Seminars in Orthodontics
EDITOR -IN-CHIEF
Elliott M. Moskowitz, DDS, MSd
EDITORIAL BOARD
EDITOR-IN-CHIEF EMERITUS
P. Lionel Sadowsky, DMD, BDS, DipOrth, MDent
Mani Alikhani, New York, NY (2017)
Rolf G. Behrents, St. Louis, MO (2017)
S. Jay Bowman, Portage, MI (2017)
James Caveney, Wheeling, WV (2015)
John Grubb, Chula Vista, CA (2015)
Greg Huang, Seattle, WA (2014)
Robert J. Isaacson, Edina, MN (2015)
Laurance Jerrold, Brooklyn, NY (2017)
Lysle E. Johnston, Jr., Eastport, MI (2015)
Donald R. Joondeph, Bellevue, WA (2015)
Robert G. Keim, Los Angeles, CA (2017)
Richard Kleefield, Norwalk, CT (2015)
Steven J. Lindauer, Richmond, VA (2015)
James A. McNamara, Jr., Ann Arbor, MI (2017)
Ravindra Nanda, Farmington, CT (2017)
INTERNATIONAL
Adrian Becker, Jerusalem, Israel (2017)
Jose´ Alexandre Bottrel, Rio de Janeiro, Brazil (2015)
Theodore Eliades, Nea Ionia, Greece (2014)
W.G. Evans, Johannesburg, South Africa (2017)
Jorge Faber, Brasilia, Brazil (2017)
Joseph Ghafari, Beirut, Lebanon (2017)
Vicente Hernandez, Alicante, Spain (2017)
Nigel Hunt, London, England (2015)
Haluk Iseri, Ankara, Turkey (2017)
Roberto Justus, Mexico City, Mexico (2015)
Sanjivan Kandasamy, Midland, WA, Australia (2017)
Peter Ngan, Morgantown, WV (2015)
Perry M. Opin, Milford, CT (2017)
Jae Hyun Park, Mesa, AZ (2017)
Sheldon Peck, Newton, MA (2014)
William R. Proffit, Chapel Hill, NC (2015)
Eugene Roberts, Indianapolis, IN (2015)
Emile Rossouw, Rochester, NY (2017)
David L. Turpin, Federal Way, WA (2017)
James L. Vaden, Cookeville, TN (2015)
Robert L. Vanarsdall, Jr., Philadelphia, PA (2015)
Katherine Vig, Columbus, OH (2017)
Christos Vlachos, Homewood, AL (2014)
Timothy T. Wheeler, Gainesville, FL (2015)
Leslie A. Will, Boston, MA (2017)
Rakesh Koul, Lucknow, India (2017)
Birte Melsen, Aarhus, Denmark (2017)
Antony McCollum, Bryanston, South Africa (2015)
Eliakim Mizarahi, Ilford, England (2015)
Bjørn Øgaard, Oslo, Norway (2017)
Nikolaos Pandis, Corfu, Greece (2017)
Pratik K. Sharma, London, UK (2017)
George Skinazi, Paris, France (2015)
John C. Voudouris, Toronto, Canada (2017)
William A. Wiltshire, Winnipeg, Canada (2015)
Björn U. Zachrisson, Oslo, Norway (2015)
 Seminars in Orthodontics
VOL 21, NO 3 SEPTEMBER 2015

Accelerated Orthodontics
Mani Alikhani, DDS, MS, PhD
Guest Editor

■ Introduction 149
Mani Alikhani

■ Biological principles behind accelerated tooth movement 151

Sarah Alansari, Chinapa Sangsuwon, Thapanee Vongthongleur, Rachel Kwal,
Miang chneh Teo, Yoo B. Lee, Jeanne Nervina, Cristina Teixeira, and Mani Alikhani

■ Micro-osteoperforations: Minimally invasive accelerated tooth movement 162

Mani Alikhani, Sarah Alansari, Chinapa Sangsuwon, Mona Alikhani,
Michelle Yuching Chou, Bandar Alyami, Jeanne M. Nervina, and Cristina C. Teixeira

■ Piezocision™-assisted orthodontics: Past, present, and future 170

Serge Dibart, Elif Keser, and Donald Nelson

■ Scope of treatment with periodontally accelerated osteogenic orthodontics therapy 176

Donald J. Ferguson, M. Thomas Wilcko, Willam M. Wilcko, and Laith Makki

■ Cyclic loading (vibration) accelerates tooth movement in orthodontic patients:

A double-blind, randomized controlled trial 187
Dubravko Pavlin, Ravikumar Anthony, Vishnu Raj, and Peter T. Gakunga

■ Photobiostimulation as a modality to accelerate orthodontic tooth movement 195

Sean Chung, Melissa Milligan, and Siew-Ging Gong

■ Molecular effects of low-energy laser irradiation during orthodontic tooth movement 203
Kazutaka Kasai, Michelle Yuching Chou, and Masaru Yamaguchi

■ Effect of low-level laser on the rate of tooth movement 210

Su Jung Kim, Michelle Yuching Chou, and Young Guk Park

■ The effects of low-intensity pulsed ultrasound on the rate of orthodontic tooth

movement 219
Hui Xue, Jun Zheng, Michelle Yuching Chou, Hong Zhou, and Yinzhong Duan

