A Comprehensive Review of the PENTOCLO Protocol and Its Applications in the Head and Neck.

Objective: To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ).

Methods: A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events.

Results: Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal.

Conclusion: PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy.