Extracellular matrix turnover and inflammation in chemically-induced TMJ arthritis mouse models.

The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies. Synovial fluid from diseased human samples revealed elevated levels of tumor necrosis factor alpha (TNF-alpha). Here, we propose to recapitulate these findings in mice by subjecting murine TMJs with TNF-alpha or CFA (Complete Freund's Adjuvant) in mandibular condyle explant cultures and by local delivery in vivo using TMJ intra-articular injections. Both TNF-alpha and CFA delivery to whole mandibular explants and in vivo increased extracellular matrix deposition and increased cartilage thickness, while TNF-alpha treated explants had increased expression of inflammatory cytokines and degradative enzymes. Moreover, the application of TNF-alpha or CFA in both models reduced cell number. CFA delivery in vivo caused soft tissue inflammation, including pannus formation. Our work provides two methods of chemically induced TMJ inflammatory arthritis through a condyle explant model and intra-articular injection model that replicate findings seen in synovial fluid of human patients, which can be used for further studies delineating the mechanisms underlying TMJ pathology.

Evaluation of mandibular morphometry in the bisphosphonate users / Evaluación de la morfometría mandibular en los usuarios de bifosfonatos

This study aimed to evaluate the effects of bisphosphonates on the mandibular bone. Bisphosphonates are drugs which are commonly used in the treatment of many diseases related to bone metabolism such as osteoporosis, breast cancer capable of bone metastasis, prostate and lung cancer and bone cancer such as multiple myeloma. Our study group consisted of a total of 100 panoramic radiographs which were obtained from the examinations of 50 individuals using bisphosphonate and 50 individuals in the control group who applied for routine dental examination to the Department of Oral and Maxillofacial Radiology of Akdeniz University Dentistry Faculty between years 2015 and 2016.The calculations of the mandibular cortical thickness (MCT), mandibular cortical index (MCI), panoramic mandibular index (PMI), condylar angle (CA), gonial angle (GA), antegonial angle (AGA), antegonial depth (AGD) and antegonial index (AGI) were made for each patient. It was found that both left and the right MCT and only the left PMI were affected by age. Only the left AGA and both the left and right MCT and AGD were affected by gender. The left and right AGI measurements of the patients using bisphosphonates were statistically lower than those of the individuals in the control group. Our results suggested that bisphosphonates had various effects on the jaw bones. However, further comprehensive studies need to be made to evaluate the longterm effect of bisphosphonates on bone metabolism.

Este estudio tuvo como objetivo evaluar los efectos de los bifosfonatos en el hueso mandibular. Los bifosfonatos son medicamentos que se usan comúnmente en el tratamiento de muchas enfermedades relacionadas con el metabolismo óseo, como la osteoporosis, el cáncer de mama, metástasis óseas, cáncer de próstata y pulmón y el cáncer de hueso como el mieloma múltiple. Nuestro grupo de estudio consistió en un total de 100 radiografías panorámicas que se obtuvieron de los exámenes de 50 individuos que utilizaron bisfosfonato y 50 individuos en el grupo de control que solicitaron un examen dental de rutina al Departamento de Radiología Oral y Maxilofacial de la Facultad de Odontología de la Universidad de Akdeniz, entre los años 2015 y 2016. En cada paciente se realizaron los cálculos del grosor cortical mandibular (GCM), índice cortical mandibular (ICM), índice mandibular panorámico (IMP), ángulo condilar (AC), ángulo gonial (AG), ángulo antegonial (AAG), profundidad antegonial ( PAG) y el índice antegonial (IAG). Se encontró que tanto el GCM izquierdo como el derecho y solo el IMP izquierdo estaban afectados por la edad. Solo el AAG izquierdo y el GCM izquierdo y derecho y el AGD fueron afectados de acuerdo al sexo. Las mediciones de IAG izquierdo y derecho de los pacientes que utilizan bifosfonatos fueron estadísticamente más bajas que las de los individuos en el grupo de control. Nuestros resultados sugirieron que los bifosfonatos tienen varios efectos en los huesos de la mandíbula. Sin embargo, es necesario realizar estudios más exhaustivos para evaluar el efecto a largo plazo de los bifosfonatos en el metabolismo óseo.

Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone.

The striking predilection of temporomandibular disorders (TMD) in women, especially during gonad-intact puberty or reproductive years, indicates that oestrogen plays an important role in the progression of TMD, but the underlying mechanism remains unclear. In this study, unilateral anterior crossbite (UAC) was used to create temporomandibular joint osteoarthritis (TMJ OA) models in rats, while 17ß-estradiol (E2) injections were applied to mimic patients with high-physiological levels of oestrogen. Micro-CT scanning, histological staining and real-time PCR assays were preformed to observe the degenerative changes in the mandibular condylar cartilage and subchondral bone. The results showed that obvious degradation was found in the condylar cartilage and subchondral bone of rats with UAC procedure, including decreased cartilage thickness, loss of extracellular matrix, increased apoptotic chondrocytes and expression of pro-inflammatory and catabolic factors, decreased bone mineral density and increased osteoclast activity. E2 supplements aggravated the condylar cartilage degradation but reversed the abnormal bone resorption in the subchondral bone induced by UAC. Our results revealed that high-physiological oestrogen plays a destructive role in condylar cartilage but a protective role in subchondral bone at the early stage of TMJ OA. These dual and distinct effects should be given serious consideration in future OA treatments.

Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERß) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERß signaling in mediating DOL effects in male mice to further decipher sex differences. METHODS: Male 21 day-old WT and ERßKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. RESULTS: ERßKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. CONCLUSIONS: The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.

Rebamipide Attenuates Mandibular Condylar Degeneration in a Murine Model of TMJ-OA by Mediating a Chondroprotective Effect and by Downregulating RANKL-Mediated Osteoclastogenesis.

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive degradation of cartilage and changes in subchondral bone. It is also one of the most serious subgroups of temporomandibular disorders. Rebamipide is a gastroprotective agent that is currently used for the treatment of gastritis and gastric ulcers. It scavenges reactive oxygen radicals and has exhibited anti-inflammatory potential. The aim of this study was to investigate the impact of rebamipide both in vivo and in vitro on the development of cartilage degeneration and osteoclast activity in an experimental murine model of TMJ-OA, and to explore its mode of action. Oral administration of rebamipide (0.6 mg/kg and 6 mg/kg) was initiated 24 h after TMJ-OA was induced, and was maintained daily for four weeks. Rebamipide treatment was found to attenuate cartilage degeneration, to reduce the number of apoptotic cells, and to decrease the expression levels of matrix metalloproteinase-13 (MMP-13) and inducible nitric oxide synthase (iNOS) in TMJ-OA cartilage in a dose-dependent manner. Rebamipide also suppressed the activation of transcription factors (e.g., NF-κB, NFATc1) and mitogen-activated protein kinases (MAPK) by receptor activator of nuclear factor kappa-B ligand (RANKL) to inhibit the differentiation of osteoclastic precursors, and disrupted the formation of actin rings in mature osteoclasts. Together, these results demonstrate the inhibitory effects of rebamipide on cartilage degradation in experimentally induced TMJ-OA. Furthermore, suppression of oxidative damage, restoration of extracellular matrix homeostasis of articular chondrocytes, and reduced subchondral bone loss as a result of blocked osteoclast activation suggest that rebamipide is a potential therapeutic strategy for TMJ-OA.

Systemic administration of strontium or NBD peptide ameliorates early stage cartilage degradation of mouse mandibular condyles.

