Most patients were diagnosed with an advanced stage of head and neck squamous cell carcinoma, majority within which the mean sampled age was 65 years old. Bonan et al. [10] reported a lower life expectancy of 58.8 years for the sample of patients from lower socioeconomic classes. Higher life expectancy may be explained by a higher socioeconomic status in earlier diagnosis and by the medical advances in the maxillofacial and oncology field in recent years. A study by Tsai et al. [11] demonstrated a 32% increased risk of development of ORN in smokers. Another study by Chronopoulos et al. [12] showed that patients who continued smoking or alcohol use were more likely to develop an ORN. For our present study, information concerning alcohol intake, drug consumption and pack-years of cigarette smoking was not consistently documented in the patients’ charts. Therefore, we could not explore the association between smoking and ORN and this is a limitation of our study.
Follow-up is crucial for the prevention and management of the oral and dental complications such as xerostomia, loss of taste, radiation mucositis, trismus, malnutrition and ORN. According to Toljanic et al. [13], dental follow-ups compliance is poor in an irradiated population, especially within the edentulous population. Their review of 334 dental charts of edentulous patients over 12 years reported an average follow-up of 7.5 months, with 51% of the patients who were lost during that period. These patients are indeed least inclined to regularly visit the dentist, as indicated by the comparable follow-up time for our edentulous patients (mean duration = 9.4 months). The duration of the follow-up period is a crucial factor to prevent complications related to RTH as suggested by our observations (9.4 months) and as demonstrated with the low ORN incidence in our patient population. These results emphasize the importance of public oral cancer prevention programs facilitating patients access to oral healthcare services and long-term care.
The incidence of ORN has significantly decreased in recent years. Our average rate of ORN was 2.2%, which is similar as those reported by other oncologic centers. For example, Sulaiman et al. [8], Moon et al. [14] and Koga et al. [15] have respectively observed an ORN rate of 0.92% in 1 194 patients, 4% in 252 patients and 4.2% in 405 patients. Before 1968, the incidence was approximately 11.8% as opposed to the last two decades, where it is closer to 3% [16,17], confirming the potential of IMRT to reduce the risk of developing ORN compared to conventional RTH [18]. IMRT uses linear accelerators to safely deliver precise radiation to a tumor while minimizing the dose to surrounding normal tissue. This is most likely one of the reasons why the ORN incidence is low. Another possible explanation of a lower incidence of ORN is the importance of dental care protocols that could have a synergistic preventive effect with IMRT [19]. The onset of ORN was early (median 9,5 months) after RTH. This is in line with other publications [11,20,21] which showed median ranges between 8 and 19 months.
Extractions prior to RTH seem to lead to a higher incidence of ORN (3.7% patients for 1,491 exodontias) and this observation is in accordance with other studies. Koga et al. [15] mentioned 0.5% ORN cases for 1,647 exodontias, Regezi et al. [22] found 2% for 311 exodontias, Sulaiman et al. [8] had 2.6% for 300 exodontias, Epstein et al. [23] described 5.4% for 454 exodontias and Bedwinek et al. [24]reported an incidence of 9%. Possible risk factors associated with ORN in patients having extractions are the unfinished alveolar bone healing in some individuals while RTH is initiated and their poorer oral health. However, as typically recommended, extractions should be carried out at least 2 weeks before starting RTH [25]. Due to oncologic imperatives and logistics, this recommendation was unfortunately not always observed in this study. The shortest delay ranged between 7 to 10 days after the extractions. Nevertheless, our incidence of ORN was similar to other studies.
Higher radiation doses are associated with increased risk of ORN [26]. In the present study, almost all ORN cases occurred in patients receiving more than 60 Gy. This emphasizes the 60 Gy threshold as an risk indicator of patients developing ORN after extraction as reported by others [6,20]. Although the risk of developing spontaneous ORN did increase with greater dose, most reported cases of ORN were induced by alveolar bone trauma such as that of dental extractions, as observed by other authors [27].
The mandible is at higher risk of developing ORN compared to the maxilla [28]. Indeed, all ORN cases in this study occurred in this region. The pattern of mandibular blood supply has been suggested as a primary reason for this site of predilection [29]. Moreover, the mandible is included in the radiation field more frequently than the maxilla. The fact that the primary tumor was located more frequently in the oropharynx region may contribute to the higher incidence of ORN in the mandible. As supported by other authors, the mandibular molar region is known to be at higher risk of developing ORN [30,31]. Moreover, since the lower molars were more frequently removed (Table III), the risk of developing ORN in that area is further increased.
Although less frequently, the maxilla can also be affected by ORN, especially in cases of nasopharyngeal cancer. Chang et al. [32] reported on 1,758 cases of nasopharyngeal carcinoma, 48 cases of ORN in the maxilla and 30 cases in the mandible Nevertheless, the risk of ORN is lower in the maxilla than in the mandible, considering the fact that maxilla is more resistant to radiation. The absence of maxillary ORN in our sample of patients parallels this observation.
Edentulous patients may develop ORN and we found an incidence of 1.7%. Surprisingly, Widmark et al. [33] mentioned an ORN frequency of 13.5%. Chang et al. [32] argued that the smaller proportion of ORN in edentulous patients compared to that reported in patients having extractions before the RTH (14%) could be explained by the fact that being edentulous several years prior RTH seems to offer a protective effect, but becoming edentulous a few weeks prior RTH does not. Bone healing and bone remodelling in the freshly edentulous patients likely increases the risk of ORN. Ensuring a proper fit of dentures is another effective way to avoid any trauma increasing ORN risks [34,35].
The worst moment for tooth extraction is considered to be during RTH [36]. However, a window between 6 weeks and 4 months after RTH may present less risk of complications for the bone following an extraction [37,38]. Past that window, the progressive fibrosis and loss of vascularity increase the risk of developing ORN. In the present study, no extraction was performed during RTH. This may be explained by the fact that meticulous attention was given to pre-RTH treatment planning in order to eliminate caries and periodontal diseases and extract teeth with a poor prognosis. Pre-RTH extractions are indicated when teeth are unrestorable or require significant restorations, present extensive caries into the pulp chamber, have periapical radiographic lesions, have moderate to severe periodontal disease (pockets under 5 to 6 mm), furcation involvement or mobility of grade 2 or more [23]. Moreover, all patients undergoing pre-RTH assessment were examined by dentists with an extensive experience in oral oncology. Post-extractions controls were also systematically performed to protect the process of socket healing.
If an extraction in the field of radiation is required, intraoperative efforts need to be made to prevent ORN. Koga et al. [15] reported ORN in 1.7% and Sulaiman et al. [8] showed an incidence of 1.8%, which is low compared to the 7.1% found by Epstein et al.14 and the 9.1% found by Horiot et al. [39]. However, Makkonen et al. [40] and Maxymiw et al. [27] reported no cases of ORN for, respectively, 88 and 126 teeth extracted after RTH. In a systematic review, Nabil et al. [41] highlighted that 7 % of the patients who underwent extractions post-RTH had developed an ORN and the ORN incidence per tooth extracted was 2%. In the present study, no case of ORN was related to post-RTH extracted tooth. This is also due to the small number of extractions done after RTH. The fact that extractions were done by experienced maxillofacial surgeons and carried out with minimal trauma [42] suggests that an atraumatic procedure is an important factor to prevent ORN. Importantly, hyperbaric oxygen therapy [43,44] was not systematically prescribed and pentoxifylline and tocopherol [45] were never used for our patients due to the lack of evidence backing their use [46]. Pentoxifylline and tocopherol should be considered only for the management of advanced ORN where surgical management is not appropriate [47,48].