Treatment of osteonecrosis of the jaw related to bisphosphonates and other antiresorptive agents

Dental implant treatment is a highly predictable therapy, but when potentially lethal symptoms or complications occur, dentists must remove the implant fixture. Recently, reports on antiresorptive agent-related osteonecrosis of the jaw have increased in the field of dental implants, although the relationship between dental implant treatment and antiresorptive agents remains unclear. Here, we report a case of antiresorptive agent-related osteonecrosis of the jaw that developed after dental implant removal. A 67-year-old Japanese woman with a medical history of osteoporosis and 7 years of oral bisphosphonate treatment was referred to our hospital with a chief complaint of painful right mandibular bone exposure. A family dentist removed the dental implants from the right mandible using a trephine drill without flap elevation in August 2016. However, the healing was impaired; she was referred to our hospital 3 months after the procedure. We performed a sequestrectomy of the mandible under general anesthesia. In conclusion, this patient's course has two important implications: First, the removal of dental implants from patients who are prescribed oral bisphosphonates for long durations can cause antiresorptive agent-related osteonecrosis of the jaw. Second, meticulous procedures are required to prevent and treat the development of antiresorptive agent-related osteonecrosis of the jaw after dental implant removal.

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

Reumatismo ◽

10.4081/reumatismo.2017.983 ◽

2017 ◽

Vol 69 (1) ◽

pp. 9 ◽

Cited By ~ 6

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.

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Platelet Rich Plasma in the Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw: Personal Experience and Review of the Literature

International Journal of Dentistry ◽

10.1155/2014/298945 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

F. Longo ◽

A. Guida ◽

C. Aversa ◽

E. Pavone ◽

G. Di Costanzo ◽

...

Keyword(s):

Surgical Therapy ◽

Personal Experience ◽

Platelet Rich Plasma ◽

Osteonecrosis Of The Jaw ◽

Bone Diseases ◽

Definitive Evidence ◽

Synthetic Drugs ◽

Antiresorptive Agents ◽

Nonsurgical Therapy ◽

Prp Gel

Bisphosphonates (BPs) are a class of synthetic drugs commonly used to treat bone metastasis and various bone diseases that cause osseous fragility (such as osteoporosis). Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common complication in patients who received BPs, especially intravenously. Recently, osteonecrosis of the jaw (ONJ) caused by chemotherapeutic not belonging to BPs drug class has been reported. For this reason, it has been proposed recently to rename BRONJ in antiresorptive agents related osteonecrosis of the jaw (ARONJ), to include a wider spectrum of drugs that may cause osteonecrosis of the jaw. The most debated topic about ARONJ/BRONJ is therapy. The most adequate procedure is far from being standardized and prevention seems to play a pivotal role. In our study, we considered 72 patients with BRONJ with nonsurgical therapy, surgical therapy, and surgical therapy with platelet rich plasma (PRP) gel to evaluate its therapeutic effect in promoting ONJ wounds healing. Good results showed by PRP in improving wound healing give away to case-control randomized studies that could give definitive evidence of its effectiveness.

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Effectiveness of surgery and hyperbaric oxygen for antiresorptive agent-related osteonecrosis of the jaw: A subgroup analysis by disease stage

PLoS ONE ◽

10.1371/journal.pone.0244859 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244859

Author(s):

Takuma Watanabe ◽

Keita Asai ◽

Shizuko Fukuhara ◽

Ryuji Uozumi ◽

Kazuhisa Bessho

Keyword(s):

