.

Temporomandibular joint ankylosis (TMJA) secondary to congenital infiltrating lipomatosis of the face (CILF) is an exceptionally uncommon condition which is characterized by the involvement of unilateral facial soft tissues and bones. In some cases, the extensive exophytic bony growth in the temporomandibular joint region often extends toward the skull base and lies near adjacent vital structures. Only very few cases of TMJA associated with CILF have been reported in the literature. The authors report a case of a 36-year-old female with right TMJA secondary to CILF. The bony overgrowth in the right temporomandibular joint region was arising from a deformed right mandibular condyle, extending towards the ipsilateral temporal bone, greater wing of the sphenoid, skull base, and approaching the lateral limit of foramen ovale, and foramen spinosum. To prevent any damage to the skull base and adjacent vital structures and to achieve adequate mouth opening, the authors have performed a unique technique of subankylotic osteotomy for the release of TMJA, instead of conventional gap arthroplasty.

Forty years of suffering chronic TMJ dysfunction: lessons learnt.

Temporomandibular joint dysfunction (TMD) is a common condition, with patients reporting symptoms to both dentists and doctors. The aetiology of TMD is likely to be multifactorial, with occlusal, parafunctional and psychological factors all potentially playing a part to varying degrees in different individuals. A personal account by a dentist, suffering from TMD for over 40 years, chronicles their experience of different treatments and concludes that supporting a patient to 'learn to live' with TMD is pivotal to management.

Loss of ß-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. ß-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of ß-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and ß-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. RESULTS: The loss of ß-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1ß) factors in condylar cartilage were increased in ß-arrestin2 null mice compared with WT mice. Moreover, the loss of ß-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. CONCLUSION: In conclusion, we demonstrated for the first time that ß-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, ß-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

[Growth disturbances of the temporomandibular joint: causes, diagnosis and treatment]. / Groeistoornissen van het kaakgewricht: oorzaken, diagnose en behandeling.

Growth disturbances of the temporomandibular Joint are characterized by mandibular asymmetry, sometimes with secondary maxillar disturbances. Although the clinical symptoms are sometimes quite severe, patients usually have no pain. There are several growth disturbances, but in this article we discuss three particular causes of facial asymmetry, namely hemimandibular growth defects; overdevelopment, underdevelopment and neoplasms of the mandibular joint. Hemimandibular overdevelopment (hyperplasia) is a growth disorder characterized by progressive asymmetry of the mandibula. Hemimandibular hypoplasia, on the other hand, is a growth disorder involving underdevelopment of the condyle mandibulae due to impingement of the growth center and ankylosing. A pronounced asymmetrical face can cause aesthetic problems and always requires diagnostics, because in addition to the hyperplasia and hypoplasia mentioned above, other causes can explain the asymmetry such as, for example, an osteoarthritis or even a tumor emanating from the base of the skull, mandibula or soft tissues.

[Temporomandibular joint disorder after dental treatment]. / TMD-klachten na een tandheelkundige behandeling.

A 56-year-old woman presented with persistent unilateral gnathological complaints after replacing an amalgam restoration. The patient reported tension and pain in the right side of her jaw, along with crackling sounds in the temporomandibular joint. Physical examination revealed tenderness in the right masseter muscle and temporomandibular joint, as well as anterior disc replacement with reduction on both sides. The initial treatment focused on providing rest to the temporomandibular joint, the Yoda exercise, and later, wet-needling. Despite initially limited improvement, the symptoms persisted. This case underscores the complexity and various treatment options for temporomandibular joint issues following dental procedures.

Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice.

BACKGROUND: Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. MATERIALS AND METHODS: To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. RESULTS: Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. CONCLUSIONS: Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

Idiopathic condylar resorption in adolescents: A scoping review.

OBJECTIVE: Idiopathic condylar resorption (ICR), also known as progressive condylar resorption, is poorly understood, particularly in adolescent patients. Therefore, this scoping review aims to summarize the available literature on the prevalence, aetiology, pathogenesis, diagnostic process, treatment and/or any outcome regarding ICR in adolescent individuals. METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and its extension for scoping reviews (PRISMA-ScR), as well as Joanna Briggs Institute studies. The search strategy was defined adopting a core search structure for each source, and the search was performed on MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus and Google Scholar. After duplicate removal, two independent reviewers screened abstracts, followed by complete articles, to achieve the definition of included studies. Data collection was performed, and the extracted data were organized in tabular form, along with a narrative summary of main findings that aligns with the objective of this review. RESULTS: Six observational studies were included in this review. Three studies focused on signs and symptoms, one on prevalence and signs and symptoms, one on treatment and one on disease pathogenesis. CONCLUSION: This scoping review revealed inadequate published research regarding prevalence, aetiology, early diagnosis, pathogenesis and treatment of ICR in adolescents.

