Osteoradionecrosis in a Torus Mandibularis Treated by Antimicrobial Photodynamic Therapy: A Case Report.

Background: Osteoradionecrosis (ORN) of the jaws is a late complication after radiotherapy to head and neck cancer. Objective: To describe a rare case of ORN of the torus mandibularis that was successfully managed exclusively with antimicrobial photodynamic therapy (aPDT). Case report: A 72-year-old man presented an exposed necrotic bone observed in the torus mandibularis, extending to the lingual alveolar ridge with no edema nor suppuration. The treatment provided a noninvasive treatment leading to spontaneous sequestrectomy of the torus in 2 weeks with complete mucosal repair in 5 weeks and absence of lesion signs and/or symptoms even after 6 months of follow-up. Conclusions: The aPDT indicated to be a satisfactory treatment for ORN affecting torus mandibularis, a region with surgical limitations, avoiding surgery.

Overview and Emerging Trends in the Treatment of Osteoradionecrosis.

OPINION STATEMENT: Osteoradionecrosis (ORN) of the mandible is a rare but devastating complication which occurs following radiation therapy for head and neck malignancies. Left untreated, ORN often results in pathologic fracture of the mandible leading to pain, trismus, difficulty eating, and overall poor quality of life. Historically, early intervention relied on hyperbaric oxygen and local debridement. Patients whose disease progressed despite therapy required segmental resection of the mandible with osseous free flap reconstruction, a highly invasive operation. Patients that presented with a moderate disease without pathologic fracture were often doomed to fail non-operative management, ultimately leading to disease progression and fracture. The traditional dichotomous treatment paradigm left a void of options for patients with moderate disease. The ideal intervention for this category of patients would provide renewed vascularity to the diseased tissue bed allowing for the osteogenesis and reestablishment of strong, load-bearing bone. The innovative technique termed the vascularized fascia lata "rescue flap" has proven to be an effective treatment for moderate ORN and will likely transform dated treatment algorithms.

Clinical study of treatment methods and associated factors in mandibular osteoradionecrosis.

This study aimed to determine the appropriate treatment methods and evaluate associated factors by comparing nonoperative treatment alone with a combination of both nonoperative and surgical treatment in 34 patients with mandibular osteoradionecrosis (mORN). The associated cure factors were analyzed by Cox regression. Propensity scores were calculated from factors that were not significant in the univariate analysis and used as covariates in the multivariate analysis. The cure rate among patients who received nonoperative and surgical treatment was higher than that observed with nonoperative treatment alone. Only the treatment method was associated with cure in both univariate and multivariate analyses.

[Predictive factors for mandibular osteoradionecrosis after irradiation of head and neck cancers]. / Facteurs prédictifs de l'ostéoradionécrose mandibulaire après irradiation des cancers des voies aérodigestives supérieures.

The identification of the different risk factors for mandibular osteoradionecrosis (ORN) must be done before and after the management of patients with head and neck cancer. Various clinical criteria for this severe radiation-induced complication are related to the patient (intrinsic radiosensitivity, malnutrition associated with thin weight loss, active smoking intoxication, microcapillary involvement, precarious oral status, hyposalivation) and/or related to the disease (oral cavity, large tumor size, tumor mandibular invasion). Therapeutic risk factors are also associated with a higher risk of ORN (primary tumor surgery, concomitant radio-chemotherapy, post-irradiation dental avulsion, preventive non-observance with the absence of stomatological follow-up and daily installation of gutters fluoride and, non-observance curative healing treatments). Finally, various dosimetric studies have specified the parameters in order to target the dose values distributed in the mandible, which increases the risk of ORN. An mean mandibular dose greater than 48-54Gy and high percentages of mandibular volume receiving 40 to 60Gy appear to be discriminating in the risk of developing an ORN.

Is Adjunctive Hyperbaric Oxygen Treatment Alone or with Surgery the Proper Management for Active and Persistent Osteoradionecrosis?

ABSTRACT: This study enrolled patients with stage 3 osteoradionecrosis. There were three treatment modalities: antibiotics, hyperbaric oxygen therapy (HBOT), and surgery. Complete healing was the primary outcome. Multiple logistic regression analysis demonstrated that surgery with HBOT improved wound healing better than HBOT alone.

Regeneration of mandibular osteoradionecrosis with autologous cross-linked serum albumin scaffold.

