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Osteonecrosis of the jaws in patients treated with bisphosphonates - histomorphologic analysis in comparison with infected osteoradionecrosis.

BACKGROUND: Patients treated with bisphosphonates because of bone metastases have been shown to develop osteonecrosis of the jaws. In the present study, we examined the histologic findings of these cases. As similarities between this disorder and infected osteoradionecrosis (IORN) are described, both lesions were compared. METHODS: We investigated eight patients with bisphosphonate treatment and osteonecrosis (four female, four male; median age: 65.6 years; cancer: multiple myeloma in five patients, breast cancer in three patients; mandibular involvement in five patients, maxillar involvement in three cases), and 10 patients suffering from IORN (all male; median age: 61.3 years; cancer: squamous cell carcinoma in nine patients, adenoid cystic carcinoma in one patient; mandibular involvement in all cases). Multicentric and bilateral involvement was common in the bisphosphonate group. Histologically, the bone revealed diffuse and patchy areas of necrosis in the bisphosphonate group, while in IORN osteonecrosis was larger and not diffusely distributed. RESULTS: In all cases, we found Actinomyces attached to the necrotic bone tissue. In five of eight bisphosphonates cases, and in six of 10 IORN cases, numerous osteoclasts could be detected close to vital bone exhibiting signs of bone resorption. Pseudoepitheliomatous hyperplasia (PH) was revealed in five of eight bisphosphonate patients, and in seven of 10 IORN patients. CONCLUSION: We conclude that Actinomyces is involved in the chronic, non-healing inflammatory processes as a characteristic feature of both diseases. Together with the associated presence of increased osteoclast numbers, we suggest that both factors may be involved in osteolytic mechanisms.

Actinomyces↗

Incidence of complicated healing and osteoradionecrosis following tooth extraction in patients receiving radiotherapy for treatment of nasopharyngeal carcinoma.

A group of 43 patients requiring tooth extraction after radiotherapy for nasopharyngeal carcinoma (NPC) was studied retrospectively to determine the incidence of post-extraction complications. It was found that because of the method used in the delivery of radiation, extraction of maxillary posterior teeth resulted in the greatest risk of complications (28.9 per cent), including a 10.5 per cent risk of osteoradionecrosis (ORN). Based on the findings, a protocol was established for the dental care of such patients. It was concluded that when extraction of maxillary posterior teeth was necessary, prophylactic antibiotics were not sufficient to prevent the complication of delayed healing. The risk of ORN was 10.5 per cent within the field of maximal radiation dose. Hyperbaric oxygen may be the better choice of preventive measures. However, in view of the low risk of ORN, wholesale prescription of hyperbaric oxygen therapy may not be indicated. An additional patient who had tooth extraction two weeks prior to radiotherapy was included to show that if adequate time for wound healing was not allowed, ORN could develop.

Adult↗

Hyperbaric oxygen in the prevention of osteoradionecrosis of the jaws.

Patients who have had their jaws irradiated as part of management of head and neck malignancy are at risk of osteoradionecrosis (ORN) following tooth extraction. Thirty-seven patients with a history of irradiation to the jaws were managed during a four year period. Twenty-nine patients received hyperbaric oxygen therapy (HBO) consisting of 20 treatments before surgery and ten treatments after. Only one (4 per cent) developed ORN. Seven patients who did not have HBO and one who did (15 per cent) developed ORN. The need for prophylactic treatment with HBO is discussed. It is recommended that prophylactic HBO is used prior to surgery for irradiated facial bones.

Adult↗

Surgical management of osteoradionecrosis of the temporal bone.

The surgical management of osteoradionecrosis of the temporal bone has met with limited success because of the difficulty in accurate assessment of the viability of nonnecrotic bone intraoperatively. Failure to resect all nonviable bone results in recurrence of a necrotic focus. With the use of hyperbaric oxygen therapy to stabilize marginal bone and oral tetracycline to label viable bone preoperatively, removal of all nonviable bone can be accomplished. Postoperatively, a second course of hyperbaric therapy enhances wound healing, thus assuring a successful outcome. This article details a successful systematic approach that was developed to resect a necrotic focus in the temporal bone of a 10-year-old boy who had undergone a full course of radiotherapy for treatment of a rhabdomyosarcoma.

