Hyperbaric oxygen therapy as an adjunct treatment of periodontitis, MRONJ, and ONJ: a systematic literature review.

OBJECTIVE: To review the available prospective literature on hyperbaric oxygen (HBO) therapy for periodontal conditions. MATERIALS AND METHODS: A comprehensive electronic and manual search was performed to identify clinical studies on adult patients who underwent hyperbaric oxygen therapy for periodontal treatments. A systematic literature search was conducted in PubMed, Cochrane, and Dentistry Oral Sciences Source databases. RESULTS: Fourteen articles were included in the final literature review, of which five were RCTs and 11 were prospective clinical studies. Four studies discussed HBO as an adjunct to nonsurgical treatment of periodontitis, eight reported on HBO and osteoradionecrosis, and one examined HBO in bisphosphonate-related necrosis of the jaws. CONCLUSIONS: HBO has shown superior efficacy compared to antibiotics as a prophylactic measure in preventing osteoradionecrosis (ORN) in patients with a history of high mandibular irradiation. Clinicians should consider referring such patients for HBO therapy before and after tooth extractions. However, for the surgical excision of existing ORN lesions, HBO therapy does not yield significant benefits but does not negatively impact outcomes either. Regarding the treatment of periodontitis patients, the variability among studies prevents definitive conclusions. HBO therapy as an adjunct to SRP in periodontitis treatment produces mixed results. CLINICAL RELEVANCE: This study's clinical relevance lies in its exploration of the potential benefits of HBO for periodontal conditions. Also, it provides clinicians with insights into when and how to integrate HBO therapy into their treatment approaches, particularly for patients with a history of irradiation and those undergoing complex dental procedures.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

The role of hyperbaric oxygen in osteoradionecrosis-a prophylactic insight.

BACKGROUND: Osteoradionecrosis (ORN) is an uncommon and debilitating consequence of head and neck radiotherapy and hyperbaric oxygen therapy (HBOT) has been advocated for prophylaxis prior to performing dentoalveolar procedures. The aim of this study was to evaluate a prophylactic HBOT protocol and describe the outcomes of susceptible individuals. METHODS: A retrospective audit of adults who attended the Oral and Maxillofacial Surgery department at the Royal Adelaide Hospital (South Australia) who received dental extractions with a history of radiotherapy to the jaws from 2008 to 2020. Data including demographic information and outcomes of osteoradionecrosis and delayed healing was recorded. RESULTS: A total of 121 individuals were eligible for case note review; 68.6% of individuals were male and 55.4% were aged over 67 years. Osteoradionecrosis occurred in 9.1% of individuals and delayed healing for 3.3%; fifteen individuals (12.4%) were unable to complete the HBOT protocol. The individuals who were diagnosed with ORN had a significant association with age (P = 0.006) and binary analysis showed alcohol consumption to be a significant predictor. CONCLUSIONS: Prophylactic HBOT protocol had a lower proportion of individuals diagnosed with ORN and those who were diagnosed were more likely to be younger males and have current alcohol consumption.

Mesenchymal stem cell therapy for treatment of osteoradionecrosis of mandible in head and neck surgery patients - A way forward into the future with promising clinical Outcomes.

Managing osteoradionecrosis is an integral part of complication management in head and neck cancer patients. While essentially an infection, the management of this complication has a considerable task for head and neck surgeons. While various measures have been discussed for the management, stem cells injection therapy is a potential management option. Mesenchymal stem cell therapy provides the local tissue with growth factors and proliferative cells that can aid a radiated tissue in the healing process. The article intends to review the bedrock of the pathology, ranging from pathophysiological and the epidemiological concerns to sparking a potential discussion on the use of mesenchymal stem cell therapy in osteoradionecrosis of mandible in head and neck cancer surgery and thus the ensuing future of the regenerative medicine. Moreover, the article has considered the management option in a developing nation thus explaining the procedural as well as the financial pitfalls and has highlighted the potential loop holes to be addressed in the management of osteoradionecrosis with stem cell therapy.

Fascio-cutaneous and fascio-periosteal free flaps for treatment of intermediate stage osteoradionecrosis of the jaws.

OBJECTIVES: Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. Despite recent advances, there are patients who fail to respond to conventional therapies. Historically, free flaps were reserved for advanced cases requiring segmental resection and composite reconstruction, with early and intermediate disease treated more conservatively. We have adopted a more active surgical approach in selected intermediate cases. STUDY DESIGN: A retrospective review of patients with intermediate stage ORN who received debridement and either fascio-cutaneous or fascio-periosteal free flap reconstruction was performed. Demographic data, ORN severity, treatment, and outcomes are described. RESULTS: From 2019, 9 cases in 7 patients were identified. All cases were Notani grade II. There were 6 Epstein stage IIa and 3 Epstein stage IIIa. The mandible was the most common site (n = 8). Of the 7 patients, 2 had oropharyngeal primaries treated with chemoradiation, and 5 had oral cavity primaries treated with surgery and adjuvant radiation therapy. Three patients had prior hyperbaric oxygen therapy, and 2 had pentoxifylline/tocopherol therapy. After debridement, the radial forearm, ulnar artery perforator, and antero-lateral thigh fascio-cutaneous free flaps were each used in 1 case and the temporoparietal fascio-periosteal free flap was used in 6 cases. There was no recurrence or progression of ORN at the site of surgery, but 2 patients developed additional sites of ORN. CONCLUSIONS: For patients with unresponsive intermediate ORN, debridement and soft tissue free flap reconstruction is an alternative to ongoing conservative management or composite resection and reconstruction.

Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1.

PURPOSE: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. METHODS AND MATERIALS: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. RESULTS: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. CONCLUSION: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

Evaluation of hyperbaric oxygen therapy for the osteoradionecrosis of the jaws: Meta-analysis.

OBJECTIVES: This study was performed to investigate the effects of hyperbaric oxygen and other approaches for treating the osteoradionecrosis of the jaws (ORNJ) systematically. METHODS: According to the preset inclusion and exclusion criteria, randomized controlled trials and cohort studies on hyperbaric oxygen in the treatment of ORNJ were screened, and foreign language databases such as PubMed, EMBASE, and Cochrane library were searched via a computer; Chinese databases such as CNKI, VIP, Wanfang data, and CBM were searched from the established database to September 2020. Relevant books were searched manually to collect all literatures on the efficacy of hyperbaric oxygen and its related therapies in ORNJ treatment. Two researchers were independent and mutually blind, the papers were selected, data were collected, and the bias risk was evaluated. If any difference was detected, it would be decided by discussion or arbitrated by a third party. The data related to the efficacy of hyperbaric oxygen and its related therapy in the treatment of the ORNJ were extracted, and the Revman5.4 software was used for Meta-analysis. In case of large heterogeneity, sensitivity analysis was performed. A funnel chart was used to evaluate possible publication bias qualitatively. RESULTS: Four randomized controlled trials and seven cohort studies were included in Meta-analyses. In ORNJ treatment, no significant differences between the group subjected to hyperbaric oxygen and both surgery and antibiotics and the group that underwent both surgery and antibiotics (RR=1.16, 95%CI: 0.86~1.58, P>0.05); between the group with hyperbaric oxygen and the group with antibiotics (RR=0.83, 95%CI: 0.63~1.09, P>0.05); between the group with hyperbaric oxygen and the group with antifibrotic drugs (RR=0.07, 95%CI: 0.00~155.86, P>0.05); between the group with single or combined use of HBO and the group with other intervention methods (RR=0.89, 95%CI: 0.67~1.19, P>0.05). CONCLUSIONS: Hyperbaric oxygen therapy cannot replace surgery and antibiotic therapy. Hyperbaric oxygen therapy is not superior to antibiotics and antifibrotic drugs, but the benefits of antifibrotic drugs should be further explored.

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.

[State of art of photobiomodulation in the management of radiotherapy adverse events: Indications and level of evidence]. / État de l'art de la photobiomodulation dans la prise en charge des effets secondaires de la radiothérapie : indications et niveaux de preuve.

PURPOSE: To evaluate the current and potential indications of photobiomodulation (PBM) and their level of evidence in the prevention or management of radiation therapy-related side effects. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that have assessed PBM in the prevention or management of radiotherapy-related side effects. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "hyposalivation"; "trismus"; "bone necrosis"; "osteoradionecrosis"; and "radiation induced fibrosis". Prospective studies were included, whereas retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has demonstrated efficacy in randomized controlled trials in the prevention and management of radiotherapy-related side effects, especially acute oral mucositis, acute radiation dermatitis, and upper extremity lymphedema. The level of evidence associated with PBM was heterogeneous, but overall was still moderate. The main shortcomings were the diversity and lack of detail in treatment protocols, which could have compromised efficiency and reproducibility of PBM results. CONCLUSION: The published data suggest that PBM may be considered as a full-fledged supportive care for patients treated with radiotherapy, or at least in the setting of a therapeutic clinical trial. However, until strong evidence has been published on its long-term safety, the use of PBM should be considered with caution, specifically when applied near areas with proven or potential tumors. The patient should be informed of the theoretical benefits and risks of PBM in order to obtain his informed consent before treatment.

[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.

Radiation therapy in head and neck cancer.

This review summarizes the beginning of radiotherapy, techniques of modern radiation therapy with different types, toxicities induced by radiotherapy and their management. Head and neck radiation therapy is still improving for the better management and control of the cancer and induced radiotherapy toxicities.

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.

