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PubMed2005

Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial.

BACKGROUND: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Is a treatment combining pentoxifylline (PTX) and tocopherol (vitamin E) boosted by clodronate effective in reversing this fibronecrotic process? METHODS: Eighteen consecutive patients previously irradiated for head and neck cancer had exteriorized mandible ORN. Length of exposed bone (L) was 13.4 +/- 8 mm, and the mean subjective objective medical management and analytic evaluation of injury (SOMA) score was 12.6 +/- 4.9. Between June 1995 and January 2002, all 18 were given a daily oral combination of 800 mg of PTX and 1000 IU of vitamin E for 6 to 24 months. In addition, the last eight patients who were the worst cases were given 1600 mg/day clodronate 5 days a week. RESULTS: The treatment was well tolerated. All patients improved at 6 months, with 84% mean L and 67% mean SOMA score reductions. Sixteen (89%) of 18 patients achieved complete recovery, 14 in 5 +/- 2.6 months. The remaining two patients exhibited a 75% response at 6 months. CONCLUSION: PTX-vitamin E boosted by clodronate is an effective treatment of mandibular ORN that induces mucosal and bone healing in a median period of 6 months.

Adult↗

PubMed2007

Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible?

BACKGROUND: This study was done to determine if pre-radiotherapy (pre-RT) dental extractions reduce the risk of osteoradionecrosis (ORN). METHODS: Between 1987 and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive RT at the University of Florida. Dentate patients underwent pretreatment dental evaluation. Teeth in the RT field were usually extracted if thought to have poor long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN using a modified staging system. Patients were excluded for local recurrence, additional RT above the clavicles, or head and neck surgery besides neck dissection. RESULTS: ORN rates were as follows: edentulous, <1%; teeth in-field with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%. Patients with poor in-field teeth and pre-RT extractions had a higher 5-year incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p = .48). Likewise, for those with in-field teeth in good condition and pre-RT extractions, the 5-year ORN incidence was higher than for those who did not undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed increased ORN risk with doses of >70 Gy, once-daily fractionation, or brachytherapy. CONCLUSION: Pre-RT extractions do not appear to reduce the risk of ORN.

Adult↗

PubMedDate not supplied

Transoral mandibulectomy in advanced osteoradionecrosis.

Because vascularity is severely compromised following radiation therapy, aseptic necrosis with secondary infection and extensive bone destruction can result in an advanced state of osteoradionecrosis. Transoral mandibulectomy is an excellent method for dealing with this difficult problem. This article discusses technical aspects of the procedure as well as applied anatomy and a case report. Evidence in the recent literature concerning hyperbaric oxygen therapy is very encouraging.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Osteoradionecrosis: predisposing factors and outcomes of therapy.

Eighty-three episodes of osteoradionecrosis are reported. Of those episodes affecting the mandible (78), 23 (29.5%) required radical resection. The most common precipitating factors were postradiation extractions (22/83), periodontal disease (19/83), and preradiation extractions (17/83). Those episodes initially located within the zone of attached mucosa fared well with conservative measures while those initially located beyond the zone of attached mucosa fared poorly. In bone necroses where the external radiation dose to the affected bone exceeded 7,000 rad, the mandibular resection rate was high (44%). The most effective way of resolving advanced bone necroses was achieved with a course of hyperbaric oxygen therapy combined with a surgical sequestrectomy.

Combined Modality Therapy↗

PubMed2006

Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT).

BACKGROUND AND PURPOSE: Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance. PATIENTS AND METHODS: Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup "at risk" for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12-46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance. RESULTS: Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm(3) were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed. CONCLUSION: Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.

Adult↗

PubMed2006

Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis--a paradoxical observation?

