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.
- SourceAvailable from: Judith E Raber-Durlacher
Article: Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT).[Show abstract] [Hide abstract]
ABSTRACT: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols.Supportive Care Cancer 09/2014; 23(1). DOI:10.1007/s00520-014-2378-x · 2.50 Impact Factor
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ABSTRACT: Osteoporotic fractures are a major cause of morbidity in the elderly population. Since postmenopausal osteoporosis is related to an increase in osteoclastic activity at the time of menopause, inhibitors of bone resorption have genuinely been considered an adequate strategy for prevention and treatment of osteoporosis. Bisphosphonates and selective oestrogen receptor modulators are widely prescribed to treat osteoporosis. However, other antiresorptive drugs have been developed for the management of osteoporosis, with the objective of providing a substantial reduction in osteoporotic fractures at all skeletal sites, combined with an acceptable long-term skeletal and systemic safety profile. Denosumab, a human monoclonal antibody to receptor activator for nuclear factor kappa B ligand, has shown efficacy against vertebral, nonvertebral and hip fractures. Its administration every 6 months as a subcutaneous formulation might significantly influence compliance and persistence to therapy. Additional results regarding long-term skeletal safety (i.e. osteonecrosis of the jaw and atypical diaphyseal femoral fracture) are needed. Odanacatib, a selective cathepsin K inhibitor, is a promising new approach to the inhibition of osteoclastic resorption, with the potential to uncouple bone formation from bone resorption. Results regarding its anti-fracture efficacy are expected in the coming months.Drugs & Aging 05/2014; 31(6). DOI:10.1007/s40266-014-0179-z · 2.50 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