Does hyperbaric oxygen therapy play a role in the management of osteoradionecrosis? A survey of Dutch oral and maxillofacial surgeons.

For decades, hyperbaric oxygen (HBO) has often been part of the treatment of osteoradionecrosis (ORN), despite controversy in the literature about its efficacy. An online survey was conducted to investigate the use of HBO in the treatment of ORN by Dutch oral and maxillofacial surgeons and to assess their perception of its efficacy. Of the 53 Dutch oral and maxillofacial surgery units contacted, 49 (92%) replied. Thirty-five were not head and neck cancer (HNC) units or preferred partner (PP-HNC) units recognized by the Dutch Head and Neck Association. All HNC and PP-HNC units (group 1) treated ORN patients, compared to only 12 (34%) of the non-HNC units (group 2). The average number of ORN patients seen and treated was higher in group 1. The units in group 1 more often referred patients for HBO therapy (HBOT) than those in group 2 (93% vs 84%). The efficacy of HBOT in curing ORN, rated on a scale of 1 to 5 points, was 3.7 in group 1 and 3.2 in group 2. This survey shows a trend towards centralization of ORN care to more experienced units. These units tend to use HBOT in curing ORN.

Therapeutic alternatives in the management of osteoradionecrosis of the jaws. Systematic review.

BACKGROUND: to systematically review the literature, comparing the healing of osteoradionecrosis (ORN) among the therapeutic alternatives: surgical, pharmacological and combined. MATERIAL AND METHODS: The review was organized according to the PRISMA protocol with regards to the following PICO question: patients with ORN of the jaws (P=Patient); all interventions reported (I = intervention); between all therapies (C=Comparison); healing of lesions (O=outcome). RESULTS: Surgical treatment was the most common choice (46.3%) followed by pharmacological treatment, exclusively (25.9%) or combined (26.9%). Treatment exclusively by surgical intervention seems to be most effective option, with 51.2% of the lesions healed, OR for healing of 5.7 (CI95% 1.9-16.9, p=0.002). Only 1 case (0.9%) corresponded to low level laser therapy. CONCLUSIONS: It seems clear that early intervention with conservative surgical combined with pharmacological methods improves the prognosis of ORN.

Evaluation of hyperbaric oxygen therapy for the osteoradionecrosis of the jaws: Meta-analysis / 华西口腔医学杂志

OBJECTIVES@#This study was performed to investigate the effects of hyperbaric oxygen and other approaches for treating the osteoradionecrosis of the jaws (ORNJ) systematically.@*METHODS@#According to the preset inclusion and exclusion criteria, randomized controlled trials and cohort studies on hyperbaric oxygen in the treatment of ORNJ were screened, and foreign language databases such as PubMed, EMBASE, and Cochrane library were searched via a computer; Chinese databases such as CNKI, VIP, Wanfang data, and CBM were searched from the established database to September 2020. Relevant books were searched manually to collect all literatures on the efficacy of hyperbaric oxygen and its related therapies in ORNJ treatment. Two researchers were independent and mutually blind, the papers were selected, data were collected, and the bias risk was evaluated. If any difference was detected, it would be decided by discussion or arbitrated by a third party. The data related to the efficacy of hyperbaric oxygen and its related therapy in the treatment of the ORNJ were extracted, and the Revman5.4 software was used for Meta-analysis. In case of large heterogeneity, sensitivity analysis was performed. A funnel chart was used to evaluate possible publication bias qualitatively.@*RESULTS@#Four randomized controlled trials and seven cohort studies were included in Meta-analyses. In ORNJ treatment, no significant differences between the group subjected to hyperbaric oxygen and both surgery and antibiotics and the group that underwent both surgery and antibiotics (RR=1.16, 95%CI: 0.86~1.58, @*CONCLUSIONS@#Hyperbaric oxygen therapy cannot replace surgery and antibiotic therapy. Hyperbaric oxygen therapy is not superior to antibiotics and antifibrotic drugs, but the benefits of antifibrotic drugs should be further explored.

Successful application of antimicrobial photodynamic and photobiomodulation therapies for controlling osteoradionecrosis and xerostomia after laryngeal carcinoma treatment: A case report of full oral rehabilitation.

We present a clinical case where a conservative treatment based on photonics [antimicrobial Photodynamic Therapy (aPDT) associated to Photobiomodulation therapy (PBMT)] of a patient with osteoradionecrosis (ORN) due to radiotherapy treatment of a laryngeal cancer. As a result of this combined treatment the ORN was controlled (e.g. the necrosis, infection and suppuration disappeared). Moreover, the symptoms reported by the patient (pain and xerostomia) also diminished along with the repair of oral mucosa. In future cases this combined therapy (e.g. PBM therapy and the aPDT) will be further examined.

