Osteoradionecrosis (ON) and Radiotherapy: Protection Recommendations – April 2023

Osteoradionecrosis (ON) and Radiotherapy:

Protection recommendations

Cyprus Oncological Society – Cyprus Oral and Maxillofacial Surgery Society – Cyprus Otolaryngological Society

This text is a product of collaboration between the Cyprus Oncology Society (OEK), the Cyprus Oral and Maxillofacial Surgery Society and the Cyprus Otolaryngology Society and is based on the publication below, whose bibliographic references and data have been updated in February 2023.

Oral dental care and Radiotherapy. Avoidance of osteoradionecrosis.

Katodrytis N, Charalambous H, Pantelas G, Hadjipetrou L, Marinou K, Michaelides H, Papacharalambous S, Jung N, Kallis S

Stomatology 2009, 66(3):83-89S

This has been approved by the Boards of Directors of the three Scientific Societies in April 2023.

1. Purpose

The purpose of this report is to document dental procedures before, during and after radiotherapy, procedures that aim to reduce complications related to radiotherapy and in particular osteoradionecrosis (ONC). Based on bibliographic references, recommendations are presented that aim to guide clinicians and implement common procedures.

2. Main topic

The relationship between tooth extraction and radiotherapy should be seriously studied since tooth extraction is considered the main cause of OAN [1,2]. Radiotherapy causes cell and vascular damage as well as a decrease in tissue oxygenation and therefore hinders the tissue repair mechanism. For the healing of the surgical wound after tooth extraction, activation of cellular elements involved in protein synthesis and the vascular network is required. The generally accepted theory is that radiotherapy causes irreversible damage to cells and vessels, resulting in tissue hypoxia and hypocytosis. Consequently, more frequent complications are expected in irradiated tissues, especially after surgical procedures such as tooth extraction [2,22]. The most recent theory of OAN is the fibroatrophic theory. According to this theory, changes in the bone vasculature lead to endothelial damage with a subsequent inflammatory response in the bone. This results in an abnormal fibroblastic response with impaired bone healing, which is prone to infection [22].   

The literature review does not reveal clear results regarding the association between the occurrence of OAN and whether extraction is performed before or after radiotherapy. Most authors report higher rates of OAN if extraction is performed after radiotherapy, considering cases with extraction after radiotherapy as high risk [21], but there are also some studies that demonstrate higher rates in cases of extraction before radiotherapy [3]. From a radiation oncological perspective, selective extraction before radiotherapy is reported to be very important [4]. Extraction 3-6 weeks before radiotherapy is also recommended by the Canadian Dental Association [20]. At the same time, it is worth noting that there are studies that do not show that extraction before radiotherapy reduces the risk of OAN [5].

It is worth mentioning that OAN, due to the preventive measures taken and advanced radiotherapy techniques (IMRT), has decreased in recent decades from 20% to 4-8% [23].

2.1 Manipulations before Radiotherapy for Head and Neck Cancer [6]

• Oral cavity examination at least 14 days before treatment.
• Postponement of unnecessary surgeries until completion of oncological treatment.
• Identification and treatment of intraoral areas with inflammation such as caries, periodontal disease, endodontic disease and mucosal lesions.
• Identification and treatment of intraoral areas with trauma or irritation.
• Identification and treatment of possible oral problems, which may be within the field of radiotherapy.
• Guiding the patient regarding proper oral hygiene.
• Patient education regarding dental prophylaxis.
• Extraction of all teeth that cannot be restored except in terminally ill patients [3,4].
• Waiting 10-14 days before radiotherapy for wound healing [3].

2 .2 Χειρισμοί κατά τη διάρκεια της Ακτινοθεραπείας [ 6]

• Monitoring oral hygiene.
• Monitor the patient for possible trismus.
• Check for muscle pain or weakness within the radiotherapy field.
• Instructions for exercising the jaw muscles by opening and closing the mouth 20 times. The exercise should be done three times a day.

2.3 Post-Radiotherapy Manipulations [ 6]

• For the first six (6) months after cancer treatment, dental follow-up is recommended every 4-8 weeks or as needed.
• To emphasize the importance of proper oral hygiene.
• Stomatitis treatment in consultation with the oncologist.
• Monitoring for any occurrence of trismus, decalcification and caries. Lifelong daily use of fluoride paste by patients who experience dry mouth.
• Avoid intraoral surgery on irradiated bone due to the risk of OAN. Tooth extraction, if unavoidable, should be performed conservatively with antibiotic coverage and possibly hyperbaric oxygen therapy.
• Extraction of teeth that cannot be restored in patients with terminal cancer is not recommended [3].