Osteoradionecrosis is one of the most severe complications of radiotherapy administered for head and neck tumors. We present the first two cases of advanced and refractory mandibular osteoradionecrosis treated by application of a novel autologous cross-linked 3D serum matrix. Patients were followed clinically and radiographically up to 24 months. Complete wound healing and intact mucosal cover were achieved in both cases. At 12 months, the radiographic values showed an almost complete regeneration of the bone defect, which continued a favourable progression increased to the maximum by 24 months after surgery. The use of an autologous serum-derived scaffold proved to be a quick, predictable, cost-effective and safe adjunct to the conservative surgical treatment of this pathology.

Autogenous free fat graft combined with platelet-rich fibrin heals a refractory mandibular osteoradionecrosis.

Osteoradionecrosis (ORN) is a well-recognized, debilitating complication of radiotherapy for patients with head and neck cancer. There is no universally accepted treatment for ORN of the jawbones. We report on a case of refractory mandibular ORN treated by sequestrectomy of mandible and autogenous transplantation of fat graft combined with platelet-rich fibrin (PRF). Improved perfusion was observed using the laser Doppler flowmetry. This case highlights the use of autogenous free fat graft and PRF as an adjunct therapy to sequestrectomy in the management of ORN.

Non-surgical treatment of adults with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible.

Non-surgical therapy has proved to be effective in chronic diffuse sclerosing osteomyelitis (DSO) of the mandible in children. Therefore we aimed to investigate the effect of non-surgical therapy in adult DSO patients. We included consecutive patients with DSO who received non-surgical therapy in our center. They all received occlusal splint therapy, counselling about the disease, and/or physiotherapy by a specialised team. The use of analgesics, preferably nonsteroidal anti-inflammatory drugs, was advised for symptomatic control during periods of exacerbation. Sixteen patients (11/5 female/male) aged 39.9 ± 15.0 years with DSO of the mandible were included. The mean duration of symptoms was 39.7 ± 26.3 months before referral to our center. Patients were treated with a broad range of treatments before referral. All patients underwent non-surgical treatment. In 12 patients this led to remission. Four patients still had complaints after 12 months of non-surgical therapy and started with intravenous bisphosphonate therapy. In our center, DSO of the mandible was successfully treated with non-surgical therapy, despite a long duration before referral and extensive pre-treatment. Considering this high success rate, we recommend this non-surgical approach as the first treatment option for DSO of the mandible. In case of persistence, alternative treatments such as bisphosphonates should be explored.

Osteoradionecrosis in a Patient Submitted to Head and Neck Radiotherapy: A Case Report / Osteoradionecrosis en un Paciente Sometido a Radioterapia de Cabeza y Cuello: Reporte de un Caso

ABSTRACT: Radiotherapy applies ionizing radiation at predetermined doses for a limited period of time in order to destroy tumors. The oral cavity, which has a high rate of cell renewal, is affected by the side effects of radiotherapy including osteoradionecrosis (ORN). This condition occurs due to irradiated bone tissue that becomes devitalized and exposed in the oral cavity. Conservative therapies are recommended for ORN lesions that are not extensive or in an early stage. Surgical intervention is necessary for extensive areas affected by necrosis. This study reports a case of ORN in the left mandibular body which resulted in a pathological fracture. The treatment consisted of segmental mandibulectomy and the use of a reconstruction plate. Also, low-level laser therapy around bone exposure was performed. After surgery, the patient underwent 6 months of follow-up and was satisfied with the outcome. However, the patient died before control of ORN was achieved due to a heart attack.

RESUMEN: La radioterapia aplica radiación ionizante a dosis predeterminadas durante un período de tiempo limitado para destruir tumores. La cavidad oral, que tiene una alta tasa de renovación celular, se ve afectada por los efectos secundarios de la radioterapia, incluida la osteorradionecrosis (ORN). Esta condición se produce debido al tejido óseo irradiado que se desvitaliza y expone en la cavidad oral. Se recomiendan terapias conservadoras para las lesiones de ORN que no son extensas o en una etapa temprana. La intervención quirúrgica es necesaria para áreas extensas afectadas por necrosis. Este estudio reporta un caso de ORN en el cuerpo mandibular izquierdo que resultó en una fractura patológica. El tratamiento consistió en mandibulectomía segmentaria y el uso de una placa de reconstrucción. Además, se realizó una terapia con láser de bajo nivel alrededor de la exposición ósea. Después de la cirugía, el paciente se sometió a 6 meses de seguimiento y quedó satisfecho con el resultado. Sin embargo, el paciente falleció antes de que se lograra el control de ORN debido a un ataque cardíaco.

