## 4 Discussion  
This review aimed to justify the combined use of a 9300 nm CO\({}_{2}\) laser and fluoride to foster the prevention of enamel caries. It summarized the in vitro data of treatment combining fluoride and the laser versus the single use of the laser and the single use of fluoride. It showed that enamel treated with the laser and fluoride sustained less mineral loss against acid challenge than the enamel treated with the laser or fluoride only. This study aimed to include original research on both enamel and dentine caries and both laboratory and clinical studies. However, no clinical or in vivo study was found after the initial search and screening. In addition, there was only one paper investigating the effect of the laser on dentine caries [42]. We did not want to draw a conclusion on dentine caries based on a single paper. Hence, we revised our objective and decided to focus on studies on enamel caries in this systematic review and meta-analysis. This review was not registered in any web or institution. Registering the review prevents duplication and minimizes the opportunity for reporting bias. We searched the PROSPERO which provides a comprehensive listing of systematic reviews registered and found no similar review. The progression of caries in dentine differs from that in enamel. Enamel caries occur mainly due to the dissolution of a mineral component as a consequence of bacterial acid attack [43], whereas both mineral dissolution and the proteolysis of the collagenous matrix are involved in dentine caries [44]. The study on dentine caries demonstrated that compared with L, F + L showed a decrease in lesion severity. However, the study found that compared with F, F + L did not show any statistical significance. Current scientific evidence of the effectiveness of the treatment combining a 9300 nm CO\({}_{2}\) laser and fluoride on the prevention of dentine caries is insufficient. It is important to carry out more research to investigate these issues. The selected studies assessed mineral loss in different ways, such as through cross-sectional microhardness or traverse microradiography. Additionally, some studies included in the meta-analysis used bovine enamel rather than human enamel. Bovine enamel is an ideal alternative for studies on enamel caries. The collection of extracted human teeth is one of the major challenges in using human enamel specimens. In addition, variations in the age of the donors can give rise to variations in the mineral density of the enamel, which can affect the results of the study. In comparison, bovine enamel is more uniform in composition. However, bovine enamel is more porous, thus forming lesions more rapidly, displaying a rate of lesion formation three times faster than in human enamel [45]. However, using bovine and human enamel data in the quantitative discussion of artificial carious \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Authors, Year [Reference]** & **[PERSON] et al.,** & **[PERSON] et al.,** & **[PERSON] et al.,** & **[PERSON] et al.,** & **[PERSON] et al.,** \\  & **2008**[37] & **2008**[38] & **2016**[17] & **2020**[39] & **2020**[40] \\ \hline Quality check of samples & - & - & - & - & Yes \\ Randomization of samples & - & - & - & - & - \\ Sample-size calculation & - & - & Yes & Yes & Yes \\ Homogeneity of samples & Yes & Yes & - & - & - \\ Details of laser parameters used & Yes & Yes & Yes & Yes & Yes \\ Fluoride application protocol & - & Yes & Yes & Yes & Yes \\ Operator & - & - & - & - & - \\ training & - & - & - & - & - \\ Blinding of & - & - & - & Yes & - \\ operator & & & & & \\ \hline Risk of bias & High & High & High & Medium & Medium \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Risk of bias of the included studies in the systematic review. lesion formation can be allowed, because the ratio of bovine enamel lesion formation rate in comparison to that in human enamel is almost constant [46]. For these reasons, we standardized the results of the studies by using a standardized mean difference rather than mean difference.