Transition of endochondral bone formation at the normal and botulinum-treated mandibular condyle of growing juvenile rat.

OBJECTIVE: The aim of this study was to understand the temporal and spatial distribution of canonical endochondral ossification (CEO) and non-canonical endochondral ossification (NCEO) of the normal growing rat condyle, and to evaluate their histomorphological changes following the simultaneous hypotrophy of the unilateral masticatory closing muscles with botulinum toxin (BTX). DESIGN: 46 rats at postnatal 4 weeks were used for the experiment and euthanized at postnatal 4, 8, and 16 weeks. The right masticatory muscles of rats in experimental group were injected with BTX, the left being injected with saline as a control. The samples were evaluated using 3D morphometric, histological, and immunohistochemical analysis with three-dimensional regional mapping of endochondral ossifications. RESULTS: The results showed that condylar endochondral ossification changed from CEO to NCEO at the main articulating surface during the experimental period and that the BTX-treated condyle presented a retroclined smaller condyle with an anteriorly-shifted narrower articulating surface. This articulating region showed a thinner layer of the endochondral cells, and a compact distribution of flattened cells. These were related to the load concentration, decreased cellular proliferation with thin cellular layers, reduced extracellular matrix, increased cellular differentiation toward the osteoblastic bone formation, and accelerated transition of the ossification types from CEO to NCEO. CONCLUSION: The results suggest that endochondral ossification under loading tended to show more NCEO, and that masticatory muscular hypofunction by BTX had deleterious effects on endochondral bone formation and changed the condylar growth vector, resulting in a retroclined, smaller, asymmetrical, and deformed condyle with thin cartilage.

Safety and Efficacy of Botulinum Toxin in the Treatment of Self-Biting Behavior in Lesch-Nyhan Disease.

BACKGROUND: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting. METHODS: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. We retrospectively analyzed six patients with LND who were treated with BoNT to prevent automutilatory behavior. RESULTS: The patient ages when started on treatment with BoNT were 4, 4.5, 6.6, 7.9, 13.9, and 32.3 years. Patients received a mean number of injections of 20, ranging from 3 to 29, over a period that ranged from 1.5 to 7.1 years. The maximum total dose of Botox was 21.3 units/kg mean and the maximum total dose of Dysport was 37.5 units/kg mean. A total of 119 injections were performed. Of these 113 (95%) were partially or completely effective. Only three of 119 injections (2.5%) produced adverse effects. CONCLUSIONS: Botulinum toxin is useful and safe for the treatment of self-biting behavior in patients with LND.

Beneficial effects of benzodiazepine on masticatory muscle dysfunction induced by chronic stress and occlusal instability in an experimental animal study.

Psychological stress and occlusal alteration are important etiologic factors for temporomandibular/masticatory muscular disorders. In particular, the exact physiologic mechanism underlying the relation by occlusal alteration and temporomandibular disorders remains unclear. Our purpose was to test the hypothesis that benzodiazepine therapy is able to prevent metabolic and vascular changes in the medial pterygoid muscle of rats under chronic stress after 14 days of unilateral exodontia. Adult Wistar rats were submitted to unpredictable chronic mild stress (10 days) and/or unilateral exodontia and their plasma and medial pterygoid muscles were removed for analysis. A pre-treatment with diazepam was used to verify its effect on stress. The parameters evaluated included anxiety behavior, plasma levels of corticosterone, metabolic activity by succinate dehydrogenase, capillary density by laminin staining and ultrastructural findings by transmission electron microscopy. Occlusal instability induced anxiety-like behavior on elevated plus-maze test and diazepam administration blocked the appearance of this behavior. Unilateral exodontia promoted in the contralateral muscle an increase of oxidative fibers and capillaries and modification of sarcoplasmic reticulum. Chronic stress caused increased glycolytic metabolism, reduced capillary density and morphological changes in mitochondria on both sides. Association of both factors induced a glycolytic pattern in muscle and hemodynamic changes. Pharmacological manipulation with diazepam inhibited the changes in the medial pterygoid muscle after stress. Our results reveal a preventive benzodiazepine treatment for stress and occlusal instability conditions affecting masticatory muscle disorders. In addition, provide insights into the mechanisms by which chronic stress and exodontia might be involved in the pathophysiology of masticatory muscular dysfunctions.

Decreased mandibular cortical bone quality after botulinum toxin injections in masticatory muscles in female adults.

This study aimed to clarify how masticatory muscle atrophy induced by botulinum toxin (BTX) injection affects cortical bone quality of the mandible using 3D modeling technology. A total of 39 young (26.9 ± 6.0 years) and 38 post-menopausal (55.3 ± 6.3 years) females were included. Computed tomography (CT) images were obtained before and after 12 months of treatment. Predictor variables were application of a stabilization splint, and/or two times of BTX injection in the bilateral temporalis and masseter muscles within a six-month interval. Outcome variables were changes in average Hounsfield units (HU) and cortical thickness of region of interest (ROI). 3D mandibular models were reconstructed using CT images, and models were used to calculate average HU and cortical thickness of ROIs, including inferior half of the lateral surface of ascending ramus, coronoid process, and temporomandibular joint condyle. Cortical bone quality at muscle insertion site was influenced by decreased muscle thickness but seemed not to be affected by decreased functional loading. Reduced functional loading seemed to influence cortical bone quality of the condyles. These effects were more remarkable in post-menopausal females. Hence, decreased masticatory muscle thickness may lead to alterations of the mandibular cortical structures, especially in post-menopausal females.

Involvement of the basal nucleus of Meynert on regional cerebral cortical vasodilation associated with masticatory muscle activity in rats.

We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical vasodilative system derived from the nucleus basalis of Meynert (NBM). In pentobarbital-anesthetized rats, parietal cortical rCBF was recorded simultaneously with electromyogram (EMG) of jaw muscles, local field potentials of frontal cortex, multi-unit activity of NBM neurons, and systemic mean arterial pressure (MAP). When spontaneous rhythmic EMG activity was observed with cortical desynchronization, an increase in NBM activity and a marked rCBF increase independent of MAP changes were observed. A similar rCBF increase was elicited by repetitive electrical stimulation of unilateral cortical masticatory areas. The magnitude of rCBF increase was partially attenuated by administration of the GABAergic agonist muscimol into the NBM. The rCBF increase persisted after immobilization with systemic muscle relaxant (vecuronium). rCBF did not change when jaw muscle activity was induced by electrical stimulation of the pyramidal tract. The results suggest that activation of NBM vasodilator neurons contributes at least in part to the rCBF increase associated with masticatory muscle activity, and that the NBM activation is induced by central commands from the motor cortex, independently of feedback from brainstem central pattern generator or contracting muscles.

Cerebral palsy and bruxism: Effects of botulinum toxin injections-A randomized controlled trial.

Objective: Cerebral palsy (CP) includes disturbances in muscular control caused by perinatal brain injury. Masticatory muscle involvement hampers functions such as chewing and talking. Bruxism and temporomandibular disorders are overrepresented. Neuromuscular blocks with botulinum toxin type A (BTX-A) may alleviate problems due to muscular hyperactivity. The aim was to evaluate masticatory muscle BTX-A injections in subjects with CP and bruxism. Methods: A prospective, parallel, randomized, placebo-controlled, and double-blind trial in 12 patients with CP was performed. End points were alterations in objective and subjective oral capacities after two BTX-A or corresponding placebo injections. Matched, healthy references were also evaluated. Results: The reference group demonstrated stronger and more efficient oral functions compared with the CP group. Subjective and objective oral capacities appeared to vary considerably between CP patients and also over time in this patient group and were poorly correlated. No significant effect of BTX-A compared with placebo on outcome variables was observed at group level, but continued treatment with BTX-A was requested by the majority of the patients. Conclusion: The evidence is unable to support the use of BTX-A for the treatment of affected masticatory muscles in CP, but the findings are inconclusive in certain respects. Larger, more homogeneous groups of CP patients need to be evaluated in future trials.

Oromandibular dystonia, mental distress and oro-facial dysfunction-A follow-up 8-10 years after start of treatment with botulinum toxin.

BACKGROUND: Oromandibular dystonia (OMD) with involuntary jaw and tongue movements may be misdiagnosed as temporomandibular disorders (TMD) and because of the complex muscle activity and involvement of several small muscles, OMD is also considered difficult to treat. OBJECTIVES: The aim was to evaluate OMD in patients 8-10 years after start of treatment with botulinum toxin (BoNT) by self-reported and standardised global scales and questionnaires. METHODS: Of 21 previously reported patients with OMD, 14 responded to a mail health questionnaire to describe the disease course and treatment effect as well as the overall impact of OMD by a visual analogue scale (VAS), the Patient Health Questionnaire (PHQ) for depression and anxiety, and the Jaw Functional Limitation Scale (JFLS). The results were analysed with non-parametric statistical analysis (Wilcoxon matched-pairs test and Spearman's rank-order correlations). RESULTS: The OMD was still present in 13 patients. In nine patients, the BoNT treatment had continued as monotherapy or combined with oral medication. VAS for OMD was significantly reduced (P < 0.04) over the years, and most patients felt improvement from the treatment. However, the patients had still some functional limitations, typically regarding jaw mobility and communication, and both JFLS and mental distress (PHQ) were significantly correlated with the OMD VAS (rS 0.77 and 0.74). CONCLUSION: The results showed marked reduction of the experienced OMD with treatment and over time, and also stressed similarities between OMD and TMD. Both dentists and neurologists should be aware of this overlap and reduce misdiagnosis by applying an interdisciplinary approach.

Tratamento de disfunções temporomandibulares com toxina botulínica tipo A / Treatment of temporomandibular disorders with botulinum toxin type A

Introdução: a disfunção temporomandibular (DTM) abrange muitos problemas clínicos nas articulações, na musculatura e em outras regiões da oroface. A origem multifatorial e sua etiologia envolvem fatores psicocomportamentais, oclusais e neuromusculares, seu diagnóstico é realizado pela anamnese detalhada, com a identificação dos fatores predisponentes, iniciadores e perpetuantes, e pelo exame físico, que consiste em palpação da musculatura, mensuração da movimentação ativa e verificação dos ruídos articulares. Objetivo: sistematizar as evidências científicas e verificar a eficácia do tratamento de disfunções temporomandibulares de origem muscular com a toxina botulínica do tipo A (TBX-A). Materiais e método: a busca bibliográfica foi realizada nas bases de dados PubMed e SciELO, com os descritores: "myofascial pain", "botulinum toxin" e "masticatory muscles". Foram analisados ensaios clínicos randomizados, que apresentaram tratamento para DTM com a utilização da TBX-A em pacientes de ambos os sexos. A qualidade metodológica dos artigos selecionados foi verificada de acordo com a escala de Jadad. Considerações finais: observou-se que o tratamento para a DTM por meio da TBX-A auxilia no tratamento de dores orofaciais permanentes como coadjuvante, aliado a tratamentos conservadores. Os estudos que demonstraram resultados clínicos significativos utilizaram uma dose total de 100 U de TBX-A, sendo 30 U nos músculos masseteres e 20 U nos músculos temporais, bilateralmente. (AU)

Introduction: temporomandibular dysfunction (TMD) involves a number of clinical problems in joints, muscles, and other orofacial regions. The multifactorial origin and etiology involve psychobehavioral, occlusal, and neuromuscular factors. The diagnosis is performed by a detailed anamnesis with the identification of predisposing factors, initiators and perpetuants, and the physical examination, which consists of muscle palpation, measurement of the active movement, and verification of joint noises. Objective: to systematize the scientific evidence and to verify the efficacy of treatment of temporomandibular disorders of muscular origin with botulinum toxin type A (TBX-A). Materials and method: the bibliographic search was performed in the PubMed and SciELO databases, with the descriptors of "myofascial pain", "botulinum toxin", "masticatory muscles". Randomized clinical trials that presented treatment for TMD with the use of TBX-A in patients of both sexes were analyzed. The methodological quality of the articles selected was verified according to the Jadad scale. Final considerations: it was observed that treatment for TMD using TBX-A helps to treat permanent orofacial pain as a support, along with conservative treatments. The studies showing significant clinical outcomes used a total dose of 100 U of TBX-A, considering 30 U for the masseter muscles and 20 U for the temporal muscles, bilaterally. (AU)

The Use of Botulinum Toxin for the Treatment of Myofascial Pain in the Masticatory Muscles.

Although the use of botulinum toxin has been recommended for the management of myofascial pain and dysfunction, the precise mechanism of its action remains undetermined and studies on its effectiveness are equivocal. Moreover, even if such treatment may temporarily relieve the symptoms, it does not address the cause of the problem. Also, its use is not free of potential complications. On this basis, botulinum toxin does not seem to be a logical treatment of myofascial pain and dysfunction.

Pilot Single-Blind Trial of AbobotulinumtoxinA in Oromandibular Dystonia.

Oromandibular dystonia (OMD) causes involuntary movements of masticatory and lingual muscles impairing eating, speaking, and swallowing. Treatment options are limited. The objective of this study was to determine the safety and efficacy of abobotulinumtoxinA (aboBoNTA) in OMD. A dose-finding study (phase 1) followed by a single session, prospective, single-blind trial (phase 2) was carried out. OMD subjects were evaluated at baseline, 6 and 12 weeks. Muscles injected were tailored to individual symptoms using EMG guidance, but the aboBoNTA dose for each muscle was pre-specified based on phase 1 results. Evaluations were Global Dystonia Rating Scale (GDS), Unified Dystonia Rating Scale (UDRS), Clinical Global Impression (CGI) improvement and severity, and quality of life (OMDQ-25). Adverse events were monitored. The lowest dosage in phase 1 resulted in adverse effects in two of three patients and thus was used in phase 2. In phase 2, adverse effects were observed in 50% of subjects including dysphagia, voice change, and soft palate weakness. Most were mild. Significant improvement was seen in quality of life (OMDQ-25), speech (BFMq21), and change in GDS, UDRS, CGI severity assessed by the unblinded investigator, but not in blinded video ratings. We conclude that aboBoNTA therapy in this study was associated with improved quality of life and was generally well tolerated in OMD, but occurrence of dysphagia dictated the importance of using low genioglossus dosing. Face to face assessment appears to be more sensitive than video assessment for change in OMD severity. Consideration of the disability in OMD places constraints on traditional placebo-control trial design. Development of novel trial designs is warranted.

Multidisciplinary management of a partially edentulous patient with oromandibular dystonia: A clinical report.

Oromandibular dystonia (OMD) is defined as a subset of movement disorders characterized by involuntary muscle contraction in different parts of the oromandibular region. This clinical report presents a multidisciplinary approach to the management of a patient with OMD. The involuntary movement of her mandible and tongue was improved with a mandibular custom occlusal device and maxillary modified removable complete denture together with botulinum toxin A injections.

Systematic review of botulinum toxin treatment for oromandibular dystonia.

Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the muscles of the jaw, lower face and tongue. It is a rare disorder but is associated with significant impairment in quality of life. Treatment with oral medications has not been successful. Surgical interventions, such as deep brain stimulation, may be of benefit but have not been adequately evaluated. Currently, botulinum toxin (BoNT) injections are regarded as the treatment of choice for OMD. However, the evidence supporting this is not available. Most studies are open label, observational studies, longitudinal clinical experience, case reports or retrospective analysis. From the available studies, OMD is responsive to appropriately targeted BoNT injections. Jaw closing dystonia responds the most robustly. Jaw opening dystonia is more complex to inject, but clinical experience is consistent with benefit. Lingual dystonia is the most difficult because injections into tongue muscles frequently give rise to dysphagia. More controlled studies are required to establish BoNT as an effective treatment for OMD.

Correction of Malocclusion by Botulinum Neurotoxin Injection into Masticatory Muscles.

