Hyperbaric Oxygen and Medication-Related Osteonecrosis of the Jaw (MRONJ): An Integrative Review

ABSTRACT: Some adjuvant treatments are available for Medication-Related Osteonecrosis of the Jaw (MRONJ) to help the pain and improve quality of life. Among these treatments is hyperbaric oxygen (HBO) which has presented controversial findings in the literature in recent years. This integrative review analyzed the results among studies published during the pas t 10 years using HBO. The PICO strategy was used and the databases PubMed, LILACS, and SCOPUS. The final search resulted in the inclusion of 7 articles. The main conclusion is that, in the majority of cases, using HBO as an adjuvant to the basic therapy improved the quality of life and/or pain of the patients.

RESUMEN: Existen algunos tratamientos adyuvantes para la osteonecrosis de la mandíbula relacionada con medicamentos (MRONJ) para aliviar el dolor y mejorar la calidad de vida de los pacientes. Entre estos tratamientos se encuentra el oxígeno hiperbárico (OHB) que ha presentado resultados controvertidos en la literatura durante los últimos años. En esta revisión integrada se analizaron los resultados de los estudios publicados durante los últimos 10 años utilizando OHB. Se utilizó la estrategia PICO y las bases de datos PubMed, LILACS y SCOPUS. La búsqueda final resultó en la inclusión de 7 artículos. La principal conclusión es que, en la mayoría de los casos, el uso de OHB como adyuvante de la terapia básica mejoró la calidad de vida y / o el dolor de los pacientes.

Tratamiento conservador de osteonecrosis maxilar asociada a medicamentos refractaria mediante el uso de protocolo PENTO: reporte de un caso / Tratamento conservador da osteonecrose maxilar associada a medicamentos refratários usando o protocolo PENTO: relato de um caso / Conservative treatment of refractory medication-related osteonecrosis of the jaw using the PENTO protocol: A case report

Resumen Paciente de 78 años consulta por sangrado sin resolución, a nivel del reborde alveolar maxilar izquierdo. Con antecedentes de metástasis óseas tratadas con ácido zoledrónico endovenoso discontinuado por alta médica y tratamiento quirúrgico previo de osteonecrosis maxilar en sitio afectado. Se observó disrupción de continuidad con inflamación a nivel del reborde óseo, con salida de contenido hemático, purulento y necrótico. Radiográficamente se observó radiolucidez difusa y osteolítica del área afectada y tejido necrótico a nivel microscópico. Se realizó aseo del área afectada, enjuagues de clorhexidina 0,12%, administración de amoxicilina/acido clavulánico y de pentoxifilina 400 mg cada 12 horas y tocoferol 1000 UI cada 24 horas. Se evaluó al mes, donde se discontinua antibioterapia y se mantiene régimen establecido con controles cada 2 semanas. A los 6 meses se evidencia resolución completa, con cicatrización de la mucosa y del tejido óseo sin recidiva.

Resumo Paciente de 78 anos consultado por sangramento sem resolução, ao nível do rebordo alveolar superior esquerdo. Com história de metástases ósseas tratadas com ácido zoledrônico endovenoso descontinuado por alta médica e tratamento cirúrgico prévio de osteonecrose maxilar no local afetado. Foi observada interrupção da continuidade com inflamação ao nível da crista óssea, com extravasamento de sangue, conteúdo purulento e necrótico. Radiograficamente, radioluscência difusa e osteolítica da área afetada e tecido necrótico foram observadas ao nível microscópico. A área afetada foi limpa, enxágue com clorexidina 0,12%, amoxicilina / ácido clavulânico e 400 mg de pentoxifilina a cada 12 horas e 1000 UI de tocoferol a cada 24 horas. Foi avaliado em um mês, quando a antibioticoterapia é descontinuada e um regime estabelecido é mantido com controles a cada 2 semanas. Aos 6 meses, é evidenciada resolução completa, com cicatrização da mucosa e do tecido ósseo sem recorrência.

Abstract A 78-year-old patient seeks care for unresolved bleeding on the left maxillary alveolar ridge. He had a history of bone metastasis treated with IV zoledronic acid, which was discontinued after medical discharge and previous surgical treatment of osteonecrosis of the jaws in the affected site. Continuity disruption with inflammation at the bone ridge was observed, with blood, purulent, and necrotic exudate. The radiograph showed diffuse and osteolytic radiolucency of the affected area, and necrotic tissue was detected at a microscopic level. The affected area was rinsed with 0.12% chlorhexidine, 400 mg amoxicillin/clavulanic acid and pentoxifylline was administered every 12 hours, and tocopherol 1000 IU every 24 hours. The area was evaluated after a month. Antibiotic therapy was discontinued, and the patient continued to be monitored every two weeks. At six months, there is complete resolution, and mucosal and bone tissue healed without recurrence.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso)

ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

Clinical profile of individuals with bisphosphonate-related osteonecrosis of the jaw: an integrative review

