Effects of Common Medications on Orthodontic Tooth Movement: A Systematic Literature Review

Eman Ibrahim Al Shayea^*

^*Correspondence: Eman Ibrahim Al Shayea, Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King saud university, Saudi Arabia, Email:

Author info »

Introduction

Orthodontic treatment is founded on the premise that the application of force on a tooth transmits cellular, chemical, and mechanical occurrences to the tissues nearby. Such results in the structural modifications lead to the movement of the tooth [1,2]. The transformations that take place in the investing bone tissue adjacent to the moving tooth are known as bone deposition and resorption. Bone deposition is the process of depositing new bone matrix by the osteoblasts, while bone resorption is the process by which osteoclasts break down the tissue in bones and hence release minerals to the blood. The biological sequence of events that causes the tooth to move following the application of mechanical forces include Extracellular matrix strain and fluid flow, cell strain, cell activation and differentiation, and finally tissue remodelling [3,4]. Acute seditious response categorized by periodontal vasodilatation, migration of leukocytes out of PDL capillaries, and sensations of pain, is usually associated with early phase of orthodontic tooth movement (OTM). Most of the orthodontic patients experience such symptoms.

Notwithstanding, orthodontic practitioners and scientific researchers have not yet comprehended the main conversion mechanism facilitated by the force generated by the moving tooth. In the past few years, however, scientific advances have enabled orthodontists and researchers to explore the role performed by some factors and released inflammatory mediators, such as prostaglandins (PGs), collagenase, calcium, and cyclic adenosine monophosphate (cAMP). Such mediators have significant roles in enhancing tooth movement subjected to orthodontic force [1,2].

The above mentioned biological sequence of events may be a brief summary of recent understanding of complex activities and interactions occurring in the PDL and alveolar bone following the application of mechanical force or action of chemical mediators. The combined effect of mechanical forces and these mediators can be synergistic, preservative, or inhibitory [1,2]. Therefore, the present research was designed in the form of systematic literature review to focus on reviewing, summarizing evidence from existing literatures, and to investigate the effects of commonly used medications on OTM. Hence, the aim is to elucidate, for orthodontists, the influence of each medication on the rate of tooth movement.

Materials and Methods

The study is a systematic literature review based on reviewing numerous relevant peer-reviewed articles and journals from electronic databases. Electronic databases including Cochrane database, Cinahl, Web of Science, Scopus, PubMed, ScienceDirect, Trip, Scielo, Lilacs, and Medline were searched from January 1982 to April 2021 to obtain sources with no language or location restrictions. Moreover, terminologies such as “tooth movement,” “orthodontic tooth movement, “drugs effects”,” and “effects of medications” were used when performing the literature search. The inclusion criteria were set by selecting the studies that fulfill the following:

Studies focused on examining the effects of medications on OTM.

Studies with experimental animal or human clinical investigations with a minimum of one control and experimental group.

Studies with local or systemic administration of welldefined medication or dietary supplements that might have side effects to bone physiology.

Studies that adequately described the administration regimes and dosages, the orthodontic force magnitude, the approach used to examine the rate of tooth movement.

Results

Based on reviewing titles and abstracts and through the computerized literature search and review of reference lists, a total of 423 articles were identified. Following the screening of these articles, 306 articles were excluded as they failed to meet the inclusion criteria. In addition, articles for which the full text was impossible to obtain, along with articles in other language than English with no translation were excluded from the study. Moreover, six duplicates were identified, and therefore were removed them from the study. This made only 72 pertinent peer-reviewed articles that met the inclusion criteria and hence were included in the present review for further analysis. The illustration in Figure 1 displays the results of the methodical literature review evaluation.

Furthermore, a summarized published data of the studies included in the review are presented in Table 1. The table shows the literatures’ year of publication, type of drug used in the study, sample size and type, dose and method of drug administration, methods of force application, and the authors’ conclusions. All the drugs reviewed have therapeutic effects, as well as, side effects that may influence the cells targeted by orthodontic forces, and hence the outcome of mechanotherapy. These drugs included different analgesics, different hormones, Immunosuppressant and immunomodulatory drugs, anticancer drug, anticonvulsants, Bisphosphonates (BPNs), Vitamin D, and fluorides. Most of the studies are experimental animal studies which constitute 84.7% of the total studies, while the clinical studies represented 15.3% of the total studies. The table shows that the majority of the studies were published between 1996 and 2014 (75%).

Table 1: Summarized published data of the studies included in the systematic review.

Discussion

This systematic literature review was conducted to focus on reviewing, summarizing evidence from existing literatures, and to investigate the impacts of commonly used medications on OTM. Furthermore, the review identifies the various effects of dosages used for each medication by identifying the approach used for drug administration, the amount and the methods of force applied during drug administration, and the techniques used to examine the OTM. Although the orthodontic diagnosis and treatment are founded on the clinical evaluation and the investigation of diagnosis records, it is usually essential for any orthodontist to perform a comprehensive medical history and make such an inquiry a major part of every orthodontic diagnosis [1,5,6].

