Growth patterns of facial muscles at the angle of the mouth: A histological study using midterm and near-term human fetuses.

At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.

Early changes in asporin levels in osteoarthritis of the temporomandibular joint.

OBJECTIVES: The present study aimed to elucidate the pathogenesis of temporomandibular joint (TMJ) osteoarthritis (TMJ-OA) in a mouse model. We investigated morphological and histological changes in the head of mandible cartilage and early immunohistochemical (IHC) changes in transforming growth factor (TGF)-ß, phosphorylated Smad-2/3 (p-Smad2/3), a TGF-ß signaling molecule, and asporin. METHODS: TMJ-OA was induced in a mouse model through unilateral partial discectomy. Micro-computed tomography (micro-CT) and safranin-O staining were performed to morphologically and histologically evaluate the degeneration of the head of mandible caused by TMJ-OA. IHC staining for TGF-ß, p-Smad2/3, and asporin was performed to evaluate the changes in protein expression. RESULTS: In the experimental group, three-dimensional (3D) morphometry revealed an enlarged head of mandible and safranin-O staining showed degeneration of cartilage tissue in the early stages of TMJ-OA compared to the control group. IHC staining revealed that TGF-ß, p-Smad2/3, and asporin expression increased in the head of mandible cartilage before the degeneration of cartilage tissue, and subsequently decreased for a short period. CONCLUSION: The findings suggested a negative feedback relationship between the expression of asporin and the TGF-ß/Smad transduction pathway, which may be involved in the degeneration of the head of mandible in the early stages of TMJ-OA. Asporin is a potential biomarker of the early stages of TMJ-OA, which ultimately leads to the irreversible degeneration of TMJ tissues.

Downregulation of SOX9 expression in developing entheses adjacent to intramembranous bone.

Entheses are classified into three types: fibrocartilaginous, fibrous, and periosteal insertions. However, the mechanism behind the development of fibrous entheses and periosteal insertions remains unclear. Since both entheses are part of the temporomandibular joint (TMJ), this study analyzes the TMJ entheses. Here, we show that SOX9 expression is negatively regulated during TMJ enthesis development, unlike fibrocartilage entheses which are modularly formed by SCX and SOX9 positive progenitors. The TMJ entheses was adjacent to the intramembranous bone rather than cartilage. SOX9 expression was diminished during TMJ enthesis development. To clarify the functional role of Sox9 in the development of TMJ entheses, we examined these structures in TMJ using Wnt1Cre;Sox9flox/+ reporter mice. Wnt1Cre;Sox9flox/+ mice showed enthesial deformation at the TMJ. Next, we also observed a diminished SOX9 expression area at the enthesis in contact with the clavicle's membranous bone portion, similar to the TMJ entheses. Together, these findings reveal that the timing of SOX9 expression varies with the ossification development mode.

Transient contribution of the sphenoid ala major to the socket of the temporomandibular joint in near-term fetuses.

The temporomandibular joint (TMJ) is a complex structure that plays a vital role in the movement of the jaw. Some anatomy and dental textbooks show that, at the medial margin, the TMJ capsule attaches to a suture between the sphenoid ala major and the temporal bone squamosa. In near-term fetuses, the ala major extends posterolaterally to approach the TMJ. In this study, we aimed to investigate the contribution of the sphenoid ala major to the socket of the TMJ in near-term fetuses. We examined histological sections from 22 human fetuses (approximately 15-40 weeks). At midterm, the lateral and superior walls of the TMJ cavity were formed by the temporal bone squamosa, whereas the ala major was distant from the joint. However, at near-term, the ala major formed the medial wall of almost the entire part of the joint cavity. The top of the TMJ was attached to both the squamosa and ala major, with the condylar head consistently separated from the sphenoid by the joint disk. We observed a significant descent of the middle cranial fossa in near-term fetuses, which brought the ala major close to the TMJ. This transient position of the TMJ near the sphenoid is likely due to brain enlargement and posterolateral growth of the ala major. After birth, occlusion causes the anterior growth of the mandibular fossa of the squamosa, which moves the ala major away from the TMJ. Similarly, the lateral growth of the sphenoid toward the squamosa suture may also stop in children.