ABSTRACT BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still the most prevalent type of osteonecrosis with clinical relevance. In Brazil, bisphosphonate use is high but there is a lack of epidemiological studies on BRONJ. OBJECTIVE: To determine the clinical profile of BRONJ in a Brazilian population through an integrative review. DESIGN AND SETTING: Integrative review of BRONJ in a Brazilian population. METHODS: Cases and clinical research on Brazilians with BRONJ between 2010 and 2019, indexed in PubMed/MEDLINE, Scopus, Web of Science and LILACS were reviewed. Age, sex, type and time of bisphosphonate intake, administration route, related diseases, region of the BRONJ, diagnostic criteria, staging, triggering factor and type of treatment were analyzed. RESULTS: Fifteen articles on 128 subjects were included. Most patients were women (82.03%); the mean age was 63 years. Intravenous zoledronic acid was mostly used (62.50%), for breast cancer treatment (46.87%). The main localization of BRONJ was the mandible (54.68%), associated mainly with tooth extractions (45.98%). The diagnostic criteria were clinical (100%) and radiographic (89.06%), mostly in stage II (68.08%). The surgical treatments were sequestrectomy (37.50%) and platelet-rich plasma (PRP) (36.71%). Microbial control was done using chlorhexidine (93.75%) and infection control using clindamycin (53.90%). CONCLUSIONS: BRONJ had higher prevalence in Brazilian women receiving treatment for breast cancer and osteoporosis. The mandible was the region most affected with a moderate stage of BRONJ, particularly when there were histories of tooth extraction and peri-implant surgery. Sequestrectomy with additional drugs and surgical therapy was the treatment most accomplished.

The effect of bisphosphonate discontinuation on the incidence of postoperative medication-related osteonecrosis of the jaw after tooth extraction

OBJECTIVES: The discontinuation of bisphosphonate (BP) treatment before tooth extraction may induce medication-related osteonecrosis of the jaw (MRONJ). Whether the long-term discontinuation of BP treatment before tooth extraction affects the risk of developing MRONJ after tooth extraction or whether extended drug holidays induce systemic side effects remains unclear. The present study assessed the incidence of MRONJ among patients who underwent tooth extraction and did not discontinue BP therapy prior to the procedure.MATERIALS AND METHODS: Patients were classified according to whether or not they discontinued BP therapy before tooth extraction. Differences in the incidence of MRONJ after tooth extraction were compared between the two groups using the chi-squared test.RESULTS: The BP-continuation (BPC) and BP-discontinuation (BPDC) groups included 179 and 286 patients, respectively. One patient in the BPC group and no patients in the BPDC group developed MRONJ (P=0.385). The patients in the BPDC group stopped receiving BP therapy at a mean of 39.0±35.5 months prior to tooth extraction.CONCLUSION: The possibility of pre-existing MRONJ in the extraction area must be considered during the extraction procedure. Routine discontinuation of BP medications for several months before the extraction procedure should be carefully considered, as evidence of its efficacy in reducing the development of post-extraction MRONJ is limited.

Bisphosphonate-related osteonecrosis of the jaw in malignant tumor patients with bone metastases: clinical analysis of six cases / 肿瘤研究与临床

Objective@#To analyze the clinical manifestation, imaging characteristics and prevention of medication-related osteonecrosis of the jaw (MRONJ) after intravenous bisphosphonate (BP) for cancer patients with bone metastases.@*Methods@#The clinical data and radiographic findings of 6 primary breast cancer patients with bone metastases diagnosed as MRONJ from January 2014 to April 2018 in Shanxi Dayi Hospital were retrospectively analyzed.@*Results@#All 6 patients were female, with the median age of 65.5 years old. All patients had no history of systemic application of hormone therapy, no history of diabetes, no history of radiation therapy, no history of metastasis of the jaw, and no history of infection. The average usage time of BP was 28 months. MRONJ occurred in 2 cases on maxilla and 4 cases on mandible. There were 2 patients with tooth extractions history in BP treatment. Clinical symptoms included maxillofacial pain, loosened teeth, fistula suppuration, and exposed sequestrum. Radiographic findings included osteolysis and bone sclerosis or the mixed manifestation of both, with or without periosteal reaction. In addition, nonhealing tooth sockets and sequestrum separation imaging were also included.@*Conclusions@#Tooth extraction is considered as an increased risk for MRONJ in patients with malignant bone metastases after BP therapy. MRONJ is more likely to appear in the mandible, but it can also appear in the maxilla. Early screening and initiation of appropriate dental care are necessary for the patients before using BP therapy.