■ Accelerated tooth movement: Do we need a new systematic review? 224

Daniel Rozen, Edmund Khoo, Hend El Sayed, Richard Niederman,
Richard McGowan, Mani Alikhani, and Cristina C. Teixeira
 Seminars in Orthodontics
VOL 21, NO 3
Introduction
O ne of the main concerns in orthodontics is
prolonged treatment duration. Lengthy
orthodontic treatment may prompt many
patients, especially adults, to either avoid treat-
ment or to seek shorter alternative solutions with
compromised results. Therefore, the search for
treatment modalities that decrease treatment
time without compromising the treatment out-
come is an active area of research in orthodontics
today.
To overcome the treatment time challenge,
one must understand the variables that control
treatment duration. In general, these variables
can be grouped into three categories: practi-
tioner-dependent, patient-dependent, and bio-
logical factors. Practitioner-dependent factors
include accurate diagnosis and treatment plan-
ning, sound mechanotherapy, appropriate
appliance design, and delivery of treatment in a
timely fashion. Patient-dependent factors include
attending scheduled appointments, compliance
with practitioners' instructions, good oral
hygiene, and maintaining the integrity of the
appliances. Biological factors are tightly regu-
lated by different molecular and cellular path-
ways and vary in magnitude for each individual.
In an ideal scenario where both the treatment
rendered by clinicians and patient cooperation
are flawless, biology would be the only factor that
dictates the rate of tooth movement in response
to orthodontic forces.
In this issue of Seminars in Orthodontics, we first
review the biological principles and molecular
mechanisms that govern tooth movement, and
the plausible points of intervention along the
molecular pathways where we are able to sti-
mulate target cells to achieve faster tooth
movement. Based on these biological principles,
we categorized the existing proposed techniques
into two types: indirect and direct. The indirect
techniques aim to activate target cells that
& 2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.sodo.2015.06.011
Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 149–150
SEPTEMBER 2015
control the rate of tooth movement by increasing
the release of upstream cytokines, while the
direct techniques utilize various stimulants to
directly activate the target cells. The indirect
techniques discussed in this Issue range from
minimally invasive techniques such as micro-
osteoperforations (MOPs) to more invasive
approaches such as piezocision and the sig-
nificantly aggressive corticotomy. The direct
techniques selected for discussion in this Issue
are vibration, laser and ultrasound, which are
seemingly more practical in clinical settings, and
have been studied more extensively than other
direct techniques. Although other direct tech-
niques may have significant academic value,
they are not the main focus of discussion in this
Issue due to the lack of extensive scientific
evidence and/or the impracticality of their clinical
application.
Where do we currently stand on accelerated
tooth movement? As the articles in this Issue
convey, the indirect techniques produce more
consistent and predictable results compared with
the direct techniques. While corticotomy and
piezocision lack conclusive scientific research,
the animal studies on MOPs have provided
strong evidence supporting the role of cytokines
in tooth movement in response to the indirect
techniques. Therefore, the main query regarding
indirect techniques is not on their effectiveness
or mechanism of action, but rather the inva-
siveness of the procedures, the ability to repeat
the procedure over the course of treatment, and
the required intervals between each application
to achieve the treatment goals while minimizing
any disturbance or side effect for the patients.
Unlike the indirect techniques, there are
more challenges as far as the direct techniques
are concerned. First, the mechanism of action of
these stimulants is either unclear or contra-
dictory. For example, the studies on vibration
and laser mostly demonstrate an osteogenic
effect, which theoretically would slow down the
rate of tooth movement. The fact that these
149
150 Alikhani
stimulants are used in the medical field to
increase bone density and accelerate bone
healing supports their osteogenic role. Second,
the human clinical trials on direct techniques
have produced conflicting results, while some
trials demonstrated positive effects on the rate of
tooth movement, others did not show any effect.
Third, even though some clinical trials showed
positive effects, they did not demonstrate a sig-
nificant increase in the rate of tooth movement
that could justify the additional cost incurred by
the device, the extra office visits, or the time
spent on the at-home applications.
While the search for more practical, effective,
inexpensive, and less invasive approaches con-
tinues, the question of how to incorporate
acceleration techniques in orthodontic treat-
ment remains the same regardless of the tech-
nique chosen. Orthodontics is not a single-stage
mechanical approach where a clinician could
merely use one arch wire throughout the treat-
ment and count on acceleration techniques to
shorten the time needed to establish an ideal,
stable occlusion. In fact, orthodontists consider-
ing the use of acceleration techniques are cau-
tioned that acceleration techniques do not take
the place of sound biomechanical treatment
plans—they are adjunctive to conventional
orthodontic treatment approaches. Orthodontic
treatment consists of many stages, and at each
stage we need to target some teeth without
moving the others. Some movements are pre-
requisites for others; for example, one should not
engage a blocked tooth to the main arch wire
until enough space is created. Application of
acceleration technique around a blocked tooth
does not change the forces and moments
required to produce a desired type of tooth
movement and therefore should not be applied
until the tooth from a mechanical standpoint is
ready to be moved. Since each stage of treatment
has its specific target teeth, acceleration techni-
ques should be simple, inexpensive, and com-
fortable enough to be repeated as often as
needed throughout the course of treatment.
The impact of acceleration techniques
extends beyond their effect on the rate of tooth
movement to many other applications due to
their temporary effect on bone density. From a
mechanotherapeutic standpoint, these localized
effects may change the anchorage properties of
individual teeth, and as a result, the application
of these techniques around a targeted tooth and
away from anchor teeth can help in reducing the
movement of anchor teeth. Another area of
interest is the anabolic effect of these techniques
that—when used wisely—could tremendously
change the boundaries of orthodontic tooth
movement and increase our ability to correct
severe orthodontic malformations non-surgically.
This phenomenon has been observed with some
indirect techniques, as they not only produce the
accelerating effect on tooth movement, but also
stimulate the formation of both cortical and
trabecular bone by stimulating the repair process.
Though many approaches discussed in this
Issue of Seminars in Orthodontics show promising
results in accelerating orthodontic tooth move-
ment, more studies are needed to evaluate their
efficiency, efficacy, and safety. Many questions
remain:
 Does faster tooth movement result in less
tipping and more bodily movement of teeth?
It seems that since bone density can tempora-
rily change in response to acceleration tech-
niques, it can in turn result in temporary
changes in the center of resistance and types
of tooth movement.
 Is retention less stable when tooth movement
is accelerated? On the contrary, current
observations demonstrate that increasing
bone-remodeling machinery increases the
stability of movement, which emphasizes the
need to understand the biology of relapse.
 Does activation of osteoclasts cause more root
resorption? Currently, it seems that many of
the acceleration techniques have a preventa-
tive effect on root resorption by either
decreasing bone density or by directly stimu-
lating cementoblasts.
The studies discussed in this Issue certainly
have advanced our understanding of the biology
controlling the rate of tooth movement, and the
molecular players that could be used towards
achieving shorter treatment duration. These are
all very important steps in elevating the ortho-
dontic specialty from art to science.
Mani Alikhani, DDS, MS, PhD
Guest Editor
Biological principles behind accelerated tooth
movement
Sarah Alansari, Chinapa Sangsuwon, Thapanee Vongthongleur, Rachel Kwal,
Miang chneh Teo, Yoo B. Lee, Jeanne Nervina, Cristina Teixeira, and
Mani Alikhani

