Osteonecrosis of the Jaw

Human jawbone represents a unique morphology due to its connection with the teeth, which are initiated by epithelial ingrowth that can form remnants and are crucial for proper bone persistence. Within this bone fatty degenerative osteonecrosis can occur and lead to inflammation and can persist with or without symptoms. Surprisingly, diagnosis and therapy of this condition are still a controversy in modern dentistry. In this review of the literature the history of this condition was redrawn. A multitude of names confused symptoms and pathophysiological ideas lead to communicative problems. Radiography is unfortunately not the most reliable imaging tool and therefore has to be supported by trans-alveolar ultrasonography. This novel method is now standardized and ready to be tested by larger groups. The most reasonable treatment is to remove the necrotic tissue. The numerous arguments and denial of the main dental community is not convincing, and the fatty degenerative osteonecrosis should be more in focus of clinical trials to improve the patients' needs and care.

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with nonsurgical management.

A case report of bevacizumab-related osteonecrosis of the jaw: Old problem, new culprit Osteonecrosis of the jaw (ONJ) is well-characterized syndrome predominantly reported in advanced stage cancer patients who had used long term bisphosphonates to treat bone metastases. Rarely, ONJ has been reported in patients who have not used bis-phosphonates. Here we present an extremely rare occurrence of ONJ that occurred in a patient who received bevacizumab containing chemotherapy without bisphosphonate therapy. A 51-year-old male with history of metastatic carcinoma of the sigmoid colon was diagnosed in December 2010. He was subsequently treated with palliative chemotherapy with infusion-al fluorouracil, leucovorin, oxaliplatin, and bevacizumab for six cycles. Bevacizumab was initiated at a dose of 5 mg/kg on a 2-week schedule. Two weeks following the last dose of chemo-therapy, the patient presented with a 2-week history of lower jaw pain, ulcer in the mouth, and difficulty chewing. He denied any recent history of dental surgery or radiation therapy at affected site. A detailed dental examination revealed a small area of bone exposure and ulcer in the right posterior mandible, measuring approximately 3 Â 3 mm in diameter. The surrounding soft tissue appeared ulcerated and necrotic, with no evidence of infection. Pantomography and axial computerized tomography revealed a minor cortical sclerotic bone lesion (Fig. 1A and B). There was no evidence of fistulae or abcesses. After curettage and primary restoration of the necrotic lesion, pathological findings consistent with osteonecrosis and actinomyces superinfec-tion were noted (Fig. 2). The suspected diagnosis of jaw osteonecrosis was confirmed. It was suggested that the patient's symptoms were likely related to his use of bevacizumab, even though there was not a period of antecedent bisphosphonate use. Actinomycosis causing infection in this case, we believe that just an incidental findings rather than a causal role. ONJ is defined by the presence and persistence of exposed bone in the jaw over a period of 6-8 weeks. Nitrogen-containing intravenous BP treatment has been implicated in 94% of ONJ cases. Development of ONJ can occur spontaneously or can be facilitated by tooth extraction, dental procedures, poor oral hygiene, and acti-nomyces infections. The pathogenesis of bisphosphonate-related ONJ is believed to involve inhibition of angiogenesis and bone formation. 1,2 Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and bone formation. Bev-acizumab (Bev), a VEGF inhibitor, has been shown to effectively treat a variety of malignancies when combined with chemother-apy. Bev has been associated with severe adverse events such as thromboembolic episodes, hypertension hemorrhage, and gastro-intestinal perforation. 3 Among Bev users, devleopment of ONJ is very rare, only having been recently reported in a small number of cases. 4,5 Thus, this case study is important in the understanding of this rare complication, emphasizing the gravity of Bev-associated ONJ. One retrospective analysis stated that ONJ incidence is not different whether a patient used Bev alone or used Bev in addition to BP therapy. 6 Despite this, Christodoulou et al. concluded that in a small retrospective study, BPs with angiogenesis inhibi-tors induce ONJ more frequently than BP alone. 7 During treatment with other anti-angiogenic agents, such as sunitinb for renal cell cancer and thalidomide for multiple myeloma, ONJ has also been reported. 8,9 To the best of our knowledge, the present case report is the first report of ONJ in a metastatic colorectal cancer patient treated with Bev alone. We believe that Bev is a primary factor in causing ONJ. In conclusion, Bev has the potential to affect oral health and cause ONJ. The chances of developing ONJ can be increased when Bev is used concurrently with BPs. It should be noted that ONJ may develop in patients who use any angiogenesis inhibitors with or without BPs. A preventive dental assessment is recommended for patients scheduled for bevacizumab and/or BP therapy. References

Abstract: The aim of this paper is to present the case of a 73 year old man with immediate implants who was admitted to the Clinic of Maxillofacial Surgery for treatment of medication-related osteonecrosis of the upper right jaw. The problem occurred after the extraction of two teeth, without considering that the patient is undergoing chemotherapy with Xgeva. The patient was diagnosed with prostate cancer in 2013. In 2015 were found metastases on the bones. According to the particular characteristics of the patient he underwent surgery under general anesthesia. The innovation in our case is that we used a placement of a PRF membrane and plastic closure of the wound. This is a new and alternative treatment method and there were no postoperative complications or wound infections, which are usually common in the postoperative period for people with medication-related osteonecrosis of the jaws.

Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ. Utilizing reverse transcription quantitative polymerase chain reaction, we evaluated miRNAs in five healthy subjects and in five MM patients with ONJ. Our experimental data revealed that a diverse miRNA signature for ONJ subjects emerged with respect to control subjects. Using the filter for in silico analysis, among the 18 miRNAs, we recognized 14 dysregulated miRNAs. All these miRNAs were significantly over-expressed in patients vs controls. Among them, six were strongly upregulated (fourfold upregulated and more). These miRNAs target numerous pathways and genes implicated in calcium ion binding, bone resorption, mineralization of bone matrix, and differentiation and maintenance of bone tissue. A modified microRNA expression profile after zoledronate therapy could participate to the onset of ONJ. Targeting these miRNAs could provide a new opportunity for the prevention or treatment of ONJ.

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression ...

O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES) com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.