Denosumab for craniofacial fibrous dysplasia: duration of efficacy and post-treatment effects.

Denosumab has been advocated as a potential treatment for the rare skeletal disorder fibrous dysplasia (FD); however, there is limited data to support safety and efficacy, particularly after drug discontinuation. We report a case of successful treatment of aggressive craniofacial FD with denosumab, highlighting novel insights into the duration of efficacy, surrogate treatment markers, and discontinuation effects. A 13-year-old girl presented with persistent pain and expansion of a maxillary FD lesion, which was not responsive to repeated surgical procedures or bisphosphonates. Pre-treatment biopsy showed high RANKL expression and localization with proliferation markers. Denosumab therapy was associated with improved pain, decreased bone turnover markers, and increased lesion density on computed tomography scan. During 3.5 years of treatment, the patient developed increased non-lesional bone density, and after denosumab discontinuation, she developed hypercalcemia managed with bisphosphonates. Pain relief and lesion stability continued for 2 years following treatment, and symptom recurrence coincided with increased bone turnover markers and decreased lesion density back to pre-treatment levels. This case highlights the importance of considering the duration of efficacy when treating patients with FD and other nonresectable skeletal neoplasms that require long-term management.

Accuracy of skeletal scintigraphy for the evaluation of mandibular growth disorders: a systematic review.

Bone scans, reflecting blood flow and metabolic activity in a region of interest, are frequently used to evaluate mandibular growth disorders. Increased uptake is a non-specific finding and can occur as a result of multiple causes. The correlation between radioactive tracer uptake and growth activity has not been consistently demonstrated. The aim of this study was to assess the accuracy of planar skeletal scintigraphy (SS), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (CT) images (SPECT/CT) in detecting abnormal mandibular growth activity compared to clinical and radiographic/tomographic methods (reference standard) and histologic findings. A systematic review was conducted following the PRISMA guidelines. Sensitivity, specificity, and accuracy were calculated for planar SS, SPECT, and SPECT/CT. Compared to the reference standard, SPECT/CT had the best diagnostic accuracy (76.5% sensitivity, 90.4% specificity, 83.2% accuracy), followed by planar SS (81.8% sensitivity, 84.5% specificity, 83.0% accuracy) and SPECT (77.7% sensitivity, 72.4% specificity, 74.5% accuracy). The results of this study indicate that SPECT/CT has the best clinical correlation, but the certainty of the evidence is low. The differences in sensitivity and specificity between the three index tests were not clinically significant. The three tests can be useful, with only a small difference in their diagnostic value. Histopathology was found not to be satisfactory as a reference standard.

Association of craniomaxillofacial fractures and blunt cerebrovascular injuries.

High energy trauma has been considered a risk factor for blunt cerebrovascular injuries (BCVI). The purpose of this study was to determine the incidence and risk factors for BCVI specifically in patients with maxillofacial fractures in an urban level I trauma center. A retrospective cohort study of patients aged ≥ 18 years, admitted to Massachusetts General Hospital (MGH) between 2007 and 2017, was implemented. There were 23,394 patients treated and entered into the MGH Trauma Registry: 22,287 sustained blunt trauma. Of the total blunt trauma patients, 68 (0.3%) had BCVI. There were 2421 patients with CMF fractures from blunt trauma (mean ± standard deviation age, 53 ± 22 years; 29.9% female included as study subjects, of whom 24 (1.0%) had BCVI). In a multivariate model, all mandible fracture (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.6-11.6, P = 0.004), crush injury, defined as blunt compression injury (OR 11.1, 95% CI 2.1-58.1, P = 0.004), and cervical spine injury (OR 10.1, 95 CI 3.7-27.5, P < 0.001) were independent risk factors for BCVI. Mortality was 4.3 times higher in craniomaxillofacial fracture patients with BCVI versus those without BCVI; complications of BCVI (stroke) contributed to the majority of deaths. Appropriate screening and treatment of BCVI in patients with maxillofacial fractures is important.

A conceptual framework for treating jaw deformities in patients with abnormal condyles: preservation versus replacement of the glenoid fossa-disc-condyle-ramus.

This article outlines a conceptual approach to the reconstruction of jaw deformities associated with abnormalities in the mandibular condyle. The authors describe a hierarchy of reconstruction, emphasizing use of the least invasive and progressing to the most complex and invasive techniques, depending on the nature and severity of the underlying deformity, prior operations, patient age, and stage of growth. Consider joint preservation orthognathic surgical correction, followed by biological techniques for replacement of the condyle, and avoid replacing a functional temporomandibular joint based only on radiographic remodeling and concerns about potential future flare-ups of disease based on anecdotal data.

