# Clinical Applications of Nano-Hydroxapatite in Dentistry
## 4 Discussion  
In the recent years, the clinical applications of nano-HAp in dentistry have progressively increased, although with non-univocal results. The application of different nano-HAp formulations has been suggested to promote enamel remineralization and prevent caries reversal [15; 16; 17]. However, for nano-HAp toothpaste, the outcome observed was similar to the application of fluoride-based toothpaste [15; 16]. Nevertheless, it should be noted that applying a fluoride-free toothpaste may be beneficial in reinforcing tooth structure while reducing the risk of fluorosis [15]. According to a Cochrane systematic review on fluoride toothpaste use in children, prevention of tooth decay is proportional to the fluoride concentration employed, although the choice of fluoride toothpaste for young children should be balanced against the risk of fluorosis [41]. Although to date a precise cut-off for fluorosis development is not available, a fluoride intake between 0.05 and 0.07 mg of fluoride per kg of body weight has been suggested [41]. Therefore, it may be concluded that nano-HAp based toothpastes can be safely used as an adjunctive means for caries prevention, in the absence of risks of fluorosis development. The combination with other bioactive materials, such as composites releasing remineralizing substances for the prevention of secondary caries, should also be investigated [42]. [PERSON] et al. [17] employed nano-HAp in combination with ozone therapy. Ozone therapy has been reported for the management of incipient caries, although at present there is no reliable evidence that the application of ozone gas to the surface of decayed teeth stops or reverses the decay process. [43; 44; 45] It can be thus concluded that there is insufficient evidence to recommend a combined treatment with nano-HAp gel and ozone therapy. Dentin hypersensitivity is the condition where the use of nano-HAp has been most extensively investigated. [PERSON] et al. [46] conducted a comprehensive systematic review on different desensitizing toothpastes, and listed toothpastes potassium, stannous fluoride, potassium and strontium, potassium and stannous fluoride, calcium sodium phosphosilicate, arginine, and nano-hydroxyapatite as effective agents in relieving the symptoms of dentin hypersensitivity. [PERSON] et al. [47] specifically focused on nano-HAp application for the relief of dentin hypersensitivity, and concluded that nano-HAp at-home and in-office treatments effectively reduced hypersensitivity compared to other desensitizing agents or placebo/negative controls. Among the nine studies included in the present review reporting on dentin hypersensitivity, two studies [18; 23] (reported more favorable outcomes in the nano-HAp treatment groups, two studies [19; 25] highlighted a superiority of nano-HAp especially in the immediate post-treatment period, while the remaining five studies [20; 21; 22; 23; 24] did not highlight a superiority of nano-HAp treatment over other desensitizing agents. In the light of the present evidence, it can be suggested that nano-HAp could be effective in reducing dentin hypersensitivity, providing non superior efficacy compared with other desensitizing agents. Application of nano-HAp in orthodontics was reported in two studies [26; 27]. Nano-HAp was found effective in reducing micro-leakage under orthodontic bands,26 while no additional effect was noted in reducing tooth discoloration following debonding [26]. The present evidence appears extremely limited, and currently hinders the possibility to draw firm conclusions on the application of nano-HAp in orthodontics. Further evaluation through RCTs is advised. Nano-HAp application as graft material inducing bone regeneration and incorporation with drugs or bioactive molecules has been extensively discussed [8]. The possibility of nano-HAp to enhance regeneration process has been reported for different purposes.