Erosion of the bone is a common problem in patients suffering from infected osteoradionecrosis (IORN) or bisphosphonate-associated osteonecrosis (BON). Besides inflammatory mechanisms and infectious agents, osteoclasts were recently suggested to be specifically involved in the osteolytic mechanisms. We therefore investigated the immunohistochemical labeling of the cysteine proteinase cathepsin K, which plays a central role in osteoclast-mediated bone resorption, in tissue specimens of patients with BON (n=9; four male, five female; mean age=69.2 years) and IORN (n=10; nine male, one female; mean age=60.5 years), and compared the results with control specimens (n=8; six male, two female; mean age=60 years). In all cases, osteoclasts were the predominant cell type expressing cathepsin K. For semiquantitative analysis, we therefore defined osteoclasts as multinuclear giant cells attached to the bone and expressing cathepsin K. Significantly higher numbers of osteoclasts were found for both types of osteonecrosis when compared with the control group (BON+IORN vs controls: P=0.0000036). Within the pathological lesions, IORN cases exhibited significantly less osteoclasts than BON (P=0.00097). Our study verified increased numbers of osteoclasts in patients suffering from BON and IORN. Although it is known that bisphosphonates (and to a lesser extent, irradiation, too) decrease osteoclast function, these findings suggest a critical involvement of osteoclasts in the mechanisms of bone destruction in the respective lesions.

Adult↗

PubMed1989

Osteoradionecrosis related to mastication and parafunction.

This article discusses mastication and parafunctional habits as possible etiologic factors in the development of osteoradionecrosis. From the three case reports presented it was noted that bone necrosis can occur after extended periods after radiation therapy, is seen most frequently in the mandible, and occurs most often at dosage levels exceeding 6500 rad. Recommendations after treatment to patients receiving 6500 rad or more should include caution regarding consistency of diet, use of existing prostheses, and the potential harmful effects of parafunctional habits.

Carcinoma, Squamous Cell↗

PubMed1986

The management of osteoradionecrosis of the jaws.

Therapeutic measures used in the management of osteoradionecrosis (ORN) of the jaws are reviewed with reference to clinical case material. The development of rational treatment regimes designed to deal with the underlying pathological problem are discussed.

Anti-Bacterial Agents↗

PubMed1992

The conservative management of osteoradionecrosis of the mandible with ultrasound therapy.

A regimen of ultrasound with local debridement and metronidazole has proved to be an effective and practicable treatment for osteoradionecrosis, achieving healing in 10/21 (48%) cases without the need for surgery or sophisticated technology. Nine further patients were successfully treated by covering the preserved mandible with a local intra-oral flap. Only 2 patients required mandibular resection with reconstruction. An ultrasound programme of 1 watt/cm2, 3 mega Hz. pulsed 1:4, 15 min a day for 60 days would seem to be optimum. However, a range of dosage needs to be further explored for inducing neovascularity and neocellularity in the irradiated tissues.

Brachytherapy↗

PubMed1986

Osteoradionecrosis of the jaws.

One hundred nine cases involving patients who had received radiation therapy for head and neck cancer were reviewed. Osteoradionecrosis of the mandible developed in only three patients in this group. Postirradiation extractions were not identified as a significant risk factor for such necrosis.

Cobalt Radioisotopes↗

PubMed2005

DNA-DNA hybridization demonstrates multiple bacteria in osteoradionecrosis.

Bone necrosis secondary to radiation was previously attributed to trauma of devitalized bone and microbiological sepsis. However, conventional microbiological technique has failed to demonstrate microorganisms throughout osteoradionecrotic bone, claimed to be hypoxic, hypovascular and hypocellular. The aim of the present study was to examine such bone for bacteria using DNA-DNA hybridization. Compared to standard culture methods this technique enables the investigation of a vast number of bacteria in a fairly short time. Twelve deep medullary specimens from resected radionecrotic mandibles were studied. A multitude of bacterial species were detected, most of them anaerobic. Porphyromonas gingivalis was the most predominant organism, followed by Fusobacterium nucleatum subspecies polymorphum. All samples contained Actinomyces, Prevotella and F. nucleatum. The results of this study indicate that bacteria, particularly anaerobes, may play a more fundamental role in the pathophysiology of osteoradionecrosis than being merely surface contaminants.

Actinomyces↗

PubMed2006

Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies.

Infected osteoradionecrosis (IORN) is one of the major complications of oral cancer radiotherapy. Recent studies showed a high prevalence of Actinomyces in IORN. In this study, the clinical follow up of IORN patients (n=25; 20 male, 5 female) with regard to Actinomyces detection in the mandible was analyzed. Within 1.6-119 months of follow up, disease control was achieved in almost 90% of the patients with Actinomyces-negative bone biopsies, but only in 25% of the Actinomyces-positive group. The presence of Actinomyces was associated with a significantly higher risk of treatment failure (P=0.004; Fisher's exact test). This held true when the data were controlled for 'extent of bone destruction', 'type of surgery' and 'soft-tissue closure' in a logistic regression analysis (P=0.018; Wald test). Since Actinomyces was detected in a significant number of patients with non-healing mucosal defects, this microbe may promote the persistence of chronic non-healing inflammatory processes. Actinomyces positivity defines a subpopulation with a clinically deteriorated course of mandibular IORN.

