_applied sciences_  
_Article_  
The Impact of Calcitriol on Orthodontic Tooth Movement: A Cumulative Systematic Review and Meta-Analysis  
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be even further extended [1; 2]. Increased duration of orthodontic treatment is associated with patient's compliance and usually more prevalent clinical side effects, such as external root resorption and enamel demineralization in the form of white spot lesions [3; 4]. As a result, orthodontists have been interested in exploring various non-surgical and surgical approaches that could potentially reduce treatment time by accelerating tooth movement [5; 6; 7]. Non-surgical approaches are non-invasive, yet they provide low quality evidence to support their effectiveness [5; 8]. Although some surgical approaches have been promisingly associated with increased rates of OTM, they are less appealing for patients due to their invasive nature and potential for postoperative discomfort [9].  
The sequence of biological events that occur during OTM has been investigated recently [10], revealing the mechanism by which various endogenous molecules, including neurotransmitters, inflammatory mediators, and cytokines, coordinate local responses to applied orthodontic forces, as well as both initiate and maintain OTM [11; 12]. Moreover, they provide possible targets for pharmacological therapies that may have the potential to accelerate or suppress tooth movement during and after orthodontic treatment [13].  
It is well established that the active form of vitamin D3, calcitriol, has an anabolic effect on bone metabolism, and its receptors are present on osteoblasts, osteoclast precursors, and osteoclasts. It appears to enhance bone turnover in the same way as parathyroid hormone does, by stimulating prostaglandin production in osteoblasts [14]. In vitro studies have also shown that CTL regulates the production of collagen type I, alkaline phosphatase, osteoclast and osteoblastic proliferation [15; 16]. In addition, evidence from animal studies suggests that CTL can enhance alveolar bone remodeling and thereafter accelerate OTM [17; 18], which is consistent with a clinical study reporting the systemic impact of CTL on enhancement of tooth movement [19] (Figure 1). In general, the stimulatory effect of CTL on osteoblasts may stabilize OTM.  
Despite the well-established role of CTL in the metabolism and remodeling of mineralized hard tissue, the evidence for its role in stimulating and enhancing tooth movement in humans remains unclear [14]. This comprehensive review attempts to summarize the existing evidence related to the influence of CTL on tooth movement initiated during orthodontic treatment, with the use of quality assessment methods and quantitative data synthesis. To date, this review herewith is the first comprehensive analysis of both animal  
Figure 1: The potential acceleration of orthodontic tooth movement. The mechanism of CTL biological effect.  
and human studies' results evaluating the impact of CTL on tooth movement generated by orthodontic forces.