Preface

In recent years, the practice of orthodontics has undergone major technological developments, including artificial intelligence. It is now more important to develop the necessary skills to understand the functioning and impact of these technologies on orthodontics. This should help identify gaps in our understanding of emerging technologies and new trends.

Artificial intelligence and digitalization are powerful tools that offer solutions to unresolved and poorly managed challenges. New trends in orthodontics make use of the advances that are being made in digital and clinical research. The finesse and sophistication of the techniques used in this discipline should allow the practice of orthodontics to defy the laws of nature.

This book explores current trends in orthodontics.

Section 1 consists of four chapters that focus on current evidence on tooth movement. Chapter 1 discusses biomarkers in saliva and gingival crevicular fluid during orthodontic treatment. Chapter 2 highlights the symbiosis between orthodontics and periodontics. Chapter 3 provides an update on some current methods of accelerating orthodontic dental movements. Chapter 4 explores the risk of root resorption during orthodontic treatment.

Section 2, which deals with digitization and workflow, includes four chapters that address issues related to modelization, workflow in an orthodontic practice, and the use of digital set-up for both orthodontic and orthognathic surgery planning.

Section 3 is dedicated to orthodontic techniques. It contains seven chapters covering recent trends in clinical techniques such as the use of bone screws, the predictability of orthodontic movement by aligner, the role of the orthodontist in the management of sleep apnea, and the assessment of orthodontic pain perception.

The final section deals with early treatment and includes three chapters highlighting the importance of the place of clinical treatments in our therapeutic arsenals.

I am grateful to the contributing authors for the science, creativity, time, and effort they put into their chapters.

> **Farid Bourzgui, D.M.D. MSc** Professor, Department of Orthodontics, Dental School, Hassan II University of Casablanca, Casablanca, Morocco

Section 1

## Current Evidence on Tooth Movement

#### **Chapter 1**

## Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid

*Sagar S. Bhat, Ameet V. Revankar and Shrinivas M. Basavaraddi*

#### **Abstract**

Several biologically active substances representing the bone deposition and resorption processes are released following damage to periodontal tissue during orthodontic movement. Biomarkers are by definition objective, quantifiable characteristics of biological processes. The analysis of saliva/salivary fluid and Gingival crevicular fluid (GCF) may be an accepted way to examine the ongoing biochemical processes associated with bone turnover during orthodontic tooth movement and fixed orthodontic treatment pain. Assessing the presence of these salivary physiological biomarkers would benefit the clinician in appropriate pain diagnosis and management objectively of various problems encountered during the orthodontic procedures and for better outcome of biomechanical therapy. Due to lack of standardized collection procedure, even though well accepted by patients, saliva is often neglected as a body fluid of diagnostic and prognostic value. A literature search was carried out in major databases such as PubMed, Medline, Cochrane library, Web of Science, Google Scholar, Scopus and EMBASE for relevant studies. Publication in English between 2000 to 2021 which estimated Saliva markers as indicators of orthodontic tooth movement was included. The list of biomarkers available to date was compiled and is presented in table format. Each biomarker is discussed separately based on the available and collected evidences. Several sensitive salivary and GCF biomarkers are available to detect the biomechanical changes occurring during orthodontic tooth movement and pain occurring during fixed orthodontic therapy. Further focussed research might help to analyze the sensitivity and reliability of these biomarkers or cytokines, which in turn can lead to the development of chairside tests to assess the pain experienced by patients during orthodontic therapy and finally the outcome of the fixed orthodontic therapy.

**Keywords:** fixed orthodontic therapy, molecular biomarkers, saliva, GCF, objectivity

#### **1. Introduction**

Biomarkers are—quantifiable criteria of biological processes that provide indications objectively. During the orthodontic procedure, the analysis of saliva/salivary

fluid and Gingival crevicular fluid (GCF) may be examined to monitor biological process/progress.

In the orthodontic treatment, emphasis is on the point of patient care for the best results, by growth modification of the craniofacial region along with alveolar bone remodeling during fixed orthodontic procedure [1]. Induction of biologically active compounds occur inside the periodontium due to the orthodontic treatment which eventually induces cellular response in different microenvironment for biological response [1]. Orthodontic treatment is considered successful by three major factors namely periodontal health, oral hygiene and optimal orthodontic forces [1, 2]. Availability of newer techniques have reduced lateral effects like, pain, periodontal diseases, abbreviate the treatment period and limit iatrogenic damages like root resorption and development of nonvital teeth. The sequential events that occur following the orthodontic tooth movement (OTM) can be illustrated by the released molecules, regarded as biomarkers [1, 2]. Biomarkers are attributes that can be quantified, these can the indicators of biological processes which may be normal or pathogenic and/or other metabolic processes [3, 4]. Other important features of the biomarkers are specificity and sensitivity, which will have the ability to notify the biological conditions/changes occurring during any process/procedures [4]. Adequate knowledge about the cellular and biological processes makes it easier to understand the biological mechanics that can shorten the treatment time avoiding the detrimental effects linked to the orthodontic treatment due to its objective characteristics [3, 4].

In the orthodontic treatment, emphasis is on the point of patient care for the best results, by growth modification of the craniofacial region along with alveolar bone remodeling during fixed orthodontic procedure [1]. Induction of biologically active compounds occur inside the periodontium due to the orthodontic treatment. This induces cellular response in different microenvironment for biological response [1]. Orthodontic treatment is considered successful by three major factors namely periodontal health, oral hygiene and optimal orthodontic forces [1, 2]. Availability of newer techniques have reduced lateral effects like, pain, periodontal diseases, abbreviate the treatment period and limit iatrogenic damages like root resorption and development of nonvital teeth. The sequential events that occur following the orthodontic tooth movement (OTM) can be illustrated by the released molecules, regarded as biomarkers [1, 2]. Biomarkers are attributes that can be quantified, these can be the indicators of biological processes which may be normal or pathogenic and/ or other metabolic processes [3, 4]. Other important features of the biomarkers are specificity and sensitivity, which will have the ability to notify the biological conditions/changes occurring during any process/procedures [4]. Adequate knowledge about the cellular and biological processes makes it easier to understand the biological mechanics that can shorten the treatment time avoiding the detrimental effects linked to the orthodontic treatment due to its objective characteristics [3, 4].

Forces induced by orthodontic therapy stimulates periodontium cells to release many chemical intermediaries like cytokines. The cytokines contribute immensely in the periodontal and alveolar bone remodeling, bone resorption and new bone deposition [5]. During the process of bone metabolism, the biomarkers are released into the circulation which indicates bone remodeling activity comprising of both osteoblastic deposition and osteoclastic resorption. Systemic circulation in the orthodontic patients indicates the skeletal maturity, this can be detected using biomarkers. And their detection locally, in saliva and gingival crevicular fluid (GCF), indicates the advancement of orthodontically induced alveolar bone remodeling [4]. Many research studies have been executed, suggestive of presence of array of molecules

#### *Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*

indicating the skeletal growth turnover. The assessment of molecular biomarkers of bone remodeling in the body fluids such as saliva, GCF etc., would guide the clinicians to arrive at a better treatment plan for orthodontic therapy at the ideal time and estimate the advent of the treatment [4, 5].

Saliva is considered a medium for the microbes and transport, which is affected by status of oral health and the quantity and types of bacteria present in the oral cavity. It is also comprising of innate immune factors and various salivary defense proteins. The fixed orthodontic therapy induces site-specific bone resorption and formation and cytokines which are released from periodontal ligament (PDL) cells.

The complex combination of serum, host inflammatory cells, structural cells of oral bacteria and the periodontium leads to the formation of the GCF which arises from the plexus of gingival blood vessels in the gingival corium, lying underneath to the epithelial lining of the dentogingival space. It can be isolated from healthy sulcus as well [3, 5].

The origination of GCF components is from blood, subgingival plaque and host tissues. Presence of the transudate of the gingival interstitial fluid due to the osmotic gradient in the healthy periodontium is observed. There will be a steady increase in the volume with inflammation and greater capillary permeability [6]. Previously GCF was known as continuous transudate but currently it is considered as inflammatory transudate [7]. GCF comprises of host-derived substances which includes cytokines, antibodies, tissue degradation products and enzymes [8]. The inflammatory exudate increases by more than 5-fold during the inflammatory conditions, such as periodontal disease and gingivitis [9].

Orthodontic forces result in a condition which can be described as a consequence of the orthodontic force, a condition persists that involves a series of inflammation and repair intended at converting it into normal tissues and [10] according to some reports GCF reflects the immune reactions arising from both orthodontic force application and periodontitis [11, 12].

Nowadays many biomarkers are detected using saliva. It was recently discovered that several new isoforms for Nerve Growth Factor (NGF), Brain derived Neurotropic Factor (BDNF) and Calcitonin gene-related peptide (CGRP) were found in the saliva [3]. Identification of these isoforms can be utilized to develop subtle ways that can be considered to be methods to detect and analyze markers related to pain. The nuclear factor kappa B ligand and of the nuclear factor kappa B/osteoprotegerin (RANK/ RANKL/OPG) signaling pathway being one of the several key factors that initiated the commencement of osteoclasts. The recruitment, differentiation and survival of osteoclasts are facilitated by the osteoblasts [12] which secretes a molecular biomarker RANKL. Induction of differentiation of immature osteoclasts into functional cells are due to the binding of RANKL with RANK (expressed at the surface of the osteoclast). Osteoblasts produce OPG which acts as a soluble receptor for RANKL. This inhibits the terminal stages of osteoclast differentiation [12].

Pain and discomfort are inevitable during orthodontic treatment [13]. Conventionally, the degree of pain is assessed subjectively using many pain scales [14]. Assessing pain objectively using salivary physiological biomarkers would benefit the clinician for appropriate pain diagnosis and management [13, 15]. The role of saliva in the diagnostic and prognostics is side-lined due to unavailability of a standardized collection procedure, even though well accepted by patients [3].

The neuropeptide, NGF protects the neurons and regenerates them. It plays an important role in hyperalgesia and its concentration increases during inflammation which is up regulated in response to noxious stimuli [16]. The occurrence and development of pain and hyperalgesia are credited to be due to the role of CGRP and BDNF. CGRP and BDNF has been implicated in migraine and headache based on increased saliva and plasma concentrations during active pain periods [16, 17].

Only a few studies have investigated the levels of these above-mentioned neuropeptides in saliva [16–18]. Several patients describe much longer periods of pain and discomfort which are common during the first 1 or 2 days of the orthodontic treatment. Scheurer et al. reported that even after 7 days of insertion of a fixed appliance, 25% of all investigated patients still reported pain [19]. According to measurements at 4 h and 24 h, the intensity of pain generally increases with time, but falls to normal levels after 7 days of the orthodontic treatment [19]. Biomarkers can be used to characterize the sequential events following OTM. The rate, amount, and the activity of the released substances/biomarkers indicates the activity of individual cells and the metabolic activity involved in the tissues and organs [1]. These potential biological markers can be collected from different tissue samples. The sampling is done as per the required biomarker and the biological processes to be studied [1, 20]. Several possible biomarkers representing many of these biological changes during specific phenomenon like pain experienced during orthodontic treatment pain, bone remodeling, inflammation and root resorption have also been proposed [20]. The clinical application can be developed from the knowledge of biomarkers that can accelerate the orthodontic treatment as well.

#### **2. Phases of orthodontic tooth movement (OTM)**

There are two types of tooth movement namely: OTM and Physiological tooth movement. The physiological tooth movement occurs slowly in the cancellous bone in buccal direction or the cortical bone [21]. In contrast, OTM can occur both rapidly or slowly, it depends on the rate, physical characteristics and amount of the force application and the biological response of the Periodontal Ligament (PDL) [22]. The orthodontic force application can change the dental and paradental tissues, including the PDL, alveolar bone, dental pulp and gingiva resulting in pressure and tension sites at the tooth region [23].

Perinetti et al. [24] through their research study state that, one bone remodeling cycle involves four main phases namely: activation, bone resorption, reversal, and bone formation. Recent studies have exhibited that several enzymes are expressed during these phases which have been designated as biomarkers during bone remodeling namely Tartrate-resistant Acid Phosphatase (TRAP), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH), Aspartate Aminotransferase (AST), and many more.

Orthodontic therapy involves the supervision, guidance and correction of growing and maturing dentofacial structures which is based on the principle that if the teeth is subjected to prolonged pressure, consequently it will lead to remodeling of the bone. This OTM is exemplified by the remodeling of dental and paradental tissues [21].

In 1962, Burstone [25] stated the three phases of tooth movement, when rates of tooth movement are plotted against time:


*Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*


#### **Table 1.**

*Phases of orthodontic tooth movement [27].*


Pilon et al. [27, 28] divided the curve of tooth movement into four phases (**Table 1**). The GCF of tooth movement contain the biomarkers that indicate these phases and signaling pathways. Considerable increased levels of concentrations of cytokines responsible for inflammation and prostaglandins are observed.

The tissue changes that are involved during OTM includes compression region (which involves osteoblasts), tension region (which involves osteoclasts), pulp tissues and dental root [29]. Several possible biological factors or biomarkers representing these biological changes during particular phenomenon that is, bone remodeling. Inflammation and root resorption, have been identified. Similarly, lactic acid dehydrogenase (LDH) and dentin sialophosphoprotien (DSPP) are also potentially observed. A research study suggests that using sampling from four different sampling procedures, that is, saliva, GCF, tissue (biopsy), and serum, the biomarkers indicative of the ongoing biological processes can be identified [29]. The suggested amount and concentration of biomarkers during OTM are the best and practical sampling or testing procedure indicative of the biological phenomenon. The amount of precise force application and duration that should be used for each tooth during OTM can be decided based on the knowledge of these biomarkers. Ultimately, it produces an optimal treatment with mild side effects or accelerate the treatment [29].