Understanding the biology of tooth movement has great importance for

developing techniques that increase the rate of tooth movement. Based on
interpretations of data on the biology of tooth movement, the resulting
accelerating techniques can be divided into two main groups: one group
stimulates upstream events to indirectly activate downstream target cells,
while the other group bypasses the upstream events and directly stimulates
downstream target cells. In both approaches, there is a general consensus
that the rate of tooth movement is controlled by the rate of bone resorption,
which in turn is controlled by osteoclast activity. Therefore, to increase the
rate of tooth movement, osteoclasts should be the target of treatment. In this
article, both approaches will be reviewed and the biological limitations of
each group will be discussed. (Semin Orthod 2015; 21:151–161.) & 2015
Elsevier Inc. All rights reserved.

Introduction specific remodeling pathways to move teeth and

O
jaws into an ideal occlusion faster?
rthodontic tooth movement is possible due
The biology of tooth movement is not a new field
to the remodeling ability of the surround-
of inquiry. What is new is that we are now designing
ing bone and soft tissue. Without this remarkable
innovative appliances and treatments that optimize
biological phenomenon, the practice—indeed,
skeletal and dental target cell responses that pro-
the very concept—of orthodontics would not be
duce controlled, safe accelerated tooth movement.
possible. Yet, orthodontic appliances are not
By identifying and harnessing reactions of the target
intentionally built to activate or inhibit specific
cells, we can develop two different approaches to
remodeling pathways and specific cells. Rather,
accelerate the rate of tooth movement: directly
they are built to generate biomechanical force
stimulate the target cells by artificial, physical, or
systems that produce the desired tooth and jaw
chemical means to increase their numbers and their
movements needed to establish an ideal occlu-
activity, or indirectly stimulate the body to recruit
sion—regardless of the cellular mediators of the
and activate more target cells. In either scenario,
response. This begs the question, should we be
identifying the target cells and understanding how
designing orthodontic appliances to target
they are activated are crucial.

Consortium for Translational Orthodontic Research, New York
University College of Dentistry, 345 E 24th St, New York, NY 10010;
Department of Orthodontics, New York University College of Dentistry,
New York, NY; Department of Developmental Biology, Harvard
School of Dental Medicine, Boston, MA.
Corresponding author at: Consortium for Translational Ortho-
dontic Research, New York University College of Dentistry, 345 E 24th
St, New York, NY 10010. E-mail: mani.alikhani@nyu.edu
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.001
Bone cells and their role in biology of
tooth movement
Bone is a dynamic tissue that remodels in
response to mechanical force. The cells that
perform this response are distributed throughout
the bone and each is specialized to perform
specific functions needed to detect force (both
its magnitude and direction), recruit cells that
resorb bone at specific sites, and activate cells to

