The pentoxifylline and tocopherol protocol and its use in the management of osteoradionecrosis of the jaws: A scoping review.

BACKGROUND

Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN.

TYPES OF STUDIES REVIEWED: The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review.

RESULTS

The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol.

CONCLUSIONS AND PRACTICAL IMPLICATIONS: The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity.