Fulminant course of osteonecrosis of the jaw in a rheumatoid arthritis patient following oral bisphosphonate intake and biologic therapy

Sir, Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a serious adverse event of bisphosphonate (BP) therapy. BONJ affects exclusively the maxillofacial bones and is defined as exposed necrotic jaw bone lasting longer than 8 weeks in patients under BP treatment and lacking a history of radiation therapy [1]. BPs are given intravenously in metastatic bone disease [2] and increasingly in oral preparations for the treatment of osteoporosis [3]. BONJ aetiology has been linked to infection [4] and immunosuppressive drugs are common in the treatment of RA. Therefore, BP therapy might be an important co-factor in the proper selection of medication for patients with RA. Here we report about a fulminant course of BONJ in an oral BP patient under treatment with IL-6 receptor antagonist tocilizumab for RA. A 74-year-old female presented in January 2007 with a left-sided perimandibular abscess. Previously tooth 35 had been extracted. Her general medical history revealed osteoporosis and severe RA. The patient had received a 20-month course of oral BP therapy (risedronate, 35 mg/week) from February 2005 until October 2006 (cumulative dose 3080 mg) for the treatment of osteoporosis. The patient was treated for RA with infliximab, an anti-TNF-α antibody (200–400 mg i.v. every 6–8 weeks from July 2005 until October 2008), in combination with MTX (15 mg/week from May 2004 until December 2008), folic acid (10 mg/week), prednisolone (5 mg/day from May 2004 until December 2008, cumulative dose 4850 mg), ibuprofen (1800 mg/day), pantoprazol (40 mg/day) and calcium plus vitamin D3 (500 mg/10 µg 2×/day). Treatment consisted of incision and drainage of the abscess under general anaesthesia and high-dose i.v. antibiotic treatment with clindamycin requiring 5 days of inpatient care. Three months later the patient presented with signs of advanced BONJ showing exposed bone and extra-oral fistula formation located in the left submandibular region. A panoramic radiograph showed persistent extraction sockets surrounded by periapical hypermineralized lines in the left mandible. Her anti-rheumatic medication was as stated above. The previous dose of infliximab had been given 8 weeks before. Surgical treatment including sequestrectomy was followed by gastric tube feeding for 10 days. After discharge, the woman was followed up bimonthly in our outpatient clinic. In December 2008, following an uneventful period of 16 months, the patient was again referred to our department with a right-side submandibular abscess, which suddenly occurred after professional dental cleaning. The abscess was immediately treated by incision and drainage in combination with high-dose i.v. antibiotic therapy, according to microbial sensitivity testing. However, the infection progressed rapidly to a life-threatening, fulminant facial phlegmone (Fig. 1), which forced multiple wide skin incisions and the insertion of numerous drains. Due to septic acute respiratory distress, the woman had to be transferred to the intensive care unit. Segmental resection of the right mandible was required following extensive osteomyelitic destruction. Mandibular discontinuity underwent titanium plate reconstruction. A 4-month stay in the intensive care unit was necessary until her medical condition could be stabilized. Four weeks prior to this fulminant onset of right-sided BONJ, the patient had received a single i.v. dose of 576 mg tocilizumab, an anti-IL-6 receptor monoclonal antibody, as biologic therapy for RA. Treatment with MTX and prednisolone was unaltered. The patient has been treated conservatively for signs of exposed bone since then and treatment with biologics has been discontinued.