scholarly journals Drug-induced osteonecrosis of the jaw: the state of the art

Reumatismo ◽  
2017 ◽  
Vol 69 (1) ◽  
pp. 9 ◽  
Author(s):  
A. Fassio ◽  
F. Bertoldo ◽  
L. Idolazzi ◽  
O. Viapiana ◽  
M. Rossini ◽  
...  
Keyword(s):  
Adverse Event ◽  
Oral Surgery ◽  
Absolute Risk ◽  
Rare Condition ◽  
Osteonecrosis Of The Jaw ◽  
Large Majority ◽  
Drug Induced ◽  
Antiresorptive Agents ◽  
Oncologic Patients ◽  
Antiresorptive Drugs

Osteonecrosis of the jaw (ONJ) is a rare adverse event of antiresorptive drugs such as bisphosphonates (BP) and denosumab (DMAb). The diagnosis of ONJ is considered in cases where exposed bone in the maxillofacial region does not heal within 8 weeks in a patient previously treated with an antiresorptive agent. In patients with osteoporosis, ONJ is reported as a very rare adverse event while in oncologic patients with bone metastases or malignant hypercalcemia the incidence is significantly higher (up to the 1-10% of the patients). The pathophysiology of ONJ is still not completely understood but it is multi-factorial. ONJ is a condition associated with poor oral health, oral surgery, and use of antiresorptive agents. Prevention is of paramount importance especially in cancer patients, in whom the large majority of cases of ONJ (>90%) are reported, but it should also be considered in osteoporotic patients, especially during dental surgical procedure. Some simple prevention procedures are effective in reducing the risk of its appearance. When ONJ unfortunately occurs, the large majority of patients can be managed conservatively. In conclusion, ONJ is a rare condition associated with antiresorptive drugs. Both osteoporotic and oncologic patients should be well informed about its low absolute risk and regarding the fact that the benefits of antiresorptive therapy far outweigh this potential risk of ONJ.

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

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.

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

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.

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

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.  

scholarly journals Paget’s disease of bone, biphosphonates and jaw osteonecrosis: a case report

NEMESIS ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 15
Author(s):  
Michele Magremanne ◽  
Anne Grysolle ◽  
Hervé Reychler
Keyword(s):  
Case Report ◽  
Paget’S Disease ◽  
Rare Event ◽  
Rare Condition ◽  
Osteonecrosis Of The Jaw ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
Bisphosphonate Treatment ◽  
Oncologic Patients

Objective: Paget’s disease of bone is characterized by a focal increase in bone resorption and accelerated bone formation leading to a weaker and disorganised bone. Bisphosphonates (BPs) have been the treatment of choice of Paget’s disease since the 1990s. Medication related osteonecrosis of the jaw (MRONJ) is a rare event in non oncologic patients. We describe a rare case of  Paget’s disease involving the maxilla with osteonecrosis in a context of bisphosphonate treatment.   Case report: an 87-year-old woman presented with 4 episodes of bone necrosis in 15 years. In this case report there is a clear chronologic association between the occurrence of MRONJ and the administration of iv BP for Paget’s disease. Maxillofacial involvement of Paget’s disease occurs in less than 15% of cases. There is a lack of information in the literature about the association of MRONJ and Paget’s disease. Even if osteonecrosis of the jaw could be a consequence of the disease, in this case, it is more in relation to the BP treatment.   Conclusions: Although MRONJ might be considered a rare condition in Paget’s disease, patients prior to starting antiresorptive therapy and in particular iv BPs should have a complete dental examination and panoramic X-Ray.   Nemesis relevance: side effect of bisphosphonate treatment  

scholarly journals Medication-Related Osteonecrosis of the Jaw: a Brief Review, Treatment and Practical Guidelines for Dentists

2017 ◽  
Vol 2 (2) ◽  
pp. 117-121
Author(s):  
Ioana-Aurița Albu-Stan ◽  
Daniel-Emil Albu ◽  
Diana Cerghizan ◽  
Lia Yero Eremie ◽  
Kinga Jánosi ◽  
...  
Keyword(s):  
Bone Fractures ◽  
Malignant Tumors ◽  
Osteonecrosis Of The Jaw ◽  
Bone Diseases ◽  
Disease Stage ◽  
Mineral Density ◽  
Treatment Protocols ◽  
Antiresorptive Agents ◽  
Antiresorptive Drugs ◽  
Practical Guidelines

AbstractOsteonecrosis of the jaws is a complication after treatment with antiresorptive drugs. Bisphosphonates (BPs) are widely used to treat conditions with bone metastases of malignant tumors such as multiple myeloma, breast cancer, prostatic cancer, as well as hypercalcemia of malignancy, osteoporosis, Paget’s disease, and osteogenesis imperfecta. Denosumab is an antiresorptive agent that is used for the treatment of osteoporosis or metastatic bone diseases. These antiresorptive agents improve the quality of life of patients by increasing strength and bone mineral density, and reducing the risk of bone fractures. More than a decade had passed since the first publication of this pathology, and the occurrence of the disease, its pathophysiology, and proper treatment methods are still not fully elucidated. Prevention is critical in medication-related osteonecrosis of the jaw, because the treatment is difficult, and there are no universally accepted treatment protocols. There is an accepted approach of palliation of symptoms and controlling the associated infections. Treatment may follow one of three procedures: conservative management of pain, conservative or extensive (segmental) surgery, depending on the disease stage.

scholarly journals Real-world Study of Antiresorptive-Related Osteonecrosis of Jaw Based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database

