2Oral and Maxillofacial Surgery Resident. Complejo Hospitalario Universitario de Granada, Spain.
3Dentist. Professor of Dentistry, University of Córdoba, Argentina.
Its mechanism of action is manifold, with recent published studies recognizing: inhibition of osteoclastic bone resorption, induction of osteoblasts to the secretion of an osteoclastmediated inhibition of bone formation, induction of apoptosis in osteoclast (“programmed cell death”), an antiangiogenic effect that reduces endothelial growth factor (EFG). Also, associated with the previous ones, there is an alteration of the macrophages and the cicatrization of the oral mucosa by involvement of the fibroblasts and keratinocytes .
Maxillary Osteonecrosis (BRONJ) associated with the use of intravenous BP in the treatment of bone metastases of solid tumors was first described by Ruggiero in 2004 . The diagnostic classification of this entity was initially proposed in 2009 . It has been recently modified in 2014, expanding to other anti-reabsorbing bone and antiangiogenic drugs .
Intraoral and oropharyngeal carcinomas have as their main risk factors alcohol, tobacco and human papillomavirus infection, especially the high risk oncogenic genotypes 16 and 18. All these factors may act separately or synergistically .
In the present study, we report a rare case of BRONJ induced by oral BP in the treatment of osteoporosis and its subsequent evolution towards squamous cell carcinoma.
Key words: Mandibular Osteonecrosis; Osteoporosis; Epidermoid Carcinoma
In March 2012 she was assessed in our ward for presenting mobility, pain and haemorrhage at the 23 tooth with a vestibular table exposure for more than 6 months. First-stage orthopantomography (Figure 1) and subsequent facial CT scan (Figure 2) were performed, confirming the existence of type III
On 6/5/2012 segmental hemimaxillectomy was performed under general anaesthesia. It confirmed squamous cell carcinoma of 0.5 cm with infiltration of bone trabeculae and anterior border invasion (pT4aN0MxR1 (SI)). Postoperative RT was administered. The patient remained in complete clinical remission until 7/8/2016, showing no tumor in imaging studies (Figure 4). PET-CT detected left submandibular hypermetabolic focus, and the decision to perform homolateral cervical dissection was made. After that, the presence of a metastatic adenopathy with nodal rupture was confirmed, initiating treatment with RT and chemotherapy.
** The TNM classification system we include in this guide is based on the latest edition published by the UICC and the American Joint Committee on Cancer (AJCC) in January 2010.
The case report presented shows certain infrequent characteristics that we will discuss below. Firstly, the absence of risk factors that predispose to developing a BRONJ, such as poor oral hygiene or surgical manoeuvers (dental extractions) during treatment with BP and presentation in the upper jaw . A proportion of jaw risk of 2:1 with respect to upper maxilla was proposed . On the other hand, it emphasizes the intensity of the BRONJ in its first manifestation (SIII), which could be attributed to a prolonged use (over 10 years) with Ibandronic acid (nitrogen BP with a greater power than alendronate, the latter usually used in the treatment of osteoporosis). Moreover, Conte-Neto et al (2011) described two cases of BRONJ in women without risk factors with alendronate therapy for more than 3 years in the posterior part of the mandible . This fact is explained because the half-life of BP in the bloodstream is very short, ranging from 30 minutes to 2 hours. Once absorbed by skeletal tissue it can persist for more than 10 years, which would explain its persistent long-term action on the bone.
The subsequent malignization of the osteonecrotic tissue in the context of BP uptake continues to be an exceptional and apparently paradoxical. BP, in consonance with different studies carried out in vitro, have antitumor properties through the inhibition of proliferation and invasion of tumor cells, inhibition of adhesion of tumor cells to bone tissue, induction of apoptosis in several malignant cell lines and inhibition of the proteolytic activity of matrix metalloproteinase’s .
Though, these are experimental studies that require their clinical application.
In the bibliography consulted, we have only found the relationship between the use of BP and esophageal carcinoma . Recently, authors like Gander report three cases of BRONJ with bone exposure underlying soft tissue of areas of malignization .
Conclusion is that BRONJ, irrespective of its clinical and radiological diagnosis, an anatomopathological study has to be performed in search of malignization areas.
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