Bisphosphonate-Related Osteonecrosis of the Jaw in an 80-Year-Old Woman with Diabetes Mellitus: Case Report.

Abstract

An 80-year-old woman presented to the emergency department with a 2-week history of progressive dyspnea, dysphagia, and odynophagia. She had no fever, cough, sputum, chest pain, or other symptoms. Her clinical history included latent autoimmune diabetes mellitus (DM) diagnosed 40 years before, with poor glycemic control (glycosylated hemoglobin 13.1%) and complicated with microvascular disease (retinopathy and polyneuropathy). She also had osteoporosis and had been receiving intravenous bisphosphonates (zoledronic acid) since she had fractured her hip 20 months earlier. She had received the first 5-mg dose 20 months earlier (November 2012) and the second 5-mg dose 9 months earlier (October 2013). On admission, physical examination revealed a ballooning in the floor of the mouth and trismus, laryngeal fibroscopy showed a pronounced protrusion toward the posterior border of the tongue, and neck computed tomography showed a large abscess on the floor of the mouth (4 × 6 × 5 cm) and serious compromise of the airway (Figure 1). She underwent urgent surgery for abscess drainage through cervicotomy under general anesthesia and endotracheal intubation. After she had been in the intensive care unit for 48 hours, a maxillofacial surgeon was requested because of suspicion of tooth infection as a possible source of the abscess. An exposed bone in the mandible that not healed was detected, although her dentist had been treating her for longer than 3 months. Any systemic or local malignancy was excluded. The affected region had not undergone any previous radiotherapy. The only risk factor for bisphosphonate-related osteonecrosis of the jaw (BRONJ) was diabetes mellitus. BRONJ is a form of avascular necrosis first described in 2003. It is defined as an area of exposed bone in the maxillofacial region that does not heal despite adequate treatment for at least 8 weeks, without local evidence of malignancy and no prior radiotherapy to the affected region. Although its pathophysiology is not fully understood, increasing evidence suggests that several events must occur for BRONJ to develop. Impaired bone repair, impaired angiogenesis or vascular repair, and poor dental hygiene (including poorly fitting dentures or dental manipulation) are the main contributors.1 The potent and prolonged inhibition of bone resorption is the primary mechanism. Long treatment and high-potency drugs increase the risk of developing BRONJ, which explains why intravenous bisphosphonates and denosumab are the most-often implicated drugs.2 The most common indications for these potent drugs are the treatment of hypercalcemia associated with breast and prostate cancer and osteolysis associated with metastatic bone disease, which could be why more than 90% of reported are in individuals with tumor pathology, but BRONJ is not exclusive to individuals with cancer. A greater and wider awareness in the prevention of fractures in individuals at risk (with osteoporosis) and the publication of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly clinical trial in 2007 and the Fracture Reduction Evaluation of Denosumb in Osteoporosis Every 6 Months trial in 2011 prompted the use of these powerful drugs in a new patient profile: older adults with comorbidities such as diabetes mellitus, hypertension, cerebrovascular disease, and dementia. Many of these concomitant diseases affect microvasculature,3 as does aging per se.4 Combined with their high rate of dental problems, this makes older adults particularly vulnerable to BRONJ when they are treated with potent bone-modifying agents.5 Diabetes mellitus seems to be an important contributor to the development of BRONJ, especially when microvascular complications are present. Microvascular ischemia of the bone, endothelial cell dysfunction, low bone turnover, and induced apoptosis of osteoblasts and osteocytes are, among others, possible indications of a poor prognosis with BRONJ in an individual with diabetes mellitus. Poor glycemic control may be a risk factor for greater severity of dental disease and microvascular complications, which may therefore increase the risk of BRONJ.6, 7 The difficulty in treating BRONJ is lack of data. In view of this, the American Association of Maxillofacial Surgeons recommends a comprehensive dental examination and preventive dentistry before beginning therapy with a bone-modifying agent.8 This case report should alert clinicians to the relationship between diabetes mellitus and bone necrosis in individuals receiving bisphosphonates. Clinicians should be aware that, not only individuals with cancer disease, but also those with comorbidities that worsen vascular repair are at a high risk for developing BRONJ. Older adults with diabetes mellitus are particularly vulnerable. Prevention is the best option and should be done before starting treatment with a bone-modifying agent. Conflict of Interest: The authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Valenzuela, Alonso-Bouzón: writing of letter. Alonso-Bouzón, Rodriguez Mañas: revision and critical review of content. Sponsor's Role: None.