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 Table of Contents  
Year : 2023  |  Volume : 15  |  Issue : 5  |  Page : 431-442

Tooth movement in immune system: A narrative review

Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia

Date of Submission21-Nov-2022
Date of Decision09-Aug-2023
Date of Acceptance25-Aug-2023
Date of Web Publication30-Oct-2023

Correspondence Address:
I Gusti Aju Wahju Ardani
Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jioh.jioh_244_22

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Aim: Applying forces to teeth causes orthodontic tooth movement. Orthodontic tooth movement necessitates bone remodeling, brought on by intricate aseptic inflammatory cellular and molecular processes. According to the “pressure-tension” theory, applying pressure to a tooth varies the blood vessels’ diameter in the periodontal ligament, which then changes the blood flow. Chemical messengers cause cellular changes as a result, which results in the remodeling of the alveolar bone. Materials and Methods: This study was obtained based on literature in journals from Pubmed, Scopus, and Web of Science databases. The review developed a method to determine whether comparable the literature was using the exact keywords before developing findings and then summarizing them into a continuous sequence. The case reports investigated patients who met the inclusion criteria for dental implants and osseointegration. There were 21 journals from PubMed, Scopus, and Web of Science databases. The present review is from research, review, and case report study with eligibility criteria. The review results discovered that according to the “pressure-tension” idea, applying pressure to a tooth modifies the blood flow by altering the periodontal ligament’s blood vessel diameter. Results: Alveolar bone remodeling results from cellular changes brought on by chemical messengers. Inflammation is the host tissue’s defensive reaction to pathogens, injury, or external objects. Vascular dilation, improved capillary permeability, increased blood flow, and leukocyte recruitment are all signs of inflammation. The first cells to arrive at the inflamed region are polymorphonuclear neutrophils. Eicosanoids, a group of hormones that includes prostaglandins, are chemical messengers. Conclusion: Several articles have suggested specific compounds as orthodontic tooth movement biomarkers. The creation of biomarkers to comprehend the ongoing biological processes related to orthodontic tooth movement is developing.

Keywords: Forces, Human and Health, Orthodontic Tooth Movement, Pressure Tension, Remodeling

How to cite this article:
Ramadayanti SL, Caesar AD, Amalia R, Warizgo DR, Ardani IA. Tooth movement in immune system: A narrative review. J Int Oral Health 2023;15:431-42

How to cite this URL:
Ramadayanti SL, Caesar AD, Amalia R, Warizgo DR, Ardani IA. Tooth movement in immune system: A narrative review. J Int Oral Health [serial online] 2023 [cited 2023 Dec 4];15:431-42. Available from:

  Introduction Top

Orthodontic tooth movement (OTM) results in avoiding putting pressure on teeth. the gingiva, alveolar bone, and periodontal ligament are among the tissues affected by this activation, along with the teeth and tissues nearby. Since some of these features may vary from person to person, it is advantageous for the orthodontist to know the specifics of the biological processes that occur as the teeth move. Gender, age, psychological state, dietary preferences, and drug use are among the factors contributing to this.[1]

Many adult patients receive orthodontic treatment; it is no longer just for children and adolescents. Therefore, orthodontic treatment is given to adults who smoke and are more likely to develop periodontal disease. Thus, the interaction of these factors (adults with past smoking, orthodontic treatment, and periodontal disease) may raise the possibility of more attachment loss and speed up the periodontium’s deterioration, which may impact orthodontic therapy.[2] It has been established that nicotine has unfavorable consequences during orthodontic treatment, including poor bracket adhesion, miniscrew failure, and unfavorable impacts on bone remodeling.[3]

The prolonged force appliance might detect changes to the tooth pulp’s blood flow that could lead to a loss of vitality. The properties of the applied orthodontic forces, such as their magnitude, appliance placement, and distribution, may affect blood flow and cause a reversible or irreversible change.[4]