Botulinum toxin (BTX) is a neurotoxin, and its injection in masticatory muscles induces muscle weakness and paralysis. This paralytic effect of BTX induces growth retardation of the maxillofacial bones, changes in dental eruption and occlusion state, and facial asymmetry. Using masticatory muscle paralysis and its effect via BTX, BTX can be used for the correction of malocclusion after orthognathic surgery and mandible fracture. The paralysis of specific masticatory muscles by BTX injection reduces the tensional force to the mandible and prevents relapse and changes in dental occlusion. BTX injection in the anterior belly of digastric and mylohyoid muscle prevents the open-bite and deep bite of dental occlusion and contributes to mandible stability after orthognathic surgery. The effect of BTX injection in masticatory muscles for maxillofacial bone growth and dental occlusion is reviewed in this article. The clinical application of BTX is also discussed for the correction of dental malocclusion and suppression of post-operative relapse after mandibular surgery.

Efficacy of botulinum toxin in treating myofascial pain and occlusal force characteristics of masticatory muscles in bruxism.

AIM AND OBJECTIVE: The present study was conducted in patients with bruxism to evaluate the effect of botulinum toxin type A (BTX-A) (Botox, Allergan, Inc., Irvine, CA, USA) in the treatment of myofascial pain and the occlusal force characteristics of masticatory muscles. MATERIALS AND METHODS: Twenty-four diagnosed with bruxism were randomly divided into three groups (n = 8) and treated by bilateral intramuscular injection of BTX-A and placebo-treated with saline placebo injections and control group where no injections were given. The clinical parameters such as pain at rest and during chewing were assessed and occlusal force analysis system to measure the distribution of occlusal force in bruxism patients. All the three groups were assessed at baseline time and at 1 week, 3 months, and 6 months follow-up appointments. Descriptive analysis showed that improvements in parameters such as pain at rest; pain during chewing clinical outcome variables were higher in the botox treated group than in the placebo-treated subjects. RESULTS: The pain at rest and at chewing decreased in the BTX-A group while remaining constant in the placebo group and control group. There was a significant change in maximum occlusal force in the BTX-A group compared with the other two groups (P < 0.05, post hoc Bonferroni test, no exact P value), and there was no significant difference between the placebo and control groups (post hoc Bonferroni test, no exact P value). CONCLUSION: Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and effective in reducing the occlusal force.

Self-Rated Communication-Related Quality of Life of Individuals With Oromandibular Dystonia Receiving Botulinum Toxin Injections.

PURPOSE: In this preliminary study, we examined self-rated communication-related quality of life (CR-QoL) of 10 control participants and 10 individuals with oromandibular dystonia (OMD) and dysarthria receiving therapeutic botulinum toxin (BoNT-A) injections. METHOD: Participants with OMD and associated dysarthria self-rated CR-QoL pre- and post- BoNT-A injection using the American Speech-Language-Hearing Association's Quality of Communication Life Scale (ASHA QCL; Paul et al., 2004). Control participants self-rated CR-QoL during a single experimental visit. RESULTS: Significant differences were found between control participants and participants with OMD on ratings of CR-QoL across all 5 domains and subdomains of the ASHA QCL. No significant differences in CR-QoL were found over the course of the BoNT-A treatment cycle. CONCLUSIONS: CR-QoL was rated lower by participants with OMD as compared with control participants across all ASHA QCL domains/subdomains with "socialization/activities" and "confidence/self-concept" having the largest effect sizes. No differences in CR-QoL were found over the course of the treatment cycle. We advocate for outcome measures that include patient report. The use of patient-reported outcome measures in conjunction with objective or impairment-based outcome measures can help inform meaningful clinical indicators of treatment success. This study adds novel information that may aid our understanding of the experience of living with OMD in this underserviced clinical population.

Toxina botulínica tipo A nas DTM musculares: há eficácia? / Botulinum toxin type A in muscle TMD: There's effectiveness?

