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Background: Cerebro-costo-mandibular syndrome (CCMS) is a rare congenital syndrome consisting of the main features of micrognathia and posterior rib gaps. Due to multiple abnormalities, patients almost have difficulty breathing with upper airway obstruction, decreased thoracic capacity, spina bifida, and scoliosis. Case presentation: We describe a case of a late preterm neonate boy presenting with low Apgar, respiratory distress, and complicated orofacial anomalies that had a poor outcome. His radiographic findings showed mandibular hypoplasia (micrognathia), chest deformity, multiple posterior rib gap defects, and abnormal costotransverse articulation. Based on physical examination and radiologic findings, the diagnosis of CCMS confirmed for the patient. Conclusion: Physicians should always consider the diagnosis of CCMS in all infants with micrognathia and rib-gap defects. These infants need careful respiratory function monitoring. Early airway management improves growth and development. In addition, their physical and psychological development should be assessed regularly. [ABSTRACT FROM AUTHOR]

Objective: To investigate the subjective risk for obstructive sleep apnea (OSA) in adolescents and young adults with isolated Robin sequence (IRS). Additionally, to investigate the association of OSA risk with respiratory signs/symptoms, and retrognathia. Design: Prospective, observational, and cross-sectional study. Setting: Tertiary reference hospital for the rehabilitation of craniofacial anomalies. Participants: Adolescents and adults (n = 30) with IRS were clinically evaluated and screened through the Berlin Questionnaire (BQ) and Respiratory Symptoms Questionnaire. The maxillomandibular relationship was assessed on lateral cephalograms of those that reached skeletal maturity (n = 13). Polysomnography (PSG) was performed in a subgroup of 4 individuals. Results: The mean age of the sample was 18.2 (±3.4) years, 17 (56.7%) were adolescents (14-19 years), and 16 were (53.3%) female, all presented a repaired cleft palate. Clinical Parameters: Systemic arterial pressure (118.0 ± 4.1/76.3 ± 4.9 mmHg), body mass index (BMI) (20.9 ± 2.8 kg/m2), neck (33.2 ± 2.3 cm), and waist circumferences (72.0 ± 5.8 cm) were within normal ranges. A skeletal class I pattern was observed in 61.5% of the participants while a class II was seen in 15.4% of them. A high risk for OSA was detected in 16.7%, and it was associated with nasal obstruction, snoring and drowsiness, and a skeletal class II pattern (P ≤.05). One patient presented with mild OSA (apnea–hypopnea index [AHI] = 10.1 events/hour) at the PSG exam. Conclusions: A high risk for OSA can be observed with a moderate frequency among adolescents and young adults with IRS, especially among those who are concurrently suffering from nasal obstruction, snoring and retrognathia. [ABSTRACT FROM AUTHOR]

Cherubism is a rare disorder characterized by proliferative fibro-osseous lesions that result in bilateral bony hyperplasia of the face. Management varies based on symptom severity and includes longitudinal follow-up, pharmacotherapy, and/or surgical debulking. Off-label treatment with denosumab, a human monoclonal antibody that binds RANKL and inhibits osteoclast function to reduce bone resorption, can be beneficial in suppressing the proliferation of bone to minimize the need for surgery and to control postoperative reproliferation. Close follow-up is needed to maintain appropriate electrolyte levels. The present case demonstrates the achievement of symptomatic control with denosumab in a child with severe refractory cherubism. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). Patients: A total of 18 unoperated patients with scaphocephaly (age = 5.2 ± 1.1m)—6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 ± 1.5m)—and 6 controls (age = 6.7 ± 2.5m). Main Outcome Measures: 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). Results: A moderate correlation was found between FB and anterior prominence (r = 0.56, P <.01) and take-off angle (r = − 0.57, P <.01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P <.01) and LPV (r = 0.43, P <.01). OHS showed strong correlation with CI (r = − 0.68, P <.01) and TI (r = 0.63, P <.01). SSM Mode 1 correlated with OHS (r = 0.66, p <.01) while Mode 3 correlated with FB (r = − 0.58, P <.01). Conclusions: Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM. [ABSTRACT FROM AUTHOR]

Objective: Functional appliances are used in orthodontics to bring about correction of mandibular retrognathism by forward positioning and eventually remodeling the condyle- glenoid fossa to retain this new position. Research has shown that these appliances have a significant effect on pharyngeal airway of patients. The aim of this study was to evaluate changes in volume and minimum constriction area in the pharyngeal airway using CBCT imaging after correction of mandibular retrognathism with an Advansync2 Class II corrector. Methods: This single-center study consisted of 20 Class II patients (mean age 14.8 years) who required correction of mandibular retrognathism. The patients were treated with the Advansync2 Class II corrector for an average of 26 weeks. CBCT records were taken at T0 (beginning of treatment) and T1 (end of functional phase). The airway was segmented into lower nasopharynx, velopharynx and oropharynx and analyzed for changes in partial volume, total volume, and minimum area using a CBCT software [NewTom 3GTM (Newtom- Cefla S.C., Verona, Italy)]. Results: The partial and total volumes were significantly larger at T1 than at T0 (p =.003,.001). In addition, minimum area also improved in each part of the airway (p =.005,.022,.001). Conclusion: The Advansync2 fixed functional appliance can be used in Class II patients requiring improvement in their airway dimensions. However, additional long-term studies are recommended to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Skeletal nongrowing class II patients with retrognathic mandible are often at risk of developing obstructive sleep apnea (OSA). This skeletal discrepancy, when severe enough, is often addressed by surgical mandibular advancement which not only achieves aesthetics, structural balance, and functional efficiency but also improves the airway function. Objective: The aim of the study was to evaluate the effectiveness of surgical mandibular advancement on airway dimensions, in nongrowing skeletal class II patients with mandibular retrognathism associated with OSA. Materials and Methods: The sample consisted of 8 patients with skeletal class II due to retrognathic mandible associated with OSA. Screening was done with functional outcomes of sleep questionnaire (FOSQ) score and confirmed with polysomnography. Pretreatment and posttreatment airway dimensions/volume were assessed and calculated on cone beam computed tomography (CBCT). Three months post surgery, oxygen saturation was recorded. Results: A statistically significant improvement in mean oxygen saturation level was observed from 87.62 ± 7.70 to 97.75 ± 0.46 and mean increase in airway volume was from 48.60 ± 7.17 to 69.48 ± 26.22. The smallest cross section increased from 137 ± 74.37 to 253.75 ± 76.67. Anteroposterior dimensions increased significantly from 6.17 ± 1.78 to 9.33 ± 2.07 and transversed from 24.56 ± 6.41 to 30.14 ± 3.35. FOSQ score improved from 9.37 ± 2.61 to 15.25 ± 0.88. Conclusion: Surgical mandibular advancement is an effective treatment option in improving airway dimensions in nongrowing skeletal class II patients with mandibular retrognathism associated with OSA. [ABSTRACT FROM AUTHOR]