RETRACTED: The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: a meta-analysis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the corresponding author and following a translated comparative examination of the two articles for similarity. It has been concluded that duplicate publication has occurred. The significantly duplicated article of the same title by same research team is: The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: A meta-analysis Chin J Stomatol Res (Electronic Edition). August 2017, Vol.11, No.4. Both articles report on a meta-analysis study and focus on the treatment of osteoradionecrosis of the jaws by pentoxifylline combined with vitamin E, with search timeframe extending 2 years later in the retracted article.

Lumbar vertebral osteoradionecrosis: a rare case report with 10-year follow-up and brief literature review.

BACKGROUND: Osteoradionecrosis (ORN) is a complication that occurs after radiotherapy for head or neck malignancies. ORN of the spine is rare, with only few cases affecting the cervical spine reported to date. To our knowledge, no case of lumbar ORN has been reported. We report a rare case of ORN in the lumbar spine that occurred 2 years after radiotherapy and perform a literature review. CASE PRESENTATION: We present a case of lumbar ORN that occurred 2 years after radiotherapy for gallbladder carcinoma. The patient was successfully treated conservatively and followed up for > 10 years. CONCLUSIONS: ORN of the spine is a rare complication of radiotherapy. Spinal ORN is clinically described as a chronic disease with a slow onset. The most common presenting symptom of spinal ORN is pain. However, as ORN progresses, spinal kyphosis and instability can lead to neurological compression and thus to induced myelopathy or radiculopathy. Treatment of spinal ORN is comprehensive, including orthosis, medication, hyperbaric oxygen therapy, surgery, and new treatment combinations of pentoxifylline and tocopherol. The surgical rate for spinal ORN is relatively high.

Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy.

BACKGROUND: Osteoradionecrosis (ORN) of the jaws is among the most serious oral complications of head and neck cancer radiotherapy, arising from radiation-induced fibro-atrophic tissue injury, manifested by necrosis of osseous tissues and failure to heal, often secondary to operative interventions in the oral cavity. It is associated with considerable morbidity and has important quality of life ramifications. Since ORN is very difficult to treat effectively, preventive measures to limit the onset of this disease are needed; however, the effects of various preventive interventions has not been adequately quantified. OBJECTIVES: To assess the effects of interventions for preventing ORN of the jaws in adult patients with head and neck cancer undergoing curative or adjuvant (i.e. non-palliative) radiotherapy. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 5 November 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 10) in the Cochrane Library (searched 5 November 2019), MEDLINE Ovid (1946 to 5 November 2019), Embase Ovid (1980 to 5 November 2019), Allied and Complementary Medicine (AMED) Ovid (1985 to 5 November 2019), Scopus (1966 to 5 November 2019), Proquest Dissertations and Theses International (1861 to 5 November 2019) and Web of Science Conference Proceedings (1990 to 5 November 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) or quasi-RCTs of adult patients 18 years or older with head and neck cancer who had undergone curative or adjuvant radiotherapy to the head and neck, who had received an intervention to prevent the onset of ORN. Eligible patients were those subjected to pre- or post-irradiation dental evaluation. Management of these patients was to be with interventions independent of their cancer therapy, including but not limited to local, systemic, or behavioural interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed risk of bias, and extracted relevant data for inclusion in the review. Authors of included studies were contacted to request missing data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four studies were identified that met pre-determined eligibility criteria, evaluating a total of 342 adults. From the four studies, all assessed as at high risk of bias, three broad interventions were identified that may potentially reduce the risk of ORN development: one study showed no reduction in ORN when using platelet-rich plasma placed in the extraction sockets of prophylactically removed healthy mandibular molar teeth prior to radiotherapy (odds ratio (OR) 3.32, 95% confidence interval (CI) 0.58 to 19.09; one trial, 44 participants; very low-certainty evidence). Another study involved comparing fluoride gel and high-content fluoride toothpaste (1350 parts per million (ppm)) in prevention of post-radiation caries, and found no difference between their use as no cases of ORN were reported (one trial, 220 participants; very low-certainty evidence). The other two studies involved the use of perioperative hyperbaric oxygen (HBO) therapy and antibiotics. One study showed that treatment with HBO caused a reduction in the development of ORN in comparison to patients treated with antibiotics following dental extractions (risk ratio (RR) 0.18, 95% CI 0.43 to 0.76; one trial, 74 participants; very low-certainty evidence). Another study found no difference between combined HBO and antibiotics compared to antibiotics alone prior to dental implant placement (RR 3.00, 95% CI 0.14 to 65.16; one trial, 26 participants; very low-certainty evidence). Adverse effects of the different interventions were not reported clearly or were not important. AUTHORS' CONCLUSIONS: Given the suboptimal reporting and inadequate sample sizes of the included studies, evidence regarding the interventions evaluated by the trials included in this review is uncertain. More well-designed RCTs with larger samples are required to make conclusive statements regarding the efficacy of these interventions.