OTM involves remodeling the bone, which is brought on by intricate aseptic inflammatory cellular and molecular processes. Recent research has revealed that the immune and skeletal systems interact reciprocally, creating the new subject of osteoimmunology. Several research studies have indicated that immune system cells’ cytokine release or interactions between cells regulate osteoclasts (OC) and osteoblasts (OB) differentiation and activation. The periodontal ligament (PDL) is the primary tissue that initiates these aseptic inflammatory processes. The result of PDL is crucial in OTM.[5] According to the “pressure-tension” theory, applying pressure to a tooth changes the PDL blood vessels’ diameter, which changes the blood flow. Chemical messengers cause cellular changes as a result, which results in the remodeling of the alveolar bone.[6],[7] In case studies displaying quick and challenging tooth movement, the orthodontist may combine various dentoalveolar operations, such as corticotomies and osteotomies, to change bone biology.[8]

  Material and Methods Top

Search screening

A narrative review was undertaken to determine whether applying more pressure to a tooth causes the blood vessels in the PDL to enlarge, changing the blood flow. Various articles were from Pubmed, Scopus, and Web of Science databases from 2018 to 2023. The reviewed articles are original research, review, case report, and clinical trial. The two researchers examined titles and abstracts following the search. The search terms were checked against full texts. The discovered reviews were examined for discussion of “orthodontic tooth movement” or “remodeling” orthodontic force. The references were also checked if a pertinent paragraph was discovered. Double findings were eliminated after additional analysis of all pertinent results and references. The entirety of the report was compiled, discussed, and settled upon among all writers for cases that appeared to be appropriate for inclusion or whenever there was insufficient information to make a conclusive judgment.

Eligibility criteria

The review sought to apply the PICOS (population, intervention, comparison, outcome, study design) eligibility criteria format. The population of interest was patients undergoing OTM that needed bone remodeling to improve the system of immune. The intervention was bone remodeling using other role pathways. The comparison was patient-accelerated OTM using gene therapy, vibration (low-intensity pulsed ultrasound), corticotomy, laser treatment, and therapy. The outcomes were bone remodeling with pressure theory as the alternative therapy for OTM, and the study design was a cross-sectional study and narrative review.

Inclusion and exclusion criteria

The inclusion criterion was as follows:

  1. Article on Orthodontic Tooth Movement

  2. Article on bone remodeling

  3. An article about the immune system

  4. Article on the pressure tension

  5. Article was a research, review, and case report study

  6. Article in the English Language

Any publication that had yet to be updated had no recent study findings and had no connection to OTM that matched the exclusion criteria. The articles summarized after the screening process as described in [Figure 1].
Figure 1: The PRISMA flow chart

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  Result Top

Numerous articles were disqualified from the initial screening based on the keywords employed since they needed to meet the present review’s eligibility criteria. The remaining five studies were excluded for other reasons, including not reporting the OTM or remodeling in orthodontic treatment. Finally, 21 summarized articles were determined to be reliable. [Table 1] and [Figure 2] describe the risk of bias that summarized articles.
Table 1: Review and risk of bias

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Figure 2: Risk of bias of the literature

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  Discussion Top

Inflammatory mediators in OTM

Prostaglandins (PGs)

Mammalian cells, including osteoblasts, produce PGs, local hormone-like chemical agents, shortly after a cell is injured. They are a byproduct of the metabolism of arachidonic acid. PGE2, a byproduct of the cascade of arachidonic acids, makes vasodilation possible by enhancing blood vessel permeability and chemotactic characteristics. Additionally, it increases bone resorption and osteoclast production. PGE2 promotes osteoclast development and a rise in the resorption of bone. PGs act as mediators of alveolar bone loss and gingival inflammation. Periodontal tissue deterioration is closely connected with PGE2 concentrations within the periodontal tissues and gingival crevicular fluid (GCF). During OTM, the GCF’s PGE2 concentrations rose.[9],[10],[11]


On the compression and sides of the periodontal tissue under strain, RANKL is strongly expressed during OTM. Sclerostin positively controls a BMP protein’s expression, inhibits canonical Wnt signaling, and increases osteocyte RANKL expression. Bone morphogenetic proteins (BMPs) stimulate the production of new bone, and during OTM, their expression rises in terms of tension, promoting osteoblast formation following mesenchymal stem cell differentiation. The hormone transforming growth factor-β (TGF-β) causes bone resorption., depending on the cell types, TGF-β concentration, and the initiating process. Combining all, BMPs or RANKL can be provided focusing on the tension to assist skeletal regrowth, while sclerostin or sclerostin can be given regarding compression to speed up osteoclastogenesis. Even though their effects are more noticeable in the late phase of OTM, the new bone formation cannot cause tooth movement to occur more quickly on the tension side.[12],[13],[14],[15],[16]

