Spotlight on Research
Dr. Jasjit Dillon
Pentoxifylline and Tocopherol (PENTO) in the Treatment of Medication-related Osteonecrosis of the Jaw (MRONJ): A Prospective, Randomized Controlled Trial to Evaluate a Novel Non-Operative Treatment
January 26, 2018
Dr. Jasjit Dillon, DDS, MBBS, FDSCRCS, FACS is Clinical Associate Professor and Chief of Service and Program Director at The University of Washington’s Harborview Medical Center, Department of Oral & Maxillofacial Surgery.
Based in Seattle, WA, Dillon is the principal researcher and is joined by a global team of co-investigators spanning multiple locations: Salvatore Ruggiero, DMD, MD, FACS, New York Center for Orthognathic and Maxillofacial Surgery (New York, NY); Anthony Morlandt, MD, DDS, Assistant Professor of OMFS, University of Alabama (Birmingham, AL); Daniel Hammer, DDS, Collaborator, Chief Resident, Walter Reed National Military Medical Center – Department of OMFS (Bethesda, MD); and Brent Ward, MD, DDS, Associate Professor, University of Michigan (Ann Arbor, MI).
Dr. Dillon was awarded one of the 2018 Osteo Science Foundation Peter Geistlich Awards to pursue research on Pentoxifylline and Tocopherol in the Treatment of Medication-related Osteonecrosis of the Jaw. Dr. Jasjit Dillon discusses her interest in this research and how this research will help in finding a solution for patients dealing with MRONJ. This project is also funded by the OMFS Foundation.
Medication-related osteonecrosis of the jaw (MRONJ) is a challenging complication of antiresorptive and antiangiogenic treatment. First reported over a decade ago, it is now a well-known entity, and its management and treatment remain a significant clinical challenge. In fact, over 6 million U.S. patients are estimated to be at risk of MRONJ.
“This is such a global problem”, explained Dr. Jasjit Dillon, Chief of Service and Program Director at the University of Washington’s Harborview Medical Center. “We – as a specialty – discovered this condition and the problems aren’t going away. We now need to take it to the next level and find a solution to help patients and improve their quality of life.”
Dillon is spearheading new research that builds on the promise that adjunctive therapy with pentoxifylline and tocopherol (PENTO) is an effective, etiology-based treatment in improving the prognosis of osteoradionecrosis of the jaw (ORN). The study’s goal is to determine if the PENTO regimen, in addition to the standard of care treatment for MRONJ, significantly reduces the areas of exposed bone compared to standard of care alone.
“We’re looking at a combination of two drugs to assess whether a patient’s bone will heal,” said Dillon. “We’ll be looking for radiographic improvement, pain improvement, and a potential decrease in the number of new lesions.”
Pentoxifylline is a commonly used medication for muscle pain associated with peripheral artery disease. It is a methylated xanthine derivative that improves peripheral blood flow, flexibility of red blood cell membranes, microcirculation, and tissue oxygenation and reduces viscosity of blood. Tocopherol (vitamin E) impairs tissue fibrosis and is a potent oxygen radical scavenger that may reduce damage caused by free radicals impacting necrosis. Because of the similar clinical presentations of ORN and MRONJ, some authors have successfully applied PENTO treatment protocols to MRONJ patients. In that regard, Dillon noted that the possible impacts of the drug study can be significant.
“One of the most exciting aspects of our study is that if PENTO is proven effective in the treatment of MRONJ, practitioners will have a regenerative treatment option for MRONJ.” While the specific model of MRONJ pathogenesis can be debated, the most recent research demonstrates an MRONJ lesion as a combination of necrotic and compromised bone. “The application of PENTO to MRONJ lesions may enhance remodeling of the compromised, yet vital bone.” However, Dillon added that for remodeling to occur alone, the tissue being remodeled must be vital. “The area that is necrotic is cleared innately, not ‘regenerated.’”
MRONJ is typically seen in cancer patients receiving intravenous bisphosphonates or other similar drugs to address cancer that has spread to the bone. Osteoporosis patients receiving these medications are also at a higher risk for MRONJ, but to a lesser degree. As such, these patients are a particular target of the study because they encounter progressive bone destruction with morbidity, along with pain and suffering. Dillon explained, “When patients take these drugs, there can be side effects, and one of them is when the jaw bone just dies, or when its ability to heal is impaired. We have a protocol, but we don’t have a cure.”
Obtaining better treatments for people who have MRONJ and identifying effective preventive measures to reduce its risk are well recognized needs within oral surgery. To that end, Dillon cited PENTO as a potential, affordable non-surgical treatment modality for MRONJ that could reduce associated morbidity and reverse progression.
Currently, standard of care management of MRONJ is limited to symptom-focused treatment consisting of antibiotics, antibacterial mouthwash, analgesics and limited debridement of necrotic bone. This study is particularly notable because the present evidence for effective PENTO treatment in MRONJ patients is anecdotal, and larger, prospective, randomized clinical trials such as this investigation are needed to evaluate effectiveness.
This study is a randomized placebo-controlled, triple-blinded trial, and while it’s just getting underway, its promise is already noteworthy. “If our study supports the results of the PENTO regimen, oral and maxillofacial surgeons and a multitude of other medical and dental providers that care for the affected patient population will have an additional non-surgical treatment modality”, explained Dillon. “We’re excited because this has the potential to help a lot of people.” Ultimately, such an approach could lead to decreased overall physical and psychological morbidity with improved patient outcomes.