There are conflicting opinions regarding the correct timing of tooth extraction [7-12]. It is generally accepted that despite scientific recommendations not to extract

teeth during radiotherapy, however, if and as long as it is a highly medically appropriate and untimely extraction, it should be performed under the least traumatic conditions possible, regardless of the time point in relation to the time of radiotherapy, and then prophylactic administration of antibiotics [2].

In planned extractions, despite the fact that there is a bibliographic recommendation to avoid extraction for approximately two (2) years after radiotherapy, on the one hand the empirical view to avoid extraction for at least six (6) months after the end of radiotherapy has prevailed, a view adopted by many medical centers, and on the other hand the bibliographically documented view that extraction during the first six (6) months after the end of treatment is the best time to limit the likelihood of OAN [7,12,13,20].

If extraction is required after four (4) months, it is appropriate for the patient to undergo hyperbaric oxygen therapy [7,9-12]. Studies have shown an increase in oxygen levels in irradiated tissues after hyperbaric oxygen therapy. Protocols typically include 20-30 sessions before and 10 sessions after tooth extraction [3,23].

2.4 Antibiotic treatment in tooth extraction after radiotherapy

Predisposing factors for its occurrence include the anatomical region of the tumor, the total radiation dose and the method of administration with an increased risk if a dose >60Gy is administered to more than 14% of the bone volume (V60>14%), the state of the dentition, as well as smoking and excessive alcohol consumption. Based on the frequency of occurrence of OAN, tooth extraction has been implicated more than any other factor [1,2,21,22]. OAN may occur more frequently after extraction of mandibular molars, which are within the radiation field [14]. Although infection after tooth extraction has been questioned as a predisposing factor, most studies and recommendations support the prophylactic administration of antibiotics [15,20].

The literature recommends the administration of antibiotics in cases of tooth extraction associated with radiotherapy. However, in general, the authors refer to the need for the use of antibiotics without providing details regarding the type, dosage and time of administration [3]. The fact is that there are different opinions regarding the regimen that should be used [14]. The most popular antibiotic in non-

In patients allergic to penicillin, amoxicillin is the preferred regimen, followed by amoxicillin + clavulanic acid (Augmentin) and the combination of amoxicillin and metronidazole, and in those allergic to clindamycin followed by metronidazole or the combination of cephalosporin and metronidazole. The duration of antibiotic administration postoperatively varies from 3 to 28 days. There is no significant difference between intravenous and oral administration [14]. Consequently, parenteral administration is indicated only where oral administration is not indicated or in cases of emergency treatment of very serious infections [15]. Due to the lack of randomized trials, treatment should be done in consultation with an oncologist [14].

It is important to mention that similar prophylactic treatment is also administered in cases of tooth extraction in patients at high risk for the occurrence of infective endocarditis and hematogenous total joint infection. In order to assist dentists in their daily practice, the American Heart Association (AHA) and the American Academy of Orthopaedic Surgeons (AAOS) have recorded guidelines that were revised in 2007 [16,17].

3. Recommendations

3.1 Prophylactic administration of antibiotics

Based on existing literature reports, it is recommended that in cases of tooth extraction in patients who have been irradiated in the oral cavity, the administration of a

Perioperative dose of Amoxicillin 2-3 g orally (po) or in patients allergic to Penicillin, Clindamycin 600 mg also orally 30′-60′ before the operation or even Azithromycin or Clarithromycin 500 mg orally also 30′-60′ before the extraction procedure [16-19]. Postoperative antibiotic administration possibly up to 5 days [14]. For Amoxicillin, a postoperative dose of 500 mg x 3/day is recommended. For Clindamycin, 150-200 mg x 3/day and Azithromycin 500 mg x 3/day.

Table 1: Summary recommendations for prophylactic antibiotic administration

Situation	Preparation	Dosage before the operation	Dosage then for 5 days
General precaution	Amoxicillin (Amoxicillin)	2-3 g po 1 hour	500mg po x 3 times a day
Unable to receive PO	Amoxicillin (Amoxicillin) Cefazolin (Cefazolin)	2 g IM or IV*30′-60′ 1 g IM or IV 30′-60′
Allergy to Penicillin	Clindamycin Azithromycin or Clarithromycin (Azithromycin or Clarithromycin)	600 mg po 30′-60′ 500 mg po 30′-60′	150-200mg po x 3 daily 500mg po x 3 times daily
Allergy to Penicillin (Penicillin) with inability to receive PO	Cefazolin (Cefazolin) Clindamycin	1 g IM or IV 30′-60′ 600 mg IV 30′-60′

*IM – intramuscular: IV – intravenous

3.2 Additional recommendations

In addition to the recommendations derived from the bibliographic references mentioned above, it could also be recommended to avoid placing implants in areas that have been irradiated, since this procedure requires surgical manipulations on the bone, which increases the risk of developing OAN.

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