OBJECTIVE: To determine whether mandibular condylar cartilage degradation induced by experimentally abnormal occlusion could be ameliorated via systemic administration of strontium or NBD peptide. METHODS: Six-week-old female C57BL/6J mice were used. From the seventh day after mock operation or unilateral anterior crossbite (UAC) treatment, the control and UAC mice were further respectively pharmacologically treated for 2 weeks or 4 weeks of saline (CON + Saline and UAC + Saline groups), SrCl2 (CON + SrCl2 and UAC + SrCl2 groups) or NBD peptide (CON + NBD peptide and UAC + NBD peptide groups). Changes in condylar cartilage and subchondral bone were assessed 21 and 35 days after mock operation or UAC procedure by histology and micro-CT. Real-time PCR and/or immunohistochemistry (IHC) were performed to evaluate changes in expression levels of col2a1, aggrecan, ADAMTS-5, tnf-α, il-1ß, nfkbia, nuclear factor-kappaB phospho-p65 in condylar cartilage, and rankl/rank/opg in both condylar cartilage and subchondral bone. RESULTS: Cartilage degradation with decreased col2a1 and aggrecan expression, and increased ADAMTS-5, tnf-α/il1-ß, nfkbia and NF-κB phospho-p65 was observed in UAC + Saline groups. Subchondral bone loss with increased osteoclast numbers and decreased opg/rankl ratio was found in UAC + Saline groups compared to age-match CON + Saline groups. Cartilage degradation and subchondral bone loss were reversed by treatment of SrCl2 or NBD peptide while the same dosage in control mice induced few changes in condylar cartilage and subchondral bone. CONCLUSIONS: The results demonstrate reverse effect of systemic administration of strontium or NBD peptide on UAC-induced condylar cartilage degradation and subchondral bone loss.

Effect of diazepam on temporomandibular joints in rats with increased occlusal vertical dimension.

Anxiolytic agents, mainly benzodiazepines, have been used to treat symptomatic disorders of the temporomandibular joint (TMJ). Our aim was to evaluate the effect of diazepam on the TMJ of rats with increased occlusal vertical dimension (iOVD). Forty male rats were randomly assigned to 4 groups: control rats were given sham iOVD plus saline solution daily for 7 days. The first experimental group was given sham iOVD plus diazepam 2.5mg/kg/intramuscularly daily for 7 days (diazepam alone group); the second had iOVD induced in molars for 7 days plus saline daily for 7 days (iOVD alone group); and the third had iOVD induced in molars for 7 days plus diazepam 2.5mg/kg/intramuscularly daily for 7 days (iOVD plus diazepam group). At the end of each experiment the animals were killed and their bilateral TMJs were removed, randomly stained with haematoxylin and eosin and sirius-red, and immunoassayed. The thickness of condylar cartilage and of fibrous, proliferating, mature, and hypertrophic layers, number of collagen fibres, and the articular area were measured. Proinflammatory cytokines (interleukin (IL)-1α, IL-1ß, IL-6, and tumour necrosis factor (TNF)-α) were also measured. ANOVA and Tukey's tests or the Kruskal-Wallis test were used to compare data among groups (α=5%). Condylar cartilage was thicker in the control group than in the other groups, the diazepam alone group being thicker than the other 2 experimental groups. There were fewer collagen fibres in the 2 groups given diazepam than in the other 2 groups, and there were no significant differences in the area of cartilage among groups. The controls had lower concentrations of all cytokines (p<0.05) than the 3 experimental groups, except for IL-6. Both iOVD groups had higher concentrations of IL-1α, IL-1ß, and IL-6 than the diazepam alone group. Diazepam alone was associated with increased concentrations of all cytokines except IL-6. We conclude that both iOVD and diazepam induced significant changes in rats' articular cartilage.

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

BACKGROUND: Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. METHODS: Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. RESULTS: When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. CONCLUSION: It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes.

Mesenchymal stem cells and platelet gel improve bone deposition within CAD-CAM custom-made ceramic HA scaffolds for condyle substitution.