#### **3. Saliva and biomarkers**

Most of the laboratory diagnostic procedures involves the analysis of the cellular and biochemical constituents of the blood. Saliva can be used in the diagnosis of

several diseases. This can be feasible and valuable for children and older adults due to the ease of collection of the fluid [30]. Saliva can be classified into two types: glandspecific saliva and whole saliva. It is feasible to collect saliva specific to different glands from individual salivary glands namely: parotid, submandibular, sublingual and minor salivary glands. Since the secretions from both the submandibular and sublingual salivary glands enter the oral cavity only through single duct known as Wharton's duct [31], hence collection of the saliva from submandibular and sublingual glands separately is challenging.

Orthodontists generally aims to gain ideal orthognathic conditions with fewer treatment times i.e.; shorter treatment time with longer treatment intervals with fewer appointments [32]. Conversely, when heavier force is applied to accelerate tooth movement, the oxygen tension in the periodontium will be conceded due to reduced vascular supply [33]. This will risk or expose the healthy supporting alveolar bone and periodontal structure leading to the slow progress of the treatment. In order to supervise the orthodontic tooth movement in a non-invasive approach in human beings, the alterations that appear during the examination of the profile and levels of various cytokines, enzymes, growth factors, and proteoglycans in saliva and GCF. Evidences support the elevated levels of several biomarkers or cytokines, that is, interleukin (IL)-1β, IL-6, epidermal growth factor (EGF), prostaglandin (PG) and proteoglycans, in the saliva and GCF [34–36]. Components of GCF namely ALP, TRAP, LDH and AST have been recognized to be potential biomarkers during OTM [37–40]. Study conducted by Shahrul et al. [41] showed that ALP, TRAP, and LDH also existed in saliva. Orthodontic treatment using a surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) approach the effects of the orthodontic treatment on salivary proteins has been performed as per the study by Zhang et al. [42]. The outcome of this approach determined the relatively low molecular weight proteins but not the identity of these proteins. Only the expression profile was cross-examined.

Saliva has protective and anti-microbial properties and contains a variety of growth factors [43, 44]. Saliva helps in the easy digestion of the food since it has lubricating functions [45]. The role of saliva and different salivary constituents responsible for its functions are summarized below in **Table 2** [30].

Salivary protein concentration ranges from 2 to 5 mg/mL which constitutes about 3% of the protein concentration of blood. Numerous proline-rich glycoproteins, immunoglobulin A and amylase are the major secretory proteins of the parotid glands, other antibacterial salivary proteins include lysozymes, peroxidases and lactoferrin. Submandibular and sublingual glands contribute mucous glycoproteins to oral fluid. Pathological analysis can be carried out using the saliva produced by specific glands. Since saliva contains constituents of other serum, whole saliva is used for the diagnosis of systemic diseases. The gingival fluid flows into the oral cavity. The constituents of gingival fluid can be derived from the local vasculature of the salivary glands. Analysis of saliva perhaps be useful for the diagnosis of different hereditary disorders, endocrine disorders, malignant, autoimmune and infectious diseases, as well as in the assessment of therapeutic levels of drugs and in the monitoring of illicit use of drugs.

Evaluation of the fluids from the individual salivary glands can help in detecting the infection and obstruction. Mixture of oral fluids can be present in the whole saliva or mixed. This may include the secretions from both the major and minor salivary glands including several constituents of non-salivary origin. The fluids of nonsalivary origin may include expectorated bronchial and nasal secretions, GCF, serum and blood derivatives from oral wounds [46–49].

Functions salivary components involved:

1.Protective functions


2.Food- and speech-related functions:


#### **Table 2.**

*The major functions of saliva [30].*

Evaluation of the systemic disorders is done by the salivary analysis of the whole saliva collected with or without stimulation. There are two procedures to collect the saliva using stimulation, they are gustatory stimulation (i.e., application of citric acid on the subject's tongue [50]; or by masticatory action (i.e., from a subject chewing on paraffin). Constituents, pH and concentration of the fluid depends on the quantity of saliva collected by the stimulation method. Unstimulated saliva is collected without gustatory, masticatory, exogenous or mechanical stimulation. The factors that affect the salivary flow rate depends on the degree of hydration, olfactory stimulation, exposure to light, body positioning, seasonal and diurnal factors. There are two appropriate methods to collect the saliva, they are by the draining or drooling method, in which saliva can drip off the lower lip. In the second methods which is the spitting method the subject expectorates saliva into a test tube [51].

Specialized epithelial cells make up the salivary glands, based on their structure, these cells can be divided into two specific regions: the ductal and acinar regions. During the primary salivary secretion, the ductal cells actively absorb most of the Na+ and Cl− ions and secrete small amounts of K+ and HCO3 − and some proteins. This modifies the primary salivary secretion into a hypotonic final salivary secretion when it enters the oral cavity [52].

In the acinar region most of the protein synthesis and secretion takes place, this is where the oral fluid is generated as well. The amino acids enter the acinar cells through active transport. After the intracellular protein synthesis, secretory stimulation releases most proteins, these are stored in storage granules [53, 54]. Description of three models for acinar fluid secretion area are available, which include the active passage of anions into the lumen and passage of osmotic gradient water from the interstitial fluid to the salivary lumen [55, 56]. Fluid obtained at the initial stage is isotonic in nature. This is derived from the local vasculature whereas the acinar cells

are water-permeable, and the ductal cells are impermeable. The autonomic nervous system(sympathetic and parasympathetic system) controls the salivary secretion and its signaling mechanism involves the binding of neurotransmitter (primarily acetylcholine and norepinephrine) to plasma membrane receptors and signal transduction *via* guanine nucleotide-binding regulatory proteins (G-proteins) and activation of intracellular calcium signaling mechanisms [52, 57–59]. A few diagnostic uses of saliva like viral infections, including hepatitis and HIV, and in the detection of certain endocrine disorders have been demonstrated.

Certain markers in the serum cannot be relied upon but with the salivary samples, the levels of certain markers are consistent than its manifestation. The components of the biomarker molecules and normal saliva have similar physicochemical characteristics. Hence the diffusion of lipophilic molecules into the saliva is easier than the lipophobic molecules. The molecules involved in the biological processes reach the saliva through different mechanisms. Hence extraction of molecules using the methods such as ultrafiltration and active transport have also been proposed for many substances recently. Whereas previously passive diffusion was the most common mechanism for drugs and hormones.

For accurate diagnosis, an appropriate relationship must be established between the biomarker concentration in serum and its concentration in saliva. Normalcy in the salivary gland function is necessary for the collection of salivary molecules or cytokines with diagnostic value. The flow rate of the saliva and its concentration is expected to vary between individuals and in the same individual under various conditions. Erratic collection of the serum markers is possible in the whole saliva due to the oral wounds and through GCF flow. Effectiveness of such samples may be questionable as these parameters may interfere in the correct diagnosis based on the salivary constituents [60]. Apart from some of the systemic disorders, other factors like the medications and radiation will affect salivary gland function, the quantity and consequently the composition of saliva [61, 62]. The whole saliva may contain some proteolytic enzymes that come from the host and there may be presence of enzymes derived from the oral microorganisms [63]. These enzymes can affect the stability, consistency and reliability of certain diagnostic biomarkers. Degradation of some molecules happened during intracellular diffusion into saliva. The diagnostic functional value of the marker may be affected by any condition or medication.

Despite the limitations of saliva to be used for diagnostic purposes, it is becoming popular as per the evidences suggested by many recent researches. Commercially available salivary diagnostic tests are currently being used by patients, researchers, and clinicians. Objective and qualitative detection that is the detection of the presence or absence of a biomarker using saliva is possible but it is not a feasible option for the quantitative diagnosis. Saliva also plays a major role in eliciting and monitoring the hormone levels, especially steroids which facilitates repeated sampling in short time intervals, which may be particularly important for hormone monitoring and avoiding patient and clinician compliance problems.

Nevertheless, before a salivary diagnostic test can replace more conventional methods, the diagnostic values of a new salivary test must be compared with the goldstandard. The effectiveness of a new test must be determined in terms of specificity, sensitivity, reproducibility and the correlation with an established disease diagnostic criterion.

The known functions of proteins identified by proteomic analysis are summarized in **Table 3**. Using the proteomics approaches, these proteins have been identified previously [32, 64, 65]. There has been no reports of the changes in the protein

*Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*


#### **Table 3.**

*Summary of identified proteins and their known functions [30].*

expression in relation to the orthodontic treatment, tooth movement and its forces. The **Table 3** lists the functions of proteins and their predictive role in the OTM.

#### **3.1 Protein S100-A9**

During acute and chronic inflammation Protein S100-A9 (S100-A9) is a calciumbinding protein that functions as a proinflammatory mediator. It is found in high concentration in an inflamed tissue. Previous research described that S100-A9 was concerned in chondrocytic and osteoblastic maturation, matriceal calcification and was noticeable in osteoclasts [66]. Therefore, the presence of osteoclast indicates an active process of bone resorption. It is also been stated that it regulates cartilage destruction and joint inflammation during antigen-induced arthritis [67]. A recent study showed an obvious downregulation of S100-A9 protein, this indicates that there may not be an involvement of the protein during bone resorption in fixed orthodontic tooth movement. Its involvement may be in the inflammatory conditions as suggested by the data from the previous study. As per the study, on day 14 of the treatment, the inflammatory process was not active. The orthodontic treatment for 14 days resulted in the downregulation of this above protein indicated by the suppression of inflammation.

#### **3.2 Immunoglobulin J chain (IgJ)**

Immunoglobulin J chain (IgJ) is a constituent of IgA or IgM, whereas Ig Alpha-1 chain C region (IgAC) is a major immunoglobulin class in the body secretions.

Both are common elements of the immune response in humans. Acute inflammatory responses were noticed in the periodontal tissues surrounding the mechanically stressed teeth, in the early phase of the OTM [24]. Recent study also exhibited an obvious downregulation of both IgAC and IgI after 14 days of the fixed orthodontic therapy. Previous study also did not show any increase of LDH after 14 days of orthodontic activation [41]. After these studies researchers suggested that no further inflammation had occurred at that period.

#### **3.3 Cysteine-rich secretory protein 3 precursor (CRISP-3)**

CRISP-3 shows the presence of the exocrine secretion and secretory granules of neutrophil in them. It has notable functions in innate immunity [68] and it is a potential biological marker for prostate cancer [69]. According to the results from the recent study after 14 days of orthodontic treatment, the presence of this protein was noticed. There is not much clarity regarding its relationship with orthodontic tooth movement.

#### **3.4 Serum albumin precursor (ALB)**

ALB and hemoglobin subunit beta (HBB) are serum proteins. These serum proteins are responsible for the increase in subjects with periodontal disease [70]. ALB is considered as a major zinc transporter in the plasma which regulates the colloidal osmotic pressure of blood [71]. The HBB is a subunit of hemoglobin containing two beta units and four subunits with two alpha. Transport of oxygen from the lung to different peripheral tissues involves the alpha and beta subunit carrying an ioncontaining molecule (heme) in each of them [72]. HBB is commonly found in the red blood cells (RBCs) but its function(s) in saliva is still unknown. Recent study showed that ALB was present only at day 0 of treatment. And its role(s) in orthodontic tooth movement is also still unclear.

#### **3.5 Protein: 14-3-3 σ**

On Day 0, an adaptor protein—14-3-3 *σ* also known as epithelial cell marker protein 1 or stratafin (SFN) was found to be present. This binds to many partners and results in the modulation of the activity of the binding partner(s). In several types of human cancers, loss of protein 14-3-3 *σ* expression has been observed suggesting its role as a tumor suppressor protein [73]. However, there is lack of evidence on the role of SFN protein in inflammation or bone resorption and formation, and the role(s) it may play during fixed orthodontic tooth movement.

Orthodontic and dentofacial orthopedic therapeutic appliances used in the treatment and correction of various maxillofacial and dento-maxillary anomalies with skeletal and dental problems most frequently believe that the orthodontic force application of high intensity can induce a localized inflammatory process around the tooth and tooth supporting structures. Due to the presence of this inflammatory process there is an increased synthesis of free radicals secondarily produced which is followed by the oxidative stress [74]. In the literature till date, there are very limited number of human studies and evidences on the oxidative stress and oxidative damage that may occur due to an aseptic inflammation in tissues caused because of orthodontic tooth movements [74].

#### *Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*

A recent study performed in 2009 by Olteanu et al. [60] compared and determined the amount of oxidative stress markers in the saliva of patients, they were treated using orthodontic appliances for a predefined stipulated time period. The time periods that were predefined for determination were: before and after 1 h of treatment, 24 h and 7 days after the initiation of the treatment. At 24 h, maximum variation was observed in the concentrations of the saliva markers of the oxidative stress for ceruloplasmin and malondialdehyde (MDA). And for the hydrogen donors at one hour respectively, and at the 7 days from the placing of an appliance, the concentrations of markers were similar to the values observed in the initial phase of the tests. Concentration of saliva markers for oxidative stress showed changes but this cannot prove pathological processes prevalent in the patients with orthodontic appliances at the level of the oral cavity.

Recently, the research study performed using saliva by Ozcan et al. [75] had the objective to evaluate the changes in some oxidative stress markers for the determining of oxidative stress damage that occurs in the process of bone and tissue remodeling, including dysfunction of periodontal tissue caused by orthodontic tooth movement. At certain time intervals, the unstimulated saliva samples of patients with fixed orthodontic appliances were collected. The time intervals followed were: just before treatment, at the 1st month of treatment and at the 6th month of treatment. Investigations were conducted using spectrophotometric method to detect nitric oxide (NO) and MDA. The TNF-α, IL-1β, and 8-OHdG levels were detected using ELISA method. In the results, at any of the predefined time period, the study did not show any significant change in the saliva in all biochemical parameters. In another study involving the unstimulated saliva samples of individuals with fixed orthodontic appliances, there were no significant differences observed when compared to the control group in kynurenine concentration [76]. And the data presented in the study at least at the first 6 months of the treatment indicate that orthodontic materials and orthodontic tooth movement used in orthodontic treatment do not cause oxidative damage in the oral cavity.

#### **4. Pain and tooth movement**

Nowadays many biomarkers are detected using saliva. It was recently discovered that several new isoforms for Nerve Growth Factor (NGF), Brain derived Neurotropic Factor (BDNF) and Calcitonin gene-related peptide (CGRP) were found in the saliva [3]. Identification of these isoforms can be utilized to develop subtle ways that can be considered to be methods to detect and analyze markers related to pain.