T cells

Immune system reactions rely on the intricate coordination of innate and adaptive immunity. T cells are essential to the adaptive immune response that starts cellular immunity. An interdisciplinary topic of study known as osteoimmunology focuses on the molecular understanding of the interactions between the immune and skeletal systems. Additionally, immune cells develop in the bone marrow, interacting with bone cells. It is thought that T cells constantly stimulate the breakdown of bone.[17],[18],[19]

Important cytokines, including tumor necrosis factor (TNF) and interferon (IFN), are primarily produced by type 1 T helper cells (Th1). During human OTM, interleukin (IL)-1, IL-6, and TNF-β expression levels are increased fluid within the gingival crevicular. The function of IFN when remodeling bones is still debatable. In the bone marrow and PDL, phagocytes and dendritic cells mediate the T-cell-associated immunological reaction. Therefore, we proposed that orthodontic force-induced alveolar bone remodeling may involve T cells.[17]


The rate of tooth movement and bone metabolism can be affected by drugs. Several of these drugs are inhibitors of calcineurin-phosphatase (cyclosporine with tacrolimus) and immunosuppressants, contributing to the reduction in glucocorticoid doses and the more exceptional longevity of transplanted individuals. However, calcineurin-phosphatase inhibitors also reduce bone mass, comparable to glucocorticoids, resulting in the most bone loss in the first 6 months following transplanting during the height of immunosuppressive drug therapy. The most widely used immunosuppressants today are those that interfere with bone metabolism, impact cytokine generation (glucocorticoids, tacrolimus-FK506, cyclosporin-CsA, and sirolimus-RAPA), and may affect tooth movement. Immunosuppressive therapy’s force, dosage, and length all affect how bone metabolism is affected.[19],[20],[21]

Chemokines and tooth movement

The small heparin-binding cytokine superfamily includes chemokines. This category of cytokines is united by their capacity to promote cell motility. The chemokines are grouped into four subfamilies based on putting C, CC, CXC, and CX3C, two highly conserved cysteine residues, at the N-terminus. These molecules differ from conventional cytokines in that they exert their physiological effects by binding to certain G proteins with heterotrimeric G protein domains and 7-transmembrane domains.[13],[34],[35]

The ligand family determines the chemokine receptor names they belong to, such as CCR for CC ligand receptors and CXCR for CXC ligand receptors. Because a given chemokine can attach to many chemokine receptors and bind to multiple chemokine receptors, the chemokine system is promiscuous or redundant. The activities accomplished in vivo by binding chemokines to their specific receptors are sometimes different. Geographical and temporal factors influence how chemokines convey biological effects in various tissues. Leukocyte, immunological, and stromal cell trafficking and homing occur when there are physiological (homeostatic chemokines) and inflammatory circumstances (inflammatory chemokines). Angiogenesis, cell growth, and death are further biological processes that chemokines promote.[13],[34],[36]

OTM: Cellular and molecular events

Remodeling encircling dental roots’ alveolar bone is necessary to facilitate tooth mobility. Hormones, growth factors, and cytokines all play a role in the intricate system of cells (osteoblasts and osteoclasts), cell contacts, and connections between cells that occur during bone remodeling (among which some result from the stretched PDL). The orthodontic force causes mechanotransduction, which happens when external strain causes a cellular response, mechanosensing, and transduction in many paradental tissues. The extracellular matrix and vasculature of the gingiva, alveolar bone, PDL, and alveolar bone are all altered as a result of it. Local periodontal cells’ proliferation, differentiation, and death, in addition to bone cell precursors and the departure of leukocytes from the microvascular compartment, assist remodeling.[5],[12],[37],[38]

In this situation, OTM begins with an aseptic acute inflammatory response and progresses to a transient, aseptic persistent inflammation. Orthodontic forces that are constant, interrupted, or intermittent that are not regions of tension or compression result when the applied force is uniform throughout the region, which results in a range of inflammatory processes and tissue remodeling reactions.[32],[37]