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 151–161 151

152 Alansari et al
deposit new bone matrix and promote mineral-
ization that will withstand mechanical force. The
mechanosensors are osteocytes, which are by far
the most numerous bone cells in the body, but
are also the least well studied because they are
embedded entirely within the bony matrix. The
bone-resorbing cells are giant multinucleated
osteoclasts, which are found on the bone surface
at resorption sites. The bone-forming cells are
osteoblasts, which spend their lives attached to
the bone surface. Finally, inflammatory cells
(specifically, T lymphocytes and macrophages)
that reside in the bone marrow are important
regulators of osteoclasts and osteoblasts.
Osteoblasts are mononuclear cells found along
the surface of bones. They are derived from
mesenchymal stem cells in the bone marrow and
synthesize collagenous and non-collagenous pro-
teins that form the organic bone matrix called
osteoid. Inactive osteoblasts that cover bone sur-
faces, particularly in the adult skeleton, are called
bone-lining cells. These cells are quiescent until
growth factors or other anabolic stimuli induce
them to proliferate and differentiate into cuboidal
osteoblasts. While osteoblasts play an important
role in maintaining the integrity of alveolar bone
during tooth movement, they are not the cells that
control the rate of tooth movement.
The osteocyte is a mature osteoblast embedded
in lacunae within the bone matrix. Although
immobile, osteocytes possess exquisitely fine
processes, which traverse the mineralized matrix
in tunnels called canaliculi, to make contact with
other osteocytes, as well as with osteoblasts
residing on the bone surface. Given their pre-
ponderance in bone, and their intricate three-
dimensional network, osteocytes are key mecha-
nosensors. Loading of bone results in strain, or
deformation, in the matrix, including the lacunae
and canaliculi. This deformation evokes osteocytic
responses via fluid shear stress (produced by
increased fluid flow in the lacuno-canalicular
system) or electrical stream potential. Osteo-
cytes orchestrate the overall remodeling response
by secreting key factors, such as prostaglandins,
nitric oxide, and insulin-like growth factors
(IGFs), which activate osteoblasts and osteoclasts
and the bone remodeling system. Under the
influence of orthodontic forces, osteocytes play a
critical role in detecting force and activating
osteoclast–osteoblast coupling, but they are not
the cells that regulate the rate of tooth movement.
In fact, it is the osteoclast that determines the
rate of bone resorption and, therefore, the rate
of tooth movement. These cells are the major
bone-resorbing cells. They are specialized mon-
ocyte/macrophage family members that differ-
entiate from hematopoietic stem cells in the
bone marrow. Mature osteoclasts are giant mul-
tinucleated cells that form from the fusion of
monocytic precursors. Terminal differentiation
in this lineage is characterized by the acquisition
of mature phenotypic markers, such as the cal-
citonin receptor and tartrate-resistant acid
phosphatase (TRAP), and the appearance of an
astounding ruffled border rich in proton pumps
that acidify the bone surface to which the cells
are attached, resulting in resorption pits.
When viewed physiologically, normal healthy
bone remodeling is a tightly choreographed
sequence of cellular activity. Mechanical force
distorts osteocytes housed in lacunae and canal-
iculi, often producing micro-fractures, which are
cleared out by osteoclasts. Osteoblasts follow to fill
in the newly excavated site. Some of those osteo-
blasts become embedded in the new bone to form
new osteocytes to replace those lost at the
remodeling site. Thus, healthy strong bone that can
withstand mechanical force applications is formed
due to signaling between osteocytes, osteoclasts,
and osteoblasts. As we will discuss below, a variation
of this response, which incorporates immune cells
and inflammatory cytokines, is key to understand
the biology of tooth movement and develop
approaches to accelerate tooth movement.
Theories on biology of tooth movement
During recent years, many theories have been
developed to explain the mechanism of tooth
movement. In general, these theories split into two
camps: one camp proposes that bone is the direct
target of mechanical force (direct view), while the
other camp proposes that it is the periodontal
ligament (PDL) that is the key target (indirect
view). According to the direct view model, com-
pression stress generated in the direction of tooth
movement directly stimulates osteoclasts, and
tension stress in the opposite direction of tooth
movement directly stimulates osteoblasts. Under
this assumption, osteocytes may play a significant
role by coordinating osteoclast and osteoblast
activity. There is significant evidence against this
proposal. First, bone does not recognize static
 Biological principles behind accelerated tooth movement
forces such as orthodontic forces.1 Second, the
lack of movement of implants and ankylosed teeth
in response to orthodontic forces argues against
the claim that bone is the target of orthodontic
forces. Third, in experiments where bone is
loaded directly, without interference of the PDL,
compression stresses stimulate bone formation,
not bone resorption.
Supporters of the indirect view of tooth
movement propose that the PDL is the primary
target of orthodontic forces. Consider the
impossibility of moving an ankylosed tooth,
which lacks a PDL. Based on this proposal, the
PDL will exhibit areas of compression and ten-
sion in response to the application of ortho-
dontic forces. Distribution of these areas varies
depending on the different types of tooth
movement, which in turn are controlled by the
magnitude of the force and the moment applied
to the tooth. Regardless of the type of tooth
movement, if the duration of force application is
limited to a few seconds, the incompressible
tissue fluid prevents quick displacement of the
tooth within the PDL space. However, if the force
on a tooth is maintained, the fluid is rapidly
squeezed out and the tooth displaces within the
PDL space, leading to the compression of the
Figure 1. Schematic representation of increase in permeability of vessels, release of chemokines, expression of
adhesion molecules, and recruitment of inflammatory and precursor cells during early events of orthodontic tooth
movement.
153
PDL. The immediate result of this displacement
is the constriction of blood vessels in the com-
pression site. Alteration in blood flow would
cause a decrease in nutrition and oxygen levels
(hypoxia). Depending on the magnitude of
pressure and level of blood flow reduction, some
of the cells will go through apoptosis, while some
cells will die non-specifically, resulting in areas of
necrosis (cell-free zone). It should be empha-
sized that apoptotic or necrotic changes are not
limited to PDL cells, and some of the osteoblasts
and osteocytes in adjacent alveolar bone also die
in response to orthodontic forces. These sequen-
ces of events lead to an aseptic, acute inflam-
matory response with the early release of che-
mokines from local cells (Fig. 1). Chemokines
are small proteins released by local cells that can
attract other cells into the area. The release of
chemokines in response to orthodontic forces
facilitates expression of adhesion molecules in
blood vessels and stimulates further recruitment
of inflammatory and precursor cells from the
microvasculature into the extravascular space.
One of the chemokines that is released during
tooth movement is monocyte chemoattractant
protein-1 (MCP-1 or CCL2),2 which plays an
important role in recruiting monocytes. These
154 Alansari et al
cells leave the bloodstream and enter the sur-
rounding tissue to become tissue macrophages or
osteoclasts. Similarly, the release of CCL3 and3
CCL5 (RANTES)4 during orthodontic tooth
movement leads to osteoclast recruitment and
activation. Within the first few hours of ortho-
dontic treatment, there is further release of a
broader spectrum of inflammatory mediators. In
addition to chemokines, cytokines are released
during orthodontic treatment. These extracellu-
lar proteins play an important role in regulating
the inflammatory process. Many cytokines are
pro-inflammatory. They amplify or maintain the
inflammatory response and activation of bone
resorption. Importantly, other cytokines are anti-
inflammatory and prevent an unrestrained
inflammatory response. The main pro-inflammatory
cytokines that are released during orthodontic tooth
movement are IL-1α, IL-1β, TNF-α, and IL-6.5 These
cytokines are produced by inflammatory cells such as
macrophages and by local cells such as osteoblasts,
fibroblasts, and endothelial cells.
Another series of inflammatory mediators that
are released during orthodontic tooth movement
are prostaglandins (PGs) and neuropeptides. PGs
are derived from the metabolism of arachidonic
acid and can mediate virtually every step of
Figure 2. Schematic representation of interaction between RANKL expressed by local cells and inflammatory
cells, and RANK expressed by precursor cells resulting in osteoclast differentiation.
inflammation such as vasodilation, increase vas-
cular permeability, and adhesion of inflammatory
cells. During orthodontic tooth movement, these
mediators can be directly produced by local cells or
by inflammatory cells in response to mechanical
stimulation, or indirectly by cytokines. For example,
TNF-α is a potent stimulator of PGE2 formation.6
Prostaglandins act locally at the site of generation
and then decay spontaneously or are enzymatically
destroyed.7,8 Similar to PGs, neuropeptides can
participate in many stages of the inflammatory
response to orthodontic forces. Neuropeptides are
small proteins, such as substance P, that transmit
pain signals, regulate vessel tone, and modulate
vascular permeability.9 The importance of all these
inflammatory makers can be appreciated in the
role that they play in osteoclastogenesis.
Osteoclastogenesis
As previously discussed, osteoclasts are multi-
nucleated giant cells that resorb bone and are
derived from hematopoietic stem cells of the
monocyte–macrophage lineage. After recruit-
ment to the compression sites, osteoclast pre-
cursors begin to differentiate into osteoclasts
(Fig. 2). Cytokines are important mediators of
 Biological principles behind accelerated tooth movement 155