PURPOSE: This study evaluated the efficacy of a regenerative approach using mesenchymal stem cells (MSCs) and CAD-CAM customized pure and porous hydroxyapatite (HA) scaffolds to replace the temporomandibular joint (TMJ) condyle. METHODS: Pure HA scaffolds with a 70% total porosity volume were prototyped using CAD-CAM technology to replace the two temporomandibular condyles (left and right) of the same animal. MSCs were derived from the aspirated iliac crest bone marrow, and platelets were obtained from the venous blood of the sheep. Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Sheep were sacrificed 4 months postoperatively. The HA scaffolds were explanted, histological specimens were prepared, and histomorphometric analysis was performed. RESULTS: Analysis of the porosity reduction for apposition of newly formed bone showed a statistically significant difference in bone formation between condyles loaded with MSC and condyles without (P < 0.05). The bone ingrowth (BI) relative values of split-mouth comparison (right versus left side) showed a significant difference between condyles with and without MSCs (P < 0.05). Analysis of the test and control sides in the same animal using a split-mouth study design was performed; the condyle with MSCs showed greater bone formation. CONCLUSION: The split-mouth design confirmed an increment of bone regeneration into the HA scaffold of up to 797% upon application of MSCs.

Effect of simvastatin injections on temporomandibular joint inflammation in growing rats.

PURPOSE: Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. METHODS: Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. RESULTS: Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. CONCLUSIONS: Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important.

The isolated mandibular ramus - a hitherto rarely described anomaly of the mandible. Pathogenesis and treatment.

INTRODUCTION: A very famous paper by Sam Pruzansky, published in 1969, was entitled "Not all dwarfed mandibles are alike". This is the topic of this paper: to describe the shape and discuss the possible pathogenesis of an extremely rare congenital dysplasia found in a unilaterally hypoplastic mandible, namely the isolated mandibular ramus. MATERIAL AND METHODS: A unique malformation of the lower jaw was found in more than 75 patients with developmental abnormalities of the mandible diagnosed and treated by the two authors in two different university hospitals over the last 40 years. We performed the following teratological experiments with laboratory rodents in order to try to understand the pathogenesis of this special dysplasia (and others): at first the normal development of the lower jaw was studied in rat and mouse foetuses. Then a variety of teratogenic drugs were applied to pregnant females and then the foetuses of these pregnancies were studied following Caesarian section. RESULTS: One rat foetus was identified which presented the identical dysplasia that had been noted in the patient described here. The dam pregnant with this foetus had been given 25 mg/kg bodyweight of 6-mercaptopurine on day 12 of pregnancy. The explanation found for the pathogenesis of this anomaly was deducted from the scientific literature regarding normal development of the mandibular condyle. CONCLUSION: The nucleus of the so-called secondary cartilage that will produce the ascending ramus (plus condyle and coronoid) is a separate growth centre which fuses a short time later with the dental bone which becomes the mandible proper by this fusion.

Effect of different doses of transforming growth factor-ß1 on cartilage and subchondral bone in osteoarthritic temporomandibular joints.

Transforming growth factor-beta (TGF-ß) plays an important part in the repair of cartilage in osteoarthritis. It has been hypothesised that intra-articular injection of TGF-ß1 promotes repair of cartilage and protects the subchondral bone from damage in osteoarthritic temporomandibular joints (TMJs). We made bilateral partial perforations of the disc to induce osteoarthritic joints in 36 rabbits. TGF-ß1 20, 40, or 80 ng were injected into the right joint, and vehicle alone was injected into the left joint. Four additional animals were used as normal controls. Microcomputed tomography was used to quantify the three-dimensional microarchitecture of subchondral bone, followed by assessment of the proteoglycan content. All joints treated with TGF-ß1 were covered by a layer of well-organised fibrocartilage, and had increased proteoglycan content and normal microarchitectural properties, whereas the joint treated by vehicle alone had typical osteoarthritis-related degradation of cartilage and sclerosis of subchondral bone. These results suggested that TGF-ß1 is an effective way of treating osteoarthritis of the TMJ.

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage.