Pain and discomfort are inevitable during orthodontic treatment [6]. Conventionally, the degree of pain is assessed subjectively using many pain scales [7]. Assessing pain objectively using salivary physiological biomarkers would benefit the clinician for appropriate pain diagnosis and management [6, 8].

These potential biological markers can be collected from different tissue samples. The sampling is done as per the required biomarker and the biological processes to be studied [1, 9]. Several possible biomarkers representing many of these biological changes during specific phenomenon like pain experienced during orthodontic treatment pain, bone remodeling, inflammation and root resorption have also been proposed [20]. The clinical application can be developed from the knowledge of biomarkers that can accelerate the orthodontic treatment as well.

Development of objective markers of nociception and pain helps in diagnosis of pain and its management. Standardization of pain assessment objectively is important to avoid bias in research studies. Tools that are sensitive and specific to pain fulfilling certain criteria's like being observer-independent, not reliant on the patient's ability to communicate and not influenced by disease characteristics are needed in developing an objective method of pain assessment [13]. A review by Cowen et al. [13] states that the objective biomarkers of nociception or pain which have been validated for clinical use, although there are currently promising strategies like monitoring changes in the autonomic nervous system, biopotentials, neuroimaging and composite algorithms. There is a serious need for theoretically promising and clinically useful objective marker for assessment of pain. Restricted use of physiological markers as 'objective' measures of pain and nociception is due to the lack of evidence in support of its use as biomarker. Biomarker research in saliva for pain and nociception as part of clinical phenotyping should be watched closely.

Fleming et al. [14] suggests that unlike the bracket type, the subjective pain experience at 4 h, 24 h, 3 days, and 7 days following fixed orthodontic appliance placement [14]. The subjective pain was recorded using Visual Analog Scale (VAS) [14].

In cross sectional study conducted by Jasim et al. [3], the levels of nerve NGF, CGRP and BDNF were determined using novel western blotting-based technology using Capillary Isoelectric Focussing (CIEF) Immunoassay. Glutamate and substance P (SP) was determined using ELISA. Numerous new isoforms were found for NGF, CGRP and BDNF in saliva. In expression and chemiluminescence levels, the isoform pattern showed significant difference between different collection methods. In this study, new sensitive methods to study pain related markers in saliva were developed. And this study was the first to:


Activation of the orthodontic appliance induces painful sensations due to the inflammatory process, this occurs as part of the tooth movement related to tissue remodeling. It is established that the immunoreactive neuron C-fos is involved in the transmission of nociceptive information expressed bilaterally in the lateral parabranchial nucleus. And ipsilaterally in the trigeminal subnucleus caudalis past the initial 24 h of orthodontic force application. Similarly, fos-like immunoreactive neurons were distributed in other brain regions such as the neocortex, thalamic nucleus and dorsal raphe [77]. Nociceptive information by tooth movement is modulated and transmitted in several regions of the brain. Endogenous pain control systems are activated by these stimuli, including descending monoaminergic pathways [78].

Initial studies suggested that through dopaminergic and serotonergic systems, the nociception is nociception is regulated [77]. Subsequently, another experiment

#### *Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*

performed showed an increase in serotonin turnover in the medulla, indicating the bulbospinal serotonergic pathway activation by nociceptive neurological response [78]. Therefore, an indirect nociceptive mechanism operating during tooth movement occurs that suggests a continuous and delayed nociceptive response, which is expected to regulate the masticatory function during active tooth movement.

A recent case report published data on administration of MK-801 in rats (a noncompetitive antagonist of N-methyl-Daspartate receptors), intraperitonially before tooth movement. The results suggested the N-methyl-D-aspartate receptors blockade along with neuronal suppression of sensory nuclear complex of the trigeminal nerve branch. Subsequently, these effects were found to increase the neuronal activity in the descending antinociceptive system, including dorsal raphe nucleus, nuclear raphe magnus, ventrolateral PAG, and Edinger-Westphal nucleus. Following, during orthodontic tooth movement, these results indicated a pharmacological way to decrease pain perception [79].

Salivary biomarkers as a measure has the potential to be an objective approach and a diagnostic tool for the studies related to pain. However, there is a need of estimating the different collection methods and develop more profound techniques for analysis. These biomarkers have a crucial part in objectively assessing the pain.

#### **5. Gingival crevicular fluid (GCF) and biomarkers**

GCF is an exudate that can be collected from the gingival sulcus in periodontium, which provides a prospective source of factors or biomarkers associated with the changes and destruction in the underlying periodontium that generally occurs during the orthodontic force application during fixed orthodontic treatment [80].

Due to its non-invasive nature and ease of repetitive sampling from the same site with the help of filter paper strips, gingival washings, platinum loops and micropipettes, GCF is commonly collected for the examination and check the levels and concentration of these biomarkers during the orthodontic force application. This fluid is easily available as that of saliva in the oral cavity and is usually used to analyze various biochemical markers [80].

The importance of GCF biomarkers in periodontal effects is tabulated in **Table 4**.

GCF which can be described as a transudate or an exudate arises at the gingival margin where its flow rate is of 0.05–0.20/min which indicates gingival inflammation [81]. Various biochemical markers such as prostaglandin production and the action of various extracellular and intracellular factors, such as IL-6, IL-1, TNF, epidermal growth factors, cathepsin, aspartate aminotransferease, microglobulin, alkaline phosphatase, and lactate dehydrogenase are analysed by this GCF.

Various cell mediators or enzymes are produced due to the remodeling changes in the PDL and the alveolar bone that can be used as the biomarkers of orthodontic treatment [66, 82]. The initial works conducted by Embery, Waddington [83] and Last et al. [84], proved the presence of many proteoglycan, tissue proteins and GAGs in GCF and also reported presence of chondroitin-4-sulphate in GCF from the pressure side of tooth movement. Biological alteration is caused in deep-seated tissues due to that the increase in chondroitin-4-sulphate since the orthodontic model is a nonplaque and non-disease-related process.

Uematsu et al. [85, 86] found elevated levels of IL-1, IL-6, TNF, epidermal growth factors, TGF 2 and microglobulin during the orthodontic treatment in the GCF. Lee et al. [87] and Grieve et al. [88] also reported stated the similar finding for IL-1, and

#### **Inflammatory mediators**


#### **Metabolic products of paradental remodeling**


#### **Enzymes**


```
GCF, Gingival crevicular fluid; IGF-1, Insulin-like growth factor-1; GAG, Glycosaminoglycans; PMN, 
Polymorphonuclear neutrophil; TNF, Tumor necrosis factor; PDL, Periodontal ligament.
```
#### **Table 4.**

*List of GCF biomarkers and their role in orthodontic tooth movement.*

PGE2. Lowney et al. [89] for TNF. Griffiths et al. [90] demonstrated the presence of osteocalcin in GCF from teeth which is subjected to the orthodontic treatment force application. A recent study by Insoft et al. [91] also found an increased level of alkaline phosphatase during the first 3 weeks of orthodontic treatment, whereas acid phosphatase increased in successive weeks. Perinetti et al. [92] also determined the aspartate aminotransferase along with the alkaline phosphatase activity in GCF. Orthodontic force application induced an increase in the lactate dehydrogense activity in GCF as per a recent study by Serra et al. [93]. After the study it is proposed to be a sensitive factor or biomarker for periodontal metabolism. Sugiyama et al. [82] suggested that cathepsin B involved in ECM degradation and reported its increase in the amount in GCF.

#### *Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*

After an orthodontic force presentation for 4–8 h Apajalahti et al. [94] found a significantly higher amount of MMP-8 in GCF. They suggested that MMP-8 reflects the enhanced periodontal remodeling, this is the effect of increased expression and activation of GCF. From the studies, it was concluded that presence of such markers in GCF during the orthodontic studies are useful in identifying the bone-remodeling activities. Therefore, GCF can be considered a promising topic for future research, as these investigations have already begun to provide an insight into the progressive aspects of remodeling.

According to the QUOROM statement suggestions, a systematic review was conducted by Allgayer et al. [95] in 2014 by strictly adhering to the guidelines suggested by PROSPERO [95]. Several key databases namely PubMed, Embase, Cochrane library, MEDLINE, and Web of Science were searched in May 2014 using the MESH terms 'Orthodontics, Corrective', 'IL-17', or 'helper 17 cell', or 'helper T Cells', or 'TH 17', 'IL 17', 'IL-23', 'crevicular fluid', 'IL 23', and using the free text terms 'GCF, gingival crevicular fluid, regulatory proteins, tooth displacement, cytokines, inflammatory factors, root resorption and canine distalization', and, by reference tracking an additional search was performed. The search results from each database were compiled, combined and the duplicate results were eliminated (**Table 5**).

The results of this systemic review provide an insight by identifying the 115 potentially relevant studies. **Table 5** below represents an overview of the outcomes. Among these studies, further analysis of the titles, abstracts, and full texts revealed that for this systematic review the major 25 studies were relevant [95]. Many studies were performed on mixed samples of young adults and adolescents, and two related studies reported the levels of GCF cytokines in different age groups (**Table 5**). More than 20 subjects were found to be recruited for only 3 studies. Out of 25 studies, seventeen of them used the maxillary canine as their study tooth, and the orthodontic force system was distalization of the canine with either continuous arch wires or sectional wires. The other eight studies addressed insertion of separation elastics (two), Hyrax appliance (two), aligning movement (three), and cervical headgear (one).

MMPs are considered to be the main endogenous chemical mediators of the pathologic destruction of tissues in periodontitis [96]. Extensive research studies have been performed to assess the levels of MMPs in GCF [97] and saliva and also, they have been found to be elevated in patients suffering with periodontitis compared to subjects with healthy periodontium. Additionally, after the periodontal therapy there was drastic decrease in the levels of MMPs in GCF. The levels of MMP-8, 9 MMP-3,10 and MMP-13,11,12 have been linked with the periodontal disease progression in GCF. MMPs also play a dominant role in the remodeling process of PDL during orthodontic tooth movement.

A study in dogs by Redlich et al. [96, 98] suggests an increase in the activity of MMP-1 and mRNA levels in the compression side of the gingiva during orthodontic tooth movement. Similarly, a study performed on rats also demonstrates an increased expression of MMP-13, mRNA, and MMP-8 in the PDL during active tooth movement [13]. Using MMP inhibitors orthodontic tooth movement can be prevented or delayed in mice and rats [96, 98]. A few studies performed on humans [96] have enumerated the presence of MMPs in GCF during orthodontic tooth movement and have stated the alterations in their levels during the orthodontic force application. Additionally, in orthodontic patients treated with fixed appliances, the total collagenase activity in the GCF has been revealed to be 10-fold that of control GCF [99].

Surprisingly, it is found that the effects of orthodontic force application on teeth affected by periodontal disease has not been significantly studied. However, a few



#### *Orthodontic Therapeutic Biomarkers in Saliva and Gingival Crevicular Fluid DOI: http://dx.doi.org/10.5772/intechopen.100733*



#### *Current Trends in Orthodontics*

retrospective and longitudinal studies [97, 99] indicated that the orthodontic force application can be tolerated by periodontally compromised teeth without any additional damage to the periodontium.

#### **6. Conclusion**

Present dissertation deals with brief insight into the biomarkers, connected to orthodontic treatment and progression. Suitable biomarkers may be used to distinguish the sequence of events following OTM. Biophysical mechanisms are involved in the displacement of tooth in the periodontal space and shift of stimulus from continuous force application. The assessment of these biological mechanisms can be done by the evaluation of rate and amount of synthesis of biomarkers in periodontium. This knowledge of the ongoing process occurring in periodontal tissues during orthodontic and dentofacial orthopedic therapies in turn may help us to make proper choice of mechanical orthodontic loading, the amount of orthodontic force application during the treatment and period of treatment may be shortened. It also helps to avoid adverse consequences such as bone loss or root resorption associated with orthodontic treatment. The essential goal is to develop a screen test based on these factors or biological markers that could be used non-invasively and easily by the orthodontist at chairside to monitor the ongoing process and detect early root resorption. Several sensitive, salivary biomarkers are available to detect the biomechanical changes occurring during orthodontic tooth movement and pain occurring during fixed orthodontic therapy. Further focussed research might help to analyze the sensitivity and reliability of these biomarkers (cytokines), which in turn can lead to the development of chairside tests to assess the pain experienced by patients during orthodontic therapy and finally the outcome of the fixed orthodontic therapy. There is an enormous scope for research in this field which may be a boon for future orthodontic treatment and modalities.

### **Conflict of interest**

None.

### **Author details**

Sagar S. Bhat\*, Ameet V. Revankar and Shrinivas M. Basavaraddi Department of Orthodontics and Dentofacial Orthopaedics, SDM College of Dental Sciences and Hospital, SDM University, Dharwad, Karnataka, India

\*Address all correspondence to: sagarbhat1994@yahoo.co.in

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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orthodontic tooth movement. J Dent Res. 2003 Dec;82(12):1018-1022.

[95] Allgayer S, Macedo de Menezes L, Rinaldi L, Roennau M. Cytokines in crevicular fluid and orthodontic force: a systematic review. Revista Odonto Ciência. 2017 Jun 1;32(2).

[96] Redlich M, Rahamim E, Gaft A, Shoshan S. The response of supraalveolar gingival collagen to orthodontic rotation movement in dogs. Am J Orthod Dentofacial Orthop. 1996 Sep 1; 110(3):247-255.

[97] Alhashimi N, Frithiof L, Brudvik P, Bakhiet M. Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines. Am J Orthod Dentofacial Orthop. 2001 Mar 1;119(3):307-312.

[98] Redlich M, Reichenberg E, Harari D, Zaks B, Shoshan S, Palmon A. The effect of mechanical force on mRNA levels of collagenase, collagen type I, and tissue inhibitors of metalloproteinases in gingivae of dogs. J Dent Res. 2001 Dec;80(12):2080-2084.

[99] Capelli Junior J, Kantarci A, Haffajee A, Teles RP, Fidel Jr R, Figueredo CM. Matrix metalloproteinases and chemokines in the gingival crevicular fluid during orthodontic tooth movement. Eur J Orthod. 2011 Mar 9;33(6):705-711.

