Which monoclonal antibody therapy is most strongly associated with medication-related osteonecrosis of the jaw (MRONJ)?

Denosumab (Prolia, Xgeva) is a fully human monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand), preventing osteoclast activation and bone resorption. It is used to treat osteoporosis, prevent skeletal-related events in bone metastases, and treat giant cell tumor of bone. Because it profoundly inhibits osteoclast function, denosumab is strongly associated with medication-related osteonecrosis of the jaw (MRONJ). The risk is especially high in patients receiving high-dose denosumab for oncologic indications. Adalimumab and infliximab target TNF-alpha and are used for autoimmune diseases; they are not strongly associated with MRONJ. Trastuzumab targets HER2 and is not associated with MRONJ.