Congenital fusion of the jaws (syngnathia) is a rare facial malformation with an unknown etiology. This disease may vary in severity with adhesion of soft tissue and bony fusion. It can be anterior fusion, unilateral or bilateral fusion, and complete fusion. The main problem of these patients is the difficulty of airway maintenance and feeding, and the most common postoperative complication is the relapse of bony fusion. Here, we report a young male patient with bony syngnathia, involving bilateral fusion of the ascending ramus and body of the mandible with the maxillary complex. We performed bone isolation by computer-assisted preoperative planning and used an insertional temporalis flap to fix the wound surface to prevent refusion of bone. [ABSTRACT FROM AUTHOR]

Aim: Some obstructive sleep apnea (OSA) patients may have mandibular retrognathia (ANB > 4.7° and SNB < 76.2°). Currently, there are no studies that have compared the effectiveness of continuous positive airway pressure (CPAP) versus mandibular advancement device (MAD) in severe OSA patients with mandibular retrognathia. We explored the efficacy of CPAP versus MAD for the treatment of severe OSA patients with mandibular retrognathia. Methods: A total of 105 patients were enrolled. Outcomes were assessed by using polysomnography, Epworth Sleepiness Scale (ESS), Snore Scale (SS), Self-rating Anxiety Scale (SAS), and compliance, before treatment and after 6 and 12 months of treatment. Results: Continuous positive airway pressure was superior to MAD in improving polysomnographic outcomes and SS score, but reported compliance was higher on MAD. There is no significant difference between the 2 treatments in terms of ESS score and SAS score. Obstructive sleep apnea patients with mandibular retrognathia showed greater improvement than those without mandibular retrognathia in terms of apnea-hypopnea index and oxygen desaturation index after MAD. Conclusion: Continuous positive airway pressure and MAD are both effective in treating severe OSA patients with mandibular retrognathia. Mandibular advancement device is a good alternative to CPAP in severe OSA patients with mandibular retrognathia. Mandibular advancement device is more effective in treating OSA patients with mandibular retrognathia than those without. Trial registration: ChiCTR2000032541. [ABSTRACT FROM AUTHOR]

Accurate segmentation of the jaw (i.e., mandible and maxilla) and the teeth in cone beam computed tomography (CBCT) scans is essential for orthodontic diagnosis and treatment planning. Although various (semi)automated methods have been proposed to segment the jaw or the teeth, there is still a lack of fully automated segmentation methods that can simultaneously segment both anatomic structures in CBCT scans (i.e., multiclass segmentation). In this study, we aimed to train and validate a mixed-scale dense (MS-D) convolutional neural network for multiclass segmentation of the jaw, the teeth, and the background in CBCT scans. Thirty CBCT scans were obtained from patients who had undergone orthodontic treatment. Gold standard segmentation labels were manually created by 4 dentists. As a benchmark, we also evaluated MS-D networks that segmented the jaw or the teeth (i.e., binary segmentation). All segmented CBCT scans were converted to virtual 3-dimensional (3D) models. The segmentation performance of all trained MS-D networks was assessed by the Dice similarity coefficient and surface deviation. The CBCT scans segmented by the MS-D network demonstrated a large overlap with the gold standard segmentations (Dice similarity coefficient: 0.934 ± 0.019, jaw; 0.945 ± 0.021, teeth). The MS-D network–based 3D models of the jaw and the teeth showed minor surface deviations when compared with the corresponding gold standard 3D models (0.390 ± 0.093 mm, jaw; 0.204 ± 0.061 mm, teeth). The MS-D network took approximately 25 s to segment 1 CBCT scan, whereas manual segmentation took about 5 h. This study showed that multiclass segmentation of jaw and teeth was accurate and its performance was comparable to binary segmentation. The MS-D network trained for multiclass segmentation would therefore make patient-specific orthodontic treatment more feasible by strongly reducing the time required to segment multiple anatomic structures in CBCT scans. [ABSTRACT FROM AUTHOR]

Robin sequence (RS) has been reported in association with single gene disorders and chromosomal abnormalities; however, it has not previously been described in connection with chromosome 1q21 microduplication. We present the first known case of a neonate diagnosed with chromosome 1q21.1 microduplication syndrome and RS requiring surgical airway intervention. This case demonstrates the value of genetic testing in cases of RS presenting with other congenital anomalies. [ABSTRACT FROM AUTHOR]

