## 4 Discussion
included in a prospective study 68 patients, 50 were ONC in treatment with BPs, the remaining 18 were OST patients as received oral BPs. In total, 205 teeth were removed and ONJ development was observed in three ONC patients under IV BP therapy [25]. Another two papers are worthy of note, although excluded, due to the absence of datum both on cumulative dose and months exposition from the control ONC group chosen. [PERSON] et al., in a case-control study on tooth extractions in ONC patients on zoledronic acid therapy, performed 267 dental extractions in 85 patients, with five cases of ONJ development [36]; and [PERSON] et al., in a retrospective cohort study, described the outcome of 216 dental extractions on 72 patients (43 ONC patients, 29 OST patients) [15]. Seven of the 72 patients developed ONJ during the follow-up period, three patients developed ONJ (4.2%) in four of the 216 extraction sites (1.9%). Regarding the occurrence of wound healing disturbance and ONJ development, a malignant underlying disease and an intravenous route of BPs administration was more common (85.7%) [15]. In OST patients, [PERSON] et al. described no evidence of ONJ on 700 patients and 1480 extractions [27]. [PERSON] et al. investigated the incidence of ONJ patients after surgical tooth extractions (651 teeth) in OST patients exposed to oral BPs (320 patients). Indeed, 11 patients developed ONJ with an uncommonly high incidence rate (3.44%) [37]. These cases, however, were not included in the statistical analysis, due to the short follow-up period. Finally, it should be noted that the present study has a long follow-up period (24 months), that is twice as long as the period suggested to exclude the onset of ONJ, following surgical procedures on patients at risk [28; 38; 39]. This characteristic of the study design counterbalances the aforementioned limitations. Due to their properties, APC have been successfully applied in the prevention of BRONJ by several authors; no studies, however, evaluated the application of PRP in post-extraction dental socket [18; 36; 40; 41; 42; 43; 44; 45]. [PERSON] et al. described the application of plasma rich in growth factors (PRGF) in a protocol for tooth extraction in ONC patients treated with intravenous BPs in two different studies with a follow up of at least 12 months. In the first report, sixty-four patients in treatment with intravenous BPs (60 ONC pts, four OST patients) were enrolled; five ONC patients developed ONJ in post-extraction sites (2.27%) [44]. In the second study sixty-three patients were enrolled (57 ONC pts,six OST pts), with one ONJ (0.99%) in an ONC patient [45]. [PERSON] et al. described a case-control study of tooth extraction on 176 ONC patients treated with intravenous BPs. In the study group (91 ONC pts, 542 extractions), the application of PRGF in tooth extraction was successful, with no evidence of ONJ with a follow up period of 24 to 60 months. Five ONJ lesions were evidenced in the control group (85 pts, 267 extractions) [36]. In a systematic review of the literature, [PERSON] evaluated these three prospective studies, defining the success rate of 99.05% on a tooth basis and 97.26% on a patient basis [18]. Recently, [PERSON] et al. described a case-control study, in which the application of platelet rich-fibrin (PRF) dental extraction procedures on 102 OST patients was evaluated. No BRONJ were observed in the study group (29 pts, 52 extractions); while, nine patients in the control group (73 pts, 166 extractions) showed a delayed recovery with bone exposure 4 weeks after surgical procedures. The authors reported wound closure within 8 weeks and no evidence of ONJ; however, the follow up period of the study was relatively short (i.e., 3 months) [43].