In Reply

Abstract

We appreciate Dr Altundag's Letter to the Editor regarding our article. 1 Corsi A, Ungari C, Riminucci M, et al: Bisphosphonate-related osteonecrosis and metastasis within the same site of the jaw [published online ahead of print January 18, 2017]. J Oral Maxillofac Surg http://dx.doi.org/10.1016/j.joms.2017.01.008. Google Scholar Dr Altundag focuses his comments on 3 different points. On the first point, data from the literature have indicated that the spine, ribs, and sternum are the most common involved skeletal sites of metastasis from breast carcinoma. 2 Kakhki V.R. Anvari K. Sadeghi R. et al. Pattern and distribution of bone metastases in common malignant tumors. Nucl Med Rev Cent East Eur. 2013; 16: 66 Crossref PubMed Scopus (93) Google Scholar However, it has been estimated that 1% of all jaw tumors represent metastatic cancer and in women the breast is the most common primary site. 3 Hirshberg A. Shapiro A.S. Kaplan I. et al. Metastatic tumors to the oral cavity—Pathogenesis and analysis of 673 cases. Oral Oncol. 2008; 44: 743 Abstract Full Text Full Text PDF PubMed Scopus (345) Google Scholar , 4 D’Silva N.J. Summerlin D.J. Cordell K.G. et al. Metastatic tumors in the jaws: A retrospective study of 114 cases. J Am Dent Assoc. 2006; 137: 1667 Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Thus, although unusual, breast cancer metastasis can occur within the jawbones and this possibility should be always kept in mind in the clinical workup. On the second point, the patient effectively received zoledronic acid for 1 year and developed osteonecrosis of the jaws (ONJ) at least 1 year after cessation of the drug. Because “the apparent half-life of zoledronic acid in bone appears to be over 360 days,” 5 European Medicines Agency Scientific discussion. Available at. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000595/WC500020933.pdfDate: 2005 Google Scholar it can be reasonably assumed that zoledronic acid was still accumulated in the mandible of the patient at least 1 year after cessation of the drug. As a consequence, tooth extraction, a well-established precipitating risk factor in the development of ONJ in oncologic patients under treatment with bisphosphonates (BPs), 6 Ruggiero S.L. Dodson T.B. Fantasia J. et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw–2014 Update. J Oral Maxillofac Surg. 2014; 72: 1938 Abstract Full Text Full Text PDF PubMed Scopus (1512) Google Scholar can putatively represent a risk factor for the development of osteonecrosis in these patients. On the third point, we completely agree with Dr Altundag that “local inflammation induced by BP-related ONJ could be a niche for metastatic breast cancer cells.” It is well established that an inflammatory microenvironment that consists of immune cells and their secretory cytokines, chemokines, and growth factors characterize the pre-metastatic niche and contribute to the metastatic properties of neoplastic cells. 7 Wu Y. Zhou B.P. Inflammation: A driving force speeds cancer metastasis. Cell Cycle. 2009; 8: 3267 Crossref PubMed Scopus (257) Google Scholar , 8 Liu Y. Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016; 30: 668 Abstract Full Text Full Text PDF PubMed Scopus (552) Google Scholar Bisphosphonate-Related Osteonecrosis and Metastasis Within the Same Site of the Jaw: Expected for Multiple Myeloma, But Unusual for Breast CancerJournal of Oral and Maxillofacial SurgeryVol. 75Issue 7PreviewI want to congratulate Corsi et al1 for the case report in which they presented a patient with breast cancer treated with zoledronic acid for skeletal metastasis in which a clinical diagnosis of bisphosphonate-related osteonecrosis of the jaw (BP-related ONJ) was made and histologic examination of the resected mandibular segment disclosed synchronous osteonecrosis and breast cancer metastasis. As the authors stated, this metastatic presentation in the mandibular region is unusual for breast cancer because bone metastases in breast cancer commonly occur in the spine, pelvis, ribs, and sternum. Full-Text PDF