Pharmacological Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) with Pentoxifylline and Tocopherol

Overview

Journal J Clin Med

Specialty General Medicine

Date 2025 Feb 13

PMID 39941644

Authors

Lukasz Slowik

Ewa Toton

Aleksy Nowak

Aleksandra Wysocka-Slowik

Maciej Okla

Zuzanna Slebioda

Affiliations

Soon will be listed here.

Abstract

This study aimed to evaluate the efficacy of pentoxifylline and tocopherol therapy in patients with medication-related osteonecrosis of the jaw (MRONJ). During this study, 43 patients participated, including 21 women and 22 men with a mean age of 66.8 years, who showed 63 areas of osteitis altogether. The diagnosis was made based on X-ray imaging and histopathological findings. All the subjects received pharmacological treatment with pentoxifylline 400 mg and tocopherol 400 IU. The study scheme consisted of initial observation and two follow-up examinations every 5-6 months. MRONJ severity, peripheral blood parameters, and CRP levels were evaluated. The obtained results were statistically analyzed. : Complete remission occurred in 46% of the subjects, with a higher rate among those taking bisphosphonates intravenously compared to oral administration. The efficacy of pentoxifylline and tocopherol treatment was not influenced by gender or lesion location. Moreover, the worst response to treatment was observed in the group with the highest disease stage, as determined in the initial study. Pentoxifylline and tocopherol therapy in MRONJ was effective in patients taking oral and intravenous bisphosphonates, in patients with osteoporosis, and undergoing oncological treatment. This treatment approach allows surgery to be avoided or significantly reduced. The good response to pharmacotherapy observed in patients with early stages of MRONJ shows an urgent need to monitor the patients treated with bisphosphonates carefully to diagnose MRONJ at the initial phase.

References

Mustacich D, Bruno R, Traber M . Vitamin E. Vitam Horm. 2007; 76:1-21. DOI: 10.1016/S0083-6729(07)76001-6. View

Otto S, Pautke C, Hafner S, Hesse R, Reichardt L, Mast G . Pathologic fractures in bisphosphonate-related osteonecrosis of the jaw-review of the literature and review of our own cases. Craniomaxillofac Trauma Reconstr. 2014; 6(3):147-54. PMC: 3773037. DOI: 10.1055/s-0033-1343776. View

AlRowis R, Aldawood A, Alotaibi M, Alnasser E, AlSaif I, Aljaber A . Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review of Pathophysiology, Risk Factors, Preventive Measures and Treatment Strategies. Saudi Dent J. 2022; 34(3):202-210. PMC: 9346931. DOI: 10.1016/j.sdentj.2022.01.003. View

Smolarek A, Suh N . Chemopreventive activity of vitamin E in breast cancer: a focus on γ- and δ-tocopherol. Nutrients. 2012; 3(11):962-86. PMC: 3257724. DOI: 10.3390/nu3110962. View

Pippi R, Giuliani U, Tenore G, Pietrantoni A, Romeo U . What is the Risk of Developing Medication-Related Osteonecrosis in Patients With Extraction Sockets Left to Heal by Secondary Intention? A Retrospective Case Series Study. J Oral Maxillofac Surg. 2021; 79(10):2071-2077. DOI: 10.1016/j.joms.2021.05.031. View

Kim K, Park W, Oh S, Kim H, Nam W, Lim S . Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw. Osteoporos Int. 2014; 25(5):1625-32. DOI: 10.1007/s00198-014-2622-8. View

Delanian S, Lefaix J . Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. 1999; 17(10):3283-90. DOI: 10.1200/JCO.1999.17.10.3283. View

Freiberger J, Padilla-Burgos R, McGraw T, Suliman H, Kraft K, Stolp B . What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg. 2012; 70(7):1573-83. DOI: 10.1016/j.joms.2012.04.001. View

Favia G, Tempesta A, Limongelli L, Crincoli V, Maiorano E . Medication-related osteonecrosis of the jaw: Surgical or non-surgical treatment?. Oral Dis. 2018; 24(1-2):238-242. DOI: 10.1111/odi.12764. View

10.

AlDhalaan N, BaQais A, Al-Omar A . Medication-related Osteonecrosis of the Jaw: A Review. Cureus. 2020; 12(2):e6944. PMC: 7067354. DOI: 10.7759/cureus.6944. View

11.

Cavalcante R, Tomasetti G . Pentoxifylline and tocopherol protocol to treat medication-related osteonecrosis of the jaw: A systematic literature review. J Craniomaxillofac Surg. 2020; 48(11):1080-1086. DOI: 10.1016/j.jcms.2020.09.008. View

12.

Cuddihy S, Ali S, Musiek E, Lucero J, Kopp S, Morrow J . Prolonged alpha-tocopherol deficiency decreases oxidative stress and unmasks alpha-tocopherol-dependent regulation of mitochondrial function in the brain. J Biol Chem. 2008; 283(11):6915-24. DOI: 10.1074/jbc.M702572200. View

13.

Drake M, Clarke B, Khosla S . Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008; 83(9):1032-45. PMC: 2667901. DOI: 10.4065/83.9.1032. View

14.

Pirbhai A, Rajak S, Goold L, Cunneen T, Wilcsek G, Martin P . Bisphosphonate-Induced Orbital Inflammation: A Case Series and Review. Orbit. 2015; 34(6):331-5. DOI: 10.3109/01676830.2015.1078380. View

15.

Anjos R, de Padua Walfrido G, de Hollanda Valente R, Gueiros L, Carvalho A, Patel P . Pentoxifylline, tocopherol, and sequestrectomy are effective for the management of advanced osteoradionecrosis of the jaws-a case series. Support Care Cancer. 2020; 29(6):3311-3317. DOI: 10.1007/s00520-020-05847-6. View

16.

Epstein M, Wicknick F, Epstein J, Berenson J, Gorsky M . Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110(5):593-6. DOI: 10.1016/j.tripleo.2010.05.067. View

17.

Hamid A, Thomas S, Bell C, Gormley M . Case series of medication-related osteonecrosis of the jaw (MRONJ) patients prescribed a drug holiday. Br J Oral Maxillofac Surg. 2023; 61(3):227-232. DOI: 10.1016/j.bjoms.2023.02.003. View

18.

Kwon Y, Lee D, Choi B, Lee J, Kim D . Short-term teriparatide therapy as an adjunctive modality for bisphosphonate-related osteonecrosis of the jaws. Osteoporos Int. 2012; 23(11):2721-5. DOI: 10.1007/s00198-011-1882-9. View

19.

Boyce B, Yao Z, Xing L . Osteoclasts have multiple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Expr. 2009; 19(3):171-80. PMC: 2856465. DOI: 10.1615/critreveukargeneexpr.v19.i3.10. View

20.

Fliefel R, Troltzsch M, Kuhnisch J, Ehrenfeld M, Otto S . Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review. Int J Oral Maxillofac Surg. 2015; 44(5):568-85. DOI: 10.1016/j.ijom.2015.01.026. View