this process. For example, TNF-α and IL-1 bind to
their receptors, TNFRII10 and IL-1R,11 respec-
tively, and directly stimulate osteoclast formation
from precursor cells and osteoclast activation
(Fig. 3). Additionally, IL-1 and IL-612 can
indirectly stimulate local cells or inflammatory
cells to express macrophage colony-stimulating
factor (M-CSF) and receptor activator of nuclear
factor κ-B ligand (RANKL). These ligands
through cell-to-cell interactions bind to their
respective receptors, c-Fms and RANK, which are
both expressed on the surface of osteoclast
precursors (Fig. 3).
Other inflammatory mediators that enhance
osteoclast formation through enhancing RANKL
expression by stromal cells are PGs, especially
PGE2.13 As mentioned before, PGs can be
produced by local cells directly in response to
orthodontic forces or indirectly as downstream of
cytokines such as TNF-α.
It should be emphasized that local cells nor-
mally try to down regulate osteoclastogenesis by
producing a RANKL decoy receptor, osteopro-
tegerin (OPG).14 Therefore, OPG levels in
compression sites should decrease to enable
tooth movement.
Different approaches to accelerate the rate
of tooth movement
The approach that a researcher selects to
accelerate the rate of tooth movement depends
on his or her interpretation of the data on the
biology of tooth movement. A researcher who
chooses to amplify body reactions to orthodontic
forces may either try to increase the release of
cytokines (if they believe that inflammatory
responses of the PDL and bone are the key factor
in controlling the rate of tooth movement) or
optimize the mechanical stimulation (if they

