Improvement of Giant Cell Lesions of the Jaw Treated With High and Low Doses of Denosumab: A Case Series.

Giant cell tumors (GCTs) and central giant cell granulomas (CGCGs) are aggressive lesions that appear in the jaw. These lesions occur in the second and third decades of life and often arise in the mandible. Clinical manifestations of these lesions vary from asymptomatic to symptomatic tooth displacement with cortical perforation. GCTs, which are characterized by multinucleated osteoclast-type giant cells that express receptor activator of nuclear factor-κB (RANK) ligand, rarely present in the jaw and have overlapping histopathologic features with CGCGs, which are composed of fibroblastic stromal cell lesions. GCTs and CGCGs have overlying histopathologic features that make distinction between the two challenging. There is a real controversy as to whether giant cell tumors and central giant cell granulomas are in fact, one and the same lesion. The majority of GCTs occur in the long bone, with surgery being the typical therapeutic option. Denosumab as a treatment modality is a fairly new concept that has been used effectively in GCTs affecting long bones. There is less experience, however, with its use for jaw lesions. This seven-case series describes the effective use of both low-dose and high-dose denosumab in the treatment of GCTs and CGCGs affecting the jaw and special dosing considerations for younger patients who present with disease. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ): initial discovery and subsequent development.

The efficacy of bisphosphonates in controlling skeletally related events in cancer patients and fractures in osteoporotic patients coupled with a relatively low level of toxicity and adverse events resulted in a widespread use of these medications in oncology and general internal medicine. However, in early 2001 a relationship had been established between these medications and a new disease entity characterized by necrosis of bone that was isolated to the jaws. This paper will present the chronology of events that led to the discovery of this new complication now known as bisphosphonate-related osteonecrosis of the jaw and review the reaction of professional organizations, the pharmaceutical industry, and government regulators.

Oral bisphosphonate therapy and osteonecrosis of the jaw: what to tell the concerned patient.

Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is encountered predominantly in cancer populations being treated with high-dose intravenous bisphosphonates for skeletal complications such as bone metastases and secondary fracture risk. A minority of BONJ lesions have been observed in patients receiving oral bisphosphonates for management of osteoporosis or osteopenia. In this paper, the current knowledge pertaining to the incidence, definition, and signs and symptoms of BONJ is presented, followed by a discussion of the incidence and consequences of osteoporotic skeletal fracture and the use of oral bisphosphonates to mitigate fracture. The risk of BONJ appears to be very small in patients taking oral bisphosphonates. In addition, the consequences of osteoporotic fracture likely have significantly greater mortality and morbidity than BONJ. Within this context, management concepts and guidelines are presented to help the dental clinician allay concerns about BONJ expressed by patients receiving oral bisphosphonate therapy.