A medicolegal perspective on osteoradionecrosis
Osteoradionecrosis (ORN) of the jaws is a well-known complication of radiation therapy to the head and neck. ORN is defined as an area of exposed necrotic bone in an area previously irradiated that fails to heal over a period of 3–6 months. Head and neck cancers are sensitive to radiotherapy (RT), which is being increasingly used with the rising prevalence of human papilloma virus positive squamous cell carcinoma, sometimes with chemotherapy. Since the advent of intensity-modulated radiation therapy (IMRT) the associated co-morbidities of radiation therapy have been minimized by limiting radiation exposure to healthy tissue and maximizing tumour control.
The incidence is around 10%, the majority of cases presenting within 3 years of completion of treatment. The mandible is more commonly affected than the maxilla. The risk factors for ORN include tumour site, tumour stage, proximity of the tumour to bone, radiation field, dose of radiation, trauma such as dental extraction/surgery before or after RT. Systemic factors include co-morbidities, smoking and drinking alcohol, immunodeficient status, and infection.
Initially, ORN presents as asymptomatic bony changes, such as a decrease in bone density, and delayed healing. However, these changes are often accompanied by oral ulcers and fistulae, which produce pus. This could be an indication that local infection is spreading. If not appropriately managed, it may become systemic and ultimately lead to sepsis. Areas of exposed bone can also develop in the mouth. Patients complain of pain, bad breath and difficulties in chewing, swallowing and speech. Some patients go on to develop osteomyelitis or mandibular fractures, resulting in facial deformities. As there is no laboratory test that is diagnostic for ORN, recognising the condition is not entirely straightforward, and clinicians should also consider the possibility of a potential recurrence of the original tumour, or the development of a secondary tumour. For many years the pathophysiology of ORN was thought to be due to hypovascular, hypoxic and hypocellular environment, secondary to RT, resulting in poor healing and the development of ORN. This led to the use of hyperbaric oxygenation (HBO) as the treatment for prevention and management of ORN. Today, this theory has been challenged by the fibroatrophic theory, which suggests the osteocytes are damaged by free radicals from the radiation therapy, and this leads to inflammation and, thus, chronic activation of fibroblasts. Essentially, this chronic inflammatory state leads to the organized fibrosis phase. In the late fibroatrophic phase, this area is acellular and fibrotic, the site’s ability to heal is compromised.
In some patients, the lesions heal by themselves over time. Therefore, initial treatment may be conservative. In cases that prove refractory to this approach, treatment is often difficult and is likely to be lengthy and complex. A variety of modalities can be used, and a multidisciplinary approach is often required in order to provide optimal treatment. Antibiotics may often be prescribed, even though ORN is not an infection. Surgical debridement, including complete excision of the affected area, is sometimes attempted, which may then require reconstructive surgery. The use of hyperbaric oxygen therapy has also been recommended, although its use is controversial, as few subsequent studies have been able to reproduce the successful results initially reported.
Recent treatment developments have focussed on the theory that inflammatory factors underlie the development of ORN. Research into the effectiveness of pentoxifylline, which acts against some inflammatory mediators, in conjunction with tocopherol, a reactive oxygen species scavenger, have been encouraging, and this combination of drugs has a synergistic effect on the progression of lesions arising as a consequence of radiotherapy. Even better results were reported when clodronate, a non-nitrogen containing bisphosphonate drug, was added to the treatment regimen. Conversely, the outcome for patients in whom ORN was caused by a dental infection was much worse, suggesting that this subset of patients have a particularly poor prognosis.
As dental treatment is a triggering factor for ORN, it is vitally important that all patients for whom radiation therapy is planned undergo a thorough pre-treatment dental examination, so that any remedial work, including any necessary tooth extractions, can be completed in good time. Ideally, the interval should be not less than 15 days, but in practice it is not always possible to adhere to this timescale, particularly if the patient’s cancer is very advanced. The importance of strict oral hygiene following treatment must be made clear to patients, and those who smoke should be encouraged to quit before commencing a course of radiotherapy.
ORN is a serious complication following the use of radiotherapy for the treatment of head and neck cancers, and it can have a significant impact on a patient’s quality of life. Current treatment options are often less than satisfactory, partly because the processes underlying the development of the condition are not yet fully understood. It is therefore vital that preventative strategies are considered before radiation treatment begins, so that the risk of ORN developing is reduced.
About Mr Zaid Sadiq
Mr Sadiq is an Oral and Maxillofacial (Head and Neck) Surgeon based at Queen Victoria Hospital in West Sussex. He had a keen interest in cancer, reconstructive surgery and tissue engineering. He is available for consultations in London and Horsham, West Sussex.
Nadella, K. R., Kodali, R. M., Guttikonda, L. K., & Jonnalagadda, A. (2015). Osteoradionecrosis of the Jaws: Clinico-Therapeutic Management: A Literature Review and Update. Journal of maxillofacial and oral surgery, 14(4), 891–901. https://doi.org/10.1007/s12663-015-0762-9.
Khoo SC, Nabil S, Fauzi AA, Yunus SSM, Ngeow WC, Ramli R. Predictors of osteoradionecrosis following irradiated tooth extraction. Radiat Oncol. 2021;16(1):130. Published 2021 Jul 14. doi:10.1186/s13014-021-01851-0
Kubota, H., Miyawaki, D., Mukumoto, N. et al. Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma. Radiat Oncol 16, 1 (2021). https://doi.org/10.1186/s13014-020-01701-5.