When the jawbone dies
A review study fills gaps in the pharmacological prevention and treatment of jaw necrosis
By Diane Peters
A diagnosis of head or neck cancer is devastating enough on its own — it can be life-threatening and life-changing, with the disease and treatments often causing pain, disfigurement and functional changes.
Adding to an already difficult situation: radiation can actually kill bone, leading to jaw necrosis, formally known as osteoradionecrosis of the mandible.
“It’s the most challenging condition in oral oncology right now,” says Aviv Ouanounou, associate professor, teaching stream at the Faculty of Dentistry. “This is one of the most feared and debilitating conditions.”
When the jawbone dies, there is often exposed bone inside the mouth, and there can be chronic infection, considerable pain, teeth can fall out and the bone can easily fracture or become deformed. Onset can happen at any time, even years after radiation treatment ends.
Ouanounou has published a review of the pharmacological treatment of jaw necrosis in the prestigious Journal of the American Dental Association. He worked with fourth year DDS student Robert Carriero, who earned accolades at the Faculty’s 2025 Research Day, and will be starting his residency in oral and maxillofacial surgery at Boston University in the fall.
As many as 10 per cent of people who receive facial radiation develop jaw necrosis — about 8,100 people are diagnosed with head and neck cancers in Canada annually, with these cancers on the rise globally.
However, dentists, oncologists and surgeons have limited guidance for the management of this complex problem. “There is a very important clinical and scientific gap that we repeatedly encounter when we are treating patients with head and neck cancers,” Ouanounou says.
The gaps include variability in guidance for determining severity stages, plus a lack of consensus on best medication combinations and dosing. This is of particular interest to Ouanounou, a practising dentist whose research focuses on dental pharmacology and therapeutics.
The information gaps aren’t surprising, since the current theory of how it develops — radiation damages the endothelial cells, impacting signalling pathways, so abnormal fibroblasts set in and cause fibrosis of bone tissue — was first proposed only in 2004.
That understanding has led to use of the PENTO protocol. It involves giving pentoxifylline, which is also used for fibrosis of the lung and liver, combined with tocopherol, a vitamin with antioxidant properties. For the related PENTOCLO protocol, doctors also add clodronate, which has anti-inflammatory and antiosteoclastic properties. This drug may cause medication-related bone necrosis. It’s also not available in the U.S., so it’s not a part of recommendations coming out of the States nor is it often used in clinical studies there.
Ouanounou and Carriero looked to 60 previous studies for their report, and found that these protocols have a high success rate. One study that treated patients for infection first and used PENTOCLO on a specific dosing regime had 100 per cent success. (Treating for infection and jaw necrosis at the same time, meanwhile, had much poorer outcomes.)
Prevention studies show treating patients before radiation begins can stop jaw necrosis from developing at all, with one dosing regime having a 96 per cent success rate. Being able to effectively prevent and treat the condition with drugs is critical, as other treatment options, including surgical resection of the bone, are difficult to manage medically and extremely debilitating for patients.
The researchers conclude their study with a call for multidisciplinary, double-blind clinical trials to fine-tune a standardized drug regime. “We set the stage for a trial,” says Ouanounou. He says multiple centres would have to be involved to get sufficient numbers of patients for this relatively rare condition.
But judging from the positive reaction he’s already getting from the dental and oncology community about his review study, he predicts teams will want to help. “The oral surgeons want to know more. The patients want answers. There is a real need here.”
Top photo: Shedrack Salami via Upsplash