#### **Chapter 2**

## Orthodontics and the Periodontium: A Symbiotic Relationship

*Betsy Sara Thomas and Mohan Alexander*

#### **Abstract**

The force applied by the orthodontist to facilitate the orderly movement of teeth to their new position may have deleterious effects on the most important structure involved in the procedure—the periodontium. This chapter endeavors to provide an overview of the biological processes that play a role in achieving the patient's as well as the orthodontist's objective.

**Keywords:** accelerated tooth movement, inflammation, periodontal ligament, alveolar bone, cytokines

#### **1. Introduction**

The art and science of orthodontics have certainly come a long way from the era of treatment using removable appliances, which mainly produced tipping movements of the teeth, to the fixed appliances that bring about bodily movements of the teeth to their desired destination. But this has not been a journey without hiccups. The quest for the perfect smile or the ideal occlusion has been marred by quite a few stories of botched-up cases, which, sometimes, could be the result of unscientific methods being utilized to achieve the promised results. But it also seems to be a story of due respect not being accorded to the most important structure in the treatment process—the periodontium. This chapter discusses the relationship that the periodontium (*and the periodontist*) shares with the specialty of orthodontics, one which, at times, tends to be taken for granted.

#### **2. Theories of tooth movement**

The force applied to the teeth during orthodontic treatment results in remodeling of the alveolar bone. The exact mechanism of how this force is converted to biological activity has not been elicited till now. Various theories try to explain this phenomenon:


Whatever be the mechanism, it seems obvious that it is the periodontium that plays a big role in achieving the treatment goals.

#### **3. The periodontium**

The periodontium has two main functions: protection and attachment. The former function is carried out by the gingiva and the latter by its three remaining parts, namely the cementum, periodontal ligaments, and the alveolar bone. It is only the gingiva that is visible in the oral cavity, the rest being covered and protected by it.

#### **3.1 Gingiva**

The primary function of the gingiva is protection, as stated earlier. Orthodontic treatment tends to be associated with gingivitis in many patients. As the presence of plaque is one of the main factors in the development of gingivitis, it could be the interference of the orthodontic brackets and elastics with effective removal of dental plaque, which might be resulting in gingivitis. However, it has been shown that because of orthodontic treatment a shift in the composition and type of bacteria can occur [1]. According to J. van Gastel, et al. [2], fixed orthodontic treatment may result in localized gingivitis, which rarely progresses to periodontitis. E. Bimstein and A. Becker [3] state that, following placement of a fixed appliance, a small amount of gingival inflammation will be visible, which could be transient in nature and does not lead to attachment loss, in the majority of the patients.

Gingival recession is considered to be one of the more common complications of orthodontic tooth movement (OTM). But in a study conducted among 205 orthodontic patients, Morris JW, et al. [4] found that "orthodontic treatment is not a major risk factor for the development of gingival recession." They further state that "although greater amounts of maxillary expansion during treatment increase the risks of post-treatment recession, the effects are minimal."

#### **3.2 Cementum**

Any treatment procedure that a human being undergoes, whether surgical or medical, can have side effects or risks involved, and orthodontic treatment is no exception. Similar to other medical procedures, the aim in orthodontics is also to minimize the risks involved in the maximum number of patients possible.

Microscopic resorption of the cementum of erupted as well as unerupted teeth is a common phenomenon. This occurs without involving the underlying dentin in the majority of cases. The resorption may be caused by local or systemic factors or can be idiopathic. Trauma from occlusion, malaligned erupting teeth, periapical as well as periodontal infections, replanted or transplanted teeth, orthodontic movement,

etc. are the local factors that may result in cementum resorption. According to some authors [5–7], root resorption is the most common side effect of orthodontic treatment and occurs within 6 months of commencement of the treatment. Anja Pejicic, et al. [8] have described three degrees of severity of orthodontically induced root resorption (OIRR): the first degree wherein there is only surface resorption of the cementum which will regenerate or remodel fully. The second degree shows deep resorption with cementum and outer dentin layers involved and this is usually repaired with cementum. In this, the original shape of the root may or may not be achieved following the repair. In their third degree, there is full resorption of the apical hard tissues evidenced by shortening of the root.

Biologic as well as mechanical factors have been highlighted as probable causes of OIRR, with tooth root morphology, abnormal root shape, previous history of trauma or root resorption, genetic and systemic factors, endodontic treatment, habits and oral health, etc. likely to be the biologic factors. Mechanical factors could be the amount of apical displacement, the magnitude of force applied, duration of treatment, whether it is continuous or intermittent force, type, extent and direction of tooth movement, etc., according to Anja Pejicic, et al. There are studies [9–12] that suggest that it is the trauma due to over-compression of the periodontal ligament that causes OIRR. It seems to be an accepted fact that orthodontic movements are not entirely translatory due to mechanical laws. This results in the concentration of orthodontic forces at the apical region. During OTM, hyalinization does occur because it is virtually impossible to prevent the occlusion of blood vessels totally. Because of this, root resorption might begin at the hyalinized region of the necrotic periodontal ligament. As hyalinized necrotic tissue develops in almost 100% of patients during orthodontic treatment, some authors believe that root resorption occurs in almost every orthodontic patient [13, 14]. It is believed that the aggressiveness of the resorbing cells, the vulnerability and sensitivity of the tissues involved and individual variation and susceptibility will decide the extent of resorption [8].

The use of light orthodontic force has been shown to minimize the extent of root resorption, especially with horizontal and vertical displacement. This could be because the apical third of the root is covered with cellular cementum, whereas the coronal third is covered with acellular cementum. Because of the increased proliferation activity, cells of the cellular cementum might be easily damaged, whereas the slowly dividing cells of the acellular cementum might be more resistant to those forces [15–17].

Nitric oxide (NO), the intra- and the intercellular signal molecule, is synthesized by the activity of neuronal, endothelial, and inducible isoforms of NO synthases (NOSs). The primary sensor of NO is soluble guanylate cyclase (sGC). It plays a very important part in many physiological as well as pathological processes and conditions and also in NO signaling. The enzymatic activity of sGC is boosted when NO binds to it. In inflammation, sGC is oxidized and becomes insensitive to NO. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts. Korkmaz Y, et al. think that if medication can be used to activate sGC in periodontal tissues of patients suffering from periodontitis in nitric oxide and heme-independent manner, it could result in a novel treatment to stop cementum resorption for such patients. They reached this conclusion after studying the α1- and β1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K. They compared this with those of osteoclasts from the same sections and noticed that under inflammatory conditions, cementoclasts showed a decreased staining intensity for both the subunits [18].

Yufei Xie, Ning Zhao, and Gang Shen [19] investigated the anti-resorptive mechanisms of cementocytes during orthodontic tooth movement. They concluded that under fluid-flow sheer stress, cementocytes stimulate the differentiation of osteoblasts and inhibit the activation of osteoclasts, showing greater potential for bone protection than alveolar bone osteocytes. And according to them, "cementocytes might play an important role in preventing one of the most common complications of orthodontic treatment – root resorption."

According to Alberto Consolaro [20], teeth with OIRR do not need:


#### **3.3 The alveolar bone**

The alveolar bone is a mineralized connective tissue and is made up of around 67% inorganic material by weight. The inorganic content is primarily calcium and phosphate, with the mineral content being typically in the form of hydroxyapatite crystals. Around 20% of the alveolar bone consists of organic material, containing both collagen and non-collagenous materials. Water constitutes the rest of the weight of the alveolar bone- ~ 15% [21]. The inner wall of the tooth socket, known as the alveolar bone proper, contains many openings through which the periodontal ligament connects with the neurovascular bundles of the cancellous bone. The interdental bone or septum is made up of cancellous supporting bone within cortical walls.

Adjacent to the PDL space is a plate of compact bone called the lamina dura, whereas the majority of alveolar bone is trabecular in nature. The alveolar bone contains many different types of cells such as adipocytes, endothelial cells, macrophages, osteoclasts, osteoblasts and osteocytes. But the crucial detail of maintaining the function as well as homeostasis of the alveolar bone is carried out by the last three types of cells. There are some differences between the osteoblasts which form bone, and the osteoclasts, which resorb bone. The former (and the osteocytes) descend from mesenchymal cells, whereas the latter originates from the monocyte or hematopoietic cells. At the same time, the osteoclasts are formed by the fusion of multiple monocytes and thus are multinucleated while the osteoblasts are mononucleated. Type I collagen, which is the most abundant protein in vertebrates, can be made by both fibroblasts and osteoblasts and it is this collagen that forms the structural and mechanical matrix of the alveolar bone. The osteoblasts contain the master switch Runx2, which helps in the differentiation of osteoblasts from the progenitor mesenchymal cells [21]. As age advances, there is a disproportion between bone deposition and resorption and this is because the number of osteoblasts decreases as we age [22]. While apposition of bone is taking place, osteoblasts get enclosed in the mineralized bone and these cells are known as the osteocytes. A lacuna can form around such an osteocyte by deposition of minerals such as calcium carbonate, hydroxyapatite and

#### *Orthodontics and the Periodontium: A Symbiotic Relationship DOI: http://dx.doi.org/10.5772/intechopen.100801*

calcium phosphate, during bone formation. The lacunae connect with each other through canaliculi, which are narrow channels through which the dendrites of osteocytes correspond using gap junctions. The bone-resorbing osteoclasts express various substances such as osteoprotegerin (OPG), chloride channel 7 (ClCN7), cathepsin K, and tartrate-resistant acid phosphatase (TRAP). Bone matrix proteins such as elastin, collagen, and gelatin are catabolized by the protease cathepsin K, whereas ClCN7 maintains osteoclast neutrality by shuffling chloride ions through the cell membrane. OPG, though a member of the TNF receptor family, is secreted and acts as a cytokine.

Among all the periodontal tissues, alveolar bone is the least stable because it is in a constant state of flux. Local factors that cause internal remodeling include agerelated changes as well as functional requirements on the tooth. Mechanical strains caused by orthodontic movements are thought to be resulting in physiologic bone adaptation together with minor injuries to the periodontium, which are reversible [23]. The pressure-tension theory of tooth movement proposes that a tooth moves in the periodontal space by creating a pressure and tension side. According to this theory, the tooth shifts its position within the periodontal ligament (PDL) space, resulting in PDL compression in some areas and PDL tension in others within a few seconds of force loading and this is brought about by chemical, rather than electric, signals as the stimulus for cellular differentiation and ultimately tooth movement. Bone resorption occurs at the compression side and bone formation at the tension side, with blood flow being decreased on the compression side and is maintained or increased on the tension side. Within minutes of force being applied, the alteration in blood flow changes the oxygen tension and the chemical environment by releasing biologically active agents such as prostaglandins and cytokines [24]. This happens especially if there is sustained force. This alteration results in less oxygen levels on the pressure side due to compression of the periodontal ligament and vice versa. It has been observed that low oxygen tension causes decreased adenosine triphosphate (ATP) activity [25]. These changes act on cellular differentiation and activity, bringing about bone resorption at the compression side and bone formation at the tension side. Schwarz (1932) correlated the tissue response to the magnitude of force, with capillary blood pressure. If the force exceeds the pressure of ~20–25 g/cm<sup>2</sup> of the root surface, tissue necrosis can occur due to the strangulated periodontium [26]. It has been shown that with the application of heavy force, blood flow tends to be cut off resulting in cell death under compression. According to Al Ansari et al., these cell deaths also include some osteocytes and osteoblasts in the adjacent alveolar bone. This causes acute inflammatory response with the release of chemokines that could attract other inflammatory and precursor cells into the extravascular space from the blood vessels. According to Taddei et al., during orthodontic movement, the chemokines known as monocyte chemo-attractant protein-1 (MCP-1) is released attracting the monocytes. These monocytes become either macrophages or osteoclasts once they exit the bloodstream and enter into the tissue. The release of other inflammatory mediators is also seen within the first few hours of tooth movement.

If the cessation of blood flow occurs because of heavy orthodontic force being applied, a delayed differentiation or recruitment of osteoclasts from adjacent bone marrow space also may occur resulting in "undermining resorption" that removes the lamina dura next to the compressed PDL. This is because no osteoclast differentiation occurs within the compressed PDL space. Under such a condition, tooth movement will take place only after this "undermining resorption" is completed, meaning only after a week or two. This also explains why tooth movement occurs within 2 to 3 days when light force is applied, because the light force will only reduce the blood flow

permitting the quick recruitment of osteoclasts either from within the periodontal ligament space or from blood. This will result in the removal of the lamina dura by the process of "frontal resorption." At the same time, it is a fact that tooth movement is a result of a combination of "undermining" as well as "frontal" resorption. This is because some degree of hyalinization almost always occurs as it is virtually impossible to clinically prevent the occlusion of blood vessels completely [24].

#### **3.4 The periodontal ligament**

Yes, the force applied by the orthodontic appliance provides the impetus for the tooth to move. But without the PDL it would be impossible for the teeth to move through the bone and reach their intended destination, in an orderly manner. The PDL, like all ligaments in the body, connects the hard tissue structures, either the cementum of adjacent teeth to each other or the cementum of the tooth to the alveolar bone.