The influence of immediate occlusal loading on micro/nano-structure of peri-implant jaw bone in rats.

PURPOSE: The objective of the present study was to ascertain the effect of immediate occlusal loading after implant placement on osseointegration and the micro/nanostructure of the surrounding bone. METHODS: After extraction of a rat maxillary right second molar, an implant was placed immediately with initial fixation (2 N< ). The implants were placed to avoid occlusal loading due to mastication, and in the loaded group, a superstructure was fabricated and subjected to occlusal loading. Bone morphometry, collagen fiber anisotropy, and biological apatite (BAp) crystallite alignment were quantitatively evaluated in both groups after extraction and fixation of the jaw bone at Days 7 and 21 after surgery. RESULTS: Osseointegration was observed in both groups. Bone morphometry showed significant differences in bone volume, trabecular number, trabecular thickness and bone mineral density (BMD) at Days 21 postoperatively (P < 0.05). A significant difference was also found in the trabecular separation at Days 7 postoperatively (P < 0.05). In the evaluation of collagen fiber anisotropy, collagen fiber bundles running differently from the existing bone were observed in both groups. In terms of BAp crystallite alignment, a specific structure was observed in the reconstructed new bone after implantation, and preferential orientation of BAp crystallite alignment was observed in the longitudinal direction of the implants in the Day 21 postoperative loaded group. CONCLUSION: When sufficient initial fixation is achieved at the time of dental implant placement, then the applied masticatory load may contribute to rapidly achieving not only bone volume, but also adequate bone quality after implant placement.

Development and growth of the temporal fascia: a histological study using human fetuses.

The temporal fascia is a double lamina sandwiching a thick fat layer above the zygomatic bony arch. To characterize each lamina, their developmental processes were examined in fetuses. We observed histological sections from 22 half-heads of 10 mid-term fetuses at 14-18 weeks (crown-rump length, 95-150 mm) and 12 near-term fetuses at 26-40 weeks (crown-rump length, 215-334 mm). The superficial lamina of the temporal fascia was not evident at mid-term. Instead, a loose subcutaneous tissue was attached to the thin, deep lamina of the temporal fascia covering the temporalis muscle. At near-term, the deep lamina became thick, while the superficial lamina appeared and exhibited several variations: i) a mono-layered thick membrane (5 specimens); ii) a multi-layered membranous structure (6) and; iii) a cluster of independent thick fasciae each of which were separated by fatty tissues (1). In the second and third patterns, fatty tissue between the two laminae was likely to contain longitudinal fibrous bands in parallel with the deep lamina. Varying proportions of the multi-layered superficial lamina were not attached to the zygomatic arch, but extended below the bony arch. Whether or not lobulation or septation of fatty tissues was evident was not dependent on age. The deep lamina seemed to develop from the temporalis muscle depending on the muscle contraction. In contrast, the superficial lamina developed from subcutaneous collagenous bundles continuous to the cheek. Therein, a difference in development was clearly seen between two categories of the fasciae.

Mentalis nerve branches supplying the lower lip revisited: a study of human fetuses and donated elderly cadavers.

PURPOSE: Little information is known about the mentalis nerve course from the lower lip approximation margin (free margin) to the upper lip. Likewise, no difference in nerve distribution has been observed between the cutaneous and mucosal parts of the lip. Therefore, this study reexamined mentalis nerve morphology. METHODS: For macroscopic observations, three fresh cadavers were dissected (one male and two females; aged 78-93). We also evaluated histological sections obtained from five donated elderly cadavers (two males and three females, aged 82-96 years) and 15 human fetuses (11-40 weeks or crown-rump length 80-372 mm). Immunohistochemical analysis for S100 protein and tyrosine hydroxylase was performed. RESULTS: In both fetuses and adult cadavers, one to three nerve branches ran upward in the submucosal tissue from the mental foramen. Near the free margin of the lip, some branches passed through the orbicularis oris muscle layer toward the lip skin, whereas others followed a reversed J-shaped course along the free margin. Nerve twigs ran in parallel beneath the mucosa, whereas wavy nerve twigs attached to the basal lamina of the lip epidermis. The difference in nerve endings abruptly occurred at the skin-mucosal junction. Tyrosine hydroxylase-positive sympathetic nerve twigs surrounded arteries and formed a branch composed of S100-negative unmyelinated fibers. CONCLUSION: The lower lip skin was innervated by a perforating branch passing through the orbicularis oris muscle, that was different from the lip mucosa. A sudden change in the nerve ending configuration at the mucocutaneous junction seemed to develop postnatally.