Anterior open bite due to idiopathic condylar resorption during orthodontic retention of a Class II Division 1 malocclusion.

A common dilemma when treating anterior open bite is understanding its etiology. Idiopathic condylar resorption (ICR) can cause open bite in affected individuals. Although it is prudent to not treat patients with ICR until active resorption has ceased, orthodontists may begin treating them because anterior open bite from ICR may not appear before or during their orthodontic treatment. This article reports a 12-year-old female who was diagnosed with ICR 10 months after completion of her orthodontic treatment for a Class II Division 1 malocclusion. When a young patient with a high mandibular angle and previous skeletal or dental Class II malocclusion returns with an open bite during the retention phase, the patient's condyles must be carefully examined to determine whether any temporomandibular joint disorder, such as ICR, is present. Currently, the controversy over the cause and the cure for ICR is continuing to challenge orthodontists in diagnoses and treatments. Orthodontists should closely monitor and offer informed treatment options to patients with risk factors for ICR or signs of its pathology that might develop at any stage of orthodontic treatment, including the retention period.

Metronidazole-induced encephalopathy caused by hyperbaric oxygen therapy in a patient with mandibular osteomyelitis.

Metronidazole (MNZ) is prescribed for the treatment of infection caused by anaerobic bacteria and protozoa. Metronidazole-induced encephalopathy (MIE) has been known to be a side-effect, although its onset ratio is unclear. However, to the best of our knowledge, MIE associated with hyperbaric oxygen therapy (HBO) has not been previously reported. Here, we present the case of a 68-year-old man with mandibular osteomyelitis who received metronidazole for 49 days and received five times HBO therapy. He visited our hospital for evaluation and treatment of peripheral neuropathy, speech disturbance, nausea, and disturbance of gait after 47 days of initiating metronidazole treatment. Brain magnetic resonance imaging revealed hyperintense lesions in the cerebellar dentate nuclei, which was consistent with MIE. The patient's ataxic symptoms improved in 15 days after the discontinuation of MNZ. This is the first report demonstrating case of MIE could be related with HBO, as far as we had searched.

Conservative Treatment of Chronic Osteomyelitis Associated with Florid Osseous Dysplasia / Tratamiento Conservador de la Osteomielitis Crónica Asociada con Displasia Ósea Florida

ABSTRACT: Florid osseous dysplasia (FOD) is an extensive form of osseous dysplasia where normal trabecular bone is substituted by fibrous connective tissue and amorphous mineralized tissue. Usually, the lesions are mainly asymptomatic and the patients should be followed with clinical and imaging examination, requiring no intervention. Nevertheless, due to the poor vascularization of the lesion and to local trauma, secondary infections and osteomyelitis may occur. Patients may present with pain, mucosal ulceration, lesion exposure in the oral cavity, fistula and swelling. In such cases, the correct diagnosis and management of the lesion is decisive to reestablish patient's health and quality of life. The aim of this article is to present a case of complicating secondary chronic osteomyelitis treated successfully with conservative intervention. A 68-year-old black female patient reported a "swelling of the gums" that was present for eleven years, with episodes of periodic pain and swelling. On physical examination, a papule with suppuration in the alveolar mucosa in the right side of the mandible was observed. Panoramic radiography and CBCT showed a mixed lesion surrounded by sclerotic bone. The patient was diagnosed with chronic osteomyelitis in association with FOD and treated with antibiotic therapy together with surgical curettage. The incidence, etiophatology, differential diagnosis, treatment and prevention of secondary osteomyelitis associated with FOD are discussed in the light of literature. This information might assist the dentists while choosing the best treatment options for similar cases.