Variables associated with stability after Le Fort I osteotomy for skeletal class III malocclusion.

The purpose of this study was to assess skeletal stability and predictors of relapse in patients undergoing an isolated Le Fort I osteotomy. A retrospective cohort study of 92 subjects undergoing Le Fort I osteotomy for Class III malocclusion was implemented. Predictor variables were demographic and perioperative factors. The primary outcome variable was postoperative skeletal position with relapse defined as >2mm sagittal and/or vertical change at A-point on serial lateral cephalograms at immediate postoperative, 1 year, and latest follow-up time points. Mean advancement at A-point was 6.28±2.63mm and mean lengthening was 0.92±1.76mm. Eight subjects (8.70%) had relapse (>2mm) in the sagittal plane, and two subjects (2.17%) in the vertical plane. No subjects required reoperation for relapse as overbite and overjet remained in an acceptable range due to dental compensation. In regression analysis, magnitude of maxillary advancement was an independent predictor of relapse in the sagittal plane (P=0.008). There were no significant predictors of relapse in the vertical plane. This study suggests that isolated Le Fort I osteotomy for correction of skeletal Class III malocclusion is a stable procedure and that greater advancement is an independent risk factor for sagittal relapse.

Frequency of cervical spine injuries in patients with midface fractures.

The aim of this retrospective cohort study was to determine the frequency and risk factors for cervical spine injury (CSI) in patients with midface fractures. Patients ≥18 years of age entered in the Massachusetts General Hospital Trauma Registry from 2007 to 2017 were identified. Those with a midface fracture, computed tomography and/or magnetic resonance imaging of the cervical spine, and complete medical records were included. There were 23,394 patients in the registry; 3950 (16.9%) had craniomaxillofacial fractures and 1822 (7.8%) had a CSI. Craniomaxillofacial fractures included fractures of the midface (n=2803, 71.0%), mandible (n=873, 22.1%), and midface plus mandible (n=274, 6.9%). The overall frequency of CSI in patients with midface fractures was 11.4% (350/3077). Patients with midface fractures had a higher risk for CSI compared to patients without a midface fracture (odds ratio 2.4, 95% confidence interval 2.1-2.4, P<0.001). In a multivariate model, nasal and orbital fractures, chest injuries, age, injury severity score, and motor vehicle crash or fall as the etiology were independent risk factors for CSI. Mortality was two times higher in subjects with CSI. Early and accurate diagnosis of CSI is a critical factor when planning the treatment of patients with these fractures.

Regional differences in temporomandibular joint inflammation in patients with juvenile idiopathic arthritis: a dynamic post-contrast magnetic resonance imaging study.

The purpose was to determine whether there are regional differences in temporomandibular joint (TMJ) inflammation in patients with juvenile idiopathic arthritis (JIA). This was a retrospective study of all patients with dynamic, contrast-enhanced magnetic resonance imaging through the TMJs at Massachusetts General Hospital between January 2015 and July 2016. The patient cohort included those with a history of JIA and control patients who underwent MRI for other routine clinical purposes. TMJ inflammation was quantified as the difference between post-gadolinium and pre-gadolinium articular T1 signal intensity normalized to post-gadolinium signal intensity of the longus capitis muscle. TMJ enhancement profiles were generated for the lateral, central, and medial portions of the TMJ. Regional differences in TMJ enhancement were investigated using basic descriptive statistics. Medial edge enhancement of the TMJs was highest in symptomatic JIA joints, followed by asymptomatic JIA, then control joints. Medial edge enhancement was a significant discriminator between symptomatic JIA TMJs and control joints (P = 0.0001), between symptomatic and asymptomatic JIA TMJs (P = 0.0003), and between asymptomatic JIA TMJs and controls (P = 0.0019). A shift in distribution of TMJ enhancement towards the medial edge that was seen uniquely in both asymptomatic and symptomatic JIA TMJs compared to control joints was found. This suggests a pattern of worsening medial edge inflammation with disease.

Clear cell odontogenic carcinoma: a rare jaw tumor. A summary of 107 reported cases.

