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

ArticleinAnticancer research 33(5):1793-7 · May 2013with54 Reads
Impact Factor: 1.83 · Source: PubMed

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.

    • "Berberine has anti-angiogenic activity via suppression of VEGF expression (Hamsa and Kuttan 2012; Jie et al. 2011). Drugs with anti-angiogenic activity, such as bisphosphonates, may induce osteonecrosis of the jaw bone (Khosla et al. 2007; Ruggiero et al. 2009; Sivolella et al. 2013). In addition, the olmesartan that the patient took from February 2015 also has an antiangiogenic effect (Abd-Alhaseeb et al. 2014 ). "
    [Show abstract] [Hide abstract] ABSTRACT: This article presents a patient with potential atypical medication-related osteonecrosis of the jaw and reviews related literatures. Case presentation A 52-year-old male showed pain in the left buccal area and had numbness on the left lower lip area. He received medications having anti-angiogenic effect for 4 years. He did not receive irradiation of the jaw regions. In histological view, most of the adipocytes were destroyed and disappeared in the scanty vascular marrow tissue, resulting in the replacement of the fatty necrosis with variable sized vacuolated empty spaces. In the immunohistochemistry analysis, the infiltrated macrophages into the marrow stromal tissue were strongly positive for lysozymes. These findings demonstrate that the presented osteonecrosis underwent a chronic and persistent granulomatous inflammatory reaction. We conclude that the present case might have been caused by anti-angiogenic drug abuse, affecting the reduction of the mandibular marrow vascularity and subsequently inducing fatty necrosis and an extensive osteolytic change of the mandible.
    Full-text · Article · Feb 2016 · SpringerPlus
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    • "Bei Patientinnen mit postmenopausaler Osteoporose, die 60 mg Denosumab s.c. alle 6 Monate erhielten, wurde auch über seltene Fälle von Kieferosteo- nekrosen [31, 32] und atypischen Femur- frakturen [33, 34] berichtet. Ob diese Fälle unter Denosumab häufiger sind als unter Bisphosphonaten, kann derzeit nicht beantwortet werden. "
    [Show abstract] [Hide abstract] ABSTRACT: Hintergrund Frakturen sind schwere Komplikationen der Osteoporose mit einschneidenden Konsequenzen für die Patientin, ihr Umfeld und die Gesellschaft. Wirksame Medikamente sind daher unentbehrlich. Alle zugelassenen Medikamente zur Behandlung der postmenopausalen Osteoporose reduzieren nachweislich das individuelle Frakturrisiko. Ziele Da jedes dieser Medikamente in der Langzeitbehandlung über ein spezifisches Wirksamkeits- und Sicherheitsprofil verfügt, stellt sich in der täglichen Praxis die Frage, ob und unter welchen Bedingungen eine Behandlungspause („drug holiday“) in Erwägung gezogen werden sollte. Material und Methoden In dieser Literaturübersicht werden die wichtigsten Erkenntnisse aus den Frakturendpunktstudien mit knochenaktiven Substanzen präsentiert. Der Schwerpunkt liegt auf deren Wirksamkeits- und Sicherheitsprofilen in der Langzeitbehandlung. Ergebnisse und Diskussion Der Nutzen der verschiedenen knochenaktiven Substanzen bezüglich der Reduktion des individuellen Frakturrisikos ist unumstritten. Dieser überwiegt eindeutig die allfälligen Risiken. Bei einzelnen Patientinnen ist ein Großteil des Nutzens bereits nach einigen Jahren Behandlung erreicht, was im Einzelfall einer Abschwächung des Nutzen-Risiko-Verhältnisses entsprechen kann. Die Dauer der Einnahme eines bestimmten Präparats sollte deshalb individuell und in Absprache mit der Patientin vereinbart werden. Wichtig erscheinen dabei insbesondere die Wahrscheinlichkeit des kausalen Zusammenhangs zwischen Therapie und möglichen Langzeitunverträglichkeiten, die Häufigkeit bzw. Seltenheit des Auftretens einer solchen Unverträglichkeit im Vergleich zum erwarteten Nutzen sowie die individuellen Patientencharakteristika (insbesondere Komorbiditäten und Komedikationen) und -präferenzen.
    Preview · Article · Feb 2015 · Gynäkologische Endokrinologie
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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. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Nov 2014 · International Journal of Clinical and Experimental Medicine
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