2021 ◽  
Author(s):  
JING PENG ◽  
LEI REN ◽  
mingli WU ◽  
xia wang ◽  
Tian wei ◽  
...  
Keyword(s):  
Adverse Event ◽  
Drug Administration ◽  
Odds Ratio ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Osteonecrosis Of The Jaw ◽  
Adverse Event Reporting ◽  
Event Reporting ◽  
Antiresorptive Drugs ◽  
Osteonecrosis Of Jaw

Objective To explore the risk signals of osteonecrosis of jaw induced by antiresorptive drugs and provide references for the clinical safety application. Method Based on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to June 2021, We chosen ‘Osteonecrosis of jaw’ as Preferred Terms (PT) and antiresorptive drugs. We used proportional reporting ratio (PRR), odds ratio (reporting odds ratio, ROR), Bayesian confidence propagation neural network (BCPNN) and multi-item Gamma-Poisson contraction (MGPS) algorithm to evaluate the association between drugs and adverse events. Results 27,065 reports related to osteonecrosis of the jaw in the FAERS dated from January 2004 to June 2021 . A total of 9 antiresorptive agents were included in the analysis. Affected patients tended to be older than 65 years. Most cases were reported from North America (39.82%) and Europe (36.15%) and were submitted by health-care professionals (81.44%). Pamidronate and clodronic acid showed a higher score than the other agents in every method. Zoledronic acid and denosumab were reported more than other agents.. Rate of hospitalization due to antiresorptive-related osteonecrosis of the jaw was from 7.66% to 28.78%; rate of fatality was from 0 to 12.78%. Conclusion All antiresorptive drugs may cause ONJ, and ONJ can be effectively prevented. Practitioners should consider the factors that may increase the likelihood of ONJ. The findings support a continued surveillance and risk factor identification studies.

Osteonecrosis of the Jaw Correlated to Bisphosphonate Therapy in Non-oncologic Patients: Clinicopathological Features of 24 Patients

2009 ◽  
Vol 36 (12) ◽  
pp. 2780-2787 ◽  
Author(s):  
GIANFRANCO FAVIA ◽  
GIOVANNI PIETRO PILOLLI ◽  
EUGENIO MAIORANO
Keyword(s):  
Side Effect ◽  
Rare Condition ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Study Cohort ◽  
Neoplastic Disease ◽  
Dental Surgery ◽  
Oncologic Patients ◽  
Oncologic Diseases ◽  
Harmful Side Effect

Objective.Osteonecrosis of the jaws (ONJ) is a well known side effect of bisphosphonate therapies in patients with multiple myeloma or other malignancies. Its real incidence is still undetermined, and only few cases of ONJ in patients taking bisphosphonates for non-oncologic diseases have been reported. It was postulated that the clinical features, predisposing factors, and treatment outcome of this subset of patients might be different from those of oncologic patients.Methods.Over a 4 year period, a total of 102 bisphosphonate-treated patients affected by ONJ were identified. Among these, 24 patients underwent bisphosphonate therapy for non-neoplastic disease and their profile was analyzed.Results.In this study cohort, bisphosphonates had been administered mainly for postmenopausal osteoporosis (20/24 patients, 83.3%), the duration of therapy until presentation of ONJ ranging from 11 to 40 months and the most common triggering event being dentoalveolar surgery. All patients were nonsmokers; 6 manifested multiple ONJ lesions and only 3 of them had possible comorbidities. Surgical debridement was performed in 19 patients for a total of 22 lesions, which were individually considered in the followup. The latter showed complete remission of ONJ in 21/22 lesions.Conclusion.Although it might be considered a rare condition in non-oncologic patients, ONJ is a harmful side effect of bisphosphonate therapies. Clinicians must be aware of this entity, inform patients of the risks related to dental surgery, and possibly undertake adequate preventive measures.

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

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.

scholarly journals On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehran Ashrafi ◽  
Farzan Ghalichi ◽  
Behnam Mirzakouchaki ◽  
Manuel Doblare
Keyword(s):  
Mathematical Model ◽  
Bone Density ◽  
Bone Remodeling ◽  
Dental Implants ◽  
Implant Design ◽  
Patient Specific ◽  
Dental Implantation ◽  
Antiresorptive Agents ◽  
Antiresorptive Drugs

AbstractBone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic–pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.

Acute Generalized Exanthematous Pustulosis With Multiple Organ Dysfunction Syndrome

2013 ◽  
Vol 22 (3) ◽  
pp. 270-273 ◽  
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Manar Al Asad ◽  
Lindsay Scratchko ◽  
Ghulam Khaleeq
Keyword(s):  
Lower Extremity ◽  
Rare Condition ◽  
Skin Condition ◽  
Multiple Organ ◽  
Drug Induced ◽  
Acute Generalized Exanthematous Pustulosis ◽  
Left Lower Extremity ◽  
Causative Drug ◽  
Diffuse Erythema ◽  
Exanthematous Pustulosis

Acute generalized exanthematous pustulosis is a rare condition characterized by sterile pustules on erythematous and edematous tissue. Mostly drug induced, this condition can also be caused by other factors. Cases due to vancomycin are rare. A 67-year-old woman with cellulitis of the left lower extremity was admitted with marked bilateral lymphedema of the lower extremities and diffuse erythema of the left lower extremity from foot to knee. She was given clindamycin and then vancomycin. On day 5, her condition worsened, with erythema involving the entire back. Although treatment with clindamycin and vancomycin was discontinued, acute generalized exanthematous pustulosis developed. After successful treatment of other complications, the skin condition improved. Because vancomycin is frequently used, clinicians should be aware of the possibility of acute generalized exanthematous pustulosis. Because the pustulosis decreases after withdrawal of the causative drug, being able to diagnose and differentiate the abnormality from other conditions is prudent.

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