This case series is a follow-up report focusing on dental and facial characteristics in patients with a rare microdeletion in chromosome 14q22.1-q22.2. Usually, these patients have severe ocular, brain, and digital abnormalities. However, this case series shows that clinical presentation can be mild. Four relatives spanning 3 generations were diagnosed with a familial autosomal dominant 2.79 Mb microdeletion in chromosome 14q22.1-q22.2. Genetic screening was done by the Bacterial Artificial Chromosome array-comparative genome hybridization and was confirmed by the fluorescence in situ hybridization technique. Dental and craniofacial data were collected from medical files, clinical examinations, clinical photos, panoramic and cephalometric radiographs, and dental casts. Written informed consent for scientific use was obtained for all family members. No larger syndrome could be identified. All cases had similar facial red flag characteristics, consisting of a long face with retrognathia and open mouth relation, associated oral clefts in varying degrees, depressed nasal bridge, delayed tooth development, hypertelorism, and low-set angular ears. The dental casts showed a distal molar occlusion and a lack of space in the dental arches. Developmental delay was noted together with limb defects such as poly- and syndactyly. Microphthalmia and hearing loss were present in the most severe cases. This rare congenital disorder, associated with facial dysmorphia, oral clefts, and tooth agenesis, can remain undiagnosed until adulthood. A family history of short stature, developmental delay, poly- or syndactyly, and micropthalmia are suggestive features. Similar reports help to raise awareness among dental practitioners, leading to an early genetic diagnosis. [ABSTRACT FROM AUTHOR]

Skeletally mature patients with cleft lip and palate commonly present with skeletofacial deformities characterized by varying degrees of intrinsic and acquired dentoskeletal and soft tissue abnormalities. These abnormalities are associated with scarring from previous surgeries and the asymmetric midline and facial contour that impose challenges for adequate reconstruction. These patients frequently require 2-jaw orthognathic surgery to improve occlusal function and for correction of facial deformities. In this article, we have detailed a 3-dimensional computer-assisted single-splint 2-jaw orthognathic surgery technique as a surgical approach for cleft skeletofacial reconstruction, allowing for the surgery to be tailored according to the specific needs and requests of the patients. Further, we have addressed the multidimensionality and specificities of cleft treatment, the wide versatility, adaptability, and applicability of this technique, and the patient-centered rationale for the adoption of this method. [ABSTRACT FROM AUTHOR]

Vertical malocclusion is a developmental condition, resulting from complex interactions among multiple etiological factors during the growth period. As a tricky dentofacial deformity clinically, long-face (LF) morphology is characterized by excessive vertical facial growth with severe disarrangement of jaws and teeth. Since the improvement of LF patients on facial profile and occlusion is often difficult and lacks long-term stability, it becomes important to unravel the etiology of LF pattern formation for early prevention and treatment. In the current studies, we identified a transgenic mouse model that exhibited a dysplastic coronoid process and LF morphology. Although the mutant mice exhibited jaw structures and occlusion comparable to controls at birth, they all acquired typical LF morphology with anterior open bite during postnatal growth, resembling clinical features of the selected skeletal class III patients. Since the coronoid process provides an insertion site for the temporalis attachment, we examined the initial development and differentiation of the temporalis and found identical results in both control and mutant mice before E17.5 when the temporal muscle makes attachment to the coronoid process. However, thereafter, we observed altered orientation and reduced size of the cross-sectional area of the temporalis in mutant mice, which persisted to the weaning stage. Biomechanical analysis and simulation modeling further support the idea that altered morphology of the coronoid process may impair the efficiency of the vertical temporalis contraction and appears to correlate with LF formation. Consistently, we present evidence that a dysplastic mandibular coronoid process was also seen in some human patients with skeletal III LF morphology. Taken together, the results presented in this study establish an association of the craniofacial bony structures with vertical patterning, which will have implications in earlier prediction for clinical precaution and intervention. [ABSTRACT FROM AUTHOR]

In clinical dentistry practice, supplemental bone surgery or jawbone defect after tooth extraction must be assisted by a bone-filling material. Cobalt-substituted hydroxyapatite (COHA) effectively promotes bone cell growth, reduces the inflammatory response, and is an antibacterial agent. COHA can therefore be used as an alveolar bone-filling material or guided bone regeneration membrane. Meanwhile, COHA can be used in magnetic resonance imaging (MRI) with negative contrast agents and targeting materials without causing metal interference with the image. Hence, COHA has received increasing amounts of attention in recent years. However, the influence of different cobalt precursors on the synthesized COHA is still unknown. Therefore, COHA synthesized from 3 cobalt precursors (cobalt chloride, cobalt nitrate, and cobalt sulfate) was compared in this study. The results show that COHA synthesized by the precursor with the smallest anion radius, cobalt chloride, has a larger particle size (239 nm) and a higher cobalt ion substitution rate (15.6%). When the cobalt ion substitution rate increases, the MRI has a stronger contrast. Bioactivity data indicate that COHAC is more susceptible to degradation and therefore releases more cobalt ions to contribute to the differentiation of bone cells. Based on these studies, COHAC prepared with the cobalt chloride precursor has a higher cobalt ion substitution rate, faster degradation rate, better image contrast, and better bioactivity. It is therefore the preferred choice of bone-filling material for alveolar bone regeneration. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss the reasons why only 15% of adolescents in the U.S. with cleft jaw deformity underwent reconstruction. Topics include the number of people with congenital clefting of the lip and palate (CL/P) in the U.S. and around the world, the guidelines from the American Cleft Palate-Craniofacial Association (ACPA) for infants with cleft palate, and the use of the National Inpatient Sampling (NIS) to study cleft orthognathic surgery volumes in the U.S.

