Osteonecrosis of the Jaws in Patients with Hereditary Thrombophilia/Hypofibrinolysis—From Pathophysiology to Therapeutic Implications

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone’s venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures.

Dental Implants in A Patient with History of Zoledronate Therapy: A Challenging Case

Implant placement in patient with history of bisphosphonate therapy is still controversial due to the risks of osteointegration failure and Biphosphonate related osteonecrosis of the jaws. Very few cases are reported. This paper aimed to report the success at 3 years follow up of 4 implants placed in a female patient with history of breast cancer and zoledronate infu-sions ( twice yearly for 2 years).

Curious Case of Rodent Poison: A Case Report

Osteonecrosis was first described as a consequence of ionizing radiation used in the treatment of malignant tumors but later a variety of causes for osteonecrosis were found which include, Medication induced, radiation induced, chemical induced and infection induced. Terms such as: bisphosphonate osteonecrosis (BON), Bisphosphonate Associated Osteonecrosis of the Jaws (BONJ), Bisphosphonate Related Osteonecrosis of the Jaws (BRONJ), Antiresorptive Osteonecrosis of the Jaw (ARONJ) and Medication Related Osteonecrosis of the Jaw (MRONJ) have all had proponents and all continue to be utilized. However, Migliorati first proposed a designation of the disease as osteochemonecrosis. This case report is about a chemical induced osteonecrosis patient who placed rat poison inside the mouth.

Bisphosphonate-induced osteonecrosis of the jaws: a literature review

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.

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

Antiresorptive 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.

Promising results of surgical management of advanced medication related osteonecrosis of the jaws using adjunctive leukocyte and platelet rich fibrin

Background Leukocyte- and platelet-rich fibrin (L-PRF) is an autologous matrix scaffold which regulates inflammation by stimulating cytokines and growth factors that are involved in the immune response. L-PRF is suggested as a viable adjunctive method to surgical interventions due to its advantages on tissue healing. This study aims to retrospectively evaluate the adjunctive role of L-PRF in surgically treated medication-related osteonecrosis of the jaws (MRONJ) patients. Methods Between January 2012 and December 2020, patients with AAOMS stage II and III MRONJ lesions, who were treated surgically with adjunctive use of L-PRF in the authors’ institution were enrolled. Surgical interventions consisted of either marginal resection or sequestrectomy with peripheral ostectomy (SPO) or curettage and L-PRF application. Medical records of these patients were retrospectively reviewed and healing was assessed according to certain parameters including mucosal closure and presence of infection, exposed bone, fistula or radiologic markers of disease progression for a minimum of 12 months. Results Thirteen patients (7 women and 6 men) with an average age of 72.4 years (± 10.61, range 54–84) were included in the study, nine of whom had AAOMS stage III and four stage II MRONJ. Three patients had a marginal resection, nine patients had sequestrectomy with peripheral ostectomy (SPO) and one patient underwent a curettage procedure. All marginal resection and six SPO patients showed complete healing while four patients, who had SPO or curettage experienced incomplete healing. Mean follow up was 20.1 ± 18.29 months. Conclusion The use of L-PRF may be a favorable adjunctive option in the treatment of MRONJ owing to its favorable effects on tissue repair, ease of application, minimally invasive and cost-effective character and autogenous nature. Trial registration Retrospectively registered.

Fat Graft in Surgical Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)

Background: Although the published literature has grown exponentially during the last few decades, managing medication-related osteonecrosis of the jaws (MRONJ) remains challenging. Since the first description of adipose-derived stem cells, cell therapy showed promising perspectives in surgical treatment of MRONJ. In this study, the beneficial effect of fat graft in surgical treatment of stage 2 and 3 MRONJ patients was assessed. Methods: A retrospective analysis of the evolution pattern of the disease was conducted comparing the outcomes of MRONJ patients who underwent sequestrectomy followed by fat graft (n = 9) and those who received sequestrectomy alone (n = 12). Results: Improvement of the disease stage was observed in 77.8% vs. 22.2% cases in group A and B, respectively (p = 0.030); disease stability was documented in 11.1% vs. 25.0% cases in group A and B, respectively (p = 0.603); worsening of MRONJ stage was observed in 11.1% vs. 50.0% cases in group A and B, respectively (p = 0.159). Conclusions: Despite the small sample size, this study suggests that fat graft may represent a promising low-risk and cost-efficient adjunctive therapy in the surgical treatment of MRONJ patients.