RESUMEN: La displasia ósea florida (DOF) es una forma de displasia ósea donde el hueso trabecular normal es sustituido por tejido conectivo fibroso y tejido mineralizado amorfo. En general, las lesiones son de origen asintomático y los pacientes deben ser seguidos con el examen clínico. Sin embargo, debido a la pobre vascularización de la lesión y al trauma local, pueden producirse lesiones secundarias y osteomielitis. Los pacientes pueden presentarse con dolor, ulceración mucosa, lesión de exposición en la cavidad oral, fístula y edema. En estos casos, el correcto diagnóstico y tratamiento de la lesión es decisivo para reestabilizar la salud y la calidad de la vida. El objetivo de este artículo consistió en presentar un caso de complicación secundaria crónica de osteomielitis tratados con tratamiento conservador. El paciente, negro, de 68 años de edad, consulta por "hinchazón de las encías" que se presentó durante once años, con episodios de dolor. En el examen intraoral, se observó una pápula con supuración en la mucosa alveolar en el lado derecho de la mandíbula. La radiografía panorámica y CBCT mostraron una lesión mixta rodeada de hueso esclerótico. El paciente fue diagnosticado con osteomielitis crónica en asociación con DOF y fue tratado con tratamiento antibiótico junto con curetaje quirúrgico. La incidencia, la etiopatología, el diagnóstico diferencial, el tratamiento y la prevención de la osteomielitis secundaria asociada con DOF se discuten a la luz de la literatura. Esta información puede ayudar a los dentistas a elegir las mejores opciones de tratamiento para casos similares.

Protocol for prospective randomised assessor-blinded pilot study comparing hyperbaric oxygen therapy with PENtoxifylline+TOcopherol± CLOdronate for the management of early osteoradionecrosis of the mandible.

INTRODUCTION: Osteoradionecrosis (ORN) of the mandible is a painful and debilitating condition occurring after radiotherapy to the head and neck to treat cancer. For decades, hyperbaric oxygen (HBO) has formed the mainstay of the early management of ORN. Literature about the efficacy of HBO is contentious. Recently, Oral and Maxillofacial surgical units in France and UK have trialled a combination of medications to treat ORN, also known as PENTOCLO (PENtoxifylline+TOcopherol±CLOdronate). This regime has shown promising results to date however randomised controlled trials in the area comparing HBO against PENTOCLO are lacking and there are no current trials registered in Europe, UK, Australia and the USA. The purpose of this pilot study is to generate a hypothesis that can be tested in large multi-centre controlled trials. METHODS AND ANALYSIS: For this pilot study we will recruit 16 patients who will be randomly allocated to one of either HBO or PENTOCLO. After a 4 week period of uniform 'pre-treatment' medication patients will be commenced on their allocated treatment. Standard follow-up examination, imaging and photographs will be taken and de-identified and then presented to two Oral and Maxillofacial surgeons for allocation of a Notani & Lyons classification score. Data for each patient will be tracked over the 18 months of treatment and follow-up. The results will then be analysed using descriptive statistics and all patients included in an intention to treat analysis. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the South Metropolitan Health Service HREC (PRN RGS0000001193). Data generated by conducting this study will be uploaded to an open access repository in a de-identified form. Results from this study will be disseminated at national and international conferences as well as peer reviewed medical publications. TRIAL REGISTRATION NUMBER: ACTRN12618001099213; Pre-results.

miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects.

BACKGROUND: Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. METHODS: Western blotting and qPCR were performed to investigate the influences of miRNA-21 on osteogenic differentiation of BMSCs. The effects of miRNA-21 on PTEN/PI3K/Akt/HIF-1α pathway were also assessed using western blotting. To further evaluate the roles of miRNA-21 in osteogenesis in vivo, we conducted animal experiments in rat and canine. New bone formation was assessed using micro-CT and histological methods. RESULTS: In the present study, we found that miRNA-21 promotes the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro. Using gain- and loss-of-function studies, we found that miRNA-21 promoted the osteogenic ability of BMSCs by increasing P-Akt and HIF-1α activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/ß-tricalcium phosphate (ß-TCP) composite into critical size defects. Radiography, micro-CT, and histology revealed significantly greater volume of new bone formation in the miRNA-21 group than in the control group. CONCLUSION: In conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1α pathway.

A Comparison of 1- and 3.2-MHz Low-Intensity Pulsed Ultrasound on Osteogenesis on Porous Titanium Alloy Scaffolds: An In Vitro and In Vivo Study.