The PDL also connects with the neurovascular bundles of the cancellous bone through the alveolar bone proper *via* the numerous openings. The PDL is a dense fibrous connective tissue structure that consists of collagenous fiber bundles, cells, vascular and neural elements, and interstitial fluid. Its primary function is to support the teeth in their sockets and at the same time allow them to withstand considerable masticatory forces. The average width of the PDL space is around 0.2 mm, with the space decreasing as age advances. The space is occupied mostly by Type 1 collagen bundles and is the thinnest near the middle third of the root. These collagen fibers are mainly divided into principal, accessory, and elastic fibers. Sharpey's fibers are the term used for the terminal portion of these fibers that insert in the alveolar bone and cementum. The principal fibers can be subdivided into the transseptal fiber (or interdental ligament) and alveolodental ligament. Some authors consider the transeptal fibers as gingival fibers because they do not have an osseous attachment. These fibers connect the cementum of adjacent teeth, with their duty being maintaining the alignment of teeth, and the alveolodental ligament group of fibers helping teeth withstand compression forces during mastication. The accessory fibers prevent rotation of the tooth and run from the alveolar bone to cementum in different planes, in a tangential manner. Many cells occupy the PDL space, namely 1) synthetic cells like fibroblasts that make up to around 60% of the total PDL cell population, osteoblasts, and cementoblasts; 2) resorptive cells such as osteoclasts, cementoclasts; 3) progenitor cells including undifferentiated mesenchymal cells; 4) defense cells such as macrophages, mast cells, and lymphocytes; and 5) remnants of the epithelial root sheath of Hertwig, which are epithelial cells. The PDL space also contains interstitial fluid, which is contributed by the circulatory system [24]. This helps the PDL space to transmit the masticatory forces (which can range from 70 to 150 newtons) etc., onto teeth, thus acting as a shock absorber.

Some of the more frequent complications of orthodontic treatment are dehiscence or fenestration of the alveolar bone. These can result in root exposure, gingival recession, and relapse of the condition.

#### **4. Inflammation and orthodontic tooth movement**

As discussed earlier, tooth loading, physiologic or otherwise, causes areas of compression and tension on the soft tissues surrounding the teeth also—the PDL, nerves, blood vessels, etc. In the PDL, there is an intimate relationship of the nerve endings with the blood vessels. Neurotransmitters such as calcitonin gene-related peptide (CGRP) and substance P are released when the nerve endings get distorted and these cause vasodilation and increased permeability of the blood vessels resulting in plasma leakage [23, 26]. OTM is achieved by the remodeling of the PDL and alveolar bone. These remodeling activities and the movement of the teeth result in an aseptic inflammatory process with the consequent increase in mediators such as prostaglandins (PGs), interleukins (ILs. IL-6, IL-7 & IL-17), the tumor necrosis factor (TNF)-α superfamily, and the receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG).

Current scientific literature suggests that arachidonic acid (AA) pathway plays a very important role in many human diseases such as cardiovascular problems, carcinogenesis as well as inflammatory conditions such as asthma, arthritis. Periodontists have been exploring the role of AA in periodontitis for some time, it being an inflammatory condition. AA can be metabolized by three specific enzyme systems, that is, cyclooxygenases, lipoxygenases, and cytochrome P450 (CYP) enzymes. One of the derivatives of the AA cascade—the prostaglandins (PGs) are produced within seconds of cell injury. PGE2 is the most abundantly seen PG in various tissues and is known for its all-around physiologic and pathological actions. It increases vascular permeability and chemotactic actions by acting as a vasodilator and at the same time, it increases bone resorption and osteoclast formation. An increase in PGs levels in the PDL and alveolar bone has been reported by Ngan, et al. [27], during orthodontic treatment. PGE2 levels in the gingival crevicular fluid (GCF) increased during OTM, according to Shetty et al. [28]. Leiker et al. [29] demonstrated that exogenous prostaglandins enhanced the rate of OTM in rats. The administration of PGE or prostaglandin receptor EP4 also enhanced the rate of tooth movement [30, 31]. It has also been demonstrated that indomethacin, a specific inhibitor of prostaglandin synthesis, reduces the rate of OTM in rats [31, 32]. As mentioned earlier, the cytokines also increase during OTM. IL-β in particular is involved with inflammation and stimulates bone resorption. It has been reported that IL-1β is produced by both macrophages and neutrophils, and is increased in inflamed gingival tissues. IL-6 is a multifunctional cytokine produced by immune cells and induces osteoclastic bone resorption. IL-17 is an inflammatory cytokine that is produced by activated T cells and it has been reported that IL-17 induces osteoclastogenesis from monocytes.

RANK ligand (RANKL) and its receptor RANK are present on osteoblasts and precursor osteoclasts, respectively. They are considered to be the key factors that stimulate osteoclast formation and osteoclastogenesis. RANKL is required for osteoclast formation with macrophage-colony-stimulating factor (MCSF) from precursor monocyte/macrophages. Osteoprotegerin (OPG) inhibits RANK–RANKL interactions [24]. It binds to RANKL and prevents RANK–RANKL ligation. Therefore, OPG prevents osteoclast differentiation and activation. Kanzaki et al. demonstrated that compression forces upregulate RANKL expression through induction of COX-2 in human PDL cells *in vitro*. They also [33] demonstrated that the amount of rat experimental tooth movement is accelerated by the transfer of the RANKL gene to the periodontal tissue, while it is inhibited by OPG gene transfer. Additionally, compression force increases RANKL and decreases OPG secretion in human PDL cells *in vitro*. The GCF levels of RANKL are increased, and the levels of OPG are decreased in experimental canine movement. Therefore, it is suggested that the RANK–RANKL system is directly involved in the regulation of orthodontic tooth movement.

All these studies suggest that these and other inflammatory cytokines may be intricately entwined with one another during OTM, and may play important roles in bone remodeling. But studies on OIRR seem to suggest that these mediators might also be the cause for the most common complication in orthodontics-root resorption.

#### **5. Accelerated orthodontic tooth movement**

A systematic review of prospective studies on the duration of orthodontic treatment suggests that the duration of orthodontic treatment varies widely but takes less than 2 years to complete, on average [34]. Most patients would like their treatment to be done in a much shorter period and in addition, longer treatment periods might increase the chances of root resorption, decalcification, etc. This has resulted in orthodontists as well as manufacturers trying to shorten the duration by using various methods to accelerate OTM (AOTM). Some of the techniques advocated in this quest to accelerate OTM are as follows:

#### **A. Those aimed at altering orthodontic mechanics**


#### **B.Altering biological response to force**


#### **C.Surgical methods**


Miles P [35] reviewed the studies involving the aforesaid techniques and was of the opinion that the technique of photobiomodulation may be of benefit but suggested that since there is limited evidence to support it, more studies will be needed before it can be applied routinely. With regard to the use of corticotomy, also he says that only low-level evidence is available and he concludes his review by suggesting that rigorous, well-designed randomized controlled trials with longer follow-up periods are necessary for all the techniques before they can be recommended.

The effects of most of the above AOTM procedures on the periodontium do not seem to have been studied in detail. The more commonly performed and studied one seems to be the corticotomies, *viz.*, the periodontally accelerated osteogenic orthodontics (PAOO).

#### **5.1 Periodontally accelerated osteogenic orthodontics**

In 2001, Wilcko, et al. [36] introduced the "periodontally accelerated osteogenic orthodontics" (PAOO) technique that they claimed shortened the duration of orthodontic treatment. This involved flap design, selective decortication, alveolar augmentation, membrane coverage, and closure using sutures. They radiographically assessed the presence of transient demineralization followed by remineralization at the corticotomy level. According to them, reversible osteopenia occurs both within the alveolar bone proper and on the surface and with this, the collagenous bony matrix also moves with the root in the same direction as the OTM. Once the OTM is completed and the teeth are retained in their predetermined position, remineralization of the matrix takes place. They claim that this demineralization-remineralization is complete in adolescents but not so much in adults and termed it the "regional acceleratory phenomenon" (RAP) of bone remodeling. They thought that this "bone matrix transportation" had made it possible to design a surgical approach, which permits extraction space closure in 3 to 4 weeks. The duration of RAP is claimed to last for 3–4 months by these authors and the amount of tooth movement during this period was double around 1 mm/month, in animal studies conducted by Iino S, et al. [37].

#### **5.2 History of osteotomies/corticotomies to speed up tooth movement**

The use of techniques to speed up orthodontic tooth movement by utilizing alveolar surgery has a history dating back to more than a century. But it is Heinrich Kole [38] who has been credited with refining the process. He proposed the idea of accelerating orthodontic movements by displacing bone blocks, more than 6 decades ago. He hypothesized that it was the cortical bone that slowed the orthodontic movement of teeth and so why not weaken it by osteotomizing it? He advocated buccal and lingual interdental corticotomies together with supra-apical horizontal osteotomies connecting the two vertical cuts. Though accelerated orthodontic movements were achieved, he encountered quite a few complications like the non-vitality of teeth. It should be noted that Kole achieved the tooth movements using removable appliances fitted with adjustable screws. Others tried to build on this technique with Duker in 1975 [39] sparing the crestal bone in his corticotomies and Suya [40] replacing the supra-apical osteotomy with a corticotomy in 1991.

According to T. Gellee, et al. [41], PAOO also allows larger tooth displacements, a reduction in the risk of root resorption, and a gain in stability after the removal of orthodontic devices.

#### **6. Periodontal therapy and orthodontics**

According to the American Association of Orthodontists, one in four orthodontic patients is an adult. Some studies suggest that almost 40% of the patients are adults. As more and more adult patients seek orthodontic treatment for various reasons, it can be challenging for the orthodontist to tailor his/her techniques to the specific patient. Many of these patients might have underlying periodontal problems that can affect the treatment process as well as its outcome. The periodontist can play an active role in ensuring the success of the orthodontic treatment—in adult patients or adolescents. This role can be before, during, or after the orthodontic treatment.

#### **6.1 Pretreatment**

A thorough periodontal examination/charting is of utmost importance for every orthodontic patient, especially if skeletal growth has been completed. This is to identify and manage active conditions such as gingivitis and periodontitis as well as conditions that result in deficiency of soft or hard tissues or both. In ideal conditions, and with good oral hygiene, gingival health can be maintained with as little as 1–2 mm of keratinized gingiva. But soft tissue grafting might be indicated under the following circumstances:


The techniques that are available to correct these conditions include the following:


Every patient should undergo professional plaque removal and root debridement before the start of the treatment. Oral hygiene instructions should be reinforced because it has been shown that orthodontic bands, elastics, etc., tend to retain plaque, resulting in gingivitis, which may then proceed to periodontitis. Orthodontically

#### *Orthodontics and the Periodontium: A Symbiotic Relationship DOI: http://dx.doi.org/10.5772/intechopen.100801*

induced remodeling process may have a positive effect on bone, so extensive osseous surgery is usually not indicated at this time. But sometimes osseous surgery might be indicated in the following conditions:


The American Academy of Periodontology's systematic review on whether periodontal phenotype modification therapy (PhMT) involving hard tissue augmentation (PhMT-b) or soft tissue augmentation (PhMT-s) has clinical benefits for patients undergoing orthodontic treatment concluded that PhMT *via* corticotomy with particulate bone grafting (PhMT-b along with CAOT) may provide clinical benefits of augmenting periodontal phenotype, accelerating tooth movement, expanding the scope of incisor movement, and enhancing post-orthodontic stability of the mandibular anterior teeth. This study also says that the benefits of PhMT-s alone during orthodontic treatment remain undetermined because of the limited studies available [42].

#### **6.2 During orthodontic treatment**

The maintenance of oral hygiene during treatment is of paramount importance. During each visit reinforcement of oral hygiene instructions have to be carried out along with motivating the patient to do so. Periodontal evaluation every 6 months and radiographic examination once in a year would be ideal. Procedures like frenectomy might have to be carried out during the treatment period if the orthodontist feels that diastema closure, etc. are being hampered by an aberrant frenum.

#### **6.3 Post-orthodontic phase**

Regular periodontal charting should be carried out in patients who have completed their treatment. Depending on the case, circumferential supracrestal fiberotomy (CSF) may have to be carried out during the end part of the treatment or after the treatment is over. This is expected to release the tension on the supraalveolar fibers following tooth de-rotation, thereby reducing the relapse risk. Reham Al-Jasser, et al. [43] in their study found that "post-treatment rotational relapse of anterior teeth subjected to CSF was minimal and statistically insignificant after 1 year of follow-up."

### **7. The periodontally compromised patient and orthodontics**

Most orthodontists may be worried about carrying out orthodontic treatment in periodontally compromised patients and with good reason. At the same time, studies show that a large percentage (~65%) of patients with moderate to severe periodontitis are interested in such treatment for esthetic and functional changes caused by pathologic tooth migration [44].

Many questions need to be answered in these periodontally compromised patients who opt for orthodontic treatment. Some of the findings of a comprehensive search on PubMed focusing on "ortho-perio treatments" are as follows [45]:

1.Best time to start orthodontic treatment following periodontal therapy.

According to the authors, in periodontally compromised cases that have undergone periodontal therapy, it is better to start orthodontic treatment as follows:

1. 3 to 6 months after non-surgical/surgical periodontal treatment and

2.9 to 12 months after regenerative surgical procedures.

2.Acceptable periodontal status for orthodontic treatment

It is important to achieve low rates of full-mouth plaque and bleeding on probing after active periodontal treatment with scores <25% of previous ones. They recommend that these low scores (i.e., optimal plaque control without clinical gingival inflammation) be reached and maintained during the entire phase of orthodontic therapy and they think that without these conditions, orthodontic tooth movement should be discontinued.

3.Biologic efficacy of orthodontic treatment

A combined periodontist-orthodontist diagnostic and treatment endeavor in periodontally compromised patients can result in improved masticatory efficiency by a more balanced occlusion brought about by a realignment of the migrated teeth. The realignment may also result in the periodontal structures being better able to carry out their assigned functions.

According to Lindhe J and Ericsson I [46], a healthy periodontium with reduced height has a capacity similar to that of a normal periodontium to adapt to traumatizing occlusal forces. Wennström JL, et al. [47] state that sites with the horizontal bone loss after periodontal therapy will not be negatively influenced by the type of tooth movement once the individualized orthodontic mechanics are established (i.e., an appropriate ratio force/% remaining periodontal support). According to Polson A, et al., if teeth are moved through or into vertical bone defects, it can increase the rate of destruction of these periodontal structures. At the same time, if the OTM into infrabony pockets is done after successful elimination of subgingival infection, it will not result in adverse effects. They concluded that this movement/treatment will not bring about changes in the periodontal ligament attachment level; instead, the formation of a long junctional epithelium is what will be achieved [48].