Figure 3. Diagram of the effect of cytokines on skeletogenesis. Cytokines can directly help in the differentiation or
activation of osteoclasts from osteoclast precursor cells. Also, cytokines can stimulate local cells to express RANKL
that interacts with its receptor (RANK) on precursor cells and help the development of osteoclasts.
156 Alansari et al
believe that orthodontic tooth movement is a
direct physiologic response to mechanical stim-
ulation). On the other hand, another researcher
who does not propose mimicking the body's
response to orthodontic forces may choose
instead to increase the rate of tooth movement by
artificially increasing the number of osteoclasts.
These approaches include local or systemic
induction of different chemical factors or
application of physical stimuli that can increase
the number of osteoclasts independent of
orthodontic forces. It should be emphasized that,
in spite of some disagreement about initial trig-
ger that starts the cascade of events leading to
bone resorption and tooth movement, all theo-
ries agree that osteoclast activation is the main
rate-controlling factor in orthodontic tooth
movement.
Stimulation of cytokines to increase the
rate of tooth movement
As previously discussed, orthodontic force indu-
ces an aseptic inflammatory response,15 during
which many cytokines and chemokines are acti-
vated and play a significant role in osteoclasto-
genesis. The importance of these molecules in
controlling the rate of tooth movement can be
appreciated through the dramatic results
obtained from studies that block their effects.
For example, injections of IL-1 receptor antag-
onist (IL-1Ra) or TNF-α receptor antagonist
(sTNF-α-RI) result in a 50% reduction in the rate
of tooth movement.16 Similarly, tooth movement
in TNF type II receptor-deficient mice is reduced
compared to wild-type mice.17 Animals that are
deficient in CC chemokine receptor 2 (CCR2),
which is a receptor for CCL2, or animals that are
deficient in CCL3, demonstrate a significant
reduction in orthodontic tooth movement and
number of osteoclasts.2 Likewise, non-steroidal
anti-inflammatory drugs (NSAIDs) reduce the
rate of tooth movement by inhibiting PG synthe-
sis.18 Inhibiting other derivatives of arachidonic
acid, such as leukotrienes, also significantly
decreases the rate of tooth movement.19
If inhibiting inflammatory markers decreases
the rate of tooth movement, it is logical to assume
that increasing their activity should significantly
increase the rate of tooth movement. Indeed,
injecting PGs into the PDL in rodents increases
the number of osteoclasts and the rate of tooth
movement.20 Systemic application of misopro-
stol, a PGE1 analog, to rats undergoing tooth
movement for 2 weeks, significantly increases the
rate of tooth movement.21 Similarly, local injec-
tion of other arachidonic acid derivatives, such as
thromboxane and prostacyclin,22 increases the
rate of tooth movement.
Unfortunately, injection of PGs to increase the
rate of tooth movement has limitations. First, due
to their very short half-life, PGs must be delivered
repeatedly. Second, local PGs injections can
cause hyperalgesia due to release of histamine,
bradykinin, serotonin, acetylcholine, and sub-
stance P from nerve endings.23
Another approach in increasing inflammatory
mediators that will increase the rate of tooth
movement is to stimulate the body to produce
these factors at a higher level. The advantage of
this approach is a coordinated increase in the
level of all inflammatory mediators. As discussed
before, many cytokines participate in response to
orthodontic forces. Injecting one cytokine does
not mimic the normal inflammatory response,
which is a balance of pro- and anti-inflammatory
mediators. However, the approach that safely
triggers the body to produce higher levels of
inflammatory mediators is not clear.
One may suggest that increasing the level of
orthodontic force should increase the level
of cytokine expression, since a higher magnitude
of force produces greater trauma to the PDL and
bone leading to higher levels of inflammation. In
fact, increasing the force magnitude is accom-
panied by higher levels of cytokine and chemo-
kine expression, but only to certain point.
Increasing the magnitude of force beyond that
point does not produce higher levels of inflam-
matory mediators or accelerated tooth move-
ment.24 This observation led to the conclusion
that there is a “biological saturation point” in
response to orthodontic forces. However, it
should be emphasized that extremely high
levels of forces may lead to the appearance of
micro-fractures in bone that can stimulate fur-
ther cytokine expression and bone resorption.
While these forces are beyond the magnitude of
orthodontic forces applied during orthodontic
treatment, the observation highlights the possi-
bility of stimulating a similar reaction in bone via
another method, thus facilitating orthodontic
tooth movement by increasing the rate of bone
resorption.
 Biological principles behind accelerated tooth movement
Animal studies have shown that introducing
small perforations in the alveolar bone [micro-
osteoperforations(MOPs)] during orthodontic
tooth movement can significantly stimulate the
expression of inflammatory mediators. While
application of orthodontic force beyond the
saturation point does not elevate the expression
and activation of inflammatory mediators beyond
certain levels, adding MOPs to the area of tooth
movement increases the level of inflammatory
mediators.25 This response is accompanied by a
significant increase in osteoclast number, bone
resorption, and localized osteopenia around all
adjacent teeth, which could explain the increase
in the rate and magnitude of tooth movement.
One may argue that the effects of the shallow
perforations on tooth movement are not a
response to increased cytokine expression, but
rather due to weakening of the bone structure.
While the effects that perforations can have on
the physical properties of the bone cannot be
ignored, the number and diameter of these
perforations are too small to have significant
impact.26 Similarly, a human clinical trial using a
canine retraction model demonstrates that
MOPs can amplify the catabolic response to
orthodontic forces. Canine retraction in the
presence of MOPs results in twice as much
distalization in comparison with patients
receiving similar orthodontic forces without
MOPs. This increase in tooth movement is
accompanied by an increase in the level of
inflammatory mediators.27
Clinical studies demonstrate that increasing
the number of MOPs significantly increases
expression of inflammatory mediators and the
magnitude of tooth movement.28 Therefore, one
should expect procedures such as orthognathic
surgery, corticotomies, or piezocision would
significantly increase the levels of inflammatory
cytokines beyond those induced by MOPs. While
increase in cytokine release is accompanied with
higher rate of tooth movement, unfortunately,
the increase in the expression of inflammatory
mediators is not sustained for a long time. A
significant decrease in cytokine activity is
observed 2–3 months after any of these
treatments. As a result, each of these
procedures would need to be repeated during
the course of orthodontic treatment, which
renders some of the above-mentioned modal-
ities impractical.
157
Recently, a modification of these techniques
has been introduced where, after selective
decortication in the form of lines and points, a
resorbable bone graft is placed over the surgical
sites. Falsely, the accelerating effect of these
techniques has been attributed to the shape of
the cuts made into the bone (block concept) and
to the bone grafts.29,30 As previously discussed in
this article, the rate of tooth movement is con-
trolled by osteoclast recruitment and activation
which is controlled by cytokine release in
response to trauma. While magnitude of trauma
( number and depth of the cuts) can affect the
magnitude of cytokine release, shape of trauma
does not affect inflammatory response. More-
over, bone grafts do not increase osteoclast
activation and as a result do not contribute to the
increase in the rate of tooth movement. There-
fore, while the application of bone grafts can
help in increasing the boundary of tooth move-
ment toward cortical bone, during routine
orthodontic treatment where teeth are moved in
trabecular bone, they are unnecessary.
Mechanical stimulation to increase the
rate of tooth movement
Another methodology that has been suggested to
increase the rate of tooth movement is the
application of high-frequency low-magnitude
forces.31 The main assumption in this hypothesis
is that bone is a direct target of orthodontic
forces, and therefore by optimizing mechanical
stimulation, it is possible to increase the rate of
tooth movement. There are many flaws in this
theory. As we discussed before, the assumption
that tooth movement is the result of direct res-
ponse of bone cells to mechanical stimulation is
incorrect, which means that optimizing the
mechanical stimulation based on bone cell
activity, especially osteocytes, is not a correct
approach. Based on this biological principle,
application of vibration and orthodontic forces
will never be able to move an ankylosed tooth. In
