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.

Comparison of Australian and New Zealand referral rates for hyperbaric oxygen in oro-facial osteoradionecrosis: evidence-based, funding constraint or clinician whim?

AIM: To compare Australian and New Zealand (NZ) rates of referral to hyperbaric units for patients with, or at risk of developing mandibular or maxillary osteoradionecrosis (ORN) due to a history of radiotherapy for oro-pharyngeal cancer. METHOD: Relevant patient treatment data from all hyperbaric units in Australia and NZ were collated and analysed. RESULTS: The rate of referral to hyperbaric units in Australia for treatment or prophylaxis of patients with, or at risk of oro-facial ORN, was 1.7 times the rate of referral in NZ. Within Australia, there was a greater than three-fold interstate variation. CONCLUSION: There is a significant referral rate difference both within Australia and between Australia and NZ for hyperbaric oxygen therapy for oro-facial ORN. Possible reasons for this difference include access to funding, logistical difficulties, clinician preference for an alternative treatment and clinician attitudes to hyperbaric oxygen.

Hyperbaric oxygen therapy as a prevention modality for radiation damage in the mandibles of mice.

BACKGROUND: Radiation therapy (RT) as part head and neck cancer treatment often leads to irradiation of surrounding normal tissue, such as mandibular bone. A reduced reparative capacity of the bone can lead to osteoradionecrosis (ORN). Hyperbaric oxygen therapy (HBOT) is used to treat ORN, based on its potential to raise the oxygen tension in tissues. However, prevention of radiation-induced damage is of great interest. Our purpose was to investigate whether HBOT could prevent radiation-induced damage to murine mandibles. METHODS: Twenty-eight mice were irradiated in the head and neck region with a single dose (15 Gy) and half of them were subsequently subjected to HBOT. Another 14 mice did not receive any treatment and served as controls. Ten and 24 weeks after RT, mandibles were harvested and analysed histologically and by microcomputed tomography (micro-CT). RESULTS: Micro-CT analysis showed a reduction in relative bone volume by RT, which was partly recovered by HBOT. Trabecular thickness and separation were also positively influenced by HBOT. Morphologically, HBOT suppressed the osteoclast number, indicating decreased resorption, and decreased the amount of lacunae devoid of osteocytes, indicating increased bone viability. CONCLUSIONS: HBOT was able to partly reduce radiation-induced effects on microarchitectural parameters, resorption, and bone viability in mouse mandibles. HBOT could therefore potentially play a role in the prevention of radiation-induced damage to human mandibular bone.

Professional attitudes in regard to hyperbaric oxygen therapy for dental extractions in irradiated patients: a comparison of two specialties.

OBJECTIVES: Mandibular osteoradionecrosis (ORN) is a serious complication of radiation therapy. The current use of hyperbaric oxygen therapy (HBO2) to prevent ORN when dental extractions are performed has been called into question. We sought to determine the current acceptability and confidence in this treatment by practitioners from two different specialties. METHODS: We surveyed both hyperbaric medicine physicians and radiation oncologists regarding their views on the use of HBO2 for the prevention of ORN. Separate web-based anonymous surveys were sent via email invitation. These two groups were compared, including statistical analysis using the chi-square test when appropriate. RESULTS: 175 radiation oncologists and 118 hyperbaric medicine physicians participated. Among those not recommending HBO2, lack of evidence was cited by 52% of radiation oncologists and 38% of hyperbaric medicine physicians (chi2 = 5.0, p = 0.03, 95%, CI 1.9% to 25.6%). A majority of radiation oncologists (79%) and hyperbaric medicine physicians (85%) believe it is important that a new randomized controlled trial (RCT) is conducted (chi2 = 1.3, p = NS). CONCLUSIONS: While HBO2 has been used for decades, recent tissue-sparing radiation techniques and advanced surgical techniques are now calling into question the continued use of HBO2 for ORN prevention. Our results demonstrate that there is overwhelming support among responding practitioners for a new RCT.

Osteoradionecrosis.

Osteoradionecrosis (ORN) is a severe complication of radiation therapy for head and neck cancer. The current theory in its pathophysiology is thought to be radiation-induced fibroatrophy of the bone. Location of primary tumor, stage of cancer, dose of radiation, oral hygiene, and smoking and alcohol use are risk factors in the development of ORN. Prevention is focused on thorough dental care before, during, and after radiation therapy. Treatment ranges from conservative management with oral rinses and local debridement to radical resection with microvascular free tissue transfer and reconstruction.

Hyperbaric oxygen in the management of late radiation injury to the head and neck. Part II: prevention.