In the context of a case presentation of a 16-year-old girl treated for retrognathia associated with Freeman-Burian syndrome (FBS), importance of early orthodontic evaluation and unique problems posed by FBS are discussed. Freeman-Burian syndrome universally presents limited oral access and risk of pulmonary complications, making immaculate oral health-care arduous but mandatory. With early identification and conscientious planning, satisfactory orthodontic and overall health outcomes can be achieved. Sella turcica bridging, when presenting in FBS in the absence of endocrine pathology, may be related to the underlying myopathy of FBS. [ABSTRACT FROM AUTHOR]

Patients with cleft lip and palate sometimes have a retruded maxilla. Here, we describe the case of a young man in whom crowding of the maxillary teeth and an anteroposterior discrepancy of the maxilla were resolved by premaxillary distraction osteogenesis (DO) using 3 individual intraoral distractors. Our experience in this patient confirms that premaxillary DO with 3 intraoral distractors and preoperative simulation can achieve stable maxillary advancement and arch expansion without impairing velopharyngeal incompetence. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the impact of maxillary advancement (Le Fort I osteotomy) on consonant proficiency in patients with cleft lip and palate (CLP) and explores how these patients and lay people perceive their speech 1 year post Le Fort I osteotomy. Design: Retrospective group study before and after treatment. Participants: All patients with CLP who had undergone Le Fort I osteotomy for maxillary retrognathia between 2007 and 2010 at Karolinska University Hospital, Sweden (n = 21). Six patients were excluded due to additional malformations and missing data. Two experienced speech and language pathologists assessed consonant proficiency, and speech accuracy was determined by lay listeners from pre- and postoperative standardized audio recordings. The patients' satisfaction with speech postoperatively was collected from medical records. Main Outcome Measures: Percentage of oral consonants correct and acoustic analysis of /s/, lay listeners' opinion, and patients' satisfaction with speech. Results: One year postoperation, 11 of the 15 patients had improved articulation, especially on the /s/-sound, without speech intervention. The mean percentage of oral consonants correct before treatment (82%) was significantly improved later (95%; P > .01). This assessment was supported by the patients' satisfaction with speech. However, lay listeners' opinion on accuracy was inconsistent. Length of maxillary advancement or change in occlusion did not correlate with change in articulation. Conclusion: Maxillary advancement performed to normalize occlusion and facial profile improved consonant proficiency in patients with CLP 1 year postoperation. Lay listeners' and patients' perceptions of speech need further exploration. [ABSTRACT FROM AUTHOR]

Mandibular prognathism (MP) is regarded as a craniofacial deformity resulting from the combined effects of environmental and genetic factors, while the genetically predetermined component is considered to play an important role to develop MP. Although linkage and association studies for MP have identified multiple strongly associated regions and genes, the causal genes and variants responsible for the deformity remain largely undetermined. To address this, we performed targeted sequencing of 396 genes selected from previous studies as well as genes and pathways related with craniofacial development as primary candidates in 199 MP cases and 197 controls and carried out a series of statistical and functional analyses. A nonsynonymous common variant of MYO1H rs3825393, C>T, p.Pro1001Leu, was identified to be significantly associated with MP. During zebrafish embryologic development, expression of MYO1H orthologous genes were detected at mandibular jaw. Furthermore, jaw cartilage defects were observed in zebrafish knockdown models. Collectively, these data demonstrate that MYO1H is required for proper jaw growth and contributes to MP pathogenesis, expanding our knowledge of the genetic basis of MP. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to quantitatively assess dentoalveolar and skeletal compensations in patients with untreated unilateral cleft lip and palate (UCLP). We hypothesized that there are significant skeletal and dental adaptations in UCLP cases compared to a comparison maxillary crossbite group. Design: A convenience retrospective sample of 30 patients with UCLP and a comparison group of 30 patients with unilateral posterior crossbite without CLP. Cone-beam computed tomography scans (CBCTs) were used to evaluate dental and skeletal compensations. In addition, alveolar bone thickness was measured at 2-mm increments in mesiodistal and faciolingual cross-sectional views along the long axis of the central incisors. Alveolar bone height was measured, and the percentage of root length supported by bone was calculated. Results: Compensations for unilateral cleft lip and palate were restricted to the cleft site and adjacent structures. Dental compensations include alteration in the position of cleft-adjacent maxillary incisors and maxillary canines. No gross skeletal compensations were found. Alveolar support of cleft adjacent incisors was similar to controls except for measurements in the most coronal and apical regions. The cleft group contralateral incisors exhibited buttressing effects and had significantly higher alveolar thickness in the coronal half of the tooth. There was less (5%) alveolar coverage of the cleft-facing aspect of the central incisor root than all other incisors. Conclusion: The bone adaptation to the presence of a cleft was localized in the vicinity of the cleft, and adaptations in the mandible were not apparent. [ABSTRACT FROM AUTHOR]

Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3ach/SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3ach mice was significantly ameliorated in Fgfr3ach/SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic potential of CNP for treatment of midfacial hypoplasia and foramen magnum stenosis in achondroplasia. [ABSTRACT FROM AUTHOR]

c-Fos homozygous mice lack osteoclasts with a failure of the teeth to erupt and with an arrest of root development. Here, we characterize the defects associated with the failure in root development and the loss of the tooth-bone interface, and we investigate the underlying causes. We show that, while homozygous c-Fos mice have no multinucleated osteoclasts, heterozygous mice have a reduction in the number of osteoclasts with a reduction in the tooth-bone interface during development and subtle skeletal defects postnatally. In the homozygous mutants bone is found to penetrate the tooth, particularly at the apical end, physically disrupting the root forming HERS (Hertwig's epithelial root sheath) cells. The cells of the HERS continue to proliferate but cannot extend downward due to the presence of bone, leading to a loss of root formation. Tooth germ culture showed that the developing tooth invaded the static bone in mutant tissue, rather than the bone encroaching on the tooth. Although c-Fos has been shown to be expressed in developing teeth, the defect in maintenance of the tooth-bone interface appears to be driven solely by the lack of osteoclasts, as this defect can be rescued in the presence of donor osteoclasts. The rescue suggests that signals from the tooth recruit osteoclasts to clear the bone from around the tooth, allowing the tooth to grow, form roots, and later erupt. [ABSTRACT FROM AUTHOR]