Child↗

The incidence and management of osteoradionecrosis of the jaws following head and neck radiotherapy.

Only 22 cases of osteoradionecrosis (ORN) of the jaws so severe as to require resection have been reported in 2,853 cases of head and neck tumours receiving radiation in doses capable of causing ORN between 1.1.1970 and 31.12.1981. But for surgical interference, including dental extractions both pre- and post-therapy, the incidence would have been even lower. The management of the irradiated patient and of established necrosis is discussed.

Dental Care↗

Osteoradionecrosis of the temporal bone: a surgical technique of treatment.

Osteoradionecrosis of the temporal bone is a well-documented complication of radiotherapy to the ear, with potentially lethal complications. Three cases of advanced disease, treated surgically, are presented. In two of these, subtotal petrosectomy with blind-sac closure of the external auditory canal was carried out via an anterior approach. The enclosed space was obliterated with pedicled temporalis muscle. Primary healing took place. One case was similarly obliterated using a prolonged posterior incision. The wound broke down, requiring a microvascular free flap for closure. Radiotherapy jeopardizes the viability of skin flaps. An anterior incision bases the flap behind on the occipital and postauricular arteries. When radiotherapy has been used, this incision has theoretical and practical advantages over a standard posterior incision.

Bone Diseases↗

Role of hyperbaric oxygen therapy in the management of mandibular osteoradionecrosis.

Hyperbaric oxygen (HBO) has been used as a tool in the management of osteoradionecrosis (ORN). However, it has not been conclusively proven to be of benefit. The precise role and guidelines for its use also have not been clearly defined. This report retrospectively analyzes 41 patients treated at the Hyperbaric Chamber Unit at the Toronto Hospital (Toronto General Division) with proven mandibular ORN from 1980 to 1985. The results show that 83% of the patients had a significant improvement with HBO therapy, judged by at least a 50% decrease in the size of the exposed bone, closing of the fistulous tract, or complete relief of symptoms. Within the group of patients who were significantly improved, 15% showed complete resolution of ORN. Seven (17%) of the patients did not benefit from the HBO. All seven patients had radiological evidence of dead bone. Based on these observations, the following conclusions can be made: 1. HBO is of benefit in the management of ORN. 2. Patients with ORN may be divided into two groups: mild and severe. 3. Cases of mild ORN will heal with HBO alone, but, in severe ORN, surgery is necessary to remove dead bone. 4. All patients with ORN should receive dental evaluation, local wound care, and a strict oral hygiene regimen. Diseased teeth should be removed prior to radiotherapy. Subsequently, any teeth that became abscessed should be extracted in conjunction with prophylactic HBO. Antibiotics play an ancillary role in the management of ORN. For patients who have received radiation to the mandible, the authors propose regular follow-up in order to detect ORN at a time when HBO can arrest the disease.

Combined Modality Therapy↗

Osteoradionecrosis (ORN) of the mandible: a laser Raman spectroscopic study.

Laser Raman spectroscopy has been used in this study to characterize mandibular bone samples from patients who had undergone radiation therapy for oral cancer. The paper discusses spectral changes resulting in osteoradionecrosis (ORN) of the mandibular bone, a serious complication that may occur after radiation therapy. Histopathological studies normally reveal the radiation damage on vascular canals and loss in bone cells, but will not reveal any structural or biochemical changes. All radiation-induced side effects are attributed to this hypovascularity and hypocellularity caused by early- and/or late-delayed effects. Our Raman studies on normal and ORN bone and on bone exposed to radiation, but not in the ORN state, show that irradiation produces immediate structural changes in the inorganic bone matrix with a slight loss in cells. ORN bone, in addition to the structural changes that had already occurred on radiation exposure, shows almost complete loss of cellular components. Since bone tissue is continuously being remodeled (dissolved and rebuilt) under normal conditions, our results suggest that the immediate structural changes in the calcium hydroxy apatite mineral part is not repaired in ORN, due to loss of the highly transient osteoblasts and osteoclasts resulting from destruction of stem cells. The spectral studies also show changes in the organic matrix, which is mostly type I collagen.