Over the years, there has been a significant expansion in medication prescriptions. This expansion has been primarily caused by the increase in the demand for medications that are effective in targeting chronic illnesses and those related to age. Also, the trend has been significantly influenced by other factors such as medical advertisements and health insurance entities [7-9]. In spite of the increase in the consumption of such medications, researchers have asserted that the demand for orthodontic treatment is expanding among children and adolescents. For instance, in the United States, 7% of children and teenagers aged 6 to 17 years are using prescribed medication for behavioural and psychological difficulties [10-12]. Clearly, the wide use of over-thecounter drugs causes various complications among patients using them excessively. These over-the-counter drugs have certain pharmaceutical substances that may have effects on tissue remodelling, tissue homeostasis, and hence orthodontic tooth movement [13,14].

Analgesics are medications used by patients as pain reliever. It is divided into Nonsteroid anti-inflammatory drugs “NSAIDs”, and non- NSAIDs which lacks antiinflammatory properties such as “Acetaminophen”. These analgesics are the commonly used medications in orthodontics for the purpose of controlling pain following force application on the teeth. According to the chemical composition, NSAIDs is subdivided into different groups such as Salicylates, Arylalkanoic acids (diclofenac), Arylpropionic acids (Profens), Oxicams and Coxibs. Several researches demonstrated their effects and action mechanisms by inhibition of Cycloxygenase activity “COX”, leading to suppress the production of all prostanoids; such as PGs, that have a significant role in bone resorption during orthodontic therapy, and hence causing a reduction in the rate of OTM [15]. The effects of a conventional NSAID “Diclofenac”, and a specific COX-2 inhibitor, “Rofecoxib” on the inhibition of OTM in rats was investigated and the studies revealed that both rofecoxib and diclofenac significantly inhibited dental movement, partially in the case of rofecoxib and totally in the case of diclofenac [16-18]. Sodagar et al reported the effect of celecoxib, a highly-selective COX-2 inhibitor, on OTM in rats. They found that bone resorption and tooth movement were inhibited by this kind of NSAID [19].

Sari et al., 2004 in clinical study compared the effects of Acetylsalicylic acid with those of Rofecoxib on PGE2. The study found that the inhibition effect of acetylsalicylic acid on PGE2 was greater than Rofecoxib, which highlights the suitability of using Rofecoxib as an analgesic to control pain without affecting the result of orthodontic treatment [20]. Same result was found in a recent study done on rats by Kirschneck et al., 2020. They found that Etoricoxib is a suitable analgesic during OTM, as it has been reported not to affect tooth movement [21]. Furthermore, several studies were conducted to evaluate the effect of different analgesics on OTM in the animals and humans. It was found that the use of Ibuprofen, and aspirin inhibit PGE2 synthesis, which in turn alters tooth movement. On the other hand, Acetaminophen had no effect on PGE2 synthesis, and was considered safe to be prescribed during orthodontic treatment without the risk of affecting the pace of tooth movement [22-24]. Similarly, Tenoxicam is shown to effectively control the pain experienced by orthodontic patients without any effects of on the OTM [25,26].

Two clinical trials evaluated the effect of injecting Prostaglandin E1 (PGE1) on the moving tooth in human patients. They portrayed a substantial advance of tooth movement in the injected side compared to the control side. They identified great differences with upsurge in tooth movement associated with the stimulation of the nearby tissues and bones. Injecting PGE1 at the site of OTM appears to be effective in stimulating the transformation of the alveolar bone and in increasing its vascularity [27,28]. Other animal experiments, as well, have shown that local application of PGE2 increases the speed of OTM [29-34].

The hormones medications reviewed in this study, which affect OTM, include calcitonin, parathyroid hormone, estrogens, insulin, thyroid hormones, relaxin, corticosteroids, immuno-suppressant and immunomodulatory drugs, anticancer drugs, and interleukin antagonists. Thyroid hormones (T3, T4) are hormones produced and released by the thyroid gland. They are responsible for regulation of metabolism. It was found that the administration of Thyroxin leads to increased bone remodeling, and hence increases the speed of OTM. Therefore, clinicians should always ensure that they prescribe low dosages of thyroid hormone medications among orthodontic patients [35,36]. In contrast, Calcitonin is another hormone secreted by the thyroid, which acts to reduce blood calcium opposing the effects of parathyroid hormone (PTH). It inactivates osteoclasts and hence inhibits bone resorption. It also stimulates the bone forming activity of osteoblasts [15], and hence minimizes post-orthodontic relapse, as recently reported in different animal studies [37,38]. Parathyroid hormone (PTH) is a hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. Animal studies on rats have shown that local or systemic injection of PTH accelerated OTM and significantly increased osteoclast activity [39-41]. Such research findings elucidate that orthodontists should be careful when treating patients using the PTH medication.