Dapagliflozin-induced drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Followed By Acute Interstitial Nephritis (AIN): A Case Report.

A 78-year-old male was admitted to the hospital with acute renal failure and generalized erythema after starting dapagliflozin 10 mg/day for chronic kidney disease (CKD). A skin biopsy revealed superficial perivascular dermatitis with eosinophils. A renal biopsy revealed lymphocytic and eosinophilic infiltration of the interstitium, and focal tubulitis. The patient was diagnosed with a dapagliflozin-induced drug reaction with eosinophilia and systemic symptoms (DRESS), followed by acute interstitial nephritis (AIN), and prednisolone therapy was therefore initiated. The patient's renal function improved, and erythema disappeared. To our knowledge, this is the first report of DRESS caused by dapagliflozin, and the patient was successfully treated with prednisolone.

Growing stylohyoideus muscle insertion to the hyoid bone with special reference to its topographical relation to the intermediate tendon of digastricus muscle: A histological study using human fetuses.

BACKGROUND: In adults, the intermediate tendon of digastricus muscle usually runs along the medial or lateral side of the stylohyoideus muscle insertion. To provide a better understanding of the variations, we examined the topographical anatomy of the muscle and tendon in fetuses. METHODS: We examined histological sections from six early-term, 26 mid-term and six near-term fetuses (approximately 8-9, 12-18 weeks and 25-33 weeks). RESULTS: At early-term, an initial sheath of intermediate tendon of digastricus muscle received the stylohyoideus muscle at the superior aspect. The muscle and tendon was distant from the hyoid. At mid-term, near the insertion to the hyoid greater horn, the stylohyoideus muscle consistently surrounded more than 2/3 of the intermediate tendon circumference. In contrast, we found no near-term specimen in which the stylohyoideus muscle surrounded the intermediate tendon. The multilayered tendon sheath was fully developed until near-term and connected to the body of hyoid by an intermuscular septum between the thyrohyoideus muscle and one or two of suprahyoid muscles. Therefore, the hyoid insertion of the styloglossus muscle was a transient morphology at mid-term. CONCLUSION: The stylohyoideus muscle insertion was appeared to move from the tendon sheath to the hyoid greater horn and, until near-term, return to the tendon sheath. A fascia connecting the tendon sheath to the body of hyoid was strengthened by the suprahyoid and infrahyoid muscles. The latter muscles seemed to regulate fixation/relaxation of the intermediate tendon to the hyoid. The stylohyoideus muscle slips sandwiching the intermediate tendon might be a rare morphology.

Analysis of Bone Mineral Density and Bone Quality of Cortical Bone in the Human Hyoid Body and Histological Observation of the Entheses.

The hyoid is the only bone in the human body that is completely independent, not forming a joint with any other bone; its position is maintained by the suprahyoid and infrahyoid muscles, as well as several ligaments. The purpose of this study was to ascertain the effect of the functional pressure arising from these muscles and ligaments on the hyoid body structure from its bone mineral density, bone quality, and histological observations. The area between the mesial-most part of each lesser horn and the center of the hyoid body was divided equally into four measurement regions. We conducted histological investigations at each measurement region and observed the entheses. To analyze bone mass and bone quality, we also measured bone mineral density (BMD) and analyzed biological apatite (BAp) crystallite orientation in the same regions. Histological observations identified periosteal insertions and fibrocartilaginous entheses. There was no significant difference in BMD between any of the measurement regions, but the preferential orientation of BAp crystallites was stronger in the infrahyoid muscles and ligaments, where fibrocartilaginous entheses are found, than in other places. This suggests that the functional pressure at these sites might exert a major effect not only on the morphological characteristics of the entheses but also on bone quality.

