## 4 Discussion  
PTH plays a major role in maintaining the serum calcium concentration [12]. If the blood calcium levels get too low, PTH stimulates resorption of bone. PTH stimulates this resorption of bone by inducing a higher activity of osteoclasts, cells that are responsible for resorbing bone [24]. Hyperparathyroidism, a condition characterized by excessive levels of PTH in the blood, causes generalized loss of lamina dura in the periodontitis and bone loss elsewhere in the body [25]. However, more recently, it has been observed that low intermittent doses of PTH actually promote bone formation [26]. Hence, low doses of intermitted PTH have been proposed for diseases such as osteoporosis [27]. The general outcomes of the studies included in this systematic review suggest that low doses of intermittent PTH may, to some extent, may have a favorable impact on alveolar bone, OTM and orthodontic retention [15; 16; 19; 20; 21; 22; 23]. However, to date, it is not clear how the hormone exerts all of those effects. [PERSON] et al. have observed that PTH increases osteocl activity to increase bone resorption mainly on the compression side to accelerate OTM [23]. [PERSON] et al. suggest that PTH induces a more rapid OTM via affecting the OPG/RANKL ratio [20]. They actually observed more pronounced changes in the OPG/RANKL ratio more during the late phases of OTM when compared to the earlier phases. Interestingly, they only detected an upregulation of OPG which may account for a reduced activity of osteoclasts and odontoblasts. Moreover, [PERSON] et al. observed that Systemic intermittent PTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/\(\beta\)-catenin interaction [16]. Nevertheless, it is evident that the exact mechanism of local or systemic administration of PTH has yet to be determined and more studies are needed to ascertain how PTH may influence the outcomes of OTM. In the studies reviewed, no distinct difference was observed between the efficacy of local or systemic PTH administration. As a matter of fact, only one study [13] looked at the differences between the effects of local and systemic PTH on OTM. Nevertheless, since systemic PTH may have undesirable adverse effects on the patient, it would be interesting to see how the local PTH administration compares with systemic injections of the hormones. To date, no clinical studies have been carried to observe the effect of PTH on the alveolar bone loss, retention, and rate of tooth movement in patients undergoing OTM. Additionally, even in the animal studies reviewed in this paper, only one study observed the effect of PTH on OTM with periodontitis [16]. Therefore, future animal studies should \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Study**} & \multirow{2}{*}{\begin{tabular}{c} **Pre-** \\ **Determined** \\ **Sample Size** \\ \end{tabular} } & \multirow{2}{*}{**Randomization**} & \multirow{2}{*}{**Approximate**} & \multirow{2}{*}{**Statistics**} & \multirow{2}{*}{**Blinding**} & \multicolumn{2}{c}{**Loss of**} & \multirow{2}{*}{\begin{tabular}{c} **Annimals** \\ **Reported If** \\ **Any** \\ \end{tabular} } & \multirow{2}{*}{\
\begin{tabular}{c} **Error** \\ **Analysis** \\ \end{tabular} } & \multirow{2}{*}{
\begin{tabular}{c} **Overall** \\ **Quality** \\ \end{tabular} } \\  & & & & & & & & \\ \hline [PERSON] et al. 2000 [23] & No & No & Yes & Yes & No & No & Low \\ [PERSON] et al. 2010 [20] & No & No & Yes & Yes & Yes & No & No & Low \\ [PERSON] et al. 2011 [21] & No & No & Yes & Yes & No & No & Low \\ [PERSON] et al. 2013 [19] & No & Yes & Yes & Yes & No & No & Medium \\ [PERSON] et al. 2018 [15] & No & Yes & Yes & Yes & No & No & Yes & Medium \\ [PERSON] et al. 2020 [16] & No & Yes & Yes & Yes & No & No & No & Low \\ [PERSON] et al. 2021 [22] & No & Yes & Yes & Yes & No & No & No & Low \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Results of the quality assessment.