Bisphosphonate-related osteonecrosis of the jaw in malignant tumor patients with bone metastases:clinical analysis of six cases / 肿瘤研究与临床

Objective To analyze the clinical manifestation, imaging characteristics and prevention of medication-related osteonecrosis of the jaw (MRONJ) after intravenous bisphosphonate (BP) for cancer patients with bone metastases. Methods The clinical data and radiographic findings of 6 primary breast cancer patients with bone metastases diagnosed as MRONJ from January 2014 to April 2018 in Shanxi Dayi Hospital were retrospectively analyzed. Results All 6 patients were female, with the median age of 65.5 years old. All patients had no history of systemic application of hormone therapy, no history of diabetes, no history of radiation therapy, no history of metastasis of the jaw, and no history of infection. The average usage time of BP was 28 months. MRONJ occurred in 2 cases on maxilla and 4 cases on mandible. There were 2 patients with tooth extractions history in BP treatment. Clinical symptoms included maxillofacial pain, loosened teeth, fistula suppuration, and exposed sequestrum. Radiographic findings included osteolysis and bone sclerosis or the mixed manifestation of both, with or without periosteal reaction. In addition, nonhealing tooth sockets and sequestrum separation imaging were also included. Conclusions Tooth extraction is considered as an increased risk for MRONJ in patients with malignant bone metastases after BP therapy. MRONJ is more likely to appear in the mandible, but it can also appear in the maxilla. Early screening and initiation of appropriate dental care are necessary for the patients before using BP therapy.

Evaluation of mandibular cortical bone ratio on computed tomography images in patients taking bisphosphonates / 대한악안면성형재건외과학회지

BACKGROUND: Bisphosphonate (BP) has the ability to thicken the cortical bone. In addition, it has been reported that the cortical bone thickened by BP has relation to the medication-related osteonecrosis of the jaw (MRONJ). Therefore, the objective of this article is to analyze the ratio as well as thickness of cortical bone in the mandible using computed tomography (CT) and to evaluate it as the predictive factor of MRONJ. METHODS: The thickness of the cortical bone was measured on a paraxial view of the CT showing the mental foramen in 95 patients: 33 patients with MRONJ (3 males, 30 females), 30 patients taking BP without MRONJ (2 males, 28 females), and 32 controls (9 males, 28 females). Also, the ratios of the cortical bone to the total bone were obtained using the measured values. Based on these results, we compared the difference of mandibular cortical bone ratio between the three groups. RESULTS: The average cortical bone thickness was measured as 3.81 mm in patients with MRONJ, 3.39 mm in patients taking BP without MRONJ, and 3.23 mm in controls. There was only a significant difference between patients with MRONJ and controls (P < 0.05). On the other hand, the average mandibular cortical bone ratio was measured as 37.9% in patients with MRONJ, 27.9% in patients taking BP without MRONJ, and 23.3% in controls. There was a significant difference between all groups (P < 0.05). CONCLUSION: The mandibular cortical bone ratio is large in order of patients with MRONJ, patients taking BP without MRONJ, and controls. This result suggests that the mandibular cortical bone ratio would be very useful to predict the development of MRONJ.

Polydeoxyribonucleotide, as a Novel Approach for the Management of Medication-Related Osteonecrosis of the Jaw: A Preliminary Observational Study

PURPOSE: Polydeoxyribonucleotide (PDRN), consisting of a mixture of deoxyribonucleotide polymers, has been suggested to have anti-inflammatory effects and enhance angiogenesis as an adenosine A(2A) receptor agonist. The aim of this study was to report the effectiveness of PDRN as an adjuvant therapy after surgical debridement in MRONJ (medication-related osteonecrosis of the jaw) patients. MATERIALS AND METHODS: Five patients (1 male, 4 females, age 65~79 years) who were diagnosed with MRONJ stage 2 or 3 underwent surgical debridement and PDRN mucosal injection. After surgical debridement, patients were subject to daily injection with 1 ml of PDRN around the surgical wound for 14 days. RESULT: The patients' symptoms gradually disappeared. The surgical wound uneventfully healed, and no recurrence was observed during the follow-up period. CONCLUSION: Although further studies are required, the present study first describes the possibility of PDRN as a useful option for MRONJ treatment.

Drug holiday as a prognostic factor of medication-related osteonecrosis of the jaw

OBJECTIVES: To identify post-treatment prognostic factors for medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: We evaluated 54 MRONJ patients who visited the Department of Dentistry, Ajou University Hospital, from May 2007 to March 2014. Twenty-one patients were surgically managed with debridement or sequestrectomy and 33 patients were conservatively managed using antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type, and drug holiday with the prognosis of MRONJ were investigated. Correlations were verified by logistic regression analysis and t-tests with a significance level of 0.05. RESULTS: Clinical outcomes were evaluated on the basis of both clinical and radiographic findings. Twelve out of 21 surgically managed patients showed a favorable prognosis and nine patients relapsed. Thirty-one of the 33 conservatively managed patients showed no specific change in prognosis, and two patients worsened. Statistical analyses of the conservative management group did not reveal any correlation of the above factors with the prognosis of conservative management. Drug holiday was the only prognostic factor in the surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t-test). CONCLUSION: Drug holiday is a prognostic factor in the surgical management of MRONJ. Because the drug holiday in the patients of the poor prognosis group occurred 1.5 to 4 months prior to surgical management, we recommend a drug holiday more than 4 months before surgery.