A Case of Combination of IgA Nephropathy and Interstitial Nephritis After COVID-19 Vaccination.

A 66-year-old male presented with renal dysfunction. At the time of presentation, his serum creatinine (sCr) was 2.55 mg/dL, estimated glomerular filtration rate (eGFR) was 20.93 ml/min/1.73 m2, urinary red blood cell (RBC) was 30-49/high power field, and urine protein-creatinine ratio was 0.43 g/gCr. The patient had no urinalysis abnormalities or renal dysfunction within the year prior to presentation but had gross hematuria after the third and fourth coronavirus disease 2019 (COVID-19) vaccinations. Therefore, immunoglobulin A nephropathy (IgAN) was suspected and a percutaneous renal biopsy was performed. Renal pathology confirmed IgAN and interstitial nephritis and glucocorticoid therapy was initiated. Glucocorticoids improved renal function, and microscopic hematuria resolved. Although previous reports have shown that the COVID-19 vaccine induces various renal diseases, complications associated with these two renal diseases are rare. In this case, while IgAN was suspected based on episodes of gross hematuria after vaccination, renal biopsy confirmed it and also revealed interstitial nephritis.

Exploratory Study of Growth of Circumference of Mandibular Fossa Adjacent to Petrous Portion of Temporal Bone Using Dried Skulls.

The morphogenetic process of development of the circumference of the mandibular fossa during tooth eruption, which involves the replacement of deciduous teeth with permanent teeth, is strongly affected by occlusion. To the best of our knowledge, no studies have investigated the effect of occlusion on this process. This study investigated the morphogenetic process of development during tooth eruption using dried skulls harvested from Indian donors. The average distance between the ala-major-squamosa suture and the foramen ovale according to age group was as follows: 3.24 mm in the 8-month-old group and 8.92 mm in the adult group. The average distance between the ala-major-squamosa suture and the apex of the articular tubercle according to age groups was as follows: 10.38 mm in the 8-month-old group and 19.34 mm in the adult group. The average distance between the point of intersection of the petrosquamous fissure and petrotympanic fissure located on the perpendicular line drawn posteriorly from the shortest distance of the medio-lateral axis between the ala-major-squamosa suture and the apex of the articular tubercle according to age group was as follows: 9.68 mm in the 8-month-old group and 14.3 mm in the adult group. These results suggest that the mandibular fossa is strongly affected by load due to occlusion, unlike the growth of the neurocranium. This indicates that the effect of occlusion is a secondary element in the morphogenetic process of development of the circumference of the mandibular fossa.

Development and growth of median structures in the human tongue: A histological study using human fetuses and adult cadavers.

Glossectomy is a surgical procedure performed to remove all or part of the tongue in patients with cancer. The removal of a significant part of the tongue has a marked effect on speech and swallowing function, as patients may lose not only the tongue muscles but also the median lingual septum (MLS). Therefore, to achieve successful tongue regeneration, it is necessary to investigate the developmental processes of not only the tongue muscles but also the MLS. This study was conducted to clarify the mutual development of the tongue muscles and the MLS in human fetuses. Serial or semi-serial histological sections from 37 embryos and fetuses (aged 5-39 weeks) as well as nine adults were analyzed. The MLS appeared at Carnegie stage 15 (CS15), and until 12 weeks of gestation, abundant fibers of the intrinsic transverse muscle crossed the septum in the entire tongue. However, in near-term fetuses and adults, the contralaterally extending muscles were restricted to the deepest layer just above the genioglossus muscle. This finding indicates that the crossing transverse muscle showed the highest density at mid-term. A thorough understanding of both the MLS and the tongue muscles is necessary for successful tongue regeneration.

Regeneration process of myotendinous junction injury induced by collagenase injection between Achilles tendon and soleus muscle in mice.

