Osteonecrosis of the Jaw Associated with Long-Term Denosumab Therapy: A Review of Published Cases

Abstract

ackground: Denosumab, a monoclonal antibody against RANKL, is used at high dose for skeletal-related events in oncology and
at low dose for osteoporosis, but both regimens carry a risk of medication-related osteonecrosis of the jaw (MRONJ).Objective: To  review published case reports/series and the epidemiologic, mechanistic and guideline literature on denosumab-associated MRONJ, contrasting oncologic and osteoporosis populations. Methods: Narrative review of case reports, case series, randomized trials, retrospective cohorts, and guidelines. Findings: Pooled oncology-trial data show MRONJ in 1.8% of denosumab-treated versus 1.3% of zoledronic acid-treated patients; a 20-year breast cancer cohort found 12% incidence with denosumab versus 3% with bisphosphonates. Published cases span multi-year high-dose oncologic exposure to osteoporosis patients developing MRONJ after a single low dose, often extraction-triggered. Unlike bisphosphonates, denosumab's effect is reversible, informing but not resolving the drug-holiday debate. Conclusions: Pre-therapy dental screening, AAOMS-staged diagnosis, and conservative-first management with surgery reserved for refractory disease remain the evidence base; drug holidays lack proven benefit.