## 4 Discussion  
Root resorption during OTM has been considered an unavoidable phenomenon [11]. However, severe resorption is considered to be a complication and has been reported in 1% to 5% of OTM procedures [11]. Accordingly, reducing root resorption during OTM is an important issue in orthodontics. In this study, the administration of 4 HR to rat models resulted in reduced root resorption induced by OTM (Figures 2 and 3). The bone turnover markers AP, OPG, RANKL, and Runx2 showed elevated expression levels in the 4 HR-administered group (Figures 4 and 5). To the best of our knowledge, this is the first report about reducing root resorption during OTM by 4 HR administration. Several studies have been conducted on the effects of various drugs or chemicals on the rate of tooth movement and root resorption [31]. Bisphosphonate binds to hydroxyapatite on the absorbing surface of bone and inhibits bone resorption through a mechanism that inhibits osteoclast migration and action and induces osteoclast apoptosis [32]. It has been reported that the administration of bisphosphonate reduces root resorption and tooth movement [33] due to its anti-inflammatory action and inhibition of osteocl activity [34]. Bisphosphonate administration has the advantage of reducing root resorption during OTM, but it significantly interferes with OTM [35]. Prednisolone administration also decreases root resorption and the rate of tooth movement [36]. Controversial results  
Figure 5: The results of histological analysis. (**a**) The control group showed multiple root resorptions (arrow heads). Thin cementum is shown in a violet color, and it was discontinuous because of root resorption. The experimental group showed continuous cementum (arrow heads, hematoxylin and eosin stain, bar = 50 μm). (**b**) The immunohistochemical staining results demonstrated that positive staining for AP, OPG, RANKL, and Runx2 was mainly found in the periodontal ligament area. The staining intensity for each marker was stronger in the experimental group compared to that in the control group (original magnification \(\times\) 200). have been reported for the effect of non-steroidal anti-inflammatory drug (NSAID) administration on root resorption [36]. It is believed that some types of NSAIDs inhibit root resorption [31] and tooth movement [37]. Lithium promotes reduced osteoclast formation by promoting the Wnt/\(\beta\)-catenin signaling system [37]. As the concentration of lithium increases, root resorption and tooth movement decrease in animal experiments [38]. As described above, most of the substances administered to reduce root resorption through a mechanism that reduces osteoclast activity have tended to decrease tooth movement speed as well as root resorption [38]. The 4 HR used in this study resulted in root resorption being reduced compared to that in the control group (Figures 2 and 3). When looking at the numbers of exclusions because of a low rate of tooth movement, they were four for the experimental group and five for the control group (Figure 1). The administration of 4 HR accelerates OTM in ovariectomized rat models [29]. The bone remodeling process is balanced through the coupling of bone resorption by osteoclasts and bone formation by osteoblasts. Medications or dietary supplements that decrease osteocl activity suppress root resorption but also hinder OTM [31]. The substances that increase bone turnover rate and increase both osteoblastic and osteocl activity may diminish root resorption and promote tooth movement. The effect of parathyroid hormone (PTH) is different according to the treatment method that is either catabolic or anabolic [39]. The long-term intermittent injection of PTH facilitates the repair of root resorption [40]. Intermittent PTH administration increases the expression levels of both RANKL and insulin-like growth factor-1, indicating that intermittent PTH stimulates both osteoclasts and osteoblasts [7]. LLLT may inhibit orthodontically induced root resorption [18] but accelerates OTM [41].