Estrogen is a substantial sex hormone that regulates bone remodeling in females. It also prevents the production of numerous cytokines that help in the bone resorption. Moreover, estrogens, prevent the osteoblasts response to PTH. Most of the previous studies evaluating the indirect effect of estrogens on OTM are experimental studies. They have shown that estrogen is similar to calcitonin, in the way it minimizes the pace of teeth movement [42-49]. Among the human studies, one clinical case report of a postmenopausal orthodontic patient concluded that the estrogens used to treat osteoporosis might have delayed OTM [50]. In addition, more rapid tooth movement was observed in female orthodontic patients during the menstrual period than in the ovulation period [51,52]. As such, the effects of estrogen levels on OTM can be taken into consideration when orthodontists select the timing for recall visits, as well as if the patient is under any oral contraceptive pills, as it contains estrogens, which inhibits tooth movement.

Relaxin is an ovarian hormone, and commonly known as a pregnancy hormone. It stimulates osteoclast and osteoblast activities. Studies conducted on animals showed that the administration of human relaxin may accelerate the early stages of orthodontic tooth movement, and prevent relapse in orthodontic practice [53-56]. In 2011, Mcgorray conducted a randomized clinical trial to compare relaxin and a placebo with regard to tooth movement and stability in human subjects. He found that no differences in tooth movement over 8 weeks of treatment or relapse at 4 weeks posttreatment were detected between groups. He attributed that to the small dosage used in the experiment [57]. Insulin is a hormone made in pancreas and regulates blood sugar levels. Injections of insulin can help treat both types of diabetes. Two experimental studies reported the effects of insulin injection on OTM. The first study evaluated the effects of induced diabetes type 1 on osteoclast recruitment and activity and, consequently, on orthodontic tooth movement in mice. This was compared with another group that was treated with insulin after diabetes induction. They found that OTM in the diabetic mice were faster, and the treatment with insulin resulted in slower OTM similar to normoglycemic rats [58]. Another study by Villarino et al., 2011 evaluated the effect of diabetes and Insulin injection on rats. The results showed that bone response to orthodontic forces in insulin-treated diabetic subjects does not differ significantly from that observed in healthy subjects [59].

Corticosteroids are prescribed as anti-inflammatory and immunosuppressive medications. They act by preventing the formation of prostaglandins, and inhibiting the intestinal calcium absorption, which leads to direct inhibition of osteoblastic function, and an increase in bone resorption. Most of studies on animals reported that the tooth movement rate increased in the chronic group that require long term corticosteroid therapy. Whereas, in acute corticosteroid ingestion, the studies reported suppressed bone turnover. This finding indicates that the orthodontic force level should be reduced and maintained more frequently in patients with chronic corticosteroid ingestion, and postponed orthodontic treatment in patients on acute steroid treatment until a time the patient is free of the drug [60,61]. Immunosuppressant and immunomodulatory are medications that work to lower the body's ability to reject a transplanted organ, and they include drugs such as glucocorticoids, cyclosporine, tacrolimus, and sirolimus. Other immunosuppressant drugs are often used to treat autoimmune disorders such as rheumatoid arthritis, psoriasis, and lupus. All these medications that work to prevent organ rejection following transplantation have been reported as having effects on bone mineral homeostasis and consequently influence OTM. In addition, the immunosuppressant drug is associated with various unwanted effects, such as gingival overgrowth, making orthodontic treatment and maintenance of oral hygiene difficult [62]. Further, the Interleukin antagonists (IL-1RA) is a protein in humans secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and it is a natural inhibitor of the pro-inflammatory effect of IL1β. The inflammatory response following orthodontic loading characterized by the release of such inflammatory mediators on periodontal tissues that is directly involved in bone resorption. This was confirmed by a study on mice treated with IL-1RA which showed diminished OTM and decreased numbers of osteoclasts. The finding suggested that IL-1RA downregulates OTM, probably by its anti-inflammatory actions [63].

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor(TNF), which is part of the inflammatory response. TNF-α antagonists are being used to treat moderate to severe diseases in patients having contraindications, not responding, or when side effects were developed to conventional systemic treatments. It was found that TNF- α plays an important role, directly or via chemokine release, in osteoclast recruitment and activation [64]. Furthermore, recent study explained the role of TNF-α in inducing sclerostin expression in osteocytes on the compression side during OTM. TNF-α enhances sclerostin expression in osteocytes; then, sclerostin increases the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) by osteocytes. Hence, the study concluded that osteoclast formation was enhanced by TNF-α through increased sclerostin expression in osteocytes on the compression side during OTM [65]. Moreover, local injection of integrin inhibitors, like echistatin and RGD peptides, on rats significantly decreased root resorption surface areas and reduced the number of root resorption lacunae in orthodontically treated teeth, as well as useful to limit or prevent OTM of specific teeth in case of enhancing anchorage [66,67].

