About three weeks later the patient visited our

About three weeks later, the patient visited our outpatient clinic complaining of gingival bleeding and pus discharge. In clinical examination bone exposure was observed in both mandibular posterior regions and bone necrosis had developed surrounding the #35=37 and 46, 47 implants installed 6 years prior (Fig. 1). Pus discharge, swelling and bleeding of mucosa were found around exposed bone. Fracture lines due to sequestration were found under the #35=37 and #46, 47 implants on panoramic radiography and axial computed tomography (CT) (Figs. 2 and 3). There was no mobility of the implants and the exposed bone. The patient answered that there was no symptom associated with implants before chemotherapy. On bone scan, hot spots were found in both mandibular posterior areas (Fig. 4). Osteomyelitis in both mandibular posterior areas was diagnosed by a radiologist. She was diagnosed with MRONJ based on examination, past medical history and medication use. After chemotherapy she had a low hemoglobin level(Hb 6.7 g/dl) on laboratory examination and required hematologic control. Appropriate medication and dressing were planned first. We administered 3rd generation cephalosporin antibiotics(Suprax®) to the patient during about 1 month for conservative treatment. During approximately 1 month of follow-up in the out-patient department, pain and swelling increased. Sequestration had increased in both mandibular posterior areas on panoramic radiograph (Fig. 5). We decided to treat the patient surgically. Under general anesthesia, sequestrectomy and removal of implants were done via an intraoral approach. After sequestrectomy, internal fixation was performed using a reconstruction plate for prevention of pathologic fracture because of the thin basal bone thickness of the left mandible (Fig. 6). Histopathologic examination of the removed bone segments and surrounding inflammatory tissue revealed acute osteomyelitis was diagnosed in the histopathologic examination (Fig. 7A and B). After surgery, we administered same Triacetyl Resveratrol sale to the patient during about 1 month. After antibiotics and surgical treatment, good healing results were observed at MRONJ sites (Fig. 8A and B). She underwent regular observation, but the cancer spread to other organs. Seventy-one days after the operation she was transferred to another hospital for hospice care and was lost to follow-up.
Discussion Proposed hypotheses for the unique localization of MRONJ exclusively to the jaws include altered bone remodeling or over suppression of bone resorption, angiogenesis inhibition, constant microtrauma, suppression of innate or acquired immunity, vitamin D deficiency, soft tissue bisphosphonates (BP) toxicity, and inflammation or infection [3]. One hypothesis of MRONJ development is inhibition of osteoclastic bone resorption and remodeling. Osteoclast differentiation and function play a vital role in bone healing and remodeling in all skeletal sites. First, antiresorptive medications are the most common medications causing MRONJ. Intravenous (IV) BPs are antiresorptive medications. IV BPs, i.e., once yearly infusion of zolendronate (Reclast®) and a parenteral formulation of ibandronate (Boniva®) administered every three months, have been approved by the FDA for management of osteoporosis [3]. Oral bisphosphonates have been approved for treatment of osteoporosis and are frequently used to treat osteopenia as well. They are also used for a variety of less common conditions such as Paget's disease of bone and osteogenesis imperfecta. Their most common use, however, is for osteopenia and osteoporosis [3]. Receptor Activator of Nuclear Factor κ B(RANK) ligand inhibitor (denosumab) is an antiresorptive agent that exists as a fully humanized antibody against RANK ligand (RANK-L) and inhibits osteoclast function and associated bone resorption. When denosumab (Prolia®) is administered subcutaneously every 6 months, there is a reduction in the risk of vertebral, non-vertebral, and hip fractures in osteoporotic patients [4]. Interestingly, in contrast to bisphosphonates, RANK-L inhibitors do not bind to bone and their effects on bone remodeling are mostly diminished within 6 months of treatment cessation. BPs and other antiresorptives such as denosumab inhibit osteoclast differentiation and function, and increase apoptosis, all leading to decreased bone resorption and remodeling. An increased remodeling rate in the jaws may explain the differential predisposition to ONJ compared to other bones in the axial or appendicular skeleton [3].