## 4 Discussion  
ONJ is a serious adverse reaction to certain medicines usually applied in the treatment of cancer and osteometabolic disease, related to the progressive destruction of bone in the mandible or maxilla [2; 7; 9; 16]. Great emphasis has been placed on preventive approaches to medication-related ONJ; however, for teeth with a poor prognosis, dental extraction is mandatory in order to eliminate any infective outbreaks of ONJ [9; 30; 31]. To date, dentoalveolar surgery is considered one of the major risk factors for developing of ONJ, with 52 to 61% of patients affected by ONJ reporting tooth extraction as the precipitating event. The estimated risk of ONJ in patients exposed to BPs for cancer therapy after tooth extraction ranges from 1.6 to 14.8%, while, in osteometabolic patients, the risk of ONJ after tooth extraction is around 0.5% [7]. Recently, a growing number of authors have suggested that dental/periodontal infection prior to dental extraction, rather than surgical procedures, may represent the main local risk factor for ONJ [31; 32; 33; 34]. Even if the pathogenesis of ONJ still remains unclear, the suppression of the osteocl activity and the lack of vascularization represents one of the major factors on pathogenesis of ONJ [2; 7; 35]. The application of APC may reduce the effects of BPs on post-extraction sockets, and it has been found that APC improves postsurgical wound healing in dental surgeries. The application of APC is linked to  
Figure 2: Clinical and radiological follow up of the same patient of Figure 1. (**E**) Clinical view at 6 months. (**F**) Detail of the panoramic X-ray at 6 months. (**G**) Clinical view at 24 months. (**H**) Detail of the panoramic X-ray at 24 months. the great number of growth factors entrapped in it, such as PDGF, TGF-b, EGF and VEGF; the release of growth factors promotes angiogenesis and stimulates the collagen production, improving bone and mucosal healing. In addition, APC is autologous, biocompatible and a safe product [19; 20; 21; 22]. In the present study, the application of PRP in post-extraction sockets was found to be successful in patients at risk due to BP assumption, as no occurrence of BRONJ was observed in a long term follow up period. Most post-extractive sites (98.41%) revealed a complete healing of the oral mucosa at the removal of sutures; only one site in the ONC group showed a small area of bone exposure after fifteen days, which resolved completely before the subsequent visit, and never showed signs of ONJ throughout the follow-up period. When findings from patients treated with PRP application were compared with those from selected historical controls [23; 24; 25; 26; 27], no statistically significant differences in the BRONJ onset were found (\(p>0.1\), for both ONC and OST patients). Limitations of the present study are (1) the small sample size, especially for ONC group, due to the provisions of Decree of the Italian Ministry of Health of 25 th November 2015 (Official Gazette of the Italian Republic no. 300 of 28 th December 2015) that expects use of APC only in non-cancer patients; and (2) the historical controls. Historical cases were derived from the literature and included both ONC and OST patients who satisfy the inclusion criteria of the study (see Section 2.3). In ONC patients, [PERSON] et al. evaluated the occurrence of ONJ in 60 high-risk patients exposed to BPs, who collectively had 185 teeth extracted, and found that five patients in this group developed ONJ. In the whole cohort, the hazard rate of ONJ was 5.6% at 1 month (n = 4) and 1.5% at 6 months (n = 1) [23]. [PERSON] et al. performed 102 tooth extractions in 43 ONC patients in treatment with zoledronate, no ONJ were observed at 12 months [24]. [PERSON] et al. evaluated the incidence of ONJ after surgical extraction in 34 ONC patients treated with intravenous BPs. A total of 62 teeth were extracted, and eight patients developed ONJ, the incidence of ONJ in terms of the number of patients was 23.5% [26] [PERSON] et al.