The purpose of this study was to summarize the currently published cases of clear cell odontogenic carcinoma (CCOC). The PubMed and Springer databases were used to collect available reports, searching for 'clear cell odontogenic carcinoma', 'CCOC', or 'clear cell ameloblastoma'. The search resulted in 75 reports detailing 107 cases between 1985 and 2018. Clinically the tumor manifests as a swelling in the posterior mandible (n=46), anterior mandible (n=33), and maxilla (n=28). Radiological analysis of 85 cases typically showed a poorly defined expansive radiolucency (n=83). Of the 70 patients with symptoms reported, 44 specified a swelling, 11 tooth mobility, seven gingival/periodontal issues, five numbness, and three decreased jaw opening. One patient presented with a neck mass. The duration of symptoms prior to seeking care was specified for 52 patients: 2 months to 1 year for 34 patients, 1-2 years for seven, 2-4 years for two, 4-7 years for six, and 7-12 years for three. The incidence of recurrence appeared to be 38 of the 88 cases where recurrence was reported. CCOC can be distinguished from other oral cancers by its distinctive histology and immunohistochemical characteristics and less aggressive behavior. Currently, treatment should be early and aggressive resection with clear surgical margins and long-term follow-up. The overall goal is to collect a cohort of patients.

Nicotine impairs distraction osteogenesis in the rat mandible.

Distraction osteogenesis (DO) has gained clinical acceptance as a surgical technique for treatment of congenital craniomaxillofacial deficiencies requiring skeletal expansion. The use of this technique elsewhere requires more information on overcoming difficult clinical settings, for which new animal models will be needed. The aim of this study was to develop and validate a model of impaired DO of the rat mandible with nicotine. Twenty rats underwent a right vertical mandibular body osteotomy, after which distraction began with custom-made percutaneous devices and a 3-day latency period, 6-day distraction (0.25 mm twice daily) and 30 days of neutral fixation. Rats received either nicotine or placebo slow-release pellets. Specimens were analysed after removal of the devices for quantitative radiographic bone fill, amount of bone advancement and histological features. The mean radiographic bone-fill score with nicotine treatment was 75% of that with placebo (P=0.0036). The nicotine-treated rats had less (49%) elongation than the placebo-treated controls (P=0.0008). Histological analysis demonstrated less bone, vascularity and cellular activity in nicotine-treated rats. This study shows that nicotine reproducibly inhibits osteogenesis, vascularity and bone lengthening in mandibular DO.

What are the defining characteristics of the most cited publications in orthognathic surgery?

The purpose of this study was to identify the characteristics associated with highly cited papers in orthognathic surgery. This was a cohort study of articles published in the English-language literature from 1900 to 2017. Citation databases were searched for papers related to orthognathic surgery and the most frequently cited papers were identified. For each paper, the following variables were collected: region of origin, time-period of publication, corresponding author specialty, journal of publication, topic area, study design, and number of citations. The outcome variable was the citation index (citations per year). North American investigators published 70% of the 100 most-cited articles in orthognathic surgery. The majority of papers were from oral and maxillofacial surgeons. Frequent content areas were diagnosis, virtual planning, fixation/stability, and complications. The majority (54%) of studies were cohort or case report/series. The mean number of citations was 235.0±126.5; the mean citation index was 9.9±6.1 citations per year. Time-period, content area, and study design were associated with the citation index (all P<0.001). Time-period, content area, and study design predicted the citation index (all P≤0.009). Among frequently cited papers in orthognathic surgery, oral and maxillofacial surgeons had the highest volume of contributions. Diagnosis, treatment planning, and complications were the most common topics studied.

Isolated microtia as a marker for unsuspected hemifacial microsomia.

OBJECTIVE: To determine the proportion of hemifacial microsomia (HFM) in patients with unilateral or bilateral "isolated" microtia. DESIGN: Prospective cohort clinical study. SETTING: University-affiliated, tertiary referral clinic for patients with microtia. PATIENTS: One hundred consecutive patients with isolated microtia. INTERVENTIONS: All the patients underwent a clinical examination and audiologic evaluation. The OMENS classification system was used to grade the severity of craniofacial features: orbital deformity, mandibular hypoplasia, ear deformity, nerve (cranial nerve VII) involvement, and soft-tissue deficiency. Each anatomical abnormality was graded from 0 (normal) to 3 (most severe) (score range, 0-15). MAIN OUTCOME MEASURES: The OMENS scores, percentage of patients with isolated microtia and undiagnosed HFM, and isolated microtia as an early clinical marker for HFM. RESULTS: Forty patients (40%) with microtia were determined to have HFM (31 unilateral and 9 bilateral). Mean patient age was 9.2 years (range, 6 weeks to 41 years), with male predominance (27 males and 13 females). The OMENS scores were less than 5 in 24 patients and 6 to 10 in 16 patients. Thirty patients had cranial nerve deficits, and 37 had mandibular asymmetry. Thirty-seven patients demonstrated conductive hearing loss, and 1 had sensorineural hearing loss. CONCLUSIONS: Isolated microtia served as an early clinical marker for asymmetrical facial growth in 40% of the patients. Isolated microtia and HFM could represent a spectrum of expression of the same developmental phenomenon.

