Medication-Related Osteonecrosis of the Jaws: Considerations on a New Antiresorptive Therapy (Denosumab) and Treatment Outcome after a 13-Year Experience

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients receiving antiresorptive therapies for bone neoplastic localizations and osteoporosis. The aim of this study was to evaluate the clinicopathological features of MRONJ in a cohort of patients treated by new antiresorptive drugs (denosumab) and the corresponding outcome after 13-year maximum follow-up. Overall, 244 patients affected by MRONJ were treated from 2003 to 2015. After clinical and radiological examinations, all lesions were staged according to a dimensional staging system and then surgically treated. All the denosumab-related lesions were classified as stage II or III, thus requiring a more or less invasive surgical approach, despite the results of many recent studies, which suggested a conservative medical approach with early resolution for MRONJ in patients on denosumab. In the current series, 86.9% of treated lesions showed complete clinical and radiological healing, while 13.1% recurred; all recurrences were detected in patients who could not interrupt chemotherapy, steroids, and/or antiresorptive drugs administration due to their general conditions. In conclusion, all oral specialists should be aware of the MRONJ risk among patients taking new antiresorptive drugs; moreover, our protocol based on surgical treatment guided by dimensional staging could be considered effective in view of the low recurrence rate.

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Dental pathologies in tumor patients with bone metastases or multiple myeloma scheduled for antiresorptive therapy

Future Oncology ◽

10.2217/fon-2020-1240 ◽

2021 ◽

Author(s):

Johannes Laimer ◽

Martin Hechenberger ◽

Daniela Müller ◽

Benjamin Walch ◽

Andreas Kolk ◽

...

Keyword(s):

Multiple Myeloma ◽

Oral Surgery ◽

Osteonecrosis Of The Jaw ◽

University Hospital ◽

Antiresorptive Therapy ◽

Jaw Cysts ◽

Dental Focus ◽

Antiresorptive Drugs ◽

The University ◽

Tooth Extractions

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe complication of mainly antiresorptive drugs. We evaluated the frequency of dentoalveolar pathologies in patients scheduled for antiresorptive therapy in a ‘real-world’ setting, also including patients with poor oral health potentially requiring tooth extractions and/or other dentoalveolar surgery. This approach is in contrast to the setting of recent randomized trials with restrictive exclusion criteria. Patients & methods: We prospectively included patients suffering from solid tumors with osseous metastases or multiple myeloma. Screening for dentoalveolar pathologies was done prior to initiation of antiresorptive therapy at the specialized MRONJ clinic of the University Hospital for Cranio-Maxillofacial and Oral Surgery, Innsbruck, Austria. Results: 119 subjects could be included. In 76 patients (63.9%), a dental focus was revealed including deep caries (24.4% of patients), chronic apical periodontitis (26.9%), periodontal disease (45.8%), root remnants (16%), jaw cysts (2.5%), partially impacted teeth (5.0%) and peri-implantitis (5.0%). Conclusion: Considering the high number of dentoalveolar pathologies (63.9%), systematic dental focus screening prior to initiation of antiresorptive therapy is of utmost importance to lower the risk for MRONJ.

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Success rate and safety of dental implantology in patients treated with antiresorptive medication: A systematic review

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-19-00088 ◽

2020 ◽

Author(s):

Ioannis Papadakis ◽

Alexandra Spanou ◽

Demos Kalyvas

Keyword(s):