Anticancer drug, also called antineoplastic drug, is effective in the treatment of malignant, or cancerous disease. A significant increase in the overall rate of childhood cancers was reported in recent decades [68]. No experimental or clinical studies were found on the effect of the anticancer drugs on the rate of OTM. However, these drugs are known to inhibit cell division and proliferation, not only destroy cancer cells but also destroy normal cells. So, they have consequences for growth, dental development, craniofacial growth, bone remodeling process, and hence complicating OTM [69]. One recent study compared the stability of orthodontic treatment in cancer survivors who had been treated with cytotoxic drugs with a generally healthy control group. The authors concluded that previous treatment with cytotoxic drug significantly decreases the stability of orthodontic treatment among cancer survivors, particularly within first year following the end of the treatment [70].

Anticonvulsants, also known as antiepileptic drugs, are a diverse group of pharmacological agents used in the treatment of epileptic seizures. It has been reported in experimental study that Valproic acid and carbamazepine can decrease bone density which may induce accelerated OTM in rats [71]. Nevertheless, Phenytoin did not show any statistically significant effects on the rate of OTM [72], the gingival enlargement that may occur after prolonged use of phenytoin making orthodontic treatment and maintenance of oral hygiene difficult [73].

Bisphosphonates (BPNs) are drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. Previous animal studies have reported the local and systemic effect of BPNs on OTM, which decreases bone resorption, inhibit OTM, and hence delay the orthodontic treatment [74-85]. These findings were further confirmed by the results obtained from case reports, case series, and retrospective cohort studies of orthodontic patients under bisphosphonate medication that exerted forces on teeth led to longer treatment duration, incomplete space closure, poor root parallelism, poor incisor alignment, and wide PDL with tooth mobility in some cases. Therefore, these drugs would be helpful if orthodontic anchorage control was needed during orthodontic treatment [50,86-90].

Vitamin D is a group of fat-soluble secosteroidsresponsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. One of the most important compounds in this group in humans, is vitamin D3 (also known as cholecalciferol ) [91].

Animal studies showed that local injection of vitamin D3 increased the number of osteoclasts, and accelerated OTM [92-95]. Moreover, same findings were found in single randomized clinical trial where the patients treated with different doses of vitamin D3. It was found that locally injected calcitriol, in dose dependent pattern, is clinical and cost effective in increasing OTM among humans [96]. The last medication considered in this review was fluorides. The main function of this medication is the mineralization of bones and teeth. Fluoride has an effect on tissue metabolism, and it increases bone mass and mineral density. It has been found in experimental study on rats that treatment with sodium fluoride during orthodontic treatment inhibits the osteoclastic activity and reduces the number of active osteoclasts, leading to minimizing OTM, and hence lengthening the orthodontic treatment [97,98].

On the other hand, the effect of fluoride on OTM were studied in humans to determine whether high and low fluoride concentrations in drinking water affected the early stages of tooth movement, when heavy and light orthodontic force were applied. The average rate of tooth movement was found to be greater in high fluoride intake patients under both light and heavy orthodontic force application [99].

Conclusion

Orthodontic tooth movement results from a remarkably complicated cascade of events including mechanical and biochemical factors, level of activity of bone cells, modeling and remodeling of the alveolar process in response to mechanical loading. By understanding the effects of common medications on the molecules that enhance or reduce homeostasis in tissues adjacent to the moving tooth subjected to orthodontic forces, orthodontists will imperatively pay more attention to the medical and drug consumption history of each patient before and during orthodontic treatment. The present review showed experimental and few clinical evidences for the effects of many prescriptions and over-thecounter drugs on OTM. Some of these drugs are Promoter drugs for OTM such as Acitominophin, Tenoxicam, PGE1, thyroid and PTH, relaxin, chronic corticosteroids ingestion, TNF inhibitors, anticonvulsants, and Vitamin D3. On the other hand, other drugs have inhibitory effects of tooth movement such as most of the NSAIDs, Calcitonin, Estrogen, Insulin, BPNs, acute Corticosteroids ingestion, IL-1RA, and Integrin inhibitors. Therefore, these suppressor drugs may be effective as an adjunctive orthodontic approach to lessen undesired tooth movement through enhancing anchorage or preventing relapse after OTM. In addition, some drugs like Phenytoin and immunosuppressant drugs might be involved in unwanted orthodontic side effects, such as gingival overgrowth, making orthodontic treatment and maintenance of oral hygiene difficult. Finally, it has become clear that further well-designed human studies are needed to be able to draw an effective conclusion on the effects of various medications on OTM.

Conflict of Interest

The author reports no conflicts of interest in this work. This work has not been published previously and is not under consideration by another journal.

References

1. Diravidamani K, Sivalingam S, Agarwal V. Drugs influencing orthodontic tooth movement: An overall review. J Pharm Bioallied Sci 2012; 4:299-303.
2. Krishnan V, Vijayaraghavan N, Manoharan M, et al. The effects of drug intake by patients on orthodontic tooth movement. Semin Orthod 2012; 18:278-285.
3. Qiao H, Gao Y, Huang Q, et al. The central nucleus of the amygdala lesion attenuates orthodontic pain during experimental tooth movement in rats. Brain Behav 2019; 10.
4. Henneman S, Von den Hoff JW, Maltha JC. Mechanobiology of tooth movement. Eur J Orthod 2008; 30:299-e306.
5. Miller C. AAOM clinical practice statement: Subject: medical history. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 121:618-9.
6. Greenwood M. Essentials of medical history-taking in dental patients. Dent Update 2015; 42:308-315.
7. Piette JD, Rosland AM, Silveira MJ, et al. Medication cost problems among chronically ill adults in the US: Did the financial crisis make a bad situation even worse? Patient Prefer Adherence 2011; 5:187-94.
8. Vyas M, Panesar A. Pharmaceutical marketing communication strategies and its influence on physician prescription preference. Int J Multidisciplinary Res 2019; 9:288–99.
9. Kesselheim AS, Huybrechts KF, Choudhry NK, et al. Prescription drug insurance coverage and patient health outcomes: A systematic review. Am J Public Health 2015; 105:e17-30.
10. Werneck EC, Mattos FS, Da Silva MG, et alEvaluation of the increase in orthodontic treatment demand in adults. Brazilian Dent Sci 2012; 15:47-52.
11. Samsonyanová L, Broukal Z. A systematic review of individual motivational factors in orthodontic treatment: Facial attractiveness as the main motivational factor in orthodontic treatment. Int J Dent 2014; 2014:938274.
12. Howie LD, Pastor PN, Lukacs SL. Use of medication prescribed for emotional or behavioral difficulties among children aged 6-17 years in the United States, 2011-2012. NCHS Data Brief 2014; 1-8.
13. Kebodeaux CD. Prescription and over-the-counter medication record integration: A holistic patient-centered approach. J Am Pharm Assoc 2019; 59:S13–7.
14. Bartzela T, Türp JC, Motschall E, et al. Medication effects on the rate of orthodontic tooth movement: A systematic literature review. Am J Orthod Dentofacial Orthop 2009; 135:16-26.
15. Tyrovola JB, Spyropoulos MN. Effects of drugs and systemic factors on orthodontic treatment. Quintessence Int 2001; 32:365-71.
16. De Carlos F, Cobo J, Diaz-Esnal B, et al. Orthodontic tooth movement after inhibition of cyclooxygenase-2. Am J Orthod Dentofacial Orthop 2006; 129:402-406.
17. De Carlos F, Cobo J, Perillan C, et al. Orthodontic tooth movement after different coxib therapies. Eur J Orthod 2007; 29:596-9.
18. Knop LA, Shintcovsk RL, Retamoso LB, et al. Non-steroidal and steroidal anti-inflammatory use in the context of orthodontic movement. Eur J Orthod 2012; 34:531-5.
19. Sodagar A, Etezadi T, Motahhary P, et al. The effect of celecoxib on orthodontic tooth movement and root resorption in rat. J Dent 2013; 10:303-11.
20. Sari E, Olmez H, Gürton AU. Comparison of some effects of acetylsalicylic acid and rofecoxib during orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2004; 125:310-5.
21. Kirschneck C, Wolf F, Cieplik F, et al. Impact of NSAID etoricoxib on side effects of orthodontic tooth movement. Ann Anat 2020; 232:151585.
22. Shetty N, Patil AK, Ganeshkar SV, et al. Comparison of the effects of ibuprofen and acetaminophen on PGE2 levels in the GCF during orthodontic tooth movement: A human study Prog Orthod 2013; 14:6.
23. Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: Their effects on orthodontic tooth movement. Am J Orthod Dentofac Orthop 2006; 130:364-70.
24. Roche JJ, Cisneros GJ, Acs G. the effect of acetaminophen on tooth movement in rabbits. Angle Orthod 1997; 67:231-236.
25. Arantes GM, Arantes VM, Ashmawi HA, et al. Tenoxicam controls pain without altering orthodontic movement of maxillary canines. Orthod Craniofac Res 2009; 12:14-9.