Therapeutic Effect ◽

Hyperbaric Oxygen ◽

Subgroup Analysis ◽

Multivariable Analysis ◽

Osteonecrosis Of The Jaw ◽

Disease Stage ◽

Antiresorptive Agent ◽

Antiresorptive Agents ◽

Before And After ◽

Extensive Surgery

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event induced by antiresorptive agents (ARAs). The purpose of this study was to evaluate variables, mainly surgery and hyperbaric oxygen (HBO) therapy, associated with treatment outcomes in patients with a diagnosis of ARONJ at a single center. We enrolled consecutive patients who presented to our hospital for the management of stage 2 or 3 ARONJ between January 2003 and December 2019. The relationship between potentially predictive factors and outcome variables was examined using statistical analyses, along with a subgroup analysis based on disease stage. Of 252 patients included in this study, 206 had stage 2 ARONJ and 46 had stage 3 ARONJ. There were 119 patients with osteoporosis and 133 with malignant disease. In total, 139 patients were healed, and the healing rate of patients with stage 3 ARONJ was lower than that of patients with stage 2 ARONJ. With regard to the combination of surgery and HBO therapy, most patients underwent HBO before and after surgery. In the univariable analysis, surgery showed a therapeutic effect in both stage 2 and 3 ARONJ, whereas HBO showed a therapeutic effect in stage 2 ARONJ. In the multivariable analysis for stage 2 ARONJ, extensive surgery showed a stronger association with healing than conservative surgery, whereas ≥46 sessions of HBO therapy was less associated with healing than was non-HBO therapy. Our findings suggest that extensive surgery is highly effective against ARONJ regardless of disease stage if there is a sequestrum separation and systemic tolerance, whereas HBO therapy before and after surgical approach can be effective. Further studies are needed to identify treatment strategies for patients with treatment-refractory ARONJ who may be forced to undergo long-term HBO therapy with the expectation of sequestrum separation.

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Comprehensive Study of the Risk Factors for Medication-Related Osteonecrosis of the Jaw Based on the Japanese Adverse Drug Event Report Database

Pharmaceuticals ◽

10.3390/ph13120467 ◽

2020 ◽

Vol 13 (12) ◽

pp. 467

Author(s):

Shinya Toriumi ◽

Akinobu Kobayashi ◽

Yoshihiro Uesawa

Keyword(s):

Risk Factors ◽

Side Effects ◽

Adverse Drug Event ◽

Femoral Fractures ◽

Principal Component ◽

Osteonecrosis Of The Jaw ◽

Drug Event ◽

Event Report ◽

Atypical Femoral Fractures ◽

Antiresorptive Agents

Medication-related osteonecrosis of the jaw (MRONJ) is associated with many drugs, including bisphosphonates (BPs). BPs are associated with atypical femoral fractures and osteonecrosis of the external auditory canal. Thus, many drugs are reported to cause adverse effects on bone. This study aimed to investigate the effects of drugs and patient backgrounds regarding osteonecrosis-related side effects, including MRONJ. This study used a large voluntary reporting database, namely, the Japanese Adverse Drug Event Report database. First, we searched for risk factors related to MRONJ using volcano plots and logistic regression analysis. Next, we searched for bone-necrosis-related side effects using principal component and cluster analysis. Factors that were significantly associated with MRONJ included eight types of BPs and denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, radium chloride, medroxyprogesterone, female, elderly, and short stature. Furthermore, antiresorptive agents (i.e., BPs and denosumab) tended to induce MRONJ and atypical femoral fractures by affecting osteoclasts. We believe these findings will help medical personnel manage the side effects of many medications.

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Osteonecrosis of the jaw: BRONJ and ARONJ

Faculty Dental Journal ◽

10.1308/rcsfdj.2014.5.2.90 ◽

2014 ◽

Vol 5 (2) ◽

pp. 90-93 ◽

Cited By ~ 8

Author(s):

Salvatore Ruggiero

Keyword(s):

Quality Of Life ◽

Bone Resorption ◽

Osteonecrosis Of The Jaw ◽

Small Subset ◽

Antiresorptive Agents ◽

Osteoclast Function

Bisphosphonates and other more recent antiresorptive agents are potent inhibitors of osteoclast function and osteoclast-mediated bone resorption. As such, they have been effectively utilised to reduce skeletally related events and improve the quality of life of patients with osteoporosis and malignant osteolytic disease. Despite these benefits, osteonecrosis of the jaw continues to be a worrisome complication in a small subset of patients receiving these drugs.