Optimization of Quantitative Dynamic Postgadolinium MRI Technique Using Normalized Ratios for the Evaluation of Temporomandibular Joint Synovitis in Patients with Juvenile Idiopathic Arthritis.

BACKGROUND AND PURPOSE: MR imaging has been shown to be useful in the diagnosis of juvenile idiopathic arthritis of the temporomandibular joint. Prior MR imaging approaches have relied mainly on the subjective interpretation of synovial enhancement as a marker for synovial inflammation. Although, more recently, several attempts have been made to quantify synovial enhancement, these methods have not taken into account the dynamic enhancement characteristics of the temporomandibular joint and the effect of sampling time. Our aim was to develop a clinically feasible, reproducible, dynamic, contrast-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis and to study the effect of sampling time on the evaluation of synovitis. MATERIALS AND METHODS: This was a retrospective study of all patients who had dynamic, contrast-enhanced coronal T1 3T MR imaging through the temporomandibular joint at our institution between January 1, 2015, and July 8, 2016. Patients in this cohort included those with a history of juvenile idiopathic arthritis and control patients who underwent MR imaging for other routine, clinical purposes. Synovial enhancement was calculated for each temporomandibular joint using 3 different types of equations termed normalization ratios. The enhancement profiles generated by each equation were studied to determine which provided the best discrimination between affected and unaffected joints, was the least susceptible to sampling errors, and was the most clinically feasible. RESULTS: A ratio of synovial enhancement (defined as the difference between the postgadolinium and the pregadolinium T1 signal of the synovium) to the postgadolinium signal of the longus capitis provided the best discrimination between affected and unaffected joints, the least susceptibility to sampling error, and was thought to be the most clinically feasible method of quantification of synovial inflammation. Additional synovial enhancement ratios studied did not provide the same level rates of discrimination between the affected and unaffected joints and were thought to be too temporally variable to provide reliable clinical use. CONCLUSIONS: We provide a robust, reproducible, dynamic gadolinium-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis.

Pediatric facial fractures: recent advances in prevention, diagnosis and management.

During the last 25 years, there have been considerable advances in the prevention, diagnosis and management of craniomaxillofacial injuries in children. When compared to adults, the pattern of fractures and frequency of associated injuries are similar but the overall incidence is much lower. Diagnosis is more difficult than in adults and fractures are easily overlooked. Clinical diagnosis is best confirmed by computed tomographic (CT) scans. Treatment is usually performed without delay and can be limited to observation or closed reduction in non-displaced or minimally displaced fractures. Operative management should involve minimal manipulation and may be modified by the stage of skeletal and dental development. Open reduction and rigid internal fixation is indicated for severely displaced fractures. Primary bone grafting is preferred over secondary reconstruction and alloplastic materials should be avoided when possible. Children require long-term follow-up to monitor potential growth abnormalities. This article is a review of the epidemiology, diagnosis and management of facial fractures in children.

Juvenile arthritis: current concepts in terminology, etiopathogenesis, diagnosis, and management.

The latest change in terminology from juvenile rheumatoid arthritis (JRA) to juvenile idiopathic arthritis (JIA), established by the International League of Associations for Rheumatology (ILAR), has resulted in some confusion for OMFS and other treating clinicians. JIA comprises a group of systemic inflammatory diseases that result in the destruction of hard and soft tissues in a single or multiple joints. In a significant number of patients, one or both temporomandibular joints (TMJ) are also involved. TMJ disease may be accompanied by pain, swelling, and limitation of motion, as well as mandibular retrognathism, open bite, and asymmetry. The purpose of this article is to provide a review, for the oral and maxillofacial surgeon, of the terminology, etiopathogenesis, diagnosis, and management of children with JIA.

Comparison of time required for traditional versus virtual orthognathic surgery treatment planning.