Systematic Review ◽

Dental Implant ◽

Late Complication ◽

Survival Rates ◽

Osteonecrosis Of The Jaw ◽

Inclusion Criteria ◽

Implant Placement ◽

Antiresorptive Agents ◽

Antiresorptive Drugs

There is no agreement of data in the subject of implant failure and the development of osteonecrosis in patients receiving antiresorptive agents. The purpose of this systematic review is to evaluate whether dental implants placed in patients on antiresorptive medication have an increased failure rate and whether the implant placement or the implant existence are risk factors for developing medication-related osteonecrosis of the jaw (MRONJ). An electronic search was conducted in PubMed/Medline and all publications fulfilling the inclusion criteria were included. The search was completed by a hand research of the references cited in all electronic identified publications and resulted in 411 articles. According to the inclusion criteria, 32 studies were included with a total of 5221 patients, 12 751 implants, 618 cases of implants loss and 136 cases of MRONJ analyzed. It cannot be established that antiresorptive medication affects the dental implant survival rates, because of small number of studies, most of them characterized by a low level of quality. The risk of MRONJ as an early or late complication is also not well established. Therefore, successful dental implant procedures on patients receiving antiresorptive medication might be possible, but more studies need to be carried out in the future to verify this topic. Apart from intravenous antiresorptive drugs, which remain an absolute contraindication, dental implantology in patients under antiresorptive medication is not a contraindication but it must be accompanied with a careful treatment planning, patients must be informed about the possible complications and large follow up periods are essential.

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Impact of Antiresorptive Agents on Maxillary Bones: a Narrative Literature Review

Journal of Health Sciences ◽

10.17921/2447-8938.2021v23n4p268-276 ◽

2021 ◽

Vol 23 (4) ◽

pp. 268-276

Author(s):

Maria Luiza da Silva Matos ◽

Pedro Henrique Bastos de OIiveira ◽

Ana Carla Barletta Sanches ◽

Tila Fortuna Costa Freire ◽

Juliana Borges de Lima Dantas ◽

...

Keyword(s):

Literature Review ◽

Adverse Effects ◽

Osteonecrosis Of The Jaw ◽

Drug Holiday ◽

Osteonecrosis Of The Jaws ◽

Antiresorptive Agents ◽

Antiresorptive Drugs ◽

Bibliographic Search ◽

Narrative Literature ◽

Narrative Literature Review

AbstractAntiresorptive drugs operate in the bone metabolism modulation and are widely used in the treatment of bone metastases and bone losses related to hormonal deficiency. Although this therapy shows satisfactory results, there are adverse effects associated with its use, such as osteonecrosis of the jaws. Medication-related osteonecrosis of the jaws (MRONJ) is, therefore, a serious and challenging condition with important implications in dentistry. The aim was to conduct a narrative literature review on anti-resorptive drugs and their latest repercussions on the maxillary bones. The review was carried out through a bibliographic search using Decs/Mesh descriptors of interest, in Portuguese and English, in the PubMed, Virtual Health Library (VHL) and Scielo databases. After applying the inclusion and exclusion criteria, a total of 33 studies were selected for analysis. It can be noticed that therapy with anti-resorptive agents is complex, especially in dental practice, since MRONJ is a complication that is difficult to manage. Regarding the therapeutic options, these are divided into conservative, surgical or adjuvant therapy, however, there are no protocols in the literature, and there is no consistency regarding the indication of the suspension of the drug administration - "Drug Holiday". Thus, it is important that the multidisciplinary team seeks strategies that minimize complications and promote control over the use of these drugs. In addition, there is a need for investigations that contribute with guidelines for the management and control of adverse effects resulting from therapy with antiresorptive drugs. Keywords: Bone Density Conservation Agents. Diphosphonates. Denosumab. Bisphosphonate-Associated Osteonecrosis of the Jaw. ResumoAs drogas antirreabsortivas atuam na modulação do metabolismo ósseo e são indicadas para o tratamento de metástases ósseas e perdas ósseas relacionadas à deficiência hormonal. Ainda que esta terapia apresente resultados satisfatórios, observam-se efeitos adversos associados ao seu uso, como a osteonecrose dos maxilares. A osteonecrose dos maxilares associada ao uso de medicamentos (OMAM) é, portanto, uma condição séria e desafiadora com implicações importantes na Odontologia. O objetivo foi realizar uma revisão narrativa de literatura sobre as drogas antirreabsortivas e suas respectivas repercussões nos ossos maxilares. A revisão foi realizada através de busca bibliográfica utilizando descritores Decs/Mesh de interesse, em português e inglês, nas bases de dados PubMed, Biblioteca Virtual de Saúde (BVS) e Scielo. Após aplicação dos critérios de inclusão e exclusão, um total de 33 trabalhos foram selecionados para análise. Pode-se constatar que a terapia com agentes antirreabsortivos é complexa, sobretudo na prática odontológica, visto que a OMAM é uma complicação de difícil manejo. Em relação às condutas terapêuticas para esta condição, divide-se em terapia conservadora, cirúrgica ou adjuvante, todavia, não existem protocolos validados na literatura, bem como não há consistência quanto à indicação do intervalo de suspensão da administração da droga - “Drug Holiday”. Desse modo, é importante que a equipe multidisciplinar busque estratégias que minimizem as complicações e promovam o controle no uso dessas drogas. Além disso, nota-se a necessidade de realizar investigações que contribuam com diretrizes para o manejo e controle dos efeitos adversos decorrentes da terapia com medicamentos antirreabsortivos. Palavras-chave: Conservadores da Densidade Óssea. Bisfosfonatos. Denosumabe. Osteonecrose Associada a Bisfosfonatos.