Class III malocclusion has been the subject of interest in many investigations because of the challenges in its treatment. The skeletal manifestation can be due to mandibular anterior positioning (prognathism) or growth excess (macrognathia), maxillary posterior positioning (retrognathism) or growth deficiency (micrognathia), or a combination of mandibular and maxillary discrepancies. A 15-year-old Asian with a skeletal Class III malocclusion and a severe anterior crossbite was treated with Alt-RAMEC protocol designed to loosen the sutures that connect the maxilla to the surrounding bones via rapid expansion and contraction on an alternating weekly basis and facemask therapy. An Angle Class I molar relationship was achieved with canine protected occlusion and incisal guidance. A wrap-around retainer was placed on the maxillary arch and a lingual bonded retainer on the mandibular arch. Treatment time was 30 months. [ABSTRACT FROM AUTHOR]

Objective: This study has investigated two new cephalometric variables, the Pi angle and Pi linear in the evaluation of anteroposterior skeletal discrepancy. Design: Retrospective cross-sectional study Setting: Manipal College of Dental Sciences, Manipal, India Subjects and method: A sample of 155 subjects (mean age 19.7 years) were subdivided into skeletal class I, II and III groups based upon ANB angle. Descriptive data were calculated for each variable and group. Receiver operating characteristics curves were used to examine sensitivity and specificity of the Pi angle in the discrimination between different skeletal groups. Correlation coefficients were obtained for each of the parameters to compare their relationship with other parameters in the class I group. Coefficient of determination, regression coefficient, regression equation and standard error of estimate were also calculated from the parameters showing significant correlation with the Pi angle. Results: Mean values for the Pi angle in skeletal class I, II and III subjects were 3.40 ( + 2.04), 8.94 (±3.16) and -3.57 (± 1.61) degrees, respectively. For the Pi linear they were 3.40 (±2.20), 8.90 (±3.56) and -3.30 (±2.30) mm for class I, II and III subjects, respectively. Receiver operating characteristic curves showed that a Pi angle greater than 5 degrees had 89% sensitivity and 82% specificity for discriminating a skeletal class II group from class I. A Pi angle of less than 1.3 degrees had 100% sensitivity and 84% specificity in discriminating skeletal class III groups from class I. The overall accuracy for discriminating class II groups from class I was 85% and for class III from class I, 90%. Thus, a cut-off point between class I and II groups could be considered a Pi angle of approximately 5 degrees and between class I and class III, approximately 1.3 degrees. There were no statistically significant correlations found between Pi angle and ANB (0.07), Beta angle (-0.04) and WITS analysis (0.19). The highest level of correlation was obtained for the Pi angle and Pi linear (0.96). Conclusion: The anglar and linear components of the Pi analysis are a suitable method for assessing anteroposterior jaw discrepancy in daily clinical practice. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI) can be used to evaluate changes that accompany skeletal muscle contraction. Purpose: To investigate whether jaw opening or closure affect the diffusion parameters of the masseter muscles (MMs). Material and Methods: Eleven healthy volunteers were evaluated. Diffusion-tensor images were acquired to obtain the primary (λ1), secondary (λ2), and tertiary eigenvalues (λ3). We estimated these parameters at three different locations: at the level of the mandibular notch for the superior site, the level of the mandibular foramen for the middle site, and the root apex of the mandibular molars for the inferior site. Results: Both λ2 and λ3 during jaw opening were significantly lower than that at rest at the superior (P = 0.006, P, 0.0001, respectively) and middle site (P = 0.004, P = 0.0001, respectively); however, the change in l1 was not significant. At the lower site, no parameter was significantly different at rest and during jaw opening. There was no significant difference in T2 between at rest (40.3±4.4 ms) and during jaw opening (39.2±2.7 ms; P = 0.12). The changes induced by jaw closure were marked at the inferior site. In the middle and inferior sites, the three eigenvalues were increased by jaw closure, and the changes in λ1 (P = 0.0145, P = 0.0107, respectively) and l2 (P = 0.0003, P = 0.0001) were significant (especially λ2). Conclusion: The eigenvalues for diffusion of the MM were sensitive to jaw position. The recruitment of muscle fibers, specific to jaw position, reflects the differences in changes in muscle diffusion parameters. [ABSTRACT FROM AUTHOR]

Bisphosphonate use has increased in veterinary medicine over the last decade. During this time, bisphosphonate related osteonecrosis of the jaws (BRONJ) in human patients has been identi-fied. Only recently was a dog model for BRONJ developedfor human oral surgery and medicine. Veterinary patients treated with bisphosphonates may be at an increased risk for BRONJ. There has been little, to no, investigation of potential long term side-effects of bisphosphonate use in veterinary patients; potential sequelae are unknown. The history of bisphosphonates, their use, and BRONJ in veterinary patients are discussed. [ABSTRACT FROM AUTHOR]

Objectives: We wished to develop an ultrasound cephalometric analysis, particularly of the antero-posterior jaw relationship, to increase the accuracy of prenatal diagnosis of retrognathism during the routine midterm test. Methods: Anatomical cephalometric analysis was performed in 18 formalinfixed human fetuses (between 16 and 39 gestational weeks), and ultrasound cephalometry was prospectively carried out in 52 pregnant women (21 to 25 gestational weeks). The same landmarks were used in the anatomical and ultrasound median sagittal planes for comparison. Four cephalometric angles were measured relative to the anterior cranial base: alveolar projection of the maxilla and the mandible, chin projection, and facial angle. The antero-posterior jaw discrepancy was calculated. Results: The projection of the maxilla was similar in the two cephalometric analyses (IC [23.39, 0.23]), whereas the values of the projection of the mandible were lower in the ultrasound sample. The slope of the regression line of the antero-posterior jaw discrepancy on fetuses' age did not show significant differences (IC [20.05, 1.54]) between anatomical and ultrasound cephalometry, although a difference of 3.23° ± 0.78° (IC [1.69, 4.77]) was observed. Despite this variability, the projections of mandible and chin were well determined by the projection of the maxilla both in the anatomical and ultrasound sample. Conclusions: Cephalometric analysis by prenatal sonography can be performed to study the antero-posterior jaw relationship. We think that this procedure could be useful to improve prenatal diagnosis of retrognathism in high-risk pregnancies. Further studies should address the reproducibility and accuracy of such analysis. [ABSTRACT FROM AUTHOR]