OBJECTIVES: Low-intensity pulsed ultrasound (LIPUS) combined with porous scaffolds can be used as a new therapy to treat bone defect repair. The aim of this study was to evaluate the effects of 1 and 3.2 MHz LIPUS on osteogenesis on porous Ti64 alloy scaffolds for both in vitro and in vivo studies. METHODS: Scaffolds were randomly divided into the high-frequency ultrasound group, low-frequency ultrasound group, and control group. Mouse pre-osteoblast cells were cultured with porous Ti-6Al-4V scaffolds in vitro to evaluate cell proliferation and differentiation. In addition, scaffolds were implanted into rabbit mandibular defects in vivo. The effects of LIPUS on bone regeneration were evaluated by observing the micro-computed tomography (micro-CT), toluidine blue staining, and von Kossa staining. RESULTS: The results revealed no significant difference in the cell counting kit-8 values between the ultrasound groups and control groups (P > .05). Compared with the control group, ultrasound promoted alkaline phosphatase activity and osteocalcin levels of the cells on the scaffolds (P < .05), but there was no significant difference between the two frequencies. In addition, histomorphologic analyses revealed that the volume and amount of new bone formation increased and that bone maturity improved in the ultrasound groups compared with the control group, but no significant difference was noted between the two frequencies. CONCLUSIONS: Under the present experimental conditions, LIPUS promoted osteoblast differentiation and promoted bone maturity on porous Ti64 scaffolds. No significant differences were noted between the two frequencies.

Histological and immunohistochemical evaluation of mandibular bone tissue regeneration.

The purpose of the study was to perform an immunohistochemical and histological evaluation of samples taken from different bone regeneration procedures in atrophic human mandible. 30 patients (15 men and 15 women, age range of 35-60 years), non-smokers, with good general and oral health were recruited in this study and divided into three groups. The first group included patients who were treated with blood Concentration Growth Factors (bCGF), the second group included patients who were treated with a mixture of bCGF and autologous bone, while the third group of patients was treated with bCGF and tricalcium phosphate/hydroxyapatite (TCP-HA). Six months after the regenerative procedures, all patients undergone implant surgery, and a bone biopsy was carried out in the site of implant insertion. Each sample was histologically and immunohistochemically examined. Histological evaluation showed a complete bone formation for group II, partial ossification for group I, and moderate ossification for group III. Immunohistochemical analysis demonstrated a statistically significant difference between the three groups, and the best clinical result was obtained with a mixture of bCGF and autologous bone.

An Update on Osteomyelitis Treatment in a Pycnodysostosis Patient.

PURPOSE: The aims of the present study were to discuss the demographic distribution and clinical characteristics of patients with pycnodysostosis (PYCD) and the onset of osteomyelitis and its treatment using a literature review. The authors also report on an update of treatment of mandibular osteomyelitis in a patient with PYCD using a buccal fat pad (BFP) as a free graft. PATIENTS AND METHODS: The study was carried out in 2 steps. In the first step, an electronic search was undertaken in PubMed in March 2018, with 17 articles being included. In the second step, the authors present a case of mandibular osteomyelitis in a 30-year-old woman with PYCD treated by sequestrectomy and a BFP as a free graft (follow-up, 24 months). RESULTS: Twenty-one cases of osteomyelitis of the jaws in patients with PYCD were included. Dental extraction, mandibular fracture, and 1 case of facial trauma represented the causes of mandibular osteomyelitis. Treatments included resection associated with antibiotics and sequestrectomy alone or associated with antibiotics. CONCLUSIONS: Despite the good results of the present case, further studies using the BFP as an adjuvant for jaw osteomyelitis are necessary to elucidate its clinical efficiency and safety.

Modern management of osteoradionecrosis.

PURPOSE OF REVIEW: Despite recent advances in radiotherapy, osteoradionecrosis (ORN) remains a common and difficult complication of radiation therapy in head and neck cancer patients. Available treatment options are complementary to its complex pathophysiology and the currently available theories of ORN development. The efficacy of hyperbaric oxygen therapy has recently been questioned, and therapies targeting the fibroatrophic process have become a focus of ORN treatment. The objective of this review is to evaluate the literature regarding ORN of the mandible, with a focus on available treatment options. RECENT FINDINGS: The recently proposed fibroatrophic theory has challenged the traditional hypovascular-hypoxic-hypocellular theory as the mechanism of ORN. Medical management targeting this fibroatrophic process offers promising results, but has yet to be confirmed with robust clinical trials. The routine use of hyperbaric oxygen therapy is not substantiated in the literature, but may be justified for select patients. Systemic steroids may also have a role, though data are limited. SUMMARY: The fibroatrophic process has gained acceptance as a main mechanism of ORN. No gold standard treatment or consensus guidelines exist, though a combination of therapeutic strategies should be considered, taking into account the severity of disease and individual patient characteristics.