Osteonecrosis of the jaw in the era of targeted therapy and immunotherapy in oncology

Abstract

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report

“…Of note, crizotinib inhibits MET proto-oncogene (MET) and Macrophage Stimulating Factor 1 Receptor (MST1R, also peviously known as RON), two receptors that regulate osteogenesis through Platelet Derived Growth Factor (PDGF). PDGF pathway is thought to be involved in sorafenib-and imatinib-induced osteonecrosis by reducing the activity of osteoclastogenic cytokines including macrophage colonystimulating factor (M-CSF) and receptor activator of nuclear factor kappa-Β ligand (RANKL) [17]. PDGF signalling might have been involved in our patient's osteitis.…”

An Approach for the Prevention, Diagnosis, and Treatment of Jaw Osteonecrosis: Report of a Case Associated with Zoledronic Acid

“…Antiresorptive use has increased in recent years due to new molecular targets and immunological drugs used for oncologic treatment. There has been a corresponding significant increase in MRONJ [ 10 ], which decreases the quality of life in these patients [ 8 ]. The antiresorptive drugs are classified into 5 classes, according to the principal agent: bisphosphonates, estrogen, selective estrogen receptor modulators, calcitonin, and denosumab.…”

“…Nifosi et al reported an increase in ONJ following oncologic treatment. Further, bone diseases such as osteoporosis are more common in postmenopausal women, due to hormonal alterations [ 10 ]. Zoledronic acid is a member of the third generation of bisphosphonates.…”

Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

“…Among the potential mechanisms capable of inducing BONJ, an essential role is attributed to the possibility that bisphosphonates may have an antiangiogenetic action capable of delaying wound healing and/or affecting microinfarction in bone and/or soft tissues [52].…”