Actinomyces↗

PubMed2005

A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients.

PURPOSE: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. METHODS AND MATERIALS: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. RESULTS: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. CONCLUSIONS: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

Female↗

PubMed2006

Osteoradionecrosis prevention myths.

PURPOSE: To critically analyze controversial osteoradionecrosis (ORN) prevention techniques, including preradiation extractions of healthy or restorable teeth and the use of prophylactic antibiotics or hyperbaric oxygen (HBO) treatments for preradiation and postradiation extractions. METHODS: The author reviewed ORN studies found on PubMed and in other article references, including studies on overall ORN incidence and pre- and postradiation incidence, with and without prophylactic HBO or antibiotics. RESULTS: Owing in part to more efficient radiation techniques, the incidence of ORN has been declining in radiation patients over the last 2 decades, but the prevention of ORN remains controversial. A review of the available literature does not support the preradiation extraction of restorable or healthy teeth. There is also insufficient evidence to support the use of prophylactic HBO treatments or prophylactic antibiotics before extractions or other oral surgical procedures in radiation patients. CONCLUSIONS: To prevent ORN, irradiated dental patients should maintain a high level of oral health. A preradiation referral for a dental evaluation and close collaboration by a multidisciplinary team can be invaluable for radiation patients. As with most other dental patients, restorable and healthy teeth should be retained in irradiated patients. The use of prophylactic HBO or antibiotics should be reconsidered for preradiation and postradiation extractions.

Antibiotic Prophylaxis↗

PubMed2004

Risk of osteoradionecrosis after extraction of impacted third molars in irradiated head and neck cancer patients.

PURPOSE: This study was performed to compare the risk of osteoradionecrosis (ORN) in head and neck cancer patients in whom 1 or more impacted third molars were extracted before radiotherapy with patients whose impacted third molars were left intact. PATIENTS AND METHODS: Eighty-one patients were selected from the medical records from 1989 to 1998. Patients had at least 1 impacted third molar and received radiotherapy for a head and neck cancer. These patients were divided into 2 groups on the basis of preirradiation extraction: group 1, patients who had impacted third molars extracted before radiotherapy (n = 55), and group 2, patients whose impacted third molars were left intact before radiotherapy (n = 38). In 12 patients of combined groups 1 and 2, at least 1 but not all of the impacted third molars were extracted before radiotherapy. RESULTS: Before radiotherapy, a total of 99 impacted third molars were extracted from the 55 patients in group 1 and a total of 55 impacted third molars were left intact in the 38 patients in group 2. After radiotherapy, a total of 7 impacted third molars were removed from 5 patients as treatment for infection (5 lower molars) or discomfort (2 upper molars). A total of 4 patients (2 from group 1 and 2 from group 2) developed ORN in the mandible. Of these 4 cases of ORN, 1 from group 1 appeared to be related to a dry socket that developed after preirradiation extraction of a lower impacted third molar, 1 from group 2 seemed to be related to infection of a lower impacted third molar after radiotherapy, and the remaining 2 cases appeared to be unrelated to an impacted third molar. CONCLUSION: Because few patients in this study developed ORN, the study failed to demonstrate whether preirradiation extraction versus retention of impacted third molars affects the risk for ORN.

Adolescent↗

PubMed2005

The role of the osteocutaneous radial forearm free flap in the treatment of mandibular osteoradionecrosis.