Os objetivos dessa revisão da literatura foram verificar a eficácia da toxina botulínica tipo A (BTX-A) na diminuição da dor em indivíduos com DTM e identificar os parâmetros ideais para o local, número de aplicações, dosagens e tempo de duração. Foram selecionados 19 artigos das bases de dados do Google Acadêmico e PubMed, que incluíram 14 artigos de pesquisa clínica e 5 de revisão sistemática. Foi possível concluir a respeito da toxina botulínica que os músculos indicados para a aplicação são principalmente os masseteres e os temporais, podendo ser aplicado também nos músculos pterigoideos, lateral e medial, digástrico e platisma. Os locais de escolha são os que apresentam maior volume e sensibilidade à palpação (pontos-gatilho) ou maior atividade eletromiográfica em repouso. As dosagens variam de um total de 10U a 400U de BTX-A por indivíduo, sendo distribuídas pelos músculos indicados. A BTX-A, em geral, é aplicada em dose única, porem alguns autores preconizam uma segunda aplicação se a primeira não fez o efeito esperado. O efeito da toxina botulínica sobre os músculos e a dor, em geral, tem duração variada, sendo relatado desde 3 a 4 semanas até 3 a 5 meses. A maioria dos estudos observou à eficácia da BTX-A na diminuição da dor de indivíduos com DTM. Porém é necessário que mais estudos clínicos randomizados, duplo cegos, multicêntricos e controlados sejam realizados para que a eficácia da BTX-A seja comprovada e para que um protocolo de atendimento seja realizado.(AU)

The objectives of this literature review were to verify the efficacy of botulinum toxin type A (BTX-A) in reducing pain of TMD patients and to identify the optimal parameters for the location, number of applications, dosages and duration. We selected 19 articles from Google Scholar and PubMed databases that included 14 articles of clinical research and 5 systematic reviews. It was concluded about BTX-A that the muscles appropriate to the application are mostly masseter and temporal and can also be applied in the pterygoid muscle lateral and medial, digastric and platysma. The choices of locations are those who have higher volume and sensitivity to palpation (trigger points) or higher EMG activity at rest. Dosages vary from a total of 10U to 400U of BTX-A by individual, being distributed by the indicated muscles. BTX-A in general is applied in a single dose, but some authors recommend a second application if the first did not make the expected effect. The effect of BTX-A on muscle and pain in general has varying duration, being reported from 3 to 4 weeks for 3 to 5 months. Most studies have noted at the effectiveness of BTX-A in patient pain reduction DTM. However more randomized, double-blind, multicenter, controlled clinical trials needs to be carried out so that the effectiveness of BTX-A could be confirmed and a management protocol, stabilished.(AU)

Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices?

BACKGROUND: Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. METHODS: This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. RESULTS: Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p < 0.001). The risk of suffering muscular alterations during oral device treatment is higher in statin patients (odds ratio 6.67, p = 0.002). CONCLUSION: Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices.

Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis.

In man, botulinum toxin type A (BTX) is injected in masticatory muscles for several indications such as trismus, bruxism, or masseter hypertrophy. Bone changes in the mandible following BTX injections in adult animal have therefore became a subject of interest. The aim of this study was to analyze condylar and alveolar bone changes following BTX unilateral injections in masseter and temporal muscles in adult rats. Mature male rats (n = 15) were randomized into 2 groups: control (CTRL; n = 6) and BTX group (n= 9). Rats of the BTX group received a single injection of BTX into right masseter and temporal muscles. Rats of the CTRL group were similarly injected with saline solution. Rats were sacrificed 4 weeks after injections. Masticatory muscles examination and microcomputed tomography (microCT) were performed. A significant difference of weight was found between the 2 groups at weeks 2, 3 and 4 (p < 0.05). Atrophy of the right masseter and temporal muscles was observed in all BTX rats. MicroCT analysis showed significant bone loss in the right alveolar and condylar areas in BTX rats. Decrease in bone volume reached -20% for right alveolar bone and -35% for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle enthesis was found on every right hemimandible in the BTX group and none in the CTRL group. BTX injection in masticatory muscles leads to a significant and major mandible bone loss. These alterations can represent a risk factor for fractures in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus enthesis may constitute an etiological factor for tori.