Response of the immune system to OTM

The initial signal to distinguish between apposition and resorption in situations with excess workload is the bone matrix’s pressure state (positive or negative), which depends on the concept that alveolar bone distortion is bone remodeling’s primary cause. When activated, the orthodontic device’s forces applied to the tooth are conveyed to nearby tissues. Peripheral nerve fibers and terminals are another impact of the pressures’ physical distortion of the paradental tissues. As the tension remains, neuropeptides held in the nerve endings inside the PDL may either stream into the ganglion or be discharged into the extracellular area.[33]

The release of angiogenic stimulus factors for groups of cells in damaged (wounded) or hypoxic tissues will release angiogenic factors (in the form of growth factors and other short-chain proteins), which can diffuse to surrounding tissues. Following this process, an inflammatory process occurs. In an inflammatory process, small blood vessels that are locally present play an essential role in the subsequent process because blood vessels are a network covered by endothelial cells, which will interact with inflammatory and angiogenic factors. These angiogenic factors can attract and promote the proliferation of endothelial cells and inflammatory cells. Before migration, inflammatory cells also secrete molecules acting as angiogenic stimuli.[39],[40],[41],[42]

Release of protease enzymes from activated endothelial cells. Angiogenic factors in the form of growth factors then binding to certain receptors found on endothelial cell receptors (EC) around the location of sluggish blood vessels. Cells in the endothelium become active when angiogenic factors attach to their receptors and cause signals to travel from the cell surface to the nucleus. Endothelial cell organelles then begin the creation of fresh molecules, such as protease enzymes, which play an essential role in the degradation of extracellular matrix to accommodate branching blood vessels.[39],[42]

Endothelial cell dissociation and degradation of the ECM lining old vessels. Dissociation of endothelial cells from surrounding cells, stimulated by angiopoietin growth factor, and the activity of enzymes produced by activated endothelial cells, such matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), are required to initiate the formation of new blood vessels. With this enzymatic system, endothelial cells from old blood vessels will degrade ECM and invade the stroma of the surrounding tissues so that endothelial cells released from ECM will be very responsive to angiogenic signals.[43],[44],[45]

Endothelial cell migration and Proteolytic proliferation degradation of the ECM is immediately followed by the migration of endothelial cells into the degraded matrix. This process is followed by endothelial cell proliferation stimulated by angiogenic factors, some of which are released from ECM degradation products, such as peptide fragments, fibrin, or hyaluronic acid. Lumen formation and creation of new ECM The migrating endothelial cells then elongate and align with other endothelial cells to create the robust branching structures of blood vessels. Endothelial cell proliferation increases along the vascular tree. The lumen is then formed by the bending (curvature) of the endothelial cells. At this stage, contact between endothelial cells is necessary. Fusion of new blood vessels and initiation of flow Blood vessel structures connected will form a series or network of blood vessels to mediate blood circulation. In the final stage, the formation of new blood vessel structures will be stabilized by mural cells (smooth muscle cells and pericytes) as the supporting tissue of newly formed blood vessels. Without mural cells, the structures and tissues between blood vessels are fragile and easily damaged.[46],[47],[48]

Orthodontic mechanical force is applied to the tooth to be corrected so that OTM occurs; the applied force starts on the surface of the tooth crown and will be continued up to the tooth’s root. The force that arises will cause the periodontal tissue on the tooth root’s surface to respond. The resulting response is an inflammatory response on two sides of the tooth when PGO occurs, namely on the pulling and pressing sides. In terms of pressure, the PDL, given orthodontic force, will be pressed and then experience hypoxia and stimulate apoptosis of fibroblast cells. The occurrence of fibroblast apoptosis stimulates an increase in reactive oxygen species, which indicates acute inflammation; heat shock protein-70 (HSP-70), which tries to compensate for the damage and hypoxia-inducible factor α (HIf-1α) which will be recognized by macrophage cells so that will cause the cell nucleus to take place Enhancer of activated B lymphocytes by nuclear factor kappa-light chain cells (NF-κB) p65-50y. NF-κB becomes active in activating target genes and inducing pro-inflammatory cytokine release, one of which is TNF-α, which causes osteoclastogenesis. During the acute inflammatory phase, vasoconstriction occurs, releasing FGF-2 by endothelial cells and other fibroblast cells that do not undergo apoptosis. TNF-α and FGF-2 help osteoclast maturation in the process of osteoclastogenesis. It is followed by bone resorption, which causes tooth movement on the pressure side.[28],[29],[47],[48],[49]