26. Juneja P, Shivaprakash G, Kambalyal PB. An overview of the role of drugs and systemic factors on orthodontic tooth movement. J Indian Orthodont Society 2008; 42:36-47.
27. Yamasaki K, Shibata Y, Imai S, et al. Clinical application of prostaglandin E1 (PGE1) upon orthodontic tooth movement. Am J Orthod 1984; 85:508-18.
28. Patil AK, Keluskar KM, Gaitonde SD. The clinical application of prostaglandin E1 on orthodontic tooth movement. J Indian Orthod Soc 2005; 38:91-98.
29. Yamasaki K, Shibata Y, Fukuhara T. The effect of prostaglandins on experimental tooth movement in monkeys (Macaca fuscata). J Dent Res 1982; 61:1444-6.
30. Leiker BJ, Nanda RS, Currier GF, et al. The effects of exogenous prostaglandins on orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop 1995; 108:380-388.
31. Sekhavat AR, Mousavizadeh K, Pakshir HR, et al. Effect of misoprostol, a prostaglandin E1 analog, on orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop 2002; 122:542-7.
32. Seifi M, Eslami B, Saffar AS. The effect of prostaglandin E2 and calcium gluconate on orthodontic tooth movement and root resorption in rats. Eur J Orthod 2003; 25:199-204.
33. Kale S, Kocadereli I, Atilla P, et al. Comparison of the effects of 1,25 dihydroxy-cholecalciferol and prostaglandin E2 on orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2004; 125:607-14.
34. Gurton AU, Akin E, Sagdic D, et al. Effects of PGI2 and TxA2 analogs and inhibitors in orthodontic tooth movement. Angle Orthod 2004; 74:526-32.
35. Shirazi M, Dehpour AR, Jafari F. The effect of thyroid hormone on orthodontic tooth movement in rats. J Clin Pediatr Dent 1999; 23:259-64.
36. Seifi M, Hamedi R, Khavandegar Z. The effect of thyroid hormone, prostaglandin E2, and calcium gluconate on orthodontic tooth movement and root resorption in rats. J Dent 2015; 16:35-42.
37. Guan L, Lin S, Yan W, et al. Effects of calcitonin on orthodontic tooth movement and associated root resorption in rats. Acta Odontol Scand 2017; 75:595-602.
38. Alnajar HA, Al Groosh DH. The effects of calcitonin on post-orthodontic relapse in rats. Clin Exp Dent Res 2020; 1-9.
39. Soma S, Iwamoto M, Higuchi Y, et al. Effects of continuous infusion of PTH on experimental tooth movement in rats. J Bone Miner Res 1999; 14:546-54.
40. Soma S, Matsumoto S, Higuchi Y, et al. Local and chronic application of PTH accelerates tooth movement in rats. J Dent Res 2000; 79:1717-24.
41. Lee HS, Heo HA, Park SH, et al. Influence of human parathyroid hormone during orthodontic tooth movement and relapse in the osteoporotic rat model: A preliminary study. Orthod Craniofac Res 2018; 21:125–131.
42. Yamashiro T, Takano-Yamamoto T. Influences of ovariectomy on experimental tooth movement in the rat. J Dent Res 2001; 80:1858-61.
43. Haruyama N, Igarashi K, Saeki S, et al. Estrous-cycle-dependent variation in orthodontic tooth movement. J Dent Res 2002; 81:406-10.
44. Arslan SG, Arslan H, Ketani A, et al. Effects of estrogen deficiency on tooth movement after force application: an experimental study in ovariectomized rats. Acta Odontol Scand 2007; 65:319–23.
45. Sirisoontorn I, Hotokezaka H, Hashimoto M, et al. Tooth movement and root resorption; the effect of ovariectomy on orthodontic force application in rats. Angle Orthod. 2011; 81:570-7.
46. Sirisoontorn I, Hotokezaka H, Hashimoto M, et al. Orthodontic tooth movement and root resorption in ovariectomized rats treated by systemic administration of zoledronic acid. Am J Orthod Dentofacial Orthop 2012; 141:563-73.
47. Celebi AA, Demirer S, Catalbas B, et al. Effect of ovarian activity on orthodontic tooth movement and gingival crevicular fluid levels of interleukin-1β and prostaglandin E(2) in cats. Angle Orthod 2013; 83:70-5.
48. Seifi M, Ezzati B, Saedi S, et al. The effect of ovariectomy and orchiectomy on orthodontic tooth movement and root resorption in wistar rats. J Dent 2015; 16:302-9.
49. Tan Z, Zhao Q, Chen Y. The mutual effects between orthodontic tooth movement and estrous cycle or estrogen1. Biological Rhythm Research 2010; 41:75–81.