AIM: To investigate the effect of excess genistein on the extracellular matrix in mandibular condylar cartilage of female rats in vivo. METHODS: Female SD rats were administered through oral gavage with genistein (50 mg/kg) or placebo daily for 6 weeks. The morphological changes of temporomandibular joints were studied with HE staining. The expression of cartilage matrix compounds (aggrecan and collagen type II), estrogen-related molecules (aromatase, estradiol, ERα and ERß) and proliferating cell nuclear antigen (PCNA) in mandibular condylar cartilage was detected using immunohistochemistry, ELISA and real-time PCR. RESULTS: The genistein treatment significantly reduced the thickness of the posterior and middle regions of mandibular condylar cartilage, and decreased the expression of collagen type II, aggrecan and PCNA. Compared with the control group, the estradiol content and expression levels of the key estradiol-synthesizing enzyme aromatase in the genistein-treatment group were significantly decreased. The genistein treatment significantly increased the expression of ERß, but decreased the expression of ERα. CONCLUSION: Excess genistein suppresses extracellular matrix synthesis and chondrocytes proliferation, resulting in thinner mandibular condylar cartilage. These effects may be detrimental to the ability of mandibular condylar cartilage to adapt to mechanical loads.

Facial symmetry evaluation after experimentally displaced condylar process fracture in methotrexate treated rats.

PURPOSE: To investigate the facial symmetry of high and low dose methotrexate (MTX) treated rats submitted to experimentally displaced mandibular condyle fracture through the recording of cephalometric measurements. METHODS: One hundred male Wistar rats underwent surgery using an experimental model of right condylar fracture. Animals were divided into four groups: A - saline solution (1 mL/week); B - dexamethasone (DEX) (0,15 mg/Kg); C - MTX low dose (3 mg/Kg/week); D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days postoperatively (n=5). Body weight was recorded. Specimens were submitted to axial radiographic incidence, and cephalometric mensurations were made using a computer system. Linear measurements of skull and mandible, as well as angular measurements of mandibular deviation were taken. Data were subjected to statistical analyses among the groups, periods of sacrifice and between the sides in each group (α=0.05). RESULTS: Animals regained body weight over time, except in group D. There was reduction in the mandibular length and also changes in the maxilla as well as progressive deviation in the mandible in relation to the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had deleterious effect on facial symmetry of rats submitted to experimentally displaced condylar process fracture.

Facial symmetry evaluation after experimentally displaced condylar process fracture in methotrexate treated rats / Avaliação da simetria facial após fratura experimental com desvio do processo condilar em ratos tratados com metotrexato

PURPOSE: To investigate the facial symmetry of high and low dose methotrexate (MTX) treated rats submitted to experimentally displaced mandibular condyle fracture through the recording of cephalometric measurements. METHODS: One hundred male Wistar rats underwent surgery using an experimental model of right condylar fracture. Animals were divided into four groups: A - saline solution (1mL/week); B - dexamethasone (DEX) (0,15mg/Kg); C - MTX low dose (3 mg/Kg/week); D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days postoperatively (n=5). Body weight was recorded. Specimens were submitted to axial radiographic incidence, and cephalometric mensurations were made using a computer system. Linear measurements of skull and mandible, as well as angular measurements of mandibular deviation were taken. Data were subjected to statistical analyses among the groups, periods of sacrifice and between the sides in each group (α=0.05). RESULTS: Animals regained body weight over time, except in group D. There was reduction in the mandibular length and also changes in the maxilla as well as progressive deviation in the mandible in relation to the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had deleterious effect on facial symmetry of rats submitted to experimentally displaced condylar process fracture.

OBJETIVO: Avaliar a simetria facial de ratos tratados com metotrexato (MTX), em dose alta e baixa, submetidos à fratura experimental do processo condilar com desvio por meio de mensurações cefalométricas. MÉTODOS: Cem ratos Wistar machos foram submetidos a procedimento cirúrgico utilizando modelo experimental de fratura de côndilo do lado direito. Os animais foram distribuídos em quatro grupos: A - soro fisiológico (1mL/semana); B - dexametasona (DEX) (0,15mg/Kg); C - MTX baixa dose (3mg/Kg/semana); D - MTX alta dose (30mg/Kg). Os períodos de sacrifício foram de 1, 7, 15, 30 e 90 dias de pós-operatório (n=5). O peso dos animais foi documentado. Foram realizadas mensurações lineares da maxila e da mandíbula, bem como angulares do desvio mandibular. Os dados foram submetidos a análises estatísticas entre os grupos, períodos de sacrifício e entre os lados em cada grupo (α=0,05). RESULTADOS: Os animais recuperaram peso ao longo do tempo, exceto no grupo D. Houve redução no comprimento mandibular com alterações também na maxila e desvio progressivo da mandíbula em relação à base do crânio no grupo D. CONCLUSÃO: O tratamento com metotrexato em alta dose teve efeito deletério na simetria facial de ratos submetidos à fratura do processo condilar.