Recently, it has become clear that peri-muscular tissues play a significant role in the deterioration of muscle function. Understanding the function and regeneration of muscle, as well as its surrounding tissues, is crucial to determining the causes of muscular illnesses. However, the regeneration process of the myotendinous junction (MTJ), the most closely related peri-muscular tissue, is still unknown. Therefore, we generated a mouse model of MTJ injury by collagenase injection and searched for the process of regeneration of the MTJ and its adjacent regions. The MTJ region was damaged by collagenase injection, which greatly increased the tendon cross sectional area. Collagenase injections increased the proportion of myofibers with a central nucleus, which is a characteristic of regenerating muscle. The collagenase injection group had myofibers with central nuclei and expressing MTJ markers. Additionally, we measured the length of MTJs using serial cross sections of the soleus muscle and discovered that MTJs at 2 weeks after collagenase injection were shorter compared to the control group, with a propensity to progressively recover their length over time. The results showed that MTJs undergo morphological regeneration even when severely damaged, and that this regeneration occurs in conjunction with muscle regeneration. We anticipate that these findings will be valuable in upcoming research on motor unit regeneration.

Structural analysis of the mylohyoid muscle as a septum dividing the floor of the oral cavity for the purposes of dental implant surgery: variety of muscle attachment positions and ranges of distribution.

OBJECTIVES: The objective was to investigate the details of the attachments of the mylohyoid muscle to the mandible anterior to the hyoid and mylohyoid lines to understand the positional relationship between the sublingual space and the mylohyoid, knowledge that is essential for dental implant surgery in the incisal region, as well as the routes of communication between the sublingual space and other spaces. METHODS: While evaluating the presence or absence of an anterior mylohyoid muscle fiber attachment to the mandible, sublingual gland herniation, spaces between muscle fascicles were also recorded as sites of penetration. The mean muscle thickness in each of these areas was also calculated. RESULTS: In all specimens, the mylohyoid originated not only from the mylohyoid line but also from the lingual surface of the center of the mandibular body (the mandibular symphysis) below the mental spines. The mylohyoid muscle fascicles were thickest in the posterior region, and further anterior to this, they tended to become thinner. Sublingual gland herniations passing through the mylohyoid were noted in the anterior and central regions, but not in the posterior region. Penetration between the muscle fascicles was most common in the central region, and no such penetration was evident in the posterior region. CONCLUSIONS: These results suggest that the mylohyoid functions only incompletely as a septum, and that routes of communication from the sublingual space to the submandibular space may be present in both the anterior and central muscle fascicles of the mylohyoid. Therefore, bleeding complications during dental implant placement in the anterior mandible can be serious issues. There is a potential for sublingual hematoma that could compromise the airway by pressing the tongue against the soft palate into the pharynx.

Anatomical consideration of ultrasonography-guided intraoral injection for temporal tendinitis.

Temporal tendinitis is characterized by acute inflammation often resulting from mechanical stress, such as repetitive jaw movements associated with jaw opening and closing and teeth clenching. Treatment for temporal tendinitis typically involves the administration of local anesthetic or corticosteroid injections. However, the complex anatomical structure of the coronoid process, to which the temporalis tendon attaches, located deep within the zygomatic arch, poses challenges for accurate injections. In this study, we aimed to establish guidelines for the safe and effective treatment of temporal tendinitis by using intraoral ultrasonography (US) to identify the anatomical structures surrounding the temporalis tendon and coronoid process. US was performed using an intraoral transducer on 58 volunteers without temporomandibular joint disease. The procedure involved placing the transducer below the occlusal plane of the maxillary second molar. Measurements were taken for the horizontal distance from the anterior border of the coronoid process, observed at the midpoint (MP) of the US images, and the depth of the coronoid process and temporalis muscle from the oral mucosa. The anterior border of the coronoid process was visualized on all US images and classified into three observed patterns at the MP: type A (anterior to the MP, 56.2%), type B (at the MP, 16.1%), and type C (posterior to the MP, 27.7%). The temporalis muscle was located at a mean depth of 3.12 ± 0.68 mm from the oral mucosa. The maxillary second molar is an intraoral landmark for visualizing the anterior border of the coronoid process. The new location information obtained using intraoral US could help identify the safest and most effective injection sites for the treatment of temporal tendinitis.

Three-dimensional Maxillofacial Morphology Measurements in Japanese Adults with Normal Occlusion.