50. Schwartz JE. Some drugs affect tooth movement. Am J Orthod Dentofacial Orthop 2005; 127:644.
51. Wang B, Yang X, Zhou J, et al. Orthodontic tooth movement at different stages of adolescent female menstrual cycle. J Clin Rehabilitative Tissue Eng Res 2014; 18:2332–2337.
52. Yang X, Dai H, Wang B, et al. Preliminary study on the best-exerted force chance in the female menstrual cycle. West China J Stomatol 2014; 32:252-5.
53. Liu ZJ, King GJ, Gu GM, et al. Does human relaxin accelerate orthodontic tooth movement in rats? Ann Acad Sci 2005; 1041:388-94.
54. Stewart DR, Sherick P, Kramer S, et al. Use of relaxin in orthodontics. Ann Acad Sci 2005; 1041:379-87.
55. Madan MS, Liu ZJ, Gu GM, et al. Effects of human relaxin on orthodontic tooth movement and periodontal ligaments in rats. Am J Orthod Dentofacial Orthop 2007; 131:8.e1-10.
56. Hirate Y, Yamaguchi M, Kasai K. Effects of relaxin on relapse and periodontal tissue remodeling after experimental tooth movement in rats. Connect Tissue Res 2012; 53:207–19.
57. McGorray SP, Dolce C, Kramer S, et al. A randomized, placebo-controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short-term stability. Am J Orthod Dentofacial Orthop 2012; 141:196-203.
58. Braga SM, Taddei SR, Andrade I, et al. Effect of diabetes on orthodontic tooth movement in a mouse model. Eur J Oral Sci 2011; 119:7-14.
59. Villarino ME, Lewicki M, Ubios AM. Bone response to orthodontic forces in diabetic Wistar rats. Am J Orthod Dentofacial Orthop 2011; 139:S76–82.
60. Kalia S, Melsen B, Verma C. Tissue reaction to orthodontic tooth movement in acute and chronic corticosteroid treatment. Orthod Craniofac Res 2004; 7:26-34.
61. Verna C, Hartig LE, Kalia S, et al. Influence of steroid drugs on orthodontically induced root resorption. Orthod Craniofac Res 2006; 9:57–62.
62. Anjusha B, Seema G. Immunosuppressant drugs: Role in periodontium. J Scientific Dent 2016; 6:60-66.
63. Salla JT, Taddei SR, Queiroz-Junior CM, et al. The effect of IL-1 receptor antagonist on orthodontic tooth movement in mice. Arch Oral Biol 2012; 57:519-24.
64. Andrade I, Silva TA, Silva GA, et al. The role of tumor necrosis factor receptor type 1 in orthodontic tooth movement. J Dent Res 2007; 86:1089-94.
65. Ohori F, Kitaura H, Marahleh A, et al. Effect of TNF-α-induced sclerostin on osteocytes during orthodontic tooth movement. J Immunol Res 2019; 2019:9716758.
66. Talic NF, Evans C, Zaki AM. Inhibition of orthodontically induced root resorption with echistatin, an RGD-containing peptide. Am J Orthod Dentofacial Orthop 2006; 129:252-60.
67. Dolce C, Vakani A, Archer L, et al. Effects of echistatin and an RGD peptide on orthodontic tooth movement. J Dent Res 2003; 82:682-6.
68. Reedijk AMJ, Kremer LC, Visser O, et al. Increasing incidence of cancer and stage migration towards advanced disease in children and young adolescents in the Netherlands, 1990-2017. Eur J Cancer 2020; 134:115-126.
69. Krishnan V, Davidovitch Z. The effect of drugs on orthodontic tooth movement. Orthod Craniofac Res 2006; 9:163-71.
70. Mitus-Kenig M, Derwich M, Czochrowska E, et al. Cancer survivors present significantly lower long-term stability of orthodontic treatment: a prospective case-control study. Eur J Orthod 2021; 12.
71. Akhoundi MSA, Sheikhzadeh S, Mirhashemi A, et al. Decreased bone density induced by antiepileptic drugs can cause accelerated orthodontic tooth movement in male Wistar rats. Int Orthod 2018; 16:73-81.
72. Pithon MM, de Oliveira Ruellas AC. Clinical and radiographic evaluation of phenobarbital (Gardenal®) influence on orthodontic movement: A study in rabbits. Rev Dent Press Ortodon Ortop Facial 2008; 13:34-42.
73. Karsten J, Hellsing E. Effect of phenytoin on periodontal tissues exposed to orthodontic force-an experimental study in rats. Br J Orthod 1997; 24:209-15.
74. Adachi H, Igarashi K, Mitani H, et al. Effects of topical administration of a bisphosphonate (risedronate) on orthodontic tooth movements in rats. J Dent Res 1994; 73:1478-86.
75. Igarashi K, Mitani H, Adachi H, et al. Anchorage and retentive effects of a bisphosphonate (AHBuBP) on tooth movements in rats. Am J Orthod Dentofacial Orthop 1994; 106:279-89.