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Possible Role of Oral Ibandronate Administration in Osteonecrosis of the Jaw: A Case Report

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201202500138 ◽

2012 ◽

Vol 25 (1) ◽

pp. 311-316 ◽

Cited By ~ 2

Author(s):

A. Notarnicola ◽

S. Lisi ◽

M. Sisto ◽

A.V. De Marino ◽

M. D'Amore

Keyword(s):

Risk Factors ◽

Osteonecrosis Of The Jaw ◽

Bisphosphonate Therapy ◽

Caucasian Woman ◽

Oral Bisphosphonate ◽

Antiresorptive Drugs ◽

Magnetic Resonance Imaging Mri ◽

Alternative Medications

We describe a case of Osteonecrosis of the Jaw (ONJ) that developed in a 65-year-old Caucasian woman with osteopenia and other risk factors who was receiving low doses of oral bisphosphonate therapy (ibandronate, 150 mg monthly). Computed tomography (CT), panoramic radiographs (OPT), 99mTc-Sn-MDP scintigraphy, and magnetic resonance imaging (MRI) were performed to study the diseased area; cytological examination also revealed the presence of suppurative material around the area of exposed bone. A diagnosis of bisphosphonate-related osteonecrosis of the jaw complicated by osteomyelitis was made. The patient was prescribed a drug protocol consisting of metronidazole 250 mg 2 times daily, chlorhexidine mouthwashes 3 times daily and chewing exercises for two months. Ibandronate was stopped and replaced with strontium ranelate. The symptoms improved and the patient is still under close follow-up. Assessment of the benefits versus risks is particularly necessary in patients with several risk factors to ascertain their eligibility for treatment with antiresorptive drugs and when this is not possible to choose alternative medications.

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Medication-related osteonecrosis of the jaw: Evidence for infection versus oversuppression.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18268 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18268-e18268

Author(s):

Kenneth Evan Fleisher ◽

Franco Muggia ◽

Robert S Glickman

Keyword(s):

Computed Tomography ◽

Medical History ◽

Metastatic Cancer ◽

Surgical Techniques ◽

Osteonecrosis Of The Jaw ◽

Outcome Variable ◽

Antibiotic Administration ◽

Antiresorptive Therapy ◽

Successful Management

e18268 Background: Antiresorptive medications are important in maintaining bone health for patients with osteoporosis, metastatic cancer and multiple myeloma. Medication-related osteonecrosis of the jaw (MRONJ) may compromise quality of life and treatment of the underlying disease. There are many controversies regarding the pathogenesis, risk and management of MRONJ. Evidence-based data that suggest osteonecrosis of the jaw (ONJ) is triggered by infection and reports of ONJ unrelated to antiresorptive therapy (ART) have confounded previous hypotheses that pathogenesis is directly attributed to ART by oversuppression of bone remodeling. The aim of this study is to determine the outcome for management of MRONJ based on eradication of infection. Methods: The investigators designed a retrospective cohort study for patients who underwent surgical management of MRONJ. Identification of infected and necrotic bone was achieved via nuclear imaging (i.e., technetium bone scan, positron emission tomography), computed tomography and/or cone beam computed tomography. Surgical techniques included bone resection (i.e., marginal, segmental), local flap, reconstruction with microvascular free flap, and/or autogenous platelet graft. Perioperative modalities included hyperbaric oxygen therapy and culture-guided antibiotic administration. We recorded medical history, location of the MRONJ lesion, type of antiresorptive therapy and duration of perioperative antiresorptive therapy. The outcome variable was postoperative healing defined by mucosal closure without signs of infection or exposed bone at the time of follow-up including cases with complications related to subsequent dental infection or treatment. Descriptive statistics were calculated for successful management, medical history and duration of perioperative antiresorptive therapy. We excluded cases treated by palliative intent, when surgery was limited or contraindicated, and/or inadequate follow-up. Results: A total of 54 patients with 59 MRONJ lesions were evaluated (40 with cancer and 14 with osteoporosis). All patients were successfully treated with 13 patients continuing ART after surgery (average follow-up 10 months) and 8 patients requiring more than 1 surgery for lesions associated with osteosclerosis. Conclusions: This study suggests that MRONJ is an infection-driven process that can be managed with various modalities to control diseased bone and facilitate healing. Patients may resume ART following successful management of MRONJ.