Provider assessment of the temporomandibular joint in Juvenile idiopathic arthritis: a retrospective analysis from the CARRA database.

BACKGROUND: Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30-45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae. Little is known about the rate at which providers evaluate TMJ involvement in their clinical practice. METHODS: Data were obtained from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Data fields related to assessment for TMJ arthritis were added in 2019. Patients were included in the study if they had a diagnosis of JIA and had data recorded between January 2020 and August 2021. Standard descriptive statistics were used to describe demographic and clinical features. RESULTS: A total of 17,761 visits were reviewed for a total of 7473 patients with JIA. A total of 52.7% of patients had maximal mouth opening (MMO) recorded as finger breadths or total incisal distance (TID). Only 8% had TID measured. A total of 5.0% had MRI with contrast performed. A total of 939 patients had a diagnosis of TMJ arthritis. Of these, 28.5% had an MRI documented, 83% had an MMO documented, and 40% had TID measured. Few patient-level characteristics were statistically related to having MMO assessed. MRI was more likely to be obtained in older and in female patients. MMO was recorded at a given visit > 80% of the time at 17 sites, and it was recorded < 1% of the time at 8 sites. MRIs were infrequently performed at all sites, with 27 sites having no MRIs obtained and only 7 sites having an MRI obtained at > 10% of visits. CONCLUSIONS: MMO is not consistently measured in patients with JIA, and it is rarely measured quantitatively. Similarly, TMJ MRIs are rarely obtained in patients with JIA. Site of care is more associated with TMJ assessments than patient-level characteristics. These data suggest that provider education is needed to improve the assessment of the TMJ in patients with JIA to enable earlier recognition and prevent long-term complications.

Temporomandibular disorders among Ehlers-Danlos syndromes: a narrative review.

This narrative review aims to demonstrate and summarize the complex relationship between Ehlers-Danlos syndromes (EDS) and temporomandibular disorders (TMD) by reviewing the results of observational studies and case reports. EDS are a set of hereditary connective tissue disorders, where generalized joint hypermobility (GJH), especially in the hypermobile subtype (hEDS), is a key symptom. Mutations have been identified in genes that impact the production or assembly of collagen for all subtypes except hEDS. While the correlation between GJH and TMD has been analysed in various studies, fewer studies have examined TMD in patients with EDS, with most showing an increased prevalence of TMD. In case-control studies, an elevated prevalence of myalgia, arthralgia and disc-related disorders was found in individuals with EDS. Various therapeutic interventions have been reported within the literature in the form of case reports and observational studies, but there are no long-term clinical trials with results on the efficacy of different therapeutic approaches to date. This review demonstrates the high prevalence of different TMDs in different subtypes of EDS, but also shows that little is known about the success of treatment thus far. Further clinical research is necessary to provide adequate guidance on targeted treatment.

Temporomandibular disorders in individuals with Marfan syndrome: an exploratory analysis.

BACKGROUND: This study aims to analyze to what extent patients with Marfan syndrome (MFS) are affected by temporomandibular disorders (TMD) and its impact on oral health-related quality of life (OHRQoL). To collect data, an online questionnaire was created to recruit participants from Germany, Austria, and Switzerland through social media and support groups. The questionnaire consists of free-text questions, the German versions of the Oral Health Impact Profile (OHIP-G14), the Depression Anxiety Stress Scale (DASS), and the Graded Chronic Pain Status (GCPS). RESULTS: A total of 76 participants with diagnosed MFS were included. Of these, 65.8% showed TMD symptoms, the most common being pain or stiffness of the masticatory muscles in the jaw angle (50.0%). Only 14.5% of the participants were already diagnosed with TMD. Of the participants with an increased likelihood of a depression disorder, 76.9% showed TMD symptoms. Of those with a critical score for an anxiety disorder, 90.9% showed TMD symptoms. 73.3% of participants with TMD symptoms reached the critical score for a stress disorder. TMD symptoms were associated with a higher risk for chronic pain. In the median, participants with TMD showed statistically notably higher OHIP-G14 scores than participants without TMD (11.5 [IQR 17] vs. 1 [IQR 3] points, p ≤ 0.001). CONCLUSION: TMD symptoms had a noticeable impact on OHRQoL in patients with MFS, i.e., chronic pain and psychological impairment. TMD seems underdiagnosed, and more research is needed to prevent the associated chronification of pain and psychological burden to improve the OHRQoL.

IncobotulinumtoxinA in refractory temporomandibular disorder due to disk dislocation: A prospective study.