Objective: A new oral appliance to treat obstructive sleep apnea in infants with Pierre Robin sequence has recently been shown to be superior to a sham procedure. We now investigate safety and long-term effects of this appliance on obstructive sleep apnea in infants with Pierre Robin sequence. Design: Case series with repetitive follow-up examinations. Setting: Tertiary neonatal intensive care unit at the University Children's Hospital Tuebingen, Germany. Patients: Fifteen infants (11 girls and four boys; median age, 5 days) with Pierre Robin sequence and obstructive sleep apnea (i.e., mixed-obstructiveapnea index 3). Intervention: A custom-made intraoral appliance with velar extension was used continuously in situ from admission until 3 months after hospital discharge. Main Outcome Measure: The mixed-obstructive-apnea index was determined prior to the intervention at admission, at discharge, and 3 months later using polygraphic sleep studies. The geometric mean of the mixed-obstructive-apnea index and its 95% confidence interval were calculated. Results: Compared with admission (mean, 17.2; 95% confidence interval, 11.1-26.7), there was a significant decrease in the mixed-obstructive-apnea index to discharge (mean, 3.8; 95% confidence interval, 2.2-6.6) and 3 months later (mean, 1.2; 95% confidence interval, 0.7-2.2; p value .001). No severe adverse events occurred. Conclusions: This oral appliance was safe and appears to treat obstructive sleep apnea effectively in infants with Pierre Robin sequence. [ABSTRACT FROM AUTHOR]

Exposed necrotic alveolar bone is a hallmark of bisphosphonate-related osteonecrosis of the jaw. However, it is unknown whether zoledronate causes soft-tissue damage via adverse actions toward periodontal fibroblasts. We therefore examined whether zoledronate causes a cytotoxic response in fibroblasts isolated from the gingiva and the periodontal ligament. We report that micromolar concentrations of zoledronate and serum-free conditions decreased cell activity, as measured by assays for formazan formation, proliferation, and protein synthesis. Under these conditions, periodontal fibroblasts underwent apoptosis and necrosis, as indicated by cleavage of PARP and membrane disruption, respectively. However, these adverse effects of zoledronate were mitigated by the presence of serum. Moreover, zoledronate bound to calcium phosphate failed to reduce cell activity. Analysis of these data suggests that the cytotoxic responses of periodontal fibroblasts require high concentrations of zoledronate and depend on the in vitro experimental conditions. Whether these findings translate into soft-tissue damage will require further investigation. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that an injured condyle during adolescence is a causative factor for reduced mandibular growth and resulting asymmetry of the mandible. The aim of this study was to examine the nature of mandibular growth after unilateral condylectomy and to elucidate the effects of mandibular advancement. Sixty growing mice were subjected to unilateral condylectomy, and then one-half of them underwent treatment with a functional appliance. After 4 wks, a unilateral condylectomy produced reduced growth of the mandible and a subsequent lateral shift to the affected side. However, reduced growth and a lateral shift of the mandible were eliminated by a functional appliance, and prominent regeneration of the condyle was also demonstrated. It was shown that mandibular advancement provides for the regeneration of cartilaginous tissues on injured condyles and recovery of reduced mandibular growth, leading to correction of the lateral shift of the mandible. [ABSTRACT FROM AUTHOR]

Despite the prevalence of craniofacial disorders, the genetic contribution remains poorly understood. Class III malocclusion represents a specific craniofacial problem that can be handicapping, both functionally and socially. We hypothesized that the Class III phenotype is genetically linked to specific loci that regulate maxillary or mandibular growth. To determine the region linked to the Class III phenotype in four Hispanic families, we performed a genome-wide scan and linkage analysis using 500 microsatellite markers. Pedigree and linkage analyses revealed that the Class III phenotype (primarily maxillary deficiency) segregates in an autosomal-dominant manner, and that 5 loci (1p22.1, 3q26.2, 11q22, 12q13.13, and 12q23) are suggestive of linkage. Candidate genes within the 12q23 region (ZLR=2.93) include IGF1, HOXC, and COL2A1. Chromosome 1 results (ZLR=2.92) were similar to those reported previously in an Asian cohort with mandibular prognathism, suggesting that a common upstream genetic element may be responsible for both mandibular prognathism and maxillary deficiency. [ABSTRACT FROM AUTHOR]

Objective: Pierre Robin sequence (PRS) involves the triad of micrognathia, glossoptosis, and cleft palate. Neonates with PRS suffer from two problems--airway obstruction and feeding difficulties--but the severity of these problems varies greatly. The resultant varying definitions of PRS have resulted in inconsistent management of those babies given the diagnosis. This in turn makes comparison of published data and communication between clinicians difficult. Historically at Birmingham Children's Hospital, the cleft team only identified babies presenting with cleft palate and severe respiratory distress as ''true'' PRS. These babies were admitted to the high-dependency neonatal ward for airway assessment and management. Babies with a mild degree of respiratory obstruction but who were managed successfully at home were not classified as having PRS despite needing considerable input from the Cleft Clinical Nurse Specialist. A system of classifying babies with PRS based on the severity of their symptoms and signs and treatment required was therefore devised and is described in this paper. Results: Since implementation, this new classification of babies with PRS into three grades has clarified care pathwaysand enhanced communication between the Cleft Clinical Nurse Specialists and other health professionals involved with the care of these babies. [ABSTRACT FROM AUTHOR]

