Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline/α-tocopherol protocols

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use.