Virtual surgical planning (VSP) is a tool for predicting complex surgical movements in three dimensions and it may reduce preoperative laboratory time. A prospective study to compare the time required for standard preoperative planning versus VSP was conducted at Massachusetts General Hospital from January 2014 through January 2015. Workflow data for bimaxillary cases planned by both standard techniques and VSP were recorded in real time. Time spent was divided into three parts: (1) obtaining impressions, face-bow mounting, and model preparation; (2) occlusal analysis and modification, model surgery, and splint fabrication; (3) online VSP session. Average times were compared between standard treatment planning (sum of parts 1 and 2) and VSP (sum of parts 1 and 3). Of 41 bimaxillary cases included, 20 were simple (symmetric) and 21 were complex (asymmetry and segmental osteotomies). Average times for parts 1, 2, and 3 were 4.43, 3.01, and 0.67h, respectively. The average time required for standard treatment planning was 7.45h and for VSP was 5.10h, a 31% time reduction (P<0.001). By eliminating all or some components of part 1, time savings may increase to as much as 91%. This study indicates that in an academic setting, VSP reduces the time required for treatment planning of bimaxillary orthognathic surgery cases.

Histology of the porcine mandibular distraction wound.

The purpose of this study was to document the progression and pattern of endosteal bone formation in a porcine mandibular distraction wound. Bone formation was assessed in a 0-day latency model (n=24 pigs) using distraction rates of 1, 2, or 4 mm/day to create a 12-mm gap. Macro-radiographs and sagittal histologic sections, from the center of the mandible, were evaluated by computer morphometrics (% bone fill) and by a semi-quantitative bone formation score. Mean percent area of new bone was 12.4% (0-25.9%), 7.5% (0-21.3%) and 3.8% (0-10.5%) in mandibles distracted at 1, 2 or 4 mm/day respectively. At all time points, percent area of new bone was highest in mandibles distracted at 1 mm/day. Bone was deposited from the margins of the osteotomy toward the center of the wound and occurred first around the inferior alveolar canal and tooth bud regions. New bone formed by intramembranous ossification alone. The results of this experiment document the contribution of endosteal bone formation in this model of distraction osteogenesis.

Temporomandibular joint dysfunction with facial pain in children.

Temporomandibular joint dysfunction with myofascial pain, a well-known clinical disorder in adults, is reported in children. In a series of 400 patients, 40 children less than 16 years of age were seen. Of these pediatric patients, 35% had a reactive depression as primary psychopathology. The multifactorial nature of the disorder is described. The need to differentiate this syndrome from recurrent otitis media and other pain syndromes is emphasized. A combined medical, oral surgical, and psychiatric management program is outlined.

Temporomandibular joint dysfunction and facial pain in children: an approach to diagnosis and treatment.

A model for the diagnosis and treatment of temporomandibular joint dysfunction and facial pain in children is presented. Emphasis is placed on systematic assessment of physical, psychologic, and behavioral factors when conservative medical therapy is inadequate for symptom relief. The model represents a multidisciplinary approach to patient care which is described through case presentations. The results of research on the incidence of primary psychopathology in 53 children and 322 adults evaluated during a 3-year period for temporomandibular joint dysfunction and facial pain are also presented. It was found that children were more likely to be psychiatrically impaired (25%) than adults (7%). Children had a variety of psychiatric diagnoses including depression, conversion and adjustment disorders, overanxious behavior, and anorexia nervosa. The benefits of a multidisciplinary approach are discussed in terms of the efficacy of this coordinated treatment effort in ameliorating symptoms.

Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a.

We report a 5-year-old girl with a large rapidly growing giant cell tumor of the mandible that recurred 2 months after the first surgical excision and 3 months after a second resection. An angiogenic protein, (bFGF), was abnormally elevated in her urine. The patient was treated with interferon alfa-2a for 1 year because this agent inhibits angiogenesis by suppressing bFGF overexpression in infantile hemangiomas and in other human tumors. During this time the bone tumor regressed and disappeared, the urinary bFGF fell to normal levels, and the mandible regenerated. She has remained tumor-free and has been off therapy for 3 years at this writing. This first successful use of interferon alfa-2a to treat a mandibular tumor in a child demonstrates: 1) low grade tumors that overexpress bFGF may respond to interferon alfa-2a, in a manner similar to life-threatening infantile hemangiomas; 2) antiangiogenic therapy, given without interruption for 1 year, was safe and effective in this patient; and 3) treatment may be continued for 1 year without the development of drug resistance.