#### *Orthodontics and the Periodontium: A Symbiotic Relationship DOI: http://dx.doi.org/10.5772/intechopen.100801*

According to Melsen B, et al. [49], "orthodontic intrusion at healthy sites can lead to new cementum formation and new collagen attachment, whereas for sites lacking proper oral hygiene, results vary from a moderate new attachment development to a worsening of the alveolar bone loss." And in a subsequent study, Melsen B [50] recommends that "the intrusion movement should be carefully planned as it can increase the risk of other adverse effects not desired in patients with a reduced periodontium, such as alveolar process reduction and root resorption."

Cassio Volponi Carvalho, et al. [51] studied the effects of orthodontic movement in the periodontal tissues of 10 adult patients with aggressive periodontitis and compared them with 10 patients with healthy periodontium. They evaluated the probing pocket depth, clinical attachment level, bleeding on probing, and dental plaque index before, during and 4 months after orthodontic treatment. They found improvement in all the above parameters, 4 months after orthodontic treatment.

Despite advances in therapeutics as well as our increased knowledge of the biological effects of orthodontic treatment, it might be better to avoid OTM in conditions such as uncontrolled infection/inflammation, inadequate anchorage, conditions where periodontal health might not improve despite periodontal therapy.

#### **8. Conclusion**

This chapter has attempted to portray the roles the periodontium, inflammation, and periodontal therapy play during the planning and execution of orthodontic treatment as well as once it is completed. It also discusses orthodontics in the periodontally compromised patient. There is a huge void in our knowledge about various aspects of the orthodontic movement of teeth and their effects on the periodontium. It is also evident that for the long-term success of orthodontic treatment, especially in the periodontally compromised patient, joining forces of the orthodontist and the periodontist would benefit patients as well as both the specialties.

#### **Conflict of interest**

The authors declare no conflict of interest.

*Current Trends in Orthodontics*

#### **Author details**

Betsy Sara Thomas1 and Mohan Alexander2 \*

1 Faculty of Dentistry, Department of Periodontology, MAHSA University, Bandar Saujana Putra, Selangor, Malaysia

2 Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, MAHSA University, Bandar Saujana Putra, Selangor, Malaysia

\*Address all correspondence to: mohan@mahsa.edu.my

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 3**

### Current Methods for Acceleration of Orthodontic Tooth Movement

*Mehmet Akin and Leyla Cime Akbaydogan*

#### **Abstract**

The awareness of the society and, accordingly, the number of patients who need orthodontic treatment has increased gradually. Nowadays, the importance of the concept of time has focused the attention of researchers on the completion of orthodontic treatments in a shorter time. Heavy forces applied to shorten the treatment period in orthodontic treatments cause many undesirable conditions, such as root resorption, crushing of periodontal fibers, and formation of hyalinization tissue. Therefore, researchers are working on methods that will accelerate orthodontic tooth movement and shorten the treatment time. In this section, applications that accelerate orthodontic tooth movement will be discussed.

**Keywords:** tooth movement, piezocision, propel, vibration, corticotomy

#### **1. Introduction**

As a result of the awareness of the society and the increasing interest in esthetic appearance, the number of patients who want to receive orthodontic treatment, especially in adults, is increasing [1]. However, one of the biggest problems in orthodontic treatments is the length of the treatment period [2]. Increased caries risk [3, 4], external root resorption risk, [5, 6] and decreased patient cooperation [7] in longterm orthodontic treatments lower its success. For some patients, the long duration of orthodontic treatment may be the only reason for their refusal [8]. The fact that the concept of time has gained importance for both patients and physicians has led researchers to work on completing orthodontic treatment in a shorter time [9].

The methods used to accelerate tooth movement in orthodontic treatment are examined under three main titles as pharmacological and biological applications, mechanical-physical applications and surgical applications [10].

#### **2. The methods used to accelerate tooth movement in orthodontic treatment**

#### **2.1 Pharmacological and biological applications**

#### *2.1.1 Prostaglandins*

Prostaglandins, especially prostaglandin E2 (PGE2), are one of the most effective regulators of bone metabolism [11]. Since prostaglandins play a role in both bone

destruction and bone formation, researchers have conducted many studies on the role of prostaglandins during tooth movement [11–14].

Yamasaki et al., in their clinical study, injected prostaglandin E1 (PGE1) submucosal into the distal canine tooth during canine distalization and reported that tooth movement occurred twice as fast. They stated that it is an effective and safe method that can be used to accelerate tooth movement without causing any side effects other than mild pain in patients [15].

Leiker et al., in an animal study examining the effects of PGE2 dose and the number of applications on orthodontic tooth movement, reported that there was no significant difference between a single dose and multiple applications; however, high doses and multiple injections may cause an increase in root resorption [12].

#### *2.1.2 Corticosteroids*

Also called steroids are a group of substances used as anti-inflammatory drugs for a wide range of conditions; its name was derived from an internal hormone produced by the adrenal cortex. Cortisone is the most famous type of this group that is used in the treatment of many inflammatory and autoimmune diseases such as rheumatoid arthritis, skin diseases, ulcerative colitis, adrenal insufficiency and asthma [16]. The effects of corticosteroid on the bone turnover were demonstrated in different studies, but the mechanism by which corticosteroids suppress the bone formation and increase bone resorption is still not really understood [17].

Ashcraft et al., in a study that included 16 New Zealand rabbits, in which they examined the effect of corticosteroids on tooth movement speed, stated that the speed of tooth movement was four times higher in the experimental group in which they gave cortisone acetate compared to the control group. In addition, in the histopathological examination of the bone sections they took, it was stated that the areas of bone resorption were higher in the experimental group than in the control group [18].

Ong et al. reported that there was no significant change in orthodontic tooth movement speed, but root resorption was less in their study on rabbits to which they applied prednisolone, a corticosteroid derivative [19].

#### *2.1.3 Parathyroid hormone*

The main task of the parathyroid hormone is to maintain the calcium balance in the body together with the hormones calcitonin and 1,25 dihydroxycholecalciferol. Parathyroid hormone accelerates bone remodeling by stimulating osteoclasts and osteoblasts [20].

Gianelly injected parathyroid hormone (PTH) locally into the distal mucosa of the upper left incisors of six rats and investigated its effect on tooth motility. As a result, he reported that the amount of tooth movement was higher in the PTH applied group [21].

Goldie and King reported in their study that in the group fed with a calcium-deficient diet, parathyroid hormone secretion increased and resulted in a decrease in bone density, resulting in increased tooth movement speed and less root resorption [22].

#### *2.1.4 1,25-Hydroxyvitamin D*

Another factor that is important in orthodontic tooth movement is 1,25 dihydroxycholecalciferol (1,25-DHCC), the active form of vitamin D, and is involved in calcium hemostasis. 1,25-DHCC stimulates bone deposition and inhibits PTH release. While it does not affect bone resorption at physiological doses, low doses stimulate the release of receptor activator nuclear kappa B ligand (RANKL) from osteoblasts, changing the receptor activator nuclear kappa B (RANK)/RANKL ratio and causing differentiation of osteoclasts. Thus, it takes part in the osteoclastic activity. It has also been shown to play a role in osteoblastic cell differentiation and bone mineralization in a dose-dependent manner in addition to its bone resorption function [14].

Collins and Sinclair examined the effects of injection of the active form of vitamin D on tooth movement in their study and reported that there was a 60% increase in tooth movement speed compared to the control group [23].

Takano-Yamamoto et al., in their study on rats, applied force to the maxillary first molar and additionally injected 1,25-dihydroxycholecalciferol locally every three days [24]. As a result, they reported that local injection of 1,25-dihydroxycholecalciferol with mechanical forces accelerated tooth movement, and the pause in tooth movement determined in the control group was not observed in the experimental group.

Kale et al., in their study evaluating the effects of locally applied 1,25-dihydroxycholecalciferol and PGE2 on orthodontic tooth movement using histological parameters, reported that both applications increased the speed of tooth movement, but the effects of the applications on the amount of tooth movement were similar [14].

#### *2.1.5 Osteocalcin*

Osteocalcin is a non-collagenous matrix protein that is abundant in bone tissue and functions as a negative regulator of mineral apposition and bone formation due to its high-binding strength with calcium and hydroxyapatite [25].

Hashimoto et al. injected local osteocalcin to the maxillary first molars of rats, while applying mesial motion with a spiral spring, and evaluated tooth movement histologically for a period of 10 days [26]. In their results, they determined that local application of osteocalcin accelerated tooth movement and explained this with the increase of osteoclast on the pressure side in the early period.

#### *2.1.6 Nitric oxide*

Nitric oxide is synthesized from arginine by the enzyme nitric oxide synthase. It is a short-lived molecule that plays a key role in the regulation of some functions of the nervous, defense, respiratory, circulatory, and reproductive systems [27]. Nitric oxide is also important in bone turnover and the regulation of pulpal blood flow [28].

Shirazi et al. injected L-arginine G-nitro-L-arginine methyl ester into experimental animals in their study. As a result, they reported increased bone remodeling and osteoclastic activity [28].

Akin et al., in their study, reported a significant increase in multinucleated osteoclasts, howship lacunae, vascularization and orthodontic tooth movement as a result of nitric oxide injection in rats [29].

#### *2.1.7 Platelet rich plasma (PRP) and platelet rich fibrin (PRF)*

Recently, there have been studies investigating the effect of PRP and PRF on orthodontic tooth movement speed. Studies have reported that these applications can accelerate orthodontic tooth movement [30–34].

In the last two decades, after a better understanding of the role of platelets in wound healing, the idea of using these cells for treatment has been proposed. The new autogenous product called PRP has been widely used in orthopedics, plastic surgery, and dentistry [35]. PRP is the plasma fraction obtained by centrifuging whole blood and containing a higher concentration of platelets than whole blood. It contains a high amount of platelets, growth factors, and coagulation factors in PRP [36].

After tooth extraction, resorptive remodeling of the alveolar bone usually occurs. This event is beneficial in accelerating tooth movement in patients with moderate crowding and undergoing fixed orthodontic treatment [37, 38].

In the literature, there are studies on the use of various bioactive grafts to increase the orthodontic tooth movement speed [39]. In orthodontic treatment, a sufficient amount of alveolar bone is required for successful orthodontic tooth movement during the closure of the extraction space. However, the application of different graft materials can promote bone formation. It has been reported that PRF has positive effects on bone healing, socket protection and acceleration of tooth movement [34].

In studies, it has been observed that PRP, which is applied at a high level, inhibits the division of bone cells and reduces bone density, and it is therefore thought that orthodontic tooth movement can be accelerated with this application [31, 40, 41]. Güleç et al., as a result of their experimental studies in which medium- and high-level PRP was injected into the mesial side of the first molar teeth of rats, showed that high-level PRP accelerated tooth movement by temporarily activating osteoclastic activity and that medium-level PRP applied at high level [31]. They reported that it accelerated tooth movement, although less than PRP. Rashid et al. reported in their study on dogs that local PRP injection can accelerate tooth movement without clinical and microscopic side effects [32].

Liou reported in their research on humans that submucosal PRP injection can increase the speed of tooth movement without surgical application and alveolar bone loss. In his clinical study, he reported that local submucosal PRP injection was 1.7 times faster in maxillary and mandibular leveling and this acceleration was PRP dose-dependent [30]. This PRP ratio (platelet count in PRP/platelet count in the blood) is <12.5. He stated that the ideal number of PRP platelets to be used to accelerate tooth movement should be 9.5–12.5 times the normal. On the other hand, PRP injection during en-masse retraction reduced alveolar bone loss by 71–77% on the pressure side, which is also dose-dependent. The optimal dose of PRP for optimal clinical performance is 11.0–12.5-folds, with submucosal injection of PRP accelerating orthodontic tooth movement and at the same time protecting the alveolar bone on the pressure side of orthodontic tooth movement. A single dose of PRP injection is effective for 5–6 months. It has been reported that the most effective period of PRP injection in accelerating tooth movement is the second half of the 4th month after the injection.

Tehranchi et al. in their study on humans, in eight patients who needed bilateral first premolar extraction, L-PRF was placed in the extraction socket on one side following a tooth extraction, and the opposite side constituted the control group. As a result of the study, tooth movement was found to be faster on the side where L-PRF was inserted into the extraction socket compared to the control side [34].

Nemtoi et al. reported that PRF placed in the extraction socket accelerates bone regeneration and tooth movement compared to the control side, and anterior and posterior teeth move faster toward the extraction cavity [33].

#### **2.2 Physical/mechanical stimulation methods**

#### *2.2.1 Resonance vibration*

In order to accelerate tooth movement, resonance or ultrasonic vibration applications are made. The application of vibration to accelerate tooth movement was first tried by Krishtab et al. [42]. Later, Ohmae et al. argued that ultrasonic vibration increases the speed of tooth movement, but they reported that ultrasonic vibration has a detrimental effect on the dental pulp [43].

Nishimura et al. showed in their study on rats that resonance vibration increases the speed of tooth movement and does not cause periodontal damage. They reported that the resonance vibration method was effective with the activation of RANK-RANKL in periodontal tissues [44].

In their study, Kau et al. had 14 patients undergoing fixed orthodontic treatment use a new commercial product, Acceledent™ (OrthoAccel Technologies, Inc., Bellaire, TX, USA) (**Figure 1**) for 20 minutes a day, in accordance with the manufacturer's recommendations [45]. They reported that there was an increase in tooth movement speed compared to the control group, which did not apply any acceleration method.

#### *2.2.2 Direct electric current and electromagnetic stimulation*

In animal studies investigating the effect of direct electric current on tooth movement, it has been reported that direct current is applied to the anode in the pressure regions and the cathode in the voltage regions, changing the bioelectric potential of the direct current and accelerating tooth movement. However, it has been reported that electrical current may have side effects such as ionic reactions causing damage to tissues and displacement of bone tissue with connective tissue [46].

Darendeliler et al. suggested that the static magnetic field accelerates tooth movement by shortening the pause period in which orthodontic tooth movement is not seen. It has been reported that the electromagnetic field affects the level of a group of enzymes responsible for the regulation of intracellular metabolism by changing the sodium-calcium exchange rate in the cell membrane, thereby increasing cellular proliferation [47]. By affecting the cellular activity in the periodontal space, it accelerates both osteoclastic and osteoblastic activities, and thus, the movement takes place in a shorter time in force-applied teeth. It has been reported that due to the stabilization of the rate of resorption due to increased bone formation, mobility in the teeth

**Figure 1.** *Acceledent™.*

decreases and pain is not observed in teeth exposed to chewing forces [48, 49]. In a study on the side effects of this method, it was reported that minor changes in blood chemistry may occur with a decrease in serum calcium level [47].