The literature contains a number of case reports on successful orthopedic treatment of hemifacial microsomia (HFM), with surprising changes in the morphology of the condyles. All of these reports regard patients who have substantially no soft tissue involvement but only severe mandibular ramus and condyle deformities. A number of cases with unexpectedly similar phenotypes diagnosed as HFM are described. The authors suggest that it is possible that all of these cases might be misdiagnosed traumatic injuries of the condyle, which present a normal functional matrix and, therefore, with growth and with the help of functional stimulation, tend to grow toward the original symmetry. [ABSTRACT FROM AUTHOR]

Findings that jaw-opening/-closing relies on both mandibular and head movements suggest that jaw and neck muscles are jointly activated in jaw function. This study tested the hypothesis that rhythmic jaw activities involve an active repositioning of the head, and that head fixation can impair jaw function. Concomitant mandibular and head-neck movements were recorded during rhythmic jaw activities in 12 healthy adults, with and without fixation of the head. In four participants, the movement recording was combined with simultaneous registration of myoelectric activity in jaw and neck muscles. The results showed neck muscle activity during jaw opening with and without head fixation. Notably, head fixation led to reduced mandibular movements and shorter duration of jaw-opening/-closing cycles. The findings suggest recruitment of neck muscles in jaw activities, and that head fixation can impair jaw function. The results underline the jaw and neck neuromuscular relationship in jaw function. [ABSTRACT FROM AUTHOR]

The article presents a case of an asymmetric mandibular dysplasia in a newborn due extrinsic compression of the jaw by the infant's shoulder. Examination revealed a severe right-sided head deviation that had been present for an extended period of time in utero. Also, there was lack of subcutaneous tissue and a prominent sternocleidomastoid muscle. Findings suggest that mandibular asymmetry is usually the result of the shoulder being raised up under the mandible as a consequence of breech of prolonged vertex presentation.

Objective: To record maxillary and mandibular displacement with articular growth and in response to bimaxillary surgical repositioning in patients with hemifacial microsomia (HFM) and to observe ipsilateral corpus/ramus growth in severely affected children. Design: Prospective roentgen stereometric analysis (mean age 7 years 10 months to 18 years 0 months) and retrospective profile and panoramic roentgenograms. Mean total observation period was 9 years 1 month. Setting: Department of Plastic and Reconstructive Surgery, Malmö University Hospital (Malmö, Sweden). Patients: Twenty-one patients consecutively diagnosed from 1976 through 1988 with HMF, five of whom had bimaxillary surgery. Interventions: Surgery was performed at the Department of Plastic and Reconstructive Surgery. Implants were inserted at the initial reconstructive surgical procedure under general anesthesia. Roentgen examinations were performed in connection with continued clinical evaluations and treatment. Main Outcome Measures: Stereo roentgenograms were digitized at the Department of Orthopedic Surgery, Malmö University Hospital (Malmö, Sweden). Results: Displacement of the jaws with articular growth and in response to bimaxillary surgical repositioning varied inter-individually with no apparent common pattern. Relapse displacement occurred several years after bimaxillary surgery. Mandibular growth changes were found in the corpus/ramus area and alveolar process on the affected side. Conclusions: A marked interindividual variability of maxillary and mandibular displacement indicates that the relevance of statistical analysis of HFM growth data may be questioned. We would suggest that precise and accurate longitudinal recordings of growth and response to surgery in individual HFM patients be more appropriate. [ABSTRACT FROM AUTHOR]

Objective: To give an epidemiological description of the clinical entity given the name Pierre Robin sequence, defined by retro- and micrognathia, cleft palate, and respiratory distress and describe other malformations and possible intrauterine impairment. Methods: Using the inclusion criteria of micrognathia, cleft palate, and neonatal respiratory distress, a retrospective population-based study of all Danish live births during 1990 through 1999 were carried out. We found 50 children, 25 boys and 25 girls, fulfilling the inclusion criteria, giving an incidence of 1 in 14,000 live births. Results: Two-thirds (n = 33) of the children had the classical U-shaped cleft palate. More than one-third (n = 19) had one or several other malformations, and in five patients the triad of Pierre Robin was a minor feature of a complex syndrome. The most common noncomplex syndrome was the Stickler syndrome found in 6 of the 50 patients. More than one-fourth (n = 17) had some kind of intrauterine impairment, with no specific obstetric diagnosis predominant. Consistent with this, the average birth weight was well below normal. Conclusions: Several authors have stated that the triad of Pierre Robin is not a nosological entity, in that it has diverse etiology and diverse pathogenesis. We conclude that the triad of Pierre Robin still can be regarded as a clinical entity, readily defined at birth, experiencing the same neonatal problems in varying degrees and hence the possibility of designing treatment protocols for later scientific evaluation. [ABSTRACT FROM AUTHOR]

The etiology of mandibular prognathism has been attributed to various genetic inheritance patterns and some environmental factors. The variation in inheritance patterns can be partly due to the use of different statistical approaches in the respective studies. The objective of this study was to investigate the role of genetic influences in the etiology of this trait. We performed segregation analysis on 37 families of patients currently being treated for mandibular prognathism. Mandibular prognathism was treated as a qualitative trait, with cephalometric radiographs, dental models, and photographs used to verify diagnosis. Segregation analysis of a prognathic mandible in the entire dataset supported a transmissible Mendelian major effect, with a dominant mode of inheritance determined to be the most parsimonious. [ABSTRACT FROM AUTHOR]

Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticato- w muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research. [ABSTRACT FROM AUTHOR]

