Denosumab and Anti-angiogenetic Drug-related Osteonecrosis of the Jaw: An Uncommon but Potentially Severe Disease.
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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ABSTRACT: During the past 2 decades, many interventions were proven effective in the management of postmenopausal osteoporosis. The objective of an anti-osteoporosis treatment is to reduce fracture rates, ideally at all skeletal sites (i.e. spine, hip, and other non-spine). The armamentarium against osteoporosis includes anti-resorptive agents (i.e. bisphosphonates, selective estrogen receptor modulators and denosumab), bone-forming agents (i.e. peptides from the parathyroid hormone family) and one agent with a dual mechanism of action (i.e. strontium ranelate). All these medications combine anti-fracture efficacy with a reasonable benefit/risk profile. However, the choice of a particular chemical entity, in one individual patient is based on the knowledge and expertise of the physician. Prioritization of drugs should be based on the individual profile of the patient, the severity of osteoporosis and the specific contraindications, warnings and precautions of use of the various available medications.Best Practice & Research: Clinical Endocrinology & Metabolism 12/2014; DOI:10.1016/j.beem.2014.09.003 · 4.91 Impact Factor
Medication-Related Osteonecrosis of the Jaws, 1st edited by Sven Otto, 01/2015: chapter Local and microvascular free flaps in patients with medication related osteonecrosis of the jaws: pages 93-102; Springer., ISBN: 978-3-662-43732-2
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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