#### *2.2.3 Low-level laser irradiation therapy*

One of the techniques developed to accelerate tooth movement is low-dose laser application. Laser is a light source obtained by stimulating and amplifying radiation [50].

Laser application: It has been stated that it stimulates the proliferation of osteoclasts, osteoblasts, and fibroblasts and thus accelerates tooth movement by affecting bone remodeling [51]. Low-dose laser application activates the cytochrome C oxidase enzyme in electron transfer, causing an increase in adenosine triphosphate (ATP) in the cell, thus accelerating the tooth movement [52]. It has been reported that low-dose laser application accelerates tooth movement through RANK-RANKL, M-CSF, and the receptor of this factor [53].

In an animal study in which the effect of low-dose laser application on tooth movement speed was examined for the first time, 10 g orthodontic force was applied to the molar teeth of experimental animals for 12 days in three parts of the teeth (buccal, palatal, mesial) for a total of 9 minutes a day, 35.3 W/cm2 (54 Joule) Gallium aluminum arsenide (GaAlAr) diode laser with a wavelength of 830 nanometers (nm) was applied. As a result of histomorphometric and histological analyzes, it was reported that there was an increase in bone remodeling and a 1.3-fold acceleration in tooth movement with laser application [54].

Cruz et al. conducted the first clinical study on the effect of low-dose laser application on tooth movement and applied only mechanical activation on one side of the arch and laser with mechanical activation on the other side in 11 patients who were planned to undergo canine distalization [55]. After each force activation, GaAlAr semiconductor diode laser was applied at a power of 780 nm and a dose of 5 J/cm2 for 10 seconds. They showed that they could accelerate tooth movement by 34% when they applied four times a month over the mucosa from the buccal and palatal of the canine tooth to the cervical, middle and apical third of the root. They also found a significant reduction in patient discomfort and pain sensation.

Seifi et al. and Yamaguchi et al. reported that laser application did not cause any change in tooth movement speed [13, 56].

There have also been several studies showing contrasting results with low-level laser therapy. Therefore, more studies are needed to distinguish the optimum wavelength, optimum energy, and optimum duration.

#### **3. Surgical methods**

#### **3.1 Corticotomy and osteotomy**

Corticotomy and osteotomy are surgical techniques that have been used clinically for many years. Osteotomy a is surgical cut in the bone, including the cortical and trabecular bone [57, 58]. Corticotomy is incisions, cut and perforation procedures performed only in the cortical bone, not involving the medullary bone [51].

Corticotomy-assisted orthodontic tooth movement was first described by LC Bryan in 1893 [59]. However, corticotomy performed by Henrich Köle in 1959 to

#### *Current Methods for Acceleration of Orthodontic Tooth Movement DOI: http://dx.doi.org/10.5772/intechopen.100221*

accelerate orthodontic tooth movement is an evolution in this regard [60]. Köle thought that the main resistance to tooth movement was the cortical bone and that tooth movement could be accelerated by disrupting the integrity and continuity of the cortical bone. Köle created "bone blocks" by making interradicular vertical corticotomy incisions on the buccal and palatal surface and subapical horizontal osteotomy incisions connecting these incisions in the buccopalatinal direction. He made the incisions only in the cortical bone without causing any damage to the cancellous bone. He reported that when high orthopedic forces are applied with adjustable screw appliances, major active tooth movement can be completed within 6–12 weeks [60].

The changes that occur in the bone after corticotomy was first described by Herald Frost as the Regional Acceleratory Phenomena (RAP) [61]. Based on this phenomenon, increasing the rate of tooth movement is not due to the decreasing bone resistance only but also the effects of the healing process on the rapidity of bone cell activation.

The most widely accepted technique today was put forward by Wilcko et al. [62, 63]. According to the results of their studies, they stated that tooth movement resulted from demineralization and remineralization in reversible osteopenia occurring in the alveolar bone during wound healing, in line with RAP, rather than bone block movement.

The Wilcko brothers introduced the technique called "accelerated osteogenic orthodontics"(AOO), in which they combined selective alveolar decortication, alveolar augmentation, and orthodontic tooth movement, later called "periodontally accelerated osteogenic orthodontics"(PAOO) or "Wilckodontics." The basic principle in this technique is to create a layer of bone of 1.5 mm or less on the root surface in the direction of intended tooth movement. Similar to techniques in which bone block is created, the flap is raised and vertical corticotomies are performed. Alternatively, horizontal corticotomies that do not descend into the medullary bone are performed under the roots of the teeth to be moved. Thus, it was stated that the vitality of the teeth was preserved. In order to accelerate healing, a bone graft was applied and RAP was modified. (**Figure 2**) As a result of the study, no periodontal problems, root resorption, luxation, and changes in alveolar bone height were found, and the duration of orthodontic treatment was reduced by 1/3 or 1/4 [62, 63].

The advantages of the technique are shortening the treatment period compared to conventional treatments, moving the teeth more, reducing hyalinization and root resorption due to the decrease in the pressure in the periodontal ligament, treating bone defects by grafting, and decreasing the recurrence rate by deteriorating tissue memory with corticotomies. The invasive surgical procedure, additional costs, risk of bone loss, and complications such as pain, edema and infection due to surgery are also disadvantages of the technique [62, 63].

The "rapid orthodontic treatment" technique developed by Chung is based on corticotomy and serial movement of the dentoalveolar segments with orthopedic forces [64]. The method is similar to the accelerated osteogenic orthodontic technique, but the difference of this technique is that the dentoalveolar segment is also moved along with the teeth [65].

#### *3.1.1 Distracting the periodontal ligament*

Liou and Huang, in their study, defined the technique as "distraction of the periodontal ligament," which is based on the formation of new bone due to the tension of the healing bone, by reducing bone resistance in principle similar to distraction

#### **Figure 2.**

*Treatment of a 23 year-old male patient. A, Before treatment, anterior view. B, After treatment, total AOO treatment time 6 months 2 weeks,anterior view. Corticotomy and bone grafting (Wilcko 2009).*

osteogenesis. The aim of this technique is to distalize in a short time, to prevent loss of anchorage in posterior teeth and resorption of canine teeth. In cases where they applied fixed treatment with first premolar extraction in this technique, the interseptal bone distal to the canine after extraction was vertically weakened with a drill [66]. Following the surgical procedures, a special tooth-supported intraoral distractors were placed and activated 0.5–1 mm per day. With this technique, the canines were moved 6.5 mm toward the extraction space in three weeks. It has been reported that this technique can accelerate tooth movement without causing serious root resorption, ankylosis and root fracture [51]. However, some conflicting results have been reported regarding the vitality of distalized canine teeth. Liou and Huang reported that 9 out of 26 teeth responded positively to the vitality test, while 7 out of 20 teeth responded positively to the vitality test after the sixth month of retraction, in the study by Sukurica et al. [66, 67]. Therefore, there are still uncertainties regarding this technique.

#### *3.1.2 Dentoalveolar distraction*

Dentoalveolar distraction differs from periodontal ligament distraction in that the tooth is moved together with the surrounding bone. Kişnişçi et al. presented this technique in order to shorten the duration of orthodontic treatment. In this technique, following the extraction of the first premolar tooth, the alveolar segment around the canine was mobilized and an intraoral distractor was placed and 0.8 mm of tooth movement per day was performed. Canine distalization was completed in 8–14 days. Researchers stated that there was no loss of anchorage, root resorption, ankylosis and discoloration in the first molar teeth [68, 69].

#### *3.1.3 Micro-osteoperforation (MOP)*

The method of creating holes in the alveolar bone to increase osteoclastic activity in order to accelerate orthodontic tooth movement is called "alveosynthesis." For this purpose, a disposable device called propel was designed by "propel orthodontics." It has been reported that microosteoperforations (MOPs) applied during canine distalization cause a significant increase in the amount of cytokines that increase osteoclast differentiation and number. It has been found that MOPs increase tooth movement 2–3 times compared to the control group during canine distalization. It was stated to be a comfortable and reliable method [70].

#### *3.1.4 Piezocision*

Corticotomy, which is one of the methods applied to accelerate orthodontic tooth movement, is an effective method, but it is a highly invasive method. Because it requires wide flap removal and bone surgery, which can cause discomfort and complications after surgery [71]. Vercellotti and Podesta, in their study, recommended the use of a piezosurgical blade in order to create safer and more precise corticotomies without causing osteonecrotic damage after flap removal in order to reduce surgical trauma and accelerate tooth movement [72]. Kim et al. applied the corticization method, which is a method that causes surgical damage to the bone without lifting the flap. They argued that this method increased the effect of BHF and accelerated tooth movement. However, due to the difficulty of accessing the periodontium and the surgical procedures, temporary dizziness was observed in the patients [73]. Most recently, Dibart et al. introduced the "piezoincision" technique, which is a new and minimally invasive method and performed without flap lifting [74].

As a result of a histological study, it has been shown that decortication with piezoincision has an effect similar to the BHF effect. In this study, it was shown histologically that transient osteopenia occurred and osteoclastic activity was stimulated in as little as one day. In addition, it has been determined that piezoincision application creates deeper demineralization areas and accordingly tooth movement is twice as fast [75] (**Figure 3**).

It has been reported that, depending on the difficulty of tooth movement and the bone morphology of the patient, the piezoincision procedure can be repeated 5–6 months later in order to reactivate the RAP [76].

**Figure 3.** *RAP with piezocision. (Dibart 2015).*

Aksakalli et al., in their study investigating the effect of piezoincision during canine distalization, reported that tooth movement speed increased, anchorage control was better in posterior teeth, and there was no transversal narrowing in the upper jaw. They also stated that periodontal health was not adversely affected [77]. It has been reported that the possibility of bacterial endocarditis should be considered in high-risk patients, since bacteremia may occur temporarily in patients with piezoincision [78].

The most important feature of piezoelectric surgery devices is that when they come into contact with soft tissue, the tissue can absorb vibrations and disperse them by converting them to a slight heat. In this case, the device cannot make the incision. When the physician realizes that the vibrations have stopped, he realizes that he is in contact with the soft tissue and stops the procedure. Even when you continue to force it in the same position, no rupture occurs in the vessels or nerves. In the worst case, the damage will usually be reversible. Due to this feature, it is possible to make precise incisions without damaging tissues such as nerves, vessels, and membranes [79]. One of the important advantages of the device is the cavitation phenomenon created by ultrasonic frequency. The cooling solution applied during the procedure takes the form of an aerosol and washes the treated area, clogs small vessels, and removes tissue residues and blood. In this way, it both reduces bleeding and provides a good viewing angle [80]. It is possible to make more precise incisions since macro-vibrations do not occur as in conventional techniques [81]. In addition, it is more comfortable for the patient as it produces less vibration and noise [82].

The vibrations created by the device and the shock waves that occur in the liquid environment act as a disinfectant and reduce the bacteria [83]. In another study, it was stated that the application of piezoincision may cause transient bacteremia and therefore the risk of bacterial endocarditis should be considered [78]. As a result of the examinations made on the bone fragments exposed during the surgical procedure, it was determined that the cells were alive and necrosis did not occur in the bone tissue [84]. It is more advantageous than conventional techniques in terms of wound healing and new bone formation, thanks to the reduction of the risk of necrosis and the ability to make precise incisions with micro-vibrations [72].

#### **4. Conclusions**

In the literature, there are many invasive and non-invasive methods that accelerate orthodontic tooth movement. More extensive studies should be done on this subject.

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Acronyms and abbreviations**


*Current Methods for Acceleration of Orthodontic Tooth Movement DOI: http://dx.doi.org/10.5772/intechopen.100221*


#### **Author details**

Mehmet Akin\* and Leyla Cime Akbaydogan Faculty of Dentistry, Alanya Alaaddin Keykubat University, Alanya, Turkey

\*Address all correspondence to: mehmet.akin@alanya.edu.tr

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 4**

## Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption

*Tara Emerick, Maria Grace Viana and Carla A. Evans*

#### **Abstract**

While the presentation of Short Root Anomaly (SRA) in Hispanic patients has been described previously, it is not known if this population is predisposed to increased orthodontic root resorption. This study evaluates the response of pre-existing short roots in Hispanic SRA patients to orthodontic treatment. Selected maxillary and mandibular teeth of 40 Hispanic SRA patients (19 male, 21 female) and 40 age and gender matched Caucasian patients (19 male, 21 female) with normal root length were evaluated for root resorption following comprehensive orthodontic treatment. The age range of the subjects was between 10 and 19 years. Relative root length was calculated before and after orthodontic treatment from digital panoramic radiographs. Overall, statistically significant root resorption occurred in the control group, but orthodontic root resorption was not significant in the Hispanic group (p > 0.05). When genders were separated, Hispanic females did experience a mild degree of root resorption in the upper incisors while resorption in Hispanic males was not significant. Caucasian females experienced greater root resorption than Caucasian males. Hispanic SRA patients may be safely treated with comprehensive orthodontics and could be at no more risk of root resorption than Caucasian patients with normal initial root length.

**Keywords:** orthodontics, short root anomaly, root resorption, Hispanics

#### **1. Introduction**

There are two main causes of short dental roots: 1) disturbances during root development or 2) resorption of well-developed roots. Developmentally short-rooted permanent teeth can be genetic, known as short root anomaly (SRA) [1, 2], or exogenous, including irradiation of the head and neck and/or chemotherapy in childhood during tooth development [3]. Resorption of dental roots as a result of orthodontic treatment is termed Orthodontically Induced Inflammatory Root Resorption (OIIRR) and is believed to result from a combination of genetics, environmental, and mechanical factors. Puranik et al. [4] identified a population of Hispanic orthodontic patients presenting with SRA. Although the Hispanic population only comprises 17.8% of the U.S. population, it is the largest minority ethnicity with 57.5 million people and continues to grow [5].

In cases of pre-existing short root length (**Figure 1**), orthodontists should be aware if greater root resorption is anticipated as normal orthodontic treatment could sentence these teeth to exfoliation or extraction. Short dental roots may complicate dental treatment planning when considering anchorage or estimating the ability of a tooth to carry masticatory forces. Two recent publications proposed such potential hazards, but did not supply clinical evidence [6, 7]. This is the first study, to the authors' knowledge, that has investigated the response of dental roots to orthodontic treatment in a Hispanic SRA population.

Root resorption is a common side effect of orthodontic treatment and is estimated to occur in 73% of orthodontically treated cases [8]. Luckily, in the majority of cases, resorption is classified as mild to moderate [9] and is clinically insignificant. While some studies have found females to experience more resorption [10], others report that gender is unlikely to have an effect on root resorption [11].

Short-root anomaly (SRA) is a developmental phenomenon in which permanent teeth never reach their normal length and appear very short and blunted [2]. Lind [1] first described SRA in 1972 as "abnormally short roots of a characteristically plump shape affecting maxillary central incisors primarily." It is considered to be familial [1] and prior to Lind, SRA was commonly misdiagnosed as root resorption. Interestingly, multiple studies have suggested a primarily autosomal dominant inheritance pattern. In a recent study by Puranik et al. [4], SRA was found to occur more frequently in Latino individuals with the majority having localized SRA and the minority having generalized SRA, in which every tooth in the mouth is affected [4].

Some studies have found that patients with short or blunted roots prior to treatment, undergo significantly more root shortening during orthodontic treatment than patients with no dental anomaly [12–14], while others have found a minor or non-significant relationship between blunted roots and root resorption with orthodontic treatment [2, 15, 16] and still others report that blunted teeth experience less resorption than normal-shaped teeth [11].

#### **Figure 1.**

*Periapical radiograph showing an example of maxillary incisors in a Hispanic female subject with localized SRA before starting orthodontic treatment.*

*Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption DOI: http://dx.doi.org/10.5772/intechopen.99538*

Some authors believe that this is due to a change in the position of the tooth's center of resistance, moving it more incisally. Studies that looked specifically at "pipetteshaped" roots, rather than blunted, consistently found greater root resorption [11]. Correlations have also been found between initial tooth length and the amount of resorption (i.e., a longer root was more likely to be resorbed with orthodontic treatment) [11, 17]. Mirabella and Artun [17] argued that teeth with longer roots require stronger orthodontic forces to move them; furthermore, the displacement of the root apex is greater during tipping and torquing movements of longer rooted teeth.

The objective of this study was to assess changes in root lengths that occur with orthodontic treatment by comparing: 1. pre-and post-treatment digital panoramic radiographs of Hispanic patients presenting with short dental root lengths; 2. the experience of Hispanic patients and Caucasian patients presenting with normal dental root lengths; and 3. gender differences within each ethnicity group.

#### **2. Comparison of treatment outcomes**

#### **2.1 Material and methods**

This was a retrospective study that included male and female Hispanic and Caucasian patients in a university orthodontic clinic. Dental records of 40 Hispanic SRA and 40 Caucasian patients were collected. In this clinic, most of the Hispanic patients are of Mexican heritage. The Hispanic group consisted of 19 male and 21 female adolescent patients and the Caucasian group consisted of 19 male and 21 female adolescent patients. The mean age of subjects was 14.7 + 1.91 years in the Caucasian group and 13.9 + 1.86 years in the Hispanic group. All pre-existing records were taken at the orthodontic clinic for comprehensive orthodontic treatment. All radiographs were taken in the Radiology Clinic. Panoramic radiographs were taken on a standard combined panoramic/cephalometric machine. All radiographs were consistent with the standard of care for all orthodontic patients in the clinic and included pre- and post-treatment panoramic radiographs. For every extraction case in the Hispanic group, an extraction case in the Caucasian group was included. All subjects were de-identified and assigned a coded number. Only the sex, ethnicity, and age in years and months at the start of treatment were retrieved from the patient chart. All subjects with developmental disorders or complicated medical histories were excluded. Individual teeth were excluded if 1) the apex was not closed, 2) the reference points were not clearly visible, 3) there was a history of dental trauma, root canal therapy, orthodontics, or an incisal or full-coverage restoration, 4) attrition or abrasion of the crown was present. In this study generalized and localized SRA patients were grouped together even though their pathogenesis may differ. IRB exemption was granted prior to data collection.

Root lengths were measured on maxillary and mandibular central and lateral incisors, and second premolars, from the apex to the midpoint of the cementoenamel junction (CEJ) on panoramic radiographs. The aforementioned teeth were selected because they are single-rooted teeth (with the exception of the variation in upper second premolar) and the root outline of these teeth can be more clearly visible on radiographs than multi-rooted teeth. Furthermore, SRA in a Mexican cohort most commonly occurred in maxillary central incisors and mandibular second premolars [4]. It is assumed that during orthodontic treatment, the crown length does not change. Therefore, the ratio between the root and crown length should reflect any

changes in root length. Crown and root lengths were measured on panoramic radiographs using the Dolphin™ digital caliper (Dolphin Imaging 11.8, Chatsworth, CA).

The Lind method of relative root length calculation was used [1] in which the midpoint of the mesial and distal CEJ (median CEJ) is used to demarcate the transition from crown to root. Root length was measured from the median CEJ (point M) to the tip of the root (point R). Crown length was measured from point M to the incisal edge or tip (point I). Relative root length was calculated by dividing point M to point R length by point I to point M length [1]. Root length guidelines set by Holtta et al. [3] were used in the measurements of all panoramic radiographs.

Statistical analysis was done using IBM SPSS Statistics for Windows (version 22.0, IBM Corp., Armonk NY). Analyses were performed by the Explore function in SPSS to check the raw data distribution by Shapiro–Wilk Tests of Normality. Parametric tests were done based on the results that the majority of the variables showed normal distribution of the data. Student Paired Sample *t*-tests were used to assess the mean differences between pre and post measurements of all the variables in each of the Hispanic and Caucasian groups with the sample gender in consideration. Independent *t*-tests were done for the mean comparisons to all study variables between groups. All values were considered statistically significant for a value of p<0.05.

#### **2.2 Results**

The Caucasian group had a statistically significant differences between pre-orthodontic treatment and post-orthodontic treatment relative root lengths (**Table 1**). The post-orthodontic treatment relative root lengths (1.87 ± 0.30) were significantly less than the initial relative root lengths (2.10 ± 0.29), indicating root resorption


#### **Table 1.**

*Mean comparison of pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Caucasian group.*

*Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption DOI: http://dx.doi.org/10.5772/intechopen.99538*

from the orthodontic treatment in the Caucasian group. The only measurements that did not show statistical significance were the lower left lateral and lower left central incisors.

Overall, there was only a mild difference between Hispanic initial relative root lengths (1.57 ± 0.27) and Hispanic post-orthodontic treatment relative root lengths (1.55 ± 0.29) (**Table 2**). Significant root resorption was seen in five teeth: UR2, UR1, UL1, LR1 and LR2. Differences were also seen in the mandibular left second premolars which increased in relative root length after orthodontic treatment. Furthermore, the percentage decrease in relative root length was consistently higher in the Caucasian group (**Tables 1** and **2**).

Genders were separated and post-treatment relative root lengths were compared against pre-treatment relative root lengths in order to further evaluate any significant root resorption that occurred with orthodontic treatment. There was no difference in post-orthodontic treatment relative root length when sexes were compared within the Hispanic group. However, there was a difference between males and females in postorthodontic treatment relative root length with Caucasian females (1.80 ± 0.28) experiencing a smaller post-orthodontic treatment relative root lengths than Caucasian males (1.95 ± 0.31). Statistically significant differences in post-orthodontic treatment relative root length were found in four teeth when Caucasian male and Caucasian female groups were compared (**Tables 3** and **4**). Specifically, the relative root lengths of UR1, UL1, LL2, and LL1 were found to be significantly less in the Caucasian female group than the Caucasian male group. Because there was no statistically significant gender difference in pre-orthodontic treatment root lengths in the Caucasian group, this finding suggests that Caucasian females experienced more root resorption from the orthodontic treatment than Caucasian males.


#### **Table 2.**

*Mean comparison of the pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Hispanic group.*


#### **Table 3.**

*Mean comparison of pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Caucasian male (CM) group.*


#### **Table 4.**

*Mean comparison of pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Caucasian female (CF) group.*

*Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption DOI: http://dx.doi.org/10.5772/intechopen.99538*

In the Caucasian male group, significance was found in five teeth: UR2, UR1, UL1, UL2, LL5 (**Table 3**). In all five teeth, the final was smaller than the initial, indicating that these teeth did in fact experience statistically significant orthodontic root resorption.

Significance between pre and post-treatment relative root length was found for nearly every tooth in the Caucasian female group: UR5, UR2, UR1, UL1, UL2, UL5, LL5, LL2, LR2, LR5 (**Table 4**). All teeth showed decreased relative root lengths posttreatment, suggesting significant root resorption from the orthodontic treatment. The only teeth that did not show a significant difference between pre and post were the two lower central incisors: the post-treatment mean relative lengths for these teeth were still smaller than the pre-treatment.

When post-treatment relative root lengths were compared to pre-treatment root lengths in Hispanic males, three teeth showed a significant difference: UR5, UL5, and LL5 (**Table 5**). However, the mean relative root lengths showed that these root lengths increased in apparent length after treatment.

Significance was found for five teeth in the Hispanic Female group: UR2, UR1, UL1, UL5, LR2 (**Table 6**). While there does appear to be mild root resorption from orthodontic treatment in UR2, UR1, UL1, and LR2; the mean relative root length for UL5 is increased in the post group, suggesting an increase in relative root length with orthodontic treatment.

#### **2.3 Discussion**


There have been many claims that SRA predisposes patients to increased orthodontic root resorption, for example the study of Wang and Feng [6]. However, it is not

#### **Table 5.**

*Mean comparison of pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Hispanic male (HM) group.*


#### **Table 6.**

*Mean comparison of pre-orthodontic relative root lengths and post-orthodontic treatment relative root lengths in the Hispanic female (HF) group.*

known if this cohort indeed experiences a higher degree of orthodontic root resorption, or if they experience a similar degree of resorption to unaffected patients, but the appearance is more suggestive due to their pre-existing short roots. If a greater degree of relative root loss does occur, the orthodontic professional should be aware so that treatment complications can be anticipated when treating Hispanic SRA patients.

Post-orthodontic treatment relative root lengths were significantly smaller than the initial relative root lengths for the Caucasian group, indicating root resorption from the orthodontic treatment. Hispanic initial relative root lengths and Hispanic post-orthodontic treatment relative root lengths were similiar. Furthermore, the percentage decrease in relative root length was consistently higher in the Caucasian group, further supporting the finding that the Caucasian subjects experienced OIIRR while the Hispanic subjects had minimal, if any. Because the treating orthodontists in this study were aware of the pre-existing short roots in the Hispanic SRA group, it is likely that these patients were treated more conservatively, with lower forces, and with greater care. Studies have also speculated that shorter roots may experience less root resorption due to 1) shorter teeth requiring less force to move and 2) the root tip being displaced a shorter distance through the bone in second and third-order tipping motions [18, 19].

In the Caucasian male group, the maxillary incisors experienced statistically significant orthodontic root resorption. This finding agrees with the literature as the upper incisors are commonly the most affected teeth in orthodontic root resorption. However, in the Caucasian female group, root resorption was found in nearly every tooth measured and to a greater extent. There was no statistically significant root

#### *Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption DOI: http://dx.doi.org/10.5772/intechopen.99538*

resorption found in the Hispanic male group. Conversely, statistically significant root resorption was found for four teeth in the Hispanic female group: UR2, UR1, UL1, and LR2 but the percentage decrease in relative root length was still mild in comparison to the degree of root resorption that both Caucasian groups (male and female) experienced. These findings that females experience greater OIIRR than males agree with other findings in the literature [10, 20].

Most teeth were bilaterally affected; however, resorption of the mandibular second premolar was the tooth that most commonly presented unilaterally. One of the limitations of this study was the assessment of closed apices in the SRA group. SRA roots are characterized by wide pulp chambers and truncated roots which is very similar in appearance to roots that are still undergoing development. Some of the second premolar measurements displayed slightly longer final root lengths than initial. Explanations for this finding are 1) some form of error in measurement, or 2) the second premolar root lengths were measured in the Hispanic group prior to cessation of root development.

Future studies are needed to complete a more detailed analysis regarding the nature of the genetic inheritance and prevalence of the SRA condition in the Hispanic population. In this study, Hispanic SRA patients were found to comprise approximately 2% of the total patient population treated in the university orthodontic clinic. A point of interest would include the geographic origins within Mexico and inheritance patterns of SRA Hispanic patients. Also, while there is much speculation regarding the etiology of SRA, the developmental process resulting in the SRA condition has yet to be determined. It is also not known whether the mechanism is the same across all subgroups of SRA.

#### **3. Conclusions**

The following conclusions were obtained from this study:


The observations of this study suggest that Hispanic SRA patients may be safely treated with comprehensive orthodontics and could be at no more risk of root resorption than Caucasian patients with normal pre-treatment root length. Clinicians are still advised to treat Hispanic SRA patients conservatively. Although more studies are needed, these findings can be considered when making educated treatment decisions for this specialized population of orthodontic patients. To the authors' knowledge, this is the first study to evaluate the response of Hispanic patients with SRA to orthodontic treatment.

#### **Acknowledgements**

The authors gratefully acknowledge substantive discussions with Drs. Chester Handelman and Ahmed Masoud.

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Tara Emerick1 , Maria Grace Viana<sup>2</sup> and Carla A. Evans3 \*

1 Private Practice, Carmel, Indiana, USA

2 Department of Orthodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA

3 Department of Orthodontics, Boston University, Boston, MA, USA

\*Address all correspondence to: caevans@bu.edu

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Short Root Anomaly in a Hispanic Population: Risk for Orthodontic Root Resorption DOI: http://dx.doi.org/10.5772/intechopen.99538*

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Section 2
