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Denosumab and Anti-angiogenetic Drug-related Osteonecrosis of the Jaw: An Uncommon but Potentially Severe Disease.

Department of Neurosciences, Section of Dentistry, University of Padua, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy. .
Anticancer research (Impact Factor: 1.87). 05/2013; 33(5):1793-7.
Source: PubMed

ABSTRACT Osteonecrosis of the jaw (ONJ) is a rare but serious lesion of the jaw characterized by exposed necrotic bone and is related to several drugs usually used for treating patients with advanced malignancies. Common therapies inducing ONJ are nitrogen-containing bisphosphonates (BPs), the human monoclonal antibody to the receptor activator of nuclear factor-kappa B ligand denosumab and some anti-angiogenic drugs, alone or in combination with BPs. The real incidence of ONJ is unknown. Several cases of ONJ in patients with cancer who underwent denosumab therapy have been reported and it seems that the overall incidence of denosumab-related ONJ is similar to that for BP-related in this population, ranging between 1-2%. The cell-surface vascular endothelial growth factor (VEGF) receptor plays a major role in cancer progression and can be targeted by drugs inhibiting the tyrosine kinase activator or other second messengers. Most angiogenesis inhibitors, such as the monoclonal antibody bevacizumab and the kinase inhibitor sunitinib, target the VEGF signaling pathway. Unfortunately, cases of bevacizumab-induced ONJ have been reported, especially in patients treated with bevacizumab and BPs in combination. There are only few studies reporting sunitinib-related ONJs. In patients with advanced cancer and malignancy-associated hypercalcemia undergoing BP, denosumab or bevacizumab therapy, enquiry into current dental health and dental examination is mandatory. Good oral hygiene, limiting of alcohol intake and stopping smoking should be suggested for all patients requiring such treatments.

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    • "The use of denosumab and its potential complications such as ON must be incorporated into the same protocols applied to the use of biphosphonates: maintaining good oral hygiene , limiting alcohol consumption and ceasing the use of cigarettes [13]. It can be concluded that denosumab is linked to ON in different conditions of oral health, and the best protocol for managing this clinical condition must be deter- mined. "
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    ABSTRACT: Osteonecrosis (ON) of the jaw has previously been linked to the use of biphosphonates; however, new drugs, also shown similar conditions. This article presents a female patient with mandibular ON related to the use of denosumab. The 55-year-old presented with bone exposure with 8 months of evolution after a dental extraction. The patient began subcutaneous injections of 60 mg denosumab four months prior to the extraction and the lesion remained after the procedure. The patient, with 14 months of follow-up, show mandible ON with no favorable evolution. The clinical condition is presented and the literature of ON associated with denosumab is discussed.
    International Journal of Clinical and Experimental Medicine 11/2014; 7(10):3707-3709. · 1.42 Impact Factor
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    ABSTRACT: Context:Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the exact pathogenesis mechanisms are not fully understood.Objective:To investigate a possible contribution of diabetes and microvascular disease to the pathophysiology of BRONJ.Design:We identified 46 patients treated with bisphosphonates who were diagnosed with BRONJ based on their medical history during 2009 to 2012, and invited them for a dental assessment to confirm the diagnosis. Diabetes diagnosis was based on the American Diabetes Association criteria. The study group was compared to a 38 control group of patients treated with bisphosphonates without evidence of BRONJ.Setting:The study was conducted at Rambam Health Care Campus, a referral center, Haifa, Israel.Results:Of the 46 patients with BRONJ, 31 (67.4%) had diabetes or impaired fasting glucose (IFG). The proportion with diabetes (37%) was higher than in the control group (26.3%; p = 0.009). The presence of diabetes or IFG increased the association with BRONJ by 2.78 fold (CI 1.27-6.07, p=0.009). The prevalence of microvascular disease (neuropathy, retinopathy, nephropathy) was significantly higher in the BRONJ than in the control group (p = 0.01). The presence of diabetic nephropathy increased the association with BRONJ by 3.9 fold (CI=1.12-13.52, p=0.02).Conclusions:This retrospective study suggests an association between diabetes, perhaps mediated through microvascular complications, and the development of BRONJ.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; 98(11). DOI:10.1210/jc.2013-2434 · 6.31 Impact Factor
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    ABSTRACT: Antiresorptive osteonecrosis of the jaws (ARONJ) is a significant and poorly understood oral complication that may affect patients receiving antiresorptive agents, such as intravenous bisphosphonate therapy. There are scarce reports of the coexistence of ARONJ and metastasis at the same jaw site in the English-language literature. In the present case, a 60-year-old white woman was referred for the evaluation of a nonhealing extraction socket. The patient was undergoing treatment with intravenous zoledronic acid to metastatic breast cancer in bone, and her medical history and clinical characteristics led to the diagnosis of ARONJ. Nevertheless, histologic analysis showed a fragment of necrotic bone and bacterial colonies associated with malignant epithelial cells that were confirmed to be metastatic breast adenocarcinoma. This case showed that jaw metastasis can occur at the same time and site of ARONJ, making diagnosis and management challenging.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 03/2014; 117(3):e264–e268. DOI:10.1016/j.oooo.2013.11.495 · 1.46 Impact Factor
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