addition, all studies in long bone and alveolar
bone24 demonstrate an osteogenic effects of
these stimulants with increases in bone density
without any resorptive effect, which logically
should delay, rather than accelerate, the rate
of tooth movement. It is possible that application
of high-frequency low-magnitude forces during
orthodontic movement stimulates a pathway far
158 Alansari et al
different from its effect on bone. If that is true,
the frequency-dependence of the stimulant is
questionable, and literature in this field should
not be used to justify applying vibration during
tooth movement.
Heat, light, electric currents and laser to
increase the rate of tooth movement
Early studies on the application of heat and light
during orthodontic tooth movement32 have
demonstrated faster tooth movement. Similarly,
animals exposed to longer hours of light also
show an increase in the rate of tooth move-
ment.33 However, the magnitude of this
acceleration was either small or could be
explained more by systemic effect of the
stimulant and not necessarily local effects.
Minute electric currents have been suggested
to increase the rate of tooth movement. In this
regard, some studies did not report any changes in
the rate of tooth movement,34 while others report
significant increase.35 Similarly, studies on static
magnetic fields produce inconsistent results on
the rate of tooth movement with some showing an
increase36 and others demonstrating no change in
the rate of tooth movement.37
Based on the piezoelectric theory, some
researchers suggest using a pulsed electro-
magnetic field to accelerate tooth movement.38
Indeed, animals that received this type of
stimulation during orthodontic tooth movement
demonstrate a faster rate of tooth movement.
Recently, more attention has been given to
possible effect of low-level laser therapy (LLLT)
on the rate of tooth movement. LLLT is a
treatment that uses low-level lasers or light-
emitting diodes to alter cellular function.
LLLT is controversial in mainstream medicine
with ongoing research to determine whether
there is a demonstrable effect. Also disputed are
the dose, wavelength, timing, pulsing, and
duration.39 The effects of LLLT appear to be
limited to a specified set of wavelengths40 and
administering LLLT below a dose range does not
appear to be effective.26
In general, the mechanism of action of LLLT is
not clear and sometimes opposite to what is
required for orthodontic tooth movement. For
example, LLLT may reduce pain related to
inflammation by dose-dependently lowering levels
of PGE2, IL-1, and TNF-α, decreasing the influx of
inflammatory cells such as neutrophils, oxidative
stress, and edema.41 Another mechanism may be
related in stimulating mitochondria to increase
the production of adenosine triphosphate (ATP)
resulting in an increase in reactive oxygen species,
which influences redox signaling, which then
affects intracellular homeostasis or cellular
proliferation.42 The final enzyme in the pro-
duction of ATP by mitochondria, cytochrome-c
oxidase, appears to directly respond to lasers,
making it a possible candidate for mediating the
properties of laser therapy.43 Due to anti-
inflammatory and osteogenic effects of LLLT,
application of LLLT to increase the rate of tooth
movement is controversial. While some studies
demonstrate increased rates of tooth movement,44
other studies did not see any effect.45 The anti-
inflammatory effect of LLLT should delay the
tooth movement, while the proliferative effect
may help increase the number of osteoblasts. On
the other hand, some studies show an increase in
the number of osteoclasts during LLLT
application with orthodontic tooth movement,46
which cannot be explained by a proliferative effect
of lasers since osteoclasts arise from precursor
cells and not proliferation of mature osteoclasts, as
some have suggested. Further studies in this
subject are clearly necessary.
Unfortunately, applying any of these physical
stimuli to increase the rate of tooth movement at
present suffers from a lack of evidence, an
unknown mechanism and general impracticality.
In addition, the magnitude of increase in the rate
of tooth movement is not significantly high to
justify their application. Nevertheless, this field
has great potential for growth.
Chemical agents to increase the rate of
tooth movement
If bone resorption is the key factor in controlling
the rate of tooth movement, application of any
agent that increases the rate of bone turnover
should increase the rate of tooth movement.
With this in mind, the application of parathyroid
hormone (PTH), vitamin D3, corticosteroids,
thyroxin, and osteocalcin have been examined. It
should be noted that other factors, such as cal-
citonin or estrogens, can prevent bone resorp-
tion and decrease the rate of tooth movement.47
PTH is secreted by the parathyroid glands and
increases the concentration of serum calcium by
 Biological principles behind accelerated tooth movement
stimulating bone resorption. A significant stim-
ulation of the rate of tooth movement by exog-
enous PTH appears to occur in a dose-dependent
manner, but only when it is continuously applied
by either systemic infusion48 or local delivery
every other day in a slow-release formulation.49 It
should be noticed that although continuous
elevation of PTH leads to bone loss,
intermittent short elevations of the hormone
level are anabolic for bone50 and perhaps cannot
increase the rate of tooth movement.
Vitamin D3 (1,25 dihydroxycholecalciferol) is
another factor that can affect the rate of bone
remodeling and therefore its possible effect on
the rate of tooth movement has been studied.
vitamin D3 regulates calcium and phosphate
serum levels by promoting their intestinal
absorption and reabsorption in the kidneys.
Furthermore, it promotes bone deposition and
inhibits PTH release. Based on these mecha-
nisms, one would expect that vitamin D3 should
decrease the rate of tooth movement. To the
contrary, it has been shown that vitamin D3 can
increase the rate of tooth movement if injected
locally.51 This effect can be related to the effect of
vitamin D3 on increasing the expression of
RANKL by local cells and therefore activation
of osteoclasts.52 Similarly, local injection of
osteocalcin (a bone matrix component) caused
rapid tooth movement due to attraction of
numerous osteoclasts into the area.53
Corticosteroids are another group of chemical
agents that have been suggested for accelerating
the rate of tooth movement. While the anti-
inflammatory effect of corticosteroids can
decrease the rate of tooth movement, in the
presence of cytokines such as IL-6 they may help
stimulate osteoclastogenesis and cause osteopo-
rosis.31 Therefore, the effect of corticosteroids on
tooth movement can vary depending on the
dosage and whether they are administered
before the expression of cytokines (induction
period) or after their presence. While some
studies demonstrate an increase in rate of tooth
movement following corticosteroid treatment,54
others did not report any changes.55,56
Another factor that may increase the rate of
tooth movement is the thyroid hormone (thy-
roxin). Thyroxin affects intestinal calcium
absorption, thus it is indirectly involved in bone
turnover and induction of osteoporosis. It has
been shown that exogenous thyroxin increases
159
the rate of tooth movement,57 which can be
related to increase in bone resorption.
Recently, the hormone Relaxin has been used
in rats to increase the rate of tooth movement.
Relaxin is capable of reducing the organization
level of connective tissues, facilitating rapid
separation between adjoining bones. Unfortu-
nately, no significant increase in the rate of tooth
movement was observed.58
The application of chemicals to accelerate
tooth movement suffers from many problems.
First, all the chemical factors have systemic effects
that raises questions about their safety during
clinical application. Second, the majority of the
factors have a short half-life; therefore multiple
applications of the chemical are required, which
is not practical. In addition, administration of a
factor in a manner that allows an even dis-
tribution along the alveolar bone surface in the
compression site is still a challenge. Uneven
distribution can change the pattern of resorption
and therefore the biomechanics of tooth
movement.
Summary and future directions
While many seemingly random approaches have
been taken to increase the rate of tooth move-
ment, a successful approach should be based on
solid biological principles where the target cells
and mechanism to stimulate those cells are well
defined. This would be possible only if theories
on biology of tooth movement are revisited. A
good accelerating technique should be afford-
able, repeatable, practical, efficient, and have no
side effects on the periodontium, including roots
and alveolar bone. At this moment, all the cur-
rent approaches are suffering from one or more
deficiencies, but it is not far from reality to claim
that we are on the right track.
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Micro-osteoperforations: Minimally invasive
accelerated tooth movement
Mani Alikhani, Sarah Alansari, Chinapa Sangsuwon, Mona Alikhani,
Michelle Yuching Chou, Bandar Alyami, Jeanne M. Nervina, and
Cristina C. Teixeira

