Endocrine Abstracts

Patient, methods and case report: A 50-years-old AAF with a PMH of multiple myeloma (MM), hypertension, and schizophrenia presented with jaw pain for 2 months. The patient had been diagnosed with MM for 10 years and had been treated with thalidomide and IV zoledronic acid for 1 year. CT scan of facial bone was consistent with osteonecrosis of the jaw with possible, superimposed osteomyelitis. Jaw biopsy revealed necrosis with a fistulous tract and filamentous organism consistent with actinomycetes.

Discussion: Numerous reports and meta-analyses have linked bisphosphonate use with a rare, but significantly increased incidence of osteonecrosis of the jaw, especially in cancer patients treated with IV bisphosphonates. This is believed to be due to an anti-angiogenic effect resulting in inhibition and apoptosis of osteoclasts. Decrease in bone circulation and cellularity may impair bone remodeling in response to skeletal injury. Through inhibition of endothelial cell proliferation, bisphosphonates may compromise intraosseous blood flow, contributing to the development of bisphosphonate-related ONJ (BRONJ). Thalidomide also exerts an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. BRONJ was initially believed to be a direct, non-infectious complication of bisphosphonate therapy, however, recent histological/microbiological data strongly suggest that actinomyces play a pivotal role in the development of BRONJ.

Conclusions: Bisphosphonates and thalidomide have anti-angiogenic effects on bone predisposing to avascular necrosis and ONJ. Actinomyces are an underrecognized agent in the pathogenesis of ONJ, which can result in superimposed osteomyelitis. Timely actinomyces specific therapy in BRONJ may improve patients outcome.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.