Adult↗

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.

Clinical Protocols↗

[Osteoradionecrosis of the jaws. Apropos of 7 cases].

Jaw osteoradionecrosis (ORN) is one of the most serious complications of cervico-facial cancer irradiation. Severity is related to major bone lysis and the difficult medical and surgical treatment. We report our experience in seven cases over a ten-year period. Mandibular localization was predominant (85%). The mean age of the patients was 36 years. The average delay to development of ORN was 5.5 years. The treatment was medico-surgical, based on wide surgical exeresis (6/7), frequently via endobuccal surgical approach (4/7). Prevention remains the best treatment of ORN associated with an accurate management of all patients who need radiotherapy.

Adult↗

Decisive diagnosis of infected mandibular osteoradionecrosis with a Tc-99m-labelled anti-granulocyte Fab'-fragment.

The accepted golden standard for detection of inflammatory bone disease is conventional three-phase bone scanning. Hyperperfusion, a high blood-pool activity and elevated bone metabolism are typical signs for an acute osteomyelitis. However, in case of subacute, chronic inflammation, neither elevated blood flow nor high blood-pool activity may be seen. This may cause difficulties in differentiating such cases from neoplastic or postoperative changes. This case report verifies the possible advantage of immunoscintigraphy with Tc-99m-labelled anti-granulocyte Fab'-fragments (LeukoScan) in a patient with infected mandibular osteoradionecrosis, who had equivocal clinical symptoms and questionable radiographic results. LeukoScan is shown to be more sensitive in case of subacute bone inflammation compared with three-phase bone scanning. However, acquisition of delayed images after 24 hours including SPECT is inevitable in case of negative scans during the first hours of investigation.

Aged↗

Dynamic MR imaging of mandibular osteoradionecrosis.

PURPOSE: Osteoradionecrotic bone has been characterised as hypovascular and metabolically inactive tissue with impaired perfusion. The present study was conducted to determine if dynamic contrast-enhanced MR imaging could provide additional information about the vascularity of radionecrotic mandibular bone. MATERIAL AND METHODS: Dynamic contrast-enhanced MR imaging was performed on 10 patients with mandibular osteoradionecrosis (ORN), and on 6 patients, irradiated for oropharyngeal tumours, without symptoms or signs of ORN. Nine patients in the ORN group received a series of 20 hyperbaric oxygen (HBO) treatments, after which the dynamic MR investigation was repeated. RESULTS AND CONCLUSION: Radiation per se did not lead to increased contrast enhancement, whereas all patients with ORN showed marked contrast enhancement of the osteoradionecrotic bone marrow. After HBO treatment, pathological contrast enhancement of the abnormal bone marrow could still be seen, but the rate of enhancement was less than before in 7 of 9 patients. Two patients had an increase in the enhancement rate. The findings suggest the existence of an increased and patent microvasculature.

Adult↗

Masticator space abnormalities associated with mandibular osteoradionecrosis: MR and CT findings in five patients.

