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CAS E R E POR T Sunitinib and Zoledronic Acid Combination Therapy for Metastatic Renal Cell Carcinoma: Alarming for Osteonecrosis of the Jaw Theresa M. Hofstede, DDS Associate Professor Department of Head and Neck Surgery, Unit 1445 The University of Texas MD Anderson Cancer Center Houston, Texas Introduction As medical treatment of serious diseases such as cancer lengthens patient survival, the side effects of new drugs are beginning to present in community dentists’ patients. The most well-known example is probably bisphosphonate related osteonecrosis of the jaw (ONJ), which was first reported in 36 patients in 2003 by Marx1; all 36 patients had been treated with zoledronic acid, an antiresorptive bisphosphonate typically used to treat osteopenia or osteoporosis or bone destruction due to cancer. In 2004, Ruggiero et al2 reported another 63 patients with osteonecrosis caused by zoledronic acid. Based on that evidence, in 2005, the United States Food and Drug Administration issued a warning for the entire bisphosphonate drug class for possible ONJ. More recently, with advancements in cancer treatment utilizing therapies such as RANK ligand inhibitors and angiogenesis inhibitors, the risk of ONJ appears to have been increased further still. Angiogenesis inhibitors short-circuit cancer growth by inhibiting blood vessel formation in tumors. One way cancer cells grow is by releasing a protein called vascular endothelial growth factor (VEGF) to signal the need for blood vessel growth; sunitinib, a tyrosine kinase inhibitor (TKI) and antiangiogenic agent, binds to receptors on epithelial or endothelial cells to block VEGF activity. After several case reports described the occurrence of osteonecrosis in cancer patients who received targeted therapies, specifically TKIs and monoclonal antibodies targeting VEGF, the American Association of Oral and Maxillofacial Surgeons in 2014 expanded the concept of bisphosphonate related ONJ to what is now termed medication related ONJ.3 Targeted therapies play an integral role in cancer care and can cause many types of oral complications. Therefore, patients should be aware of the potential complications caused by angiogenesis inhibitors in addition to bisphosphonates. Here we present a case in which a patient receiving sunitinib with a history of zoledronic acid therapy developed extensive ONJ. Alexander M. Won, DDS Assistant Professor Department of Head and Neck Surgery, Unit 1445 The University of Texas MD Anderson Cancer Center Houston, Texas Keywords: Osteonecrosis, medication related osteonecrosis, jaw disease, bone necrosis Corresponding Author: Alexander M. Won, DDS, Assistant Professor, Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030; Phone: 713-745-8353; Fax: 713-794-4662 E-mail: amwon@mdanderson.org Richard Cardoso, DDS, MS Assistant Professor Department of Head and Neck Surgery, Unit 1445 The University of Texas MD Anderson Cancer Center Houston, Texas Adegbenga O. Otun, BDS Assistant Professor Department of Head and Neck Surgery, Unit 1445 The University of Texas MD Anderson Cancer Center Houston, Texas Mark Chambers, DMD, MS Professor Department of Head and Neck Surgery, Unit 1445 The University of Texas MD Anderson Cancer Center Houston, Texas Figure 1. Kidney Cancer Journal 49


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