Safe, minimally invasive, and cost-effective treatments are being sought to

shortened orthodontic treatment time. Based on the well-known principle
that orthodontic force triggers inflammatory pathways and osteoclast
activity, we hypothesized that controlled micro-trauma in the form of
micro-osteoperforations (MOPs) will amplify the expression of inflammatory
markers that are normally expressed during orthodontic treatment and that
this amplified response will accelerate both bone resorption and tooth
movement. We tested our hypothesis in an animal model and in a human
clinical trial. In adult rats, MOPs treatment significantly increased molar
protraction with concomitant increase in inflammatory cytokine expression,
osteoclastogenesis, and alveolar bone remodeling. Likewise, in human
subjects, MOPs increased the rate of canine retraction concomitant with
increased TNFa and IL-1b levels in gingival crevicular fluid. Moreover, MOPs
treatment did not produce additional pain or discomfort in the patients
tested. Our data supports our conclusion that MOPs offers a safe, minimally
invasive, and easy mechanism to accelerate orthodontic tooth movement.
(Semin Orthod 2015; 21:162–169.) & 2015 Elsevier Inc. All rights reserved.

A major challenge in orthodontics is

decreasing treatment time without com-
promising treatment outcome. Assuming that
mechanotherapy and cooperation are optim-
ized for any given patient, the rate-limiting step
in treatment time will be the patient’s biological
response to mechanotherapy. Thus, identifying
and, more importantly, harnessing the cellular
regulators of tooth movement are essential if
we are to safely shorten orthodontic treatment
time.
Consortium for Translational Orthodontic Research, New York
University College of Dentistry, New York, NY; Department of
Developmental Biology, Harvard School of Dental Medicine, Boston,
MA; Department of Orthodontics, New York University College of
Dentistry, 345 East 24th Street, New York, NY 10010.
Corresponding author: ct40@nyu.edu
New York University filed a patent on microperforations when the
animal studies were completed (J Dent Res. 89:1135-41; 2010).
Propel Orthodontics Inc. licensed this patent from NYU and developed
a tool to facilitate the procedure. They did not participate in or support
this study. NYU purchased the Propel tools used in this study.
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.002
Biology of tooth movement
The now well-known sequence of biological
responses to orthodontic forces begins with
compression and tension in the periodontal lig-
ament (PDL). Compression and tension imme-
diately deform and constrict blood vessels, and
damage cells in the periodontal tissues. The initial
aseptic, acute inflammatory response is marked by
a flood of chemokines and cytokines from local-
ized cells, such as osteoblasts, fibroblasts, and
endothelial cells. Many of these cytokines are pro-
inflammatory and sustain the inflammatory
response by recruiting inflammatory cells and
osteoclast precursors from the PDLs extravascular
space. Infiltrating inflammatory cells maintain
high chemokine and cytokine levels to support
osteoclast precursor differentiation into multi-
nucleated giant cells that perform the time-
consuming process of resorbing alveolar bone
that is needed for teeth to move. Equally impor-
tant is the continued presence of anti-
inflammatory chemokines and cytokines, which
temper the destructive pro-inflammatory and
osteolytic processes. Thus, the more we know
about the pro- and anti-inflammatory responses of

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 162–169 162

 Micro-osteoperforations
alveolar bone, PDL and inflammatory cells to
orthodontic force, the better we can develop