Intra-articular corticosteroid injections to the temporomandibular joints are safe and appear to be effective therapy in children with juvenile idiopathic arthritis.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intra-articular corticosteroid injections (IACIs) of the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) when administered by an oral and maxillofacial surgeon without imaging guidance. MATERIALS AND METHODS: This was a retrospective study of children with JIA, seen at a single center, who were selected based on having received IACIs of the TMJ. All subjects received the intervention, which consisted of referral to a single oral and maxillofacial surgeon for TMJ IACI with 5 to 10 mg triamcinolone hexacetonide, under general anesthesia. Primary outcomes assessed in all subjects were the safety of the procedure and efficacy as determined by the change in maximal incisal opening (MIO). In addition, a subset of 31 subjects underwent repeat magnetic resonance imaging of the TMJ, permitting analysis of the change in the acute and chronic findings of arthritis in those patients. RESULTS: Sixty-three patients (68% female) received 137 IACIs. The mean age for diagnosis of JIA was 8.5 years, and the mean age at presentation for TMJ injections was 10 years. The injections were well tolerated: only 1 patient developed the steroid complication of hypopigmentation, and none developed degeneration or ankylosis. In terms of efficacy, the mean MIO increased from 40.8 ± 0.93 to 43.5 ± 0.90 mm (P = .001); in addition, changing the unit of analysis to individual joints, in patients who underwent repeat magnetic resonance imaging examination, 51% of TMJs showed magnetic resonance imaging evidence of improvement of arthritic changes, of whom 18% had complete resolution of TMJ arthritis. CONCLUSIONS: The results indicate that IACI of the TMJ can be safely performed by experienced oral and maxillofacial surgeons without a requirement for computed tomographic guidance. In addition, these results show that IACI may be effective in the management of TMJ arthritis, although further studies are required.

Pathophysiology and pharmacologic control of osseous mandibular condylar resorption.

PURPOSE: When osseous mandibular condylar resorption occurs there can be many different diagnoses: inflammatory arthritis, TMJ compression, trauma, hormone imbalances, and others. While each diagnosis has its own original inciting event, the pathophysiological pathway for articular bone loss is the same. The aim of this article is to review the relevant literature on condylar resorption and the use of pharmacotherapy to control arthritic erosions and resorption. MATERIALS AND METHODS: The literature search was performed using PubMed database with various combinations of related keywords. Preference was given to clinical trials when reviewing articles. RESULTS: The literature reveals that common cellular level events associated with articular resorption include the activation of osteoblasts by cytokines, free radicals, hormone imbalances and/or potent phospholipid catabolites. The osteoblast then activates the recruitment of osteoclasts and promotes the release of matrix degrading enzymes from the osteoclast. Research into articular erosions has focused on elucidating the important steps in the bone destructive pathways and interfering with them by pharmacological means. The use of antioxidants, tetracyclines, omega-3 fatty acids, non-steroidal anti-inflammatories and inflammatory cytokine inhibitors to aid in preventing and controlling articular bone loss including osseous mandibular condylar resorption has been successful. CONCLUSION: By understanding the known pathways that lead to condylar resorption and the individual patient's susceptibilities, targeted pharmacotherapy might be able to disturb these pathways and prevent further condylar resorption. Basic clinical investigations and randomized clinical trials are still required, but the present science is encouraging.