Osteoradionecrosis (ORN) of the jaws is a feared complication of treatment for head and neck cancer, and understandably much attention has been given to its prevention; good oral hygiene, careful preventative dental care, and extractions done before radiotherapy have been highlighted by many authors. Such necessary dental extractions when the healing capacity of the bone is normal will, it is hoped, reduce the incidence of subsequent ORN. This review considers the optimal dental management of patients before radiotherapy as well as the evidence base for treatment with hyperbaric oxygen (HBO) before extractions in patients who have had radiotherapy.

Protective effects of baicalin on ligature-induced periodontitis in rats.

BACKGROUND AND OBJECTIVE: Baicalin is a flavonoid compound purified from the medicinal plant, Scutellaria baicalensis Georgi, and has been reported to possess anti-inflammatory and antioxidant activities. The purpose of this study was to test the ability of baicalin to influence the progression of experimental periodontitis in rats, as well as the expression of cyclooxygenase-2 and inducible nitric oxide synthase. MATERIAL AND METHODS: Adult male Sprague-Dawley rats were subjected to placement of a nylon thread around the bilateral lower first molars and killed after 7 d. Baicalin (50, 100 or 200 mg/kg) was supplied to the animals by oral gavage, starting 1 d before the induction of periodontitis. The ligature group consisted of rats subjected to periodontitis and receiving vehicle (0.5% carboxymethylcellulose) alone. The alveolar bone loss and the area fraction occupied by collagen fibers were assessed. The expression of cyclooxygenase-2 and inducible nitric oxide synthase protein in the gingiva were detected by immunohistochemistry and western blotting. RESULTS: Baicalin-treated groups presented with lower alveolar bone loss than that of the ligature group, reaching statistical significance at the dose of 200 mg/kg (p = 0.009). The area fraction of collagen fibers was significantly higher in the baicalin (200 mg/kg)-treated group than in the ligature group (p = 0.047). Baicalin treatment significantly down-regulated the protein expression for cyclooxygenase-2 (p = 0.000) and inducible nitric oxide synthase (p = 0.003), compared with the ligature group. CONCLUSION: Baicalin protects against tissue damage in ligature-induced periodontitis in rats, which might be mediated, in part, by its inhibitory effect on the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These activities could support the continued investigation of baicalin as a potential therapeutic agent in periodontal disease.

Immediate placement of implants and appliance in an irradiated patient: a case study.

PURPOSE: The purpose of this study was to evaluate the immediate placement of implants and appliance using hyperbaric oxygenation on a 45-year-old male with a history of squamous cell carcinoma of the floor of the mouth. MATERIALS: Five Nobel Biocare implants between the mental foamina were used along with a course of pre- and postsurgical hyperbaric oxygenation. RESULTS: After 39 months, the patient is symptom free and shows no signs of rejection. Conclusion Using an accepted hyperbaric oxygenation protocol when placing and restoring immediate implants in this patient resulted in a successful treatment outcome.

Dietary supplementation of omega-3 fatty acid and circulating levels of interleukin-1beta, osteocalcin, and C-reactive protein in rats.

BACKGROUND: In this study, we evaluated the effects of two different regimes of dietary supplementation of omega-3 fatty acid on serum levels of interleukin-1 beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis was induced by repeated injections of Escherichia coli lipopolysaccharide (LPS). Thirty-nine adult male Sprague-Dawley rats were divided into four study groups as follows: an LPS positive control group; a saline (negative) control group; and two different groups with omega-3 fatty acid dietary supplementation, one in which we gave the supplement subsequent to disease induction (TO3) and the other in which the agent was started prior to and continued subsequent to LPS injections (P + TO3). In the TO3 group, omega-3 fatty acid administration was performed for 14 days following induction of experimental periodontitis. In the P + TO3 group, omega-3 fatty acid was given for 14 days prior to the start of LPS injections and was continued for another 14 days subsequent to the induction of experimental periodontitis. On day 15 of the first LPS injection, serum samples were obtained and rats were sacrificed. Serum samples were analyzed for IL-1beta, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: LPS injection resulted in statistically significantly more bone loss compared to the saline control group (P <0.05). None of the omega-3 fatty acid administration groups showed evidence that this fatty acid was effective in preventing LPS-induced alveolar bone loss. TO3 and P + TO3 groups revealed significantly higher IL-1beta and OC levels than the LPS group (P <0.05). The study groups exhibited no significant differences in the serum CRP levels. CONCLUSIONS: Omega-3 fatty acid administration does not seem to influence circulating levels of CRP. The significantly increased serum OC level observed in both omega-3 fatty acid regimes is curious and could have an effect on bone turnover, as could the further significant increase in serum IL-1beta, which could counteract any osteoblastic induction by OC through promotion of osteoclast activity. The lack of a therapeutic benefit of omega-3 fatty acid in this study, despite the effects on OC and IL-1beta, is difficult to explain, and further studies are required to more fully assess the potential role of this fatty acid in periodontal treatment.

Protective effects of etoricoxib, a selective inhibitor of cyclooxygenase-2, in experimental periodontitis in rats.

BACKGROUND: The purpose of the present study was to evaluate the effect of a potent selective cyclooxygenase-2 (COX-2) inhibitor, etoricoxib, on the prevention of alveolar bone loss in experimental periodontitis induced in rats. METHODS: Ninety Wistar rats were separated into three experimental groups. Cotton ligatures were placed at the gingival margin level of lower right first molars. The rats were randomly assigned to one of the following groups: control received a daily oral dose of 1 ml/kg of saline solution; Eto1 received 6 mg/kg of etoricoxib; Eto2 received 12 mg/kg of etoricoxib. Serum levels of etoricoxib and white blood cells were determined. Standardized digital radiographs were taken after death at 3, 5, 10, 18 and 30 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat. RESULTS: One-way analysis of variance (anova) indicated that groups treated with both doses of etoricoxib had significantly (p < 0.05) less alveolar bone loss when compared to controls. Furthermore, etoricoxib treatment significantly inhibited the leukocytosis observed 3 days after the induction of periodontitis. CONCLUSION: These data provide evidence that systemic therapy with etoricoxib can retard alveolar bone loss in a ligature-induced periodontitis model in rats.

[Mandibular osteoradionecrosis: sword of Damocles of radiotherapy for head and neck cancers?]. / L'ostéoradionécrose mandibulaire: épée de damoclès de la radiothérapie cervico-faciale?

Radiotherapy of head and neck cancer is efficient but may have severe late effects. Although unfrequent, mandibular radionecrosis is the most dreadful. A cascade of events leads from hyposialia to bone destruction through extensive caries and trauma linked to tooth removal. Prevention is based on oral hygiene and use of daily topical fluorides. Antibiotics and hyperbaric oxygen can be effective as a conservative management. Progressive osteonecrosis is best treated by mandible resection and reconstruction with microvascular free bone flaps. Patient compliance to prophylaxis is of major importance. The need for periodic follow-up under the supervision of the radiation oncologist is stressed and illustrated by a clinical case having experienced disastrous consequences.

TMJ fractures in children: importance of functional activation of muscles in preventing mandibular asymmetries and facial maldevelopment.

Normal development of the mandible as well as some portions of the upper jaw and face are related to good function of the masticatory apparatus: the integrity and interaction of bony and soft-tissue structures may be highly disturbed by injury of the TM joints and result in facial and occlusal disharmonies. When the neuromuscular system is in harmony, the mandibular muscles collectively exert their effect on both position and movement of the jaw and the loading of forces on the TM joints is optimal and balanced. Unfortunately, TMJ fractures may alter completely this balance with loss of the support to the mandible against the temporal component and loss of the functional effect of the lateral pterygoid muscle on the mandible. Disturbances in the harmonious interplay of the masticatory muscles may result in facial alteration and asymmetries. If not treated, the dysplastic patterns of growth continues and worsens during the years.

A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach.

The treatment of delayed radiation injuries (soft tissue and bony radiation necrosis) is one of thirteen conditions approved by the Hyperbaric Oxygen Therapy Committee of the Undersea and Hyperbaric Medical Society as appropriate indications for hyperbaric oxygen (HBO2). This paper provides a systematic review of the literature reporting the results of HBO2 therapy in the treatment and/or prophylaxis of delayed radiation injury. Since the introduction of the concept of evidence based medicine, the medical community in general has set out to apply more critical and stringent standards in evaluating published support for therapeutic interventions. Evidence based medicine is designed to discover the best evidence available and apply it in daily practice for treatment of the individual patient. The preferred level of evidence is the randomized controlled trial, however, other evidence has merit as well. In this review, seventy-four publications are represented reporting results of applying HBO2 in the treatment or prevention of radiation injuries. These are appraised in an evidence-based fashion by applying three established systems of evaluation. All but seven of these publications report a positive result when HBO2 is delivered as treatment for or prevention of delayed radiation injury. These results are particularly impressive in the context of alternative interventions. Without HBO2, treatment often requires radical surgical intervention, which is likely to result in complications. Other alternatives including drug therapies are rarely reported, and for the most part have not been the subject of randomized controlled trials. Based on this review, HBO2 is recommended for delayed radiation injuries for soft tissue and bony injuries of most sites. Of note, an increasing body of evidence supports HBO2 for radiation-induced necrosis of the brain. For other radiation-induced neurological injuries, additional study is required before recommendations for routine hyperbaric therapy can be made.

Hyperbaric oxygen therapy and mandibular osteoradionecrosis: a retrospective study and analysis of treatment outcomes.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is recognized as an adjunctive treatment for osteoradionecrosis (ORN). It may also be used prophylactically in patients who require dental extractions and are at high risk for developing ORN. This article reviews the treatment outcomes of patients treated with HBO therapy at the Toronto General Hospital from 1985 to 1997. MATERIALS AND METHODS: A total of 297 charts of patients treated with HBO were reviewed. Criteria assessed included age of patient, gender, original diagnosis, radiation dose, time between radiation treatment and onset of ORN, presence or absence of fracture, orocutaneous fistula, pain, history of a precipitating event triggering ORN, medical status, HBO therapy (total oxygen time, number of dives), method of treatment of ORN and follow-up period. Minimum patient follow-up time for inclusion in the study was 6 months. RESULTS: Adequate information to meet the inclusion criteria was obtained for 75 patients. Group A (51 patients) had been treated for overt ORN with HBO alone, HBO with sequestrectomy, or HBO with sequestrectomy and reconstruction. Group B (24 patients at risk for developing ORN) had been treated with HBO prophylactically for dental extractions. In group A, only 3 patients (5.9%) failed to show improvement. In group B, only one patient (4.2%) had complications during healing. CONCLUSIONS: Encouraging results were achieved when HBO was used in the 2 groups described above. This paper supports existing literature on the potential benefit of HBO as a prophylactic agent and adjunctive treatment of ORN.

A review of the Marx protocols: prevention and management of osteoradionecrosis by combining surgery and hyperbaric oxygen therapy.

The 30/10 protocol is employed in the treatment of established osteoradionecrosis. No surgery should be attempted before the first 30 HBO treatments have provided sufficient angiogenesis to support surgical wounding. After 30 treatments surgical management can be staged according to the extent of improvement achieved after HBO and the size of sequestrum or area of osteolysis. If the ORN extends to the inferior border of the mandible or if it manifests as an orocutaneous fistula or pathological fracture, discontinuity resection of the necrotic bone and soft tissue will be required to resolve the disease. Unless HBO and surgery are combined in the management of ORN, the results are not long lasting or satisfactory. Even though resection of stage three ORN seems unduly aggressive, it has stood the test of time. By using the Marx protocols in the treatment of ORN, more than 95 per cent of patients can be successfully cured of their disease with predictable, functional and aesthetically acceptable outcomes.

Titanium osseointegrated implants combined with hyperbaric oxygen therapy in previously irradiated mandibles.

STATEMENT OF PROBLEM: Treatment for head and neck malignancies commonly involves radiation therapy. As a result of this therapy the vascular supply to irradiated structures is altered and results in decreased tissue perfusion. In addition to vascular changes, bony structures undergo a reduction in osteoblastic and osteoclastic activity. These tissue alterations, especially in the mandible, enhance the risk of osteoradionecrosis. To avoid this occurrence, many patients who have undergone radiation therapy do not receive elective preprosthetic surgeries, including implant therapy. PURPOSE OF STUDY AND METHODS: This report presents the preliminary results of placing 18 titanium screw implants into previously irradiated mandibles in conjunction with hyperbaric oxygen therapy. RESULTS: Of the 18 implants placed, 17 (94%) were judged to be osseointegrated at the abutment connection. One implant did not receive an abutment and was "put to sleep." The remaining 16 (88%) were used for prosthetic rehabilitation. CONCLUSION: The use of implants in irradiated tissues may provide a means of enhancing prosthetic rehabilitation while reducing the risk of tissue trauma that may develop into osteoradionecrosis.

Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin.

A prospective randomized trial comparing hyperbaric oxygen and systemic antibiotics in the prevention of osteoradionecrosis was presented. The results indicated, in a high-risk population who required tooth removal in irradiated mandibles, that up-front hyperbaric oxygen produced an incidence of osteoradionecrosis of 5.4% as compared with the antibiotic group of 29.9% (P = .005). Hyperbaric oxygen should be considered a prophylactic measure when post-irradiation dental care involving trauma to tissue is necessary.