INTRODUCTION: Temporomandibular disorders (TMD) may include conditions involving the temporomandibular joint and/or masticatory muscles. Approximately 20 % of patients are refractory to first-line therapies. This study aims to evaluate the effects and safety of incobotulinumtoxinA in the treatment of refractory TMD due to disk dislocation. MATERIAL AND METHODS: A quasi-experimental one-arm prospective study was conducted. Target population included individuals with a diagnosis of TMD due to disk dislocation. Patients were treated with electromyography or ultrasound guided injection of incobotulinumtoxinA in the masticatory muscles (20 U into each masseter and pterygoideus lateralis). Pain was assessed using the pain numerical rating scale, maximum unassisted mouth opening was measured in mm, and adverse events were registered at baseline, week 4, week 12 and week 24 post-treatment. Statistical analysis used the Wilcoxon test for the comparison of paired samples and the Mann-Whitney U test for independent samples, considering a p-value ≤ 0.05 as significant. RESULTS: 51 patients with 75 painful temporomandibular joints due to disk dislocation (38 with reduction and 37 without) were included. A significant reduction in pain from a pre-treatment mean of 6.08/10 to a post-treatment mean of 2.04/10 (week 4), 3.18/10 (week 12), and 3.65/10 (week 24) was observed (p < 0.001). A significant decrease in maximum unassisted mouth opening from a pre-treatment mean of 36.45 mm to a post-treatment mean of 32.29 mm at week 4 was observed (p < 0.001). DISCUSSION: Botulinum toxin injection of the masticatory muscles is safe and seems equally effective in reducing pain in patients with refractory TMD due to disk dislocation.

Primary hyperoxaluria: Description of a new oral finding and review of literature.

OBJECTIVES: Oro-dental manifestations of hyperoxaluria and dental management of affected patients are rarely reported in the literature. We describe a new oral presentation of primary hyperoxaluria (PH) and review relevant literature about oro-dental manifestations and management of dental complications of hyperoxaluria. METHODS: A case report of a 44-year-old female who presented with symptoms of temporomandibular joint dysfunction due to hyperoxaluria was described according to the CARE guidelines. In addition, an extensive search of biomedical databases (PubMed, Medline, Google Scholar, and Embase) for articles describing oro-dental manifestations and/or dental management in patients with hyperoxaluria was performed using the key words ("oral" and/or "hyperoxaluria" and/or "dental" and/or "oxalosis"). Included articles were reviewed and data about patient demographics, disease type and stage, oral and dental manifestations, and dental treatment outcome were retrieved and analyzed. RESULTS: A total of 14 articles describing the oral and dental manifestations in 15 patients with hyperoxaluria were included. Tooth mobility, root resorption, and radiographic alterations were consistently described in all cases. Oral manifestations were described mainly in PH at late stages, and only after the onset of chronic renal disease. Dental management in all reported cases was palliative and aimed to relive pain and treat periodontal infection. Tooth loss due to extraction or uncontrolled mobility was the ultimate outcome in almost all reported cases. CONCLUSION: Oral and dental manifestations in hyperoxaluria are rarely reported in the literature. Management of tooth mobility and root resorption in hyperoxaluria is challenging and clinical guidelines and evidence-based recommendations are lacking. Early diagnosis and treatment of hyperoxaluria might be the only effective approach to prevent dental and periodontal complications of the disease.

Acromegaly: Overview and associated temporomandibular joint disorders.

OBJECTIVE: To provide a review on acromegaly and its orofacial manifestations, with a focus on associated arthropathies and temporomandibular joint disorders (TMD). METHODS: A review of current literature was performed through an electronic search of three databases: PubMed, ScienceDirect, and Google Scholar. The literature review was focused on the following topics of interest: etiology, diagnosis, and management of acromegaly, orofacial manifestations of acromegaly, acromegalic arthropathies, and acromegaly-associated TMD. RESULTS: Acromegaly is a chronic multisystem condition in which excessive production of growth hormone in adults, most commonly caused by benign pituitary adenomas, leads to somatic overgrowth. Orofacial changes are considered hallmarks of the disease. It is important for dentists to recognize signs and symptoms of acromegaly, as this may help to achieve early diagnosis and improve overall disease prognosis. Acromegalic arthropathies typically involve large joints, however, the temporomandibular joints (TMJ) can be affected. TMD associated with acromegaly is under-recognized and poorly characterized in current literature. CONCLUSION: In the appropriate clinical context, acromegaly should be considered as part of the differential diagnosis for patients presenting with TMD. Further studies are needed to better characterize the nature of TMD associated with acromegaly and to define the role of TMJ involvement in early diagnosis.