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Bisphosphonate-induced osteonecrosis of the jaws: a literature review

Brazilian Journal of Case Reports ◽

10.52600/2763-583x.bjcr.2021.1.4.190-198 ◽

2021 ◽

Vol 1 (4) ◽

pp. 190-198

Author(s):

Nayane de Andrade Teófilo ◽

Caio Denardin ◽

Thiago Quirino Mota Da Silva ◽

Túlio Garcia Margute ◽

Andrei Rabenschlag Rossato ◽

...

Keyword(s):

Literature Review ◽

Adverse Effects ◽

Digital Library ◽

Research Problem ◽

Osteonecrosis Of The Jaw ◽

Exclusion Criteria ◽

Osteonecrosis Of The Jaws ◽

The Subject ◽

Library Websites

Bisphosphonates are widely used, whether in osteoporosis or malignant bone disorders. Therefore, it is necessary that there is sufficient knowledge about the adverse effects of this drug, especially in relation to Osteonecrosis of the Jaws Developed by Bisphosphonates, which is a pathology generated in the gnathic bones. So, the following question was asked in the research problem: What is the current situation regarding the use of bisphosphonates and the onset of osteonecrosis of the jaw? Searches were carried out on digital library websites in search of articles and research in books by renowned authors. Inclusion and exclusion criteria for articles found were defined. The verification of each article was carried out so that it could have perspective and follow-up on the subject discussed. The following databases were used: PUBMED, BIREME and LILACS, and SCIELO between the years 2007 to 2019. It was concluded then that Bisphosphonates play a very important role as a cause of osteonecrosis of the jaws, where the prognosis will be worse if the patient is treated with intravenous rather than oral types.

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A New Medical Record Proposal to the Prognostic Risk Assessment for MRONJ in Oncologic Patients: “Sapienza Head and Neck Unit” Proposal

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041851 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1851

Author(s):

Edoardo Brauner ◽

Silvia Mezi ◽

Alessandro Ciolfi ◽

Chiara Ciolfi ◽

Resi Pucci ◽

...

Keyword(s):

Multidisciplinary Approach ◽

Bone Cancer ◽

Osteonecrosis Of The Jaw ◽

Individual Risk ◽

Medical Report ◽

Oncologic Patients ◽

Antiangiogenic Drugs ◽

Dental Screening ◽

The Individual

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event associated with antiresorptive and antiangiogenic drugs. The use of these drugs in the treatment of cancer patients with bone metastasis is necessary and standardized in the literature. A multidisciplinary approach for the patient’s management is strongly recommended. Therefore, it should be necessary to integrate the path of these subjects with a dedicated dental screening in order to first assess the individual risk of developing a MRONJ, and then to plan dental treatments and oral hygiene sessions, and finally to schedule a follow-up to intercept and treat early osteonecrosis. The aim of this manuscript is to propose a new simple medical report to evaluate patients affected by metastatic bone cancer in order to reduce the risk of developing MRONJ.

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Awareness of Medication-Related Osteonecrosis of the Jaws amongst Dental Professionals in Poland

Applied Sciences ◽

10.3390/app11114821 ◽

2021 ◽

Vol 11 (11) ◽

pp. 4821

Author(s):

Monika Teślak ◽

Hanna Sobczak ◽

Iwona Ordyniec-Kwaśnica ◽

Barbara Kochańska ◽

Barbara Drogoszewska

Keyword(s):

The Body ◽

Antiresorptive Therapy ◽

Osteonecrosis Of The Jaws ◽

Level Of Knowledge ◽

Medical University ◽

Self Administered Questionnaire ◽

Dental Professionals

Background: Medication-Related Osteonecrosis of the Jaws (MRONJ) is a serious complication of antiresorptive therapy. The aim of the study was to assess the level of knowledge and awareness regarding MRONJ among Polish dentists and students of dentistry. Methods: The online self-administered questionnaire was sent out electronically among dentists in Poland and dentistry students of the Medical University of Gdansk. The results obtained were statistically analyzed. The results were considered statistically significant if the condition p ≤ 0.05 was met. Results: A total of 203 respondents participated in this survey. A total of 94.6% of them declared knowledge of the term MRONJ. However, the length of bisphosphonates persistence in the body was known to 51.5% of participants, while the knowledge of oral and maxillofacial surgeons concerning this topic was significantly higher (87.0%). Conclusion: Dental and maxillofacial surgeons presented the highest level of knowledge about MRONJ. The remaining groups did not differ in their knowledge. It must be noted that the knowledge of the students was similar to that of dentists. A better level of knowledge by dentists could contribute to a decline of the occurrence of the disease in future. Theoretical and practical initiatives should be promoted to improve the knowledge about MRONJ.

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Conservative Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Retrospective Cohort Study

Antibiotics ◽

10.3390/antibiotics10020195 ◽

2021 ◽

Vol 10 (2) ◽

pp. 195

Author(s):

Elena M. Varoni ◽

Niccolò Lombardi ◽

Giulio Villa ◽

Alberto Pispero ◽

Andrea Sardella ◽

...

Keyword(s):

Conservative Management ◽

Prognostic Score ◽

Clinical History ◽

Osteonecrosis Of The Jaw ◽

Pharmacological Therapy ◽

Complete Healing ◽

High Rate ◽

Secondary Outcome ◽

Severe Side Effect

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of bisphosphonates and anti-resorptive drugs prescribed for treatment of severe osteoporosis, Paget’s disease, and bone malignancies. The aim of this study was to evaluate the clinical outcome of a combined pharmacological and surgical management strategy on patients affected by MRONJ. Materials and methods: Medical records of patients with MRONJ were retrospectively examined to collect clinical history data. Conservative management included an initial pharmacological phase with antibiotics and antiseptic agents, followed by surgical intervention to remove bone sequestrum. Primary outcomes were healing from MRONJ at short term (1 month after surgery) and at longer term (3 months after surgery). Secondary outcome was assessment of recurrences at longer-term follow-up. Results: Thirty-five patients were included in the study with mean follow-up of 23.86 ± 18.14 months. Seven cases showed spontaneous exfoliation of necrotic bone during pharmacological therapy, which in one case did not require any further intervention. At 1-month posttreatment, 31 out of 35 (88.5%) patients showed complete healing. The 25 patients who were followed for at least 3 months revealed a healing rate of 92% (23/25). Recurrences occurred in 7 patients out 23 who showed the long-term healing, after a mean period of 7.29 ± 3.45 months. The prognostic score (University of Connecticut Osteonecrosis Numerical Scale—UCONNS) was significantly higher (p = 0.01) in patients with poor healing as compared to complete healing, both at 1 and 3 months posttreatment. Conclusions: A MRONJ treatment approach based on a combined pharmacological and surgical treatment strategy showed a high rate of healing and few recurrences.

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Total thymectomy for thymic lymphoepithelioma-like carcinoma—report of two cases

Surgical Case Reports ◽

10.1186/s40792-019-0706-6 ◽

2019 ◽

Vol 5 (1) ◽

Author(s):

Sachi Kawagishi ◽

Naoko Ose ◽

Masato Minami ◽

Soichiro Funaki ◽

Takashi Kanou ◽

...

Keyword(s):

Surgical Resection ◽

Thymic Carcinoma ◽

Clinical Manifestations ◽

Staging System ◽

Early Recurrence ◽

Anterior Mediastinum ◽

Total Resection ◽

Distant Lymph Node Metastasis ◽

Long Term Follow Up

Abstract Background Thymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized. Case presentation Two patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease. Conclusion We report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.

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