Teeth and periodontal mechanoreceptors play important roles in regulating jaw movements during mastication. However, little is known concerning how jaw movements develop without tooth eruption. To answer this question, we studied masticatory behavior in the osteopetrotic mouse, where tooth eruption does not occur and periodontal mechanoreceptors are missing. A masticatory sequence of the osteopetrotic mouse was divided into two stages: incision and chewing. Incision is characterized by small amplitude and rapid (7 Hz) open-close jaw movements, while slow (5 Hz) and large amplitude open-close jaw movements characterize chewing. The frequency and properties of jaw movements were comparable with those in the normal mouse, though the osteopetrotic mouse had a higher cycle number during incision than did the normal mouse. These results indicate that conversion from sucking to mastication occurs in the anodontic mouse, and the central pattern generator producing the masticatory rhythm develops almost normally without tooth eruption. [ABSTRACT FROM AUTHOR]

A 12-year-old girl with maxillo-nasal dysplasia (Binder's syndrome), featuring maxillary hypoplasia and relative mandibular prognathism, presented with a Class III incisal relationship. Her treatment was managed orthodontically. The principal features of the syndrome and management of these cases is discussed. [ABSTRACT FROM AUTHOR]

The common methods for treating anterior disk displacement without reduction (ADDwor) are not based on randomized controlled clinical trials. Our study evaluated non-surgical treatments in 69 MRI-confirmed ADDwor subjects (m/f= 6/63). Subjects were randomly assigned to a control group and one of two treatment groups. Outcomes included maximum mouth opening, visual analogue scale of pain, and daily activity limitation. Calibrated examiners collected data at the initial interview and at 0, 2, 4, and 8 weeks of treatment. At the eight-week point, within-group improvements were present for all variables, for all groups. Between-group differences were not highly evident, with only mean daily activity limitation for the self-care/NSAID group being significantly lower than that of the occlusal appliance/jaw mobilization + self-care/NSAID group at the two- and four-week time-points. These results suggest that ADDwor subjects will improve with only minimal treatment intervention, and no significant difference was evident for the treatments tested and the control condition. [ABSTRACT FROM AUTHOR]

It has often been hypothesized that a large tongue leads to an enlargement of the mandible and therefore contributes to the development of mandibular prognathism. We examined (1) whether the tongue volume in human subjects with mandibular prognathism was larger than that in subjects with good occlusion and (2) whether the tongue volume and the pharyngeal capacity correlated with the morphological characteristics of dento-skeletal structures. Magnetic resonance images of the tongue and its surrounding structures were recorded for female adult volunteers with good occlusion (control group, n = 10) and patients with mandibular prognathism (test group, n = 16). Lateral cephalograms were obtained for the patients. No significant differences were determined for the tongue volume or the pharyngeal capacity between the two groups. The tongue volume did not correlate with the pharyngeal capacity (r =0.280, p = 0.166). The tongue volume correlated with the facial angle (r = 0.548, p = 0.028), the Y-axis (r = 0.539, p = 0.031), and the angle nasion-A point-pogonion (r = 0.540, p = 0.031). These results suggest that the tongue volume is accounted for by the combined horizontal and vertical location of the chin and symphysis, but do not support the conventional clinical surmise that large tongue volume is inherent in patients with mandibular prognathism. [ABSTRACT FROM AUTHOR]

Masseter muscle silent periods were assessed in 24 children divided into three groups according to their stage of dental development (primary, mixed, and permanent). Surface electrode EMG data, timing code, and microphone input were recorded on magnetic tape. A visual record was obtained by playing the tape into an optical oscillograph; measurements were made from the photo-sensitive paper. The results indicate the latency and silent period durations of clenched jaw jerks were similar among the three groups. For the subjects in this study, the mean latency and silent period durations of the masseter muscle during clenched jaw jerks were 14.9 ms (milli-seconds) and 27.0 ms. [ABSTRACT FROM AUTHOR]

Nocturnal electromyographic recordings of masseter muscle activity were performed on 20 bruxist and ten control subjects. Each subject collected two 24-hour urine samples. An analysis of urinary catecholamine content was performed. A positive relationship was found between increased epinephrine content and high levels of nocturnal masseter muscle activity. [ABSTRACT FROM AUTHOR]

The rhythm dependency and reproducibility of the jaw motion error for open-close-clench movements in man have been investigated. The results indicate that the error strongly depends upon the rhythm of movements. Sometimes there is a significant difference (p < 0.05) between corresponding series of jaw motion errors indicating a lack of reproducibility of the error at a repeat test. [ABSTRACT FROM AUTHOR]

The article reports that hemifacial spasm is a disorder characterized by intermittent, chronic, unilateral contractions of the facial musculature. Although hemifacial spasm has been recognized us a diagnostic entity, the basic pathophysiology of this syndrome is not established. The association of hemifacial spasm with a vascular lesion compressing the seventh nerve was first recorded 100 years ago. Since then, several authors have observed vascular abnormalities close to the intracranial seventh nerve in patients with hemifacial spasm.

It is now increasingly evident that chromosomal abnormalities underlie a goodly proportion of congenital abnormalities, between 5 and 15 per cent of children with congenital abnormalities showing evidence of chromosomal deletions or aberrations. Since dentofacial defects are particularly common in developmental abnormalities, and to an extent not in accordance with the concept of stage-specificity, the possible chromosomal basis of dentofacial defects represents a problem in its own right and, when the chromosomal type is known, provides new indications as to the role of chromosomes in controlling developmental timing. [ABSTRACT FROM AUTHOR]

The article present research examining the effects of various levels of lathyrus odoratus in the diet on the growth of the mandibular ramus and articulation in laboratory rats. Particular attention was paid to evaluating the influence of protein and amino acid supplementation on observed changes. Results suggest beta-amino-propionitrile from sweet peas produces a metabolic defect causing the mandible and skeleton to respond with new bone formation in regions of mechanical topical stress.