# Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Retrospective Clinical Audit

**Authors:** Niccolò Lombardi, Virina Basta, Chiara Morelli, Giulia Ghidini, Giovanni Lodi, Elena M. Varoni

PMC · DOI: 10.3390/antibiotics15030280 · Antibiotics · 2026-03-10

## TL;DR

This study evaluated the effectiveness of combining antibiotics with pentoxifylline and tocopherol for treating jaw bone disease in patients on antiresorptive therapy, finding no significant improvement over antibiotics alone.

## Contribution

The study introduces a clinical audit of a new treatment protocol (PENTO) for MRONJ and evaluates its efficacy compared to standard antibiotic therapy.

## Key findings

- Complete healing was achieved in 56 out of 92 cases with a mean follow-up of nearly 10 months.
- No significant difference in healing rates or recurrence was found between the PENTO and antibiotic-only groups.

## Abstract

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging complication in patients receiving antiresorptive therapy. Management strategies range from conservative pharmacological approaches to extensive surgical resection of necrotic bone. This clinical audit retrospectively evaluated the clinical outcomes of patients undergoing sequestrectomy for MRONJ, comparing those treated with antibiotics alone with those receiving antibiotics in combination with the pentoxifylline–tocopherol (PENTO) protocol. The PENTO protocol was introduced at our institution in 2021 and has since been routinely prescribed for all MRONJ patients. Methods: We analyzed 92 MRONJ sites treated with sequestrectomy. Conservative management consisted of antibiotic therapy, with or without adjunctive PENTO (pentoxifylline 800 mg/day and tocopherol 800 IU/day, administered both preoperatively and postoperatively). The primary outcome was healing at three months post-surgery, while the secondary outcome was disease recurrence during longer-term follow-up. Results: Complete healing was achieved in 56 of the 92 sites, with a mean follow-up of 9.98 ± 12.76 months among healed cases. No statistically significant differences in healing rates were observed between the PENTO and antibiotic-only groups. The overall recurrence rate was 12.5%, with no significant difference between the groups. Conclusions: Overall, surgical management of MRONJ resulted in favorable outcomes in a substantial proportion of patients. Within the limitations of this retrospective clinical audit, the addition of PENTO to antibiotic therapy appeared generally well tolerated, but could not result in a significant improvement in healing rates or reduction in recurrences, compared with antibiotic therapy alone, in this patient cohort.

## Linked entities

- **Chemicals:** pentoxifylline (PubChem CID 4740), tocopherol (PubChem CID 14986)
- **Diseases:** osteonecrosis of the jaw (MONDO:0018378)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}
- **Diseases:** periapical infection (MESH:D010483), bone sequestration (MESH:D001998), multiple myeloma (MESH:D009101), infection (MESH:D007239), Osteonecrosis of the Jaw (MESH:D059266), nausea (MESH:D009325), bleeding (MESH:D006470), injury to (MESH:D014947), dizziness (MESH:D004244), bloating (MESH:C535647), disease (MESH:D004194), ORN (MESH:D010025), hypotension (MESH:D007022), bone lesions (MESH:D001847), Jaw (MESH:D007571), penicillin allergy (MESH:D008586), pain (MESH:D010146), Osteonecrosis of (MESH:D010020), abdominal discomfort (MESH:D000007), ischemia (MESH:D007511), tachycardia (MESH:D013610), dyspnea (MESH:D004417), headache (MESH:D006261), fistula (MESH:D005402), Paget's disease (MESH:C537701), diabetes mellitus (MESH:D003920), osteolysis (MESH:D010014), vascular disorders (MESH:D002561), osteometabolic disorders (MESH:D009358), chest pain (MESH:D002637), tooth extraction (MESH:D014076), malignancies (MESH:D009369), fibrosis (MESH:D005355), hypertension (MESH:D006973), diarrhea (MESH:D003967), flushing (MESH:D005483), breast and prostate cancer (MESH:D001943), osteoporosis (MESH:D010024), MUCONN (MESH:C564098), necrotic (MESH:D009336), algodystrophy (MESH:D012019), inflammation (MESH:D007249), hypercalcemia (MESH:D006934), fracture (MESH:D050723), vomiting (MESH:D014839), arrhythmias (MESH:D001145)
- **Chemicals:** Bisphosphonates (MESH:D004164), deltacortene (MESH:C407664), Tocopherol (MESH:D024505), Er: YAG (-), brigatinib (MESH:C000598580), ribociclib (MESH:C000589651), lenalidomide (MESH:D000077269), paclitaxel (MESH:D017239), eribulin (MESH:C490954), trastuzumab (MESH:D000068878), amoxicillin (MESH:D000658), dexamethasone (MESH:D003907), amoxicillin/clavulanic acid (MESH:D019980), chlorhexidine (MESH:D002710), methylxanthine (MESH:C008514), Denosumab (MESH:D000069448), clarithromycin (MESH:D017291), vitamin E (MESH:D014810), metronidazole (MESH:D008795), cefixime (MESH:D020682), teriparatide (MESH:D019379), Pentoxifylline (MESH:D010431), methotrexate (MESH:D008727), steroid (MESH:D013256), tamoxifen (MESH:D013629), clavulanic acid (MESH:D019818), zoledronate (MESH:D000077211), prednisone (MESH:D011241)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC13024484/full.md

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Source: https://tomesphere.com/paper/PMC13024484