Clinical Efficacy of Pentoxifylline, Tocopherol, and Clodronate Therapy for Osteoradionecrosis: A Systematic Review and Meta-Analysis
In brief
PENTOCLO-treated jaw osteoradionecrosis patients reached median healing in nine months
In pooled data from three observational studies involving 99 patients, the median time to complete mucosal healing was nine months; the share still unhealed fell from about 71% at six months to 6% at three years. All six included studies had serious or critical risk of bias and no untreated comparison groups, so whether PENTOCLO improves healing remains unknown.
- Journal
- Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons (Q1)
- Published
- 19 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Matthew Woliansky, Cheryl Chen, James Badlani
- PMID
- 42976940
- DOI
- 10.1016/j.joms.2026.10.005
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 4 November 2026): Systematic review of treatment for jaw osteoradionecrosis
Abstract
BACKGROUND: Osteoradionecrosis (ORN) of the jaws is a complication of radiation therapy whose most appropriate treatment has been considered and debated in the international literature for several decades. Pentoxifylline, tocopherol, and clodronate (PENTOCLO) therapy shows promise for the management of ORN, but clinical evidence remains scientifically unsubstantiated. PURPOSE: To evaluate the clinical efficacy of PENTOCLO for head and neck cancer-related ORN, focusing on mucosal healing and treatment duration to inform future randomized controlled trials. DATA SOURCES: MEDLINE via PubMed, CINAHL, Embase, Cochrane CENTRAL, Web of Science, and Google Scholar were searched for articles published between 2005 and August 2025. STUDY SELECTION: Eligible studies were peer-reviewed, English-language articles evaluating subjects with head and neck cancer-related ORN treated primarily with PENTOCLO. Case reports, expert opinions, and abstract-only publications were excluded. DATA EXTRACTION AND SYNTHESIS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyse guidelines, 2 reviewers extracted data and assessed risk of bias using Risk Of Bias In Non-randomized Studies - of Interventions. Published aggregate survival data were used to reconstruct individual-level time-to-event and censoring data, which were pooled to generate Kaplan-Meier survival models. MAIN OUTCOME(S) AND MEASURE(S): Complete mucosal healing, analyzed as a time-to-event outcome, to estimate the median time to healing and cumulative healing trajectories. RESULTS: Six observational studies were eligible (N = 303 total subjects; n = 192 receiving PENTOCLO; mean age: 55.0 to 65.0 years; 78.5% male). Three studies provided reconstructible time-to-event data for Kaplan-Meier pooling (n = 99 research subjects). Pooled median time to complete mucosal healing was 9.0 (interquartile range: 6.0 to 28.0) months, with the unhealed proportion declining from 70.7% at 6 months to 6.3% at 36 months. Complete healing ranged from 35.2 to 100%; pathological fractures averaged 40.1 months of therapy. Risk of bias was serious (n = 3) to critical (n = 3), with no untreated control groups. CONCLUSIONS AND RELEVANCE: Subjects receiving PENTOCLO demonstrated progressive mucosal healing. However, lacking comparative control cohorts, these observational findings describe single-arm healing trajectories rather than comparative efficacy, underscoring the need for randomized controlled trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.