OBJECTIVE: To evaluate the role of the osteocutaneous radial forearm free flap (OCRFFF) in the treatment of mandibular osteoradionecrosis (ORN). STUDY DESIGN AND SETTING: Retrospective case review of patients who underwent OCRFFF oromandibular reconstruction after resection of nonviable tissue at an academic tertiary care center because of ORN. Patients with reconstructions other than OCRFFF were excluded from this study. RESULTS: Nine patients underwent a composite oromandibular resection for ORN with a reconstruction using an OCRFFF between April 1998 and February 2003. All patients had failed previous less aggressive surgical and medical management of the ORN. Mean follow-up was 36 months (range, 14-67 months). There were no flap failures or significant immediate postoperative or long-term complications observed. All patients had successful restoration of mandibular integrity and continuity, with 100% success rate of stabilization of ORN. All patients were able to tolerate PO diet, with only one third having to supplement their diet with gastrostomy feedings, compared with 89% gastrostomy dependence preoperatively. CONCLUSIONS: Primary or adjuvant radiotherapy for head and neck malignancies can result in ORN of the mandible. This difficult problem often requires surgical intervention. In our experience, the OCRFFF can be successfully used for oromandibular reconstruction, even in the setting of the heavily radiated tissue with excellent postoperative outcomes. SIGNIFICANCE: This is the first study that demonstrates the efficacy of the OCRFFF as a treatment of mandibular ORN.

Aged↗

PubMed2003

Reconstructive options in the treatment of osteoradionecrosis of the craniomaxillofacial skeleton.

Osteoradionecrosis (ORN) of the craniomaxillofacial skeleton is a serious and debilitating complication that can occur following radiation therapy in the head and neck. Patients require effective treatment, which eradicates diseased tissue and restores function with minimal additional morbidity in a single stage, a requirement fulfilled in many cases by free tissue transfer. In a 6-year period from 1994 to 1999, 21 patients with ORN were treated by wide resection and free-flap reconstruction. The median interval between radiation therapy and ORN was 4 years (range: 1-33 years). The median radiation dose was 6000cGy. The affected areas were the mandible (15 patients), the temporal bone (three patients), the maxilla (one patient), the cervical vertebrae (one patient) and the frontal bone (one patient). Clinical symptoms included pain, ulceration, a persistent draining fistula, exposure of bone or hardware, and pathological fracture or non-union of bone. Six patients had had previous unsuccessful attempts at conservative surgical resection. Ten patients had preoperative hyperbaric oxygen (HBO) therapy. A number of different flaps were used for reconstruction in these patients. These included free fibula flaps (13 patients), iliac crest flaps (two patients), scapula flaps (three patients) and rectus abdominis flaps (three patients). All patients achieved relief from their presenting symptoms and primary bone or wound healing. One flap (4.8%) was lost. This was successfully reconstructed in a subsequent procedure. There were three flap re-explorations, two for arterial thrombosis and one for venous thrombosis. Conservative measures, such as limited debridement and HBO therapy, may be effective in preventing the progression of ORN. However, they fail to eradicate established ORN, which requires radical surgical resection followed by functional reconstruction with well-vascularised tissue.

Aged↗

PubMedDate not supplied

Osteoradionecrosis of the cervical vertebrae and occipital bone: a case report and brief review of the literature.

Osteoradionecrosis (ORN) is a common complication of radiation therapy. We present the first case reported in the literature of ORN involving the first and second cervical vertebrae and occipital bone in a patient who was treated with surgery and radiation therapy 9 years prior for a TxN3M0 squamous cell carcinoma of the left neck arising from an unknown primary origin. A brief review of the pathophysiology and treatment of this pathological process is also presented. Although the mandible is the most commonly affected site in the head and neck, ORN may develop in an unusual location without any preceding trauma and display an insidious but rapidly progressive course. The pathophysiology of ORN is believed to be a complex metabolic and homeostatic deficiency created by radiation-induced cellular injury and fibrosis, which is characterized by the formation of hypoxic, hypovascular, and hypocellular tissue. The irradiated bone loses its capability to increase the metabolic requirements and nutrient supply required to replace normal collagen and cellular components lost through routine wear. This results in tissue breakdown and the formation of a chronic nonhealing wound. Infection plays only a contaminant role, with trauma being a possible initiating factor. Diagnosis of ORN begins with a complete physical examination, including fiberoptic examination and biopsy of any suspicious lesion to eliminate the possibility of recurrent tumor. Treatment of ORN commonly requires the debridement of necrotic bone and hyperbaric oxygen therapy. The head and neck surgeon must possess a high degree of suspicion to promptly diagnose ORN and initiate early treatment. Because of similarities in clinical presentation, the most important step in the initial management of suspected ORN is to eliminate the possibility of tumor recurrence or a new primary.

Bone Diseases↗