Accurate orthodontic analysis and diagnosis based on anatomical landmarks is essential to the success of orthodontic treatment. Helical computed tomography (CT) has evolved markedly, and dentists can now quickly obtain 3-dimensional (3D) reconstruction data using this imaging modality. The planning of orthodontic treatment had traditionally been based on cephalometric analysis using 2D landmarks. This study aimed to collect 3D morphological data using CT images to establish new landmarks for analysis and diagnosis in orthodontic treatment. Twenty male and 20 female adult Japanese dry skulls with of normal occlusion were selected. The skulls were scanned using a multidetector helical CT system (SIEMENS, Volume Zoom Plus 4, Germany). Models were reconstructed using 3D measurement software (Simplant, Dentsply Sirona, Tokyo, Japan) and 45 landmarks determined. Three-dimensional measurement for a total of 30 items representing these landmarks was then performed. The results provided 3D standard values for maxillofacial morphology in adult Japanese individuals with normal occlusion. These measurement items should allow the disadvantages of 2D cephalometric analysis to be overcome.

Improvement in Tubulointerstitial Nephritis With Glucocorticoid Therapy in an Anorexia Nervosa Patient.

Anorexia nervosa is a psychiatric disorder that is often diagnosed in adolescents and young adults. Renal-related complications of anorexia nervosa include abnormal water metabolism, electrolyte abnormalities, and nephrocalcinosis, which may lead to irreversible renal damage. Furthermore, tubulointerstitial nephritis has been reported as a renal pathological feature of anorexia nervosa. Immunosuppressive therapy, such as with glucocorticoids, has been recommended for idiopathic interstitial nephritis treatment; however, the effectiveness of immunosuppressive therapy for interstitial nephritis in patients with anorexia nervosa remains unestablished. Here, we report a case of interstitial nephritis in a patient with anorexia nervosa whose renal function was successfully improved with glucocorticoid therapy. The patient was a 38-year-old woman who was referred for renal dysfunction (estimated glomerular filtration rate: 7.6 mL/min/1.73 m2). She had anorexia nervosa and repeated episodes of vomiting. Hypokalemia (K: 2.1 mEq/L) and metabolic alkalosis (HCO3-: 54.2 mEq/L) were observed. Fluid therapy and potassium supplementation did not improve renal function; therefore, a percutaneous renal biopsy was performed. The renal pathology results revealed interstitial fibrosis, inflammatory cell infiltration in the interstitium, and tubulitis, suggesting a diagnosis of tubulointerstitial nephritis. Glucocorticoid therapy improved the patient's renal function to an estimated glomerular filtration rate of 19.91 mL/min/1.73 m2, and the renal function remained stable thereafter. This case suggests that glucocorticoid therapy may be considered for the treatment of interstitial nephritis in patients with anorexia.

Effect of the Correction of Bilateral Differences in Masseter Muscle Functional Pressure on the Mandible of Growing Rats.

The objective of this study is to clarify the effect of restoring the lowered masticatory muscle functional pressure and correcting bilateral differences in masticatory muscle functional pressure on jawbone growth during growth and development with a quantitative evaluation of the changes in the micro/nanostructural characteristics of entheses. Male Wistar rats aged 4 weeks were divided into an experimental group injected with a botulinum toxin serotype A (BoNT/A) formulation to reduce muscle function (BTX group) and a control group (CTRL group). They were euthanised after 6, 8, 10, 12, and 16 weeks after measuring the difference between the midline of the upper and lower incisors. The mandibles were harvested for histological examination, second harmonic generation imaging, and the quantitative evaluation of biological apatite (BAp) crystal alignment. The midline difference decreased with age in weeks. In rats from 6 weeks after BoNT/A administration to 12 weeks after administration, the collagen fibre bundle diameter was significantly smaller in the BTX group; the difference between the two groups decreased with increasing age. BAp crystal alignment was significantly different on the x-axis and the y-axis on the BTX group from 6 weeks after BoNT/A administration to 10 weeks after administration. Asymmetry of mandibular bone formation caused by load imbalance during growth could be corrected by the adjustment of the function of the masseter muscle on either side.