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Both denosumab (DMB) and bisphosphonates (BPs), antiresorptive drugs (ARDs) used for the treatment of osteoporosis and oncological disorders, are known for their potential to cause medication-related osteonecrosis of the jaws (MRONJ). Besides ARDs, statins were recently associated with MRONJ development, especially in patients taking higher doses of statins for a longer period of time. Here, we report a case of a female patient with osteoporosis using statins and treated with alendronate for 3 years who rapidly developed MRONJ stage III after only a single low dose of DMB. After partial maxillectomy complete healing was observed without any recurrence. We performed a literature review of cases with MRONJ triggered by a single low dose of DMB, with or without previous application of other ARDs. Only six similar cases of patients who developed MRONJ after a single low dose of DMB following previous BP therapy have been reported so far. Besides these, literature reports one patient who developed MRONJ after a single dose of DMB following romosozumab treatment and five cases developing MRONJ after a single dose of DMB even without any previous ARD treatment. We suggest that before DMB therapy is initiated, all factors predisposing to MRONJ development should be considered.