Tooth movement should be ideally during hemostasis alveolar bone remodeling, and there is inflammation which causes resorption in the alveolar bone’s pressure zone, followed by inflammation which causes apposition within the alveolar bone as compensation. Towards the pull’s side, fibroblast cells in the PDL will experience stretching, which stimulates them to secrete heat shock protein-10 (HSP-10) to refold the protein and secrete several growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-B (TGF-B) which functions to maintain the stability of fibroblast cells. Secretion from VEGF, TGF-B, and HSP-10 will be recognized by macrophage cells as a Resolution Associate Molecule Pattern (RAMP) so that macrophages undergo polarization from M1 (NF-κB p65-50) to M2 (NF-κB p50-50) which tends to be anti-inflammatory. M2 will secrete Interleukin-10 (IL-10). Increased secretion of IL-10, VEGF, and TGF-B on the PGO pull side will stimulate RUNX2 activation, which causes osteoprotegerin (OPG) expression on the surface of osteoblast cells to increase, and osteoblastogenesis occurs on the pull side.[24],[31],[38],[49],[50]

PDL and bone cell physical and chemical changes

The tooth moves within the PDL area due to orthodontic force, which causes blood vessels to become more compressed as the PDL’s pressure rises. The translocation of ions and molecules, followed by the displacement of extracellular fluid, causes the movement of tissue fluid and interactions with cell surface charges. The levels of intracellular “second messengers” alter as a result of these charges including Ca2+, adenosine3′, 5′-monophosphate (cAMP), and guanosine3′, 5′-monophosphate, which are likely to interact with the cell membrane of osteocytes (cGMP). These second messengers will change the synthesis and secretion of cellular products, cell proliferation, motility, and other processes.[1],[27],[30],[50],[51],[52],[53]

Peripheral nerve fiber changes: Nervous system

Orthodontic pressure causes nerve endings to deform, releasing a neurotransmitter that reacts centrally by streaming toward the ganglion and peripherally by interacting with nearby target cells, mainly in the walls of blood vessels.[1]

Immune system cells change

Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptides (VIP), among others, are neuropeptides produced by activated peripheral nerve endings. The extravascular migration of macrophages and lymphocytes will occur due to changes in the neurological system, immune system cells, and contact with vascular endothelial cells. There will then be the creation and secretion of various types of mediators. These reactions are inflammatory processes, which are intricate, dynamic reactions of the body to injury. It is an endeavor to repair or replace damaged tissue and counteract unpleasant stimuli. These inflammatory-like activities alter the creation and secretion of cell products, cell proliferation, motility, and other aspects of PDL and bone cells. Alveolar bone remodeling was the result. As these compounds are apparent to perform important roles in bone cell activity both normally and pathologically, recent research on the processes governing bone remodeling has emphasized the function of cytokines. (cyto= cell, kines= kinesis).[1]

The function of inflammation in tooth mobility

An issue for the host tissues caused by viruses, damage, or foreign bodies might trigger inflammation as a protective reaction. Inflammation is indicated by leukocyte recruitment, increased blood flow, vascular dilatation, and enhanced capillary permeability. the initial cells to go to the inflammatory area are neutrophils with polymorphonuclear granules. Chemical messengers known as prostaglandins are members of the eicosanoids family of hormones.[23],[26]

Eicosanoids are classified into three major groups: prostaglandins, thromboxanes, and leukotrienes. Phospholipase A2 converts arachidonic acid found in phospholipids into arachidonic acid, which the body uses to create prostaglandins. The most significant prostaglandin subtypes are D, E, F, G, H, and I. Leukocytes create prostaglandin E2, whereas endothelial cells and platelets produce prostacyclin synthase and thromboxane synthase, respectively, and leukocytes produce prostaglandin I2. Inflammatory cells such as mast cells and macrophages also produce leukotrienes. The mechanical stresses applied during PDL and alveolar bone cells are affected by orthodontic therapy to deform physically, which activates pathways like the prostaglandin E2 (PGE2) pathway and modifies the structure and function of the extracellular, cell membrane, and cytoskeletal proteins.[54],[55]

The part that cytokines play in the mechanically induced bone remodeling cells releases cytokines8, which act as mediators and control the activity of other cells. “Cytokines” are the initial lymphokines discovered to be generated by lymphocytes. Anti-inflammatory cells generate a variety of cytokines, which are involved varying degrees of inflammation. These cytokines, which include TNF, interleukin-1 beta, alpha, and gamma, have been involved in mediating the in vitro bone remodeling process.[56] The initial indicator of bone resorption is the production of interleukin-1 beta (IL-1β). Another pair of inflammatory cytokines are PGE2 and interleukin-6 that might heighten bone resorption due to osteoclasis (IL-6). Further, osteoblastic cells regulate the osteoclastic process RANKL production enhances osteoclastic differentiation.[14],[57]

Furthermore, the idea that orthodontic forces may have biological processes that occur before tooth movement is supported by the fact that bone formation brought about by orthodontic forces led to elevated levels of ALP in the fluid in the human gingival crevicular. Nitric oxide (NO), which arises from nitric oxide synthase, an endothelial enzyme (eNOS), or induced nitric oxide synthase (iNOS), is essential for controlling how bones respond relating mechanical strain. Both bone growth and osteocyte apoptosis are prevented by it. Additionally, it promotes osteoclastic activity.[58]

Cellular transmission of mechanical forces that trigger biological responses through transitory aseptic inflammatory processes involving numerous agents of inflammation. These regional activities are the basis for achieving periodontal remodeling, enabling tooth movement. Focus on the involvement of numerous chemical and biological components, especially those that emerge after applying orthodontic forces, is what the following paragraphs of this paper are meant to do. It was discovered that nuclear factor kappa B receptor activator (RANKL), NF-κB activator of receptors (RANK), and decoy receptor for OPG all have significant effects on how bone metabolism is regulated.[49],[59]

Under tensile tension, PDL fibroblasts create cytokines, such as interleukin-1 (IL-1) and IL-6, which alter the periodontium’s tension side (1); Through autocrine and paracrine pathways, IL-1 and IL-6, respectively, induce matrix metalloproteinase (MMP) and prevent PDL cells from inhibiting metalloproteinase production (TIMP) (2); Angiogenesis is facilitated by the forced activation of fibroblasts that produce VEGF (3); MMPs’ degradation of the extracellular matrix promotes capillary creation and cell growth; PDL cells (4); cells lining the bones and osteoblasts (5) synthesize the structural matrix and more molecules to begin the biosynthetic phase.[25],[49],[59]

Periodontium remodeling on the side of compression. In this hypothetical model, interleukin-1 (IL-1) and IL-6 are produced by cells of the PDL compressed (1); IL-1 and IL-6 control nuclear factor-B receptor activator ligands through autocrine and paracrine actions (RANKL) (2); and matrix metalloproteinase (MMP), osteoblasts and PDL cells reveal (3); generated from osteoblast MMP degrades the osteoid layer on the surface of unmineralized bone (4); on the bone’s surface are mononuclear precursor cells and destroy the mineral matrix are stimulated to develop and function as osteoclasts by RANKL (5). MMP expression by osteocytes near the bone surface is controlled by alveolar bone deformation.[49],[59]

  Conclusion Top

Numerous articles have suggested specific compounds as OTM biomarkers. The creation of biomarkers has progressed to understand better the ongoing biological processes underlying OTM. Various compounds have been suggested as biomarkers based on sequential reactions and released molecules. The discovery of perspective OTM biomarkers can also benefit from the knowledge of stem cell development and the osteoblastic and osteoclastic activities involved in bone production and resorption, respectively.



Financial support and sponsorship


Conflict of interest

The authors affirm that they have no known conflicts of interest or close personal ties that may have impacted the studies presented in this investigation.

Authors contributions

Concepts, Design, Definition of intellectual content, Literature search: SLR, AOC, RA, DRW, IWA; Data acquisition, Data analysis: SLR, IWA; Manuscript Praparation and Editing: SLR, AOC, RA, DRW, IWA; Manuscript review: SLR, IWA.

Ethical policy and Institutional Review board statement

Not applicable.

Patient declaration of consent

Not applicable.

Data availability statement

The literature used in this review article was obtained from Pubmed, Scopus, Web of Sciences, and Google Scholar.

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  [Table 1]


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