BACKGROUND AND PURPOSE: Imaging of patients with a clinical diagnosis of mandibular osteoradionecrosis (ORN) is often performed to support that clinical suspicion, evaluate the extent of the disease, or exclude coexistent tumor recurrence. The purpose of our study was to describe the clinical, MR imaging, and CT features of five patients with mandibular ORN associated with prominent soft-tissue abnormality in the adjacent masticator muscles. METHODS: The MR and CT examinations of five patients with mandibular ORN associated with soft-tissue abnormalities in the adjacent masticator muscles were reviewed. All patients had received external beam radiotherapy for primary head and neck malignancies, with a total radiation dose range of 60 Gy to 69 Gy in 30 to 38 fractions. RESULTS: CT revealed the typical osseous findings of cortical disruption, trabecular disorganization, and fragmentation in all five patients. Abnormal diffuse enhancement of the adjacent masseter and pterygoid muscles was noted in all patients. Four patients had prominent mass-like thickening of these muscles adjacent to the osseous abnormality. Of the three patients who underwent MR imaging, all showed homogeneous abnormal T1 hypointensity, T2 hyperintensity, and intense enhancement of the bone marrow in the involved mandible. The masticator muscles adjacent to the osseous abnormality also showed abnormal T2 hyperintensity and intense diffuse enhancement on MR images. CONCLUSION: Mandibular ORN can be associated with prominent soft-tissue thickening and enhancement in the adjacent musculature. These changes can appear mass-like and are not related to tumor recurrence or metastatic disease.

Adolescent↗

Osteoradionecrosis of the temporal bone in nasopharyngeal carcinoma after radiotherapy: a case report.

Osteoradionecrosis of the temporal bone after external-beam radiotherapy for nasopharyngeal carcinoma is not uncommon following a long posttreatment interval. We describe the case of a man who had experienced this complication 13 years after he had undergone such radiotherapy. His condition resolved after removal of dead bone from the external auditory canal, followed by antibiotic therapy and periodic aural toileting.

Aged↗

Free omental transfer for osteoradionecrosis of the mandible.

Osteoradionecrosis (ORN) of the mandible can arise following therapeutic radiotherapy for head and neck cancer. The incidence is quoted as 10-15%. Conservative and surgical therapies used for ORN have included vascularized osteocutaneous flap transfers, hyperbaric oxygen and ultrasound therapy. We have used an omental transfer for ORN without a segmental resection. We wrapped the affected mandible within the omentum in order to promote revascularization and neocellularity. Four patients suffering from ORN have undergone omental transfers. Two cases developed pathologic fractures postoperatively that were successfully treated by conservative management. In all cases, the patients' intractable pain improved, and no patient showed recurrence of ORN or wound dehiscence. Postoperative bone scintigrams showed the same degree of accumulation in the lesion as in normal adjacent bone. These results demonstrate the effectiveness of omental transfer and suggest that omental transfer has a promising place in the management of ORN.

Aged↗

Hyperbaric oxygen in the therapeutic management of osteoradionecrosis of the facial bones.

This paper reviews all 17 cases of facial bone osteoradionecrosis (ORN) which were treated in Adelaide, South Australia, in a nine-year period (1987 1996). This was 1.2% of all cases of head and neck cancer treated with radiotherapy (RT). Fourteen cases received treatment following the Marx principles of staging and the protocols of hyperbaric oxygen plus or minus surgery. The three exclusions were two patients who died of recurrent cancer before treatment was complete and one who declined treatment. The eleven cases of mandibular ORN occurred within a few years of the initial RT treatment. All except one occurred after surgical trauma, with dental extractions being the factor in nine cases. All responded to HBO, with or without surgery depending on stage. The three cases of temporal bone ORN were all of late spontaneous onset. All were stage I and all responded to HBO alone. This study shows that the incidence of ORN in Adelaide is low, probably through use of conservative doses of RT and good preventative protocols. The treatment with HBO plus or minus surgery was effective.

Aged↗

Osteoradionecrosis of the mandible.

Osteoradionecrosis is a major complication of surgery or trauma in previously irradiated bone in the absence of tumor persistence. Radiation-induced vascular insufficiency rather than infection causes bone death. It occurs most commonly in the mandible after head and neck irradiation. Risk factors include the total radiation dose, modality of treatment, fraction size and dose rate, oral hygiene, timing of tooth extractions as well as the continued use of tobacco and alcohol. This condition is often painful, debilitating, and may result in significant bone loss. The recommended treatment guidelines are irrigation, antibiotics, hyperbaric oxygen therapy, and surgical techniques, including hemimandibulectomy and graft placements.

Anti-Bacterial Agents↗