76. Igarashi K, Adachi H, Mitani H, et al. Inhibitory effect of the topical administration of a bisphosphonate (risedronate) on root resorption incident to orthodontic tooth movement in rats. J Dent Res 1996; 75:1644-9.
77. Alatli I, Hellsing E, Hammarström L. Orthodontically induced root resorption in rat molars after 1-hydroxyethylidene-1,1-bisphosphonate injection. Acta Odontol Scand 1996; 54:102-108.
78. Kim TW, Yoshida Y, Yokoya K, et al. An ultrastructural study of the effects of bisphosphonate administration on osteoclastic bone resorption during relapse of experimentally moved rat molars. Am J Orthod Dentofac Orthop 1999; 115:645-53.
79. Liu L, Igarashi K, Haruyama N, et al. Effects of local administration of clodronate on orthodontic tooth movement and root resorption in rats. Eur J Orthod 2004; 26:469-73.
80. Keles A, Grunes B, Difuria C, et al. Inhibition of tooth movement by osteoprotegerin vs. pamidronate under conditions of constant orthodontic force. Eur J Oral Sci 2007; 115:131-6.
81. Fujimura Y, Kitaura H, Yoshimatsu M, et al. Influence of bisphosphonates on orthodontic tooth movement in mice. Eur J Orthod 2009; 31:572-7.
82. Karras JC, Miller JR, Hodges JS, et al. Effect of alendronate on orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop 2009; 136:843-7.
83. Choi J, Baek SH, Lee JI, et al. Effects of clodronate on early alveolar bone remodeling and root resorption related to orthodontic forces: A histomorphometric analysis. Am J Orthod Dentofacial Orthop 2010; 138:548.e1-8.
84. Kaipatur NR, Wu Y, Adeeb S, et al. Impact of bisphosphonate drug burden in alveolar bone during orthodontic tooth movement in a rat model: a pilot study. Am J Orthod Dentofacial Orthop 2013; 144:557-67.
85. Venkataramana V, Chidambaram S, Reddy BV, et al. Impact of bisphosphonate on orthodontic tooth movement and osteoclastic count: An animal study. J Int Oral Health 2014; 6:1-8.
86. Krieger E, d'Hoedt B, Scheller H, et al. Orthodontic treatment of patients medicated with bisphosphonates-a clinical case report. J Orofac Orthop 2013; 74:28-39.
87. Lotwala RB, Greenlee GM, Ott SM, et al. Bisphosphonates as a risk factor for adverse orthodontic outcomes: a retrospective cohort study. Am J Orthod Dentofacial Orthop 2012; 142:625–634.e623.
88. Rinchuse DJ, Rinchuse DJ, Sosovicka MF, et al. Orthodontic treatment of patients using bisphosphonates: a report of 2 cases. Am J Orthod Dentofacial Orthop 2007; 131:321-6.
89. Zahrowski JJ. Optimizing orthodontic treatment in patients taking bisphosphonates for osteoporosis. Am J Orthod Dentofacial Orthop 2009; 135:361–74.
90. www.nihcm.org
91. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014; 21:319–29.
92. Collins MK, Sinclair PM. The local use of vitamin D to increase the rate of orthodontic tooth movement. Am J Orthod 1988; 94:278–84.
93. Takano-Yamamoto T, Kawakami M, Yamashiro T. Effect of age on the rate of tooth movement in combination with local use of 1,25(OH)2D3 and mechanical force in the rat. J Dent Res 1992; 71:1487-92.
94. Kale S, Kocadereli I, Atila P, et al. Comparison of the effects of 1,25 –dehydroxycholecalciferol and prostaglandin E2 on orthodontic tooth movement. Am J Orthod 2004; 125:607-14.
95. Kawakami M, Takamo-Yamamoto T. Local injection of 1,25-dihydroxyvitamin D3 enhanced bone formation for tooth stabilization after experimental tooth movements in rats. J of Bone and Mineral Metabolism 2004; 22:541-6.
96. Al-Hasani N, Glares G, Albustani A, et al. Clinical efficacy of locally injected calcitriol in orthodontic tooth movement. Int J Pharm Pharm Sci 2011; 3:139-43.
97. Hellsing E, Hammarström L. The effects of pregnancy and fluoride on orthodontic tooth movements in rats. Eur J Orthod 1991; 13:223-30.
98. Gonzales C, Hotokezaka H, Karadeniz EI, et al. Effects of fluoride intake on orthodontic tooth movement and orthodontically induced root resorption. Am J Orthod Dentofacial Orthop 2011; 139:196-205.
99. Karadeniz EI, Gonzales C, Elekdag-Turk S, et al. The effect of fluoride on orthodontic tooth movement in humans. A two- and three-dimensional evaluation. Aust Orthod J 2011; 27:94-101.