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Concentration of Penicillin G in Jawbone Affected by Antiresorptive Agent-Related Osteonecrosis Following a Single Preoperative Dose

Antibiotics ◽

10.3390/antibiotics10010017 ◽

2020 ◽

Vol 10 (1) ◽

pp. 17

Author(s):

Philipp Poxleitner ◽

Michael Andreas Ermer ◽

Rainer Trittler ◽

Carolin Lena Feuerstein ◽

Jörg-Elard Otten ◽

...

Keyword(s):

Antibiotic Therapy ◽

High Performance ◽

Limit Of Detection ◽

Cost Effective ◽

Osteonecrosis Of The Jaw ◽

Penicillin G ◽

Serum Samples ◽

Median Concentration ◽

Antiresorptive Agent ◽

Antiresorptive Agents

The aim of this study was to evaluate the concentration of penicillin G in bone affected by antiresorptive agent-related osteonecrosis of the jaw (ARONJ) following a single preoperative dose of 10 million international units (6000 mg). ARONJ is a major concern in patients administered antiresorptive agents for conditions associated with pathologically increased bone resorption. Antibiotic therapy is a key component of most treatment approaches for ARONJ and penicillin based regimens, providing a cost effective therapy option with a favorable side effect profile, are administered most frequently. In this study, high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was applied to evaluate penicillin G concentration in serum and bone samples of 19 patients suffering from ARONJ and undergoing surgical treatment under perioperative intravenous (IV) antibiotic therapy. Penicillin G bone concentrations were above the limit of detection (0.1 μg/g bone tissue) in 16 out of 19 samples, with a median concentration of 2.7 μg/g (range 0.1–8.8 μg/g). Penicillin G concentrations in intraoperative serum samples were above the limit of detection in all serum samples, with a median concentration of 116 μg/mL (range 1–232 μg/mL). Thus, considering bacteria frequently found in ARONJ lesions, penicillin G at levels providing adequate antimicrobial activity was detected in the serum and 16 out of 19 osteonecrotic lesions of patients suffering from ARONJ.

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Application of Photodynamic Therapy in the Treatment of Osteonecrosis of the Jaw

10.5772/intechopen.94257 ◽

2020 ◽

Author(s):

Marko Vuletić ◽

Božana Lončar Brzak ◽

Igor Smojver ◽

Luka Marković ◽

Mato Sušić ◽

...

Keyword(s):

Photodynamic Therapy ◽

Alveolar Bone ◽

Treatment Protocol ◽

Signs And Symptoms ◽

Osteonecrosis Of The Jaw ◽

Osteoblastic Activity ◽

Antiresorptive Agents ◽

Local Trauma ◽

Mechanisms Of Development ◽

Tissue Trauma

Osteonecrosis as term represents the death of bone tissue in the body and causes of necrosis can be different. Medication-related osteonecrosis of the jaws (MRONJ) is nowadays known as an inability of the alveolar bone to respond to a local trauma and it can result in severe local and systemic complications. In the etiology of medication-related osteonecrosis there are antiangiogenic and antiresorptive agents which have great effect on alveolar bone, producing an imbalance between resorption (osteoclastic activity) and deposition (osteoblastic activity). The exact mechanisms of development are not todays completely resolved. It is thought that it is a result from combination of medication interactions, microbiological contamination of the area and local tissue trauma. Typical signs and symptoms are painful mucosal lesions, swelling, exposed necrotic bone in the jaws, discomfort and dysesthesias. There is currently no gold standard or clearly defined treatment protocol for the disease itself. Process of treatment is demanding and main goal is to eliminate pain, control infection of soft and hard tissue and minimize progression of osteonecrosis. Besides the conventional surgical treatment, photodynamic therapy can be a viable supportive tool of initial and advanced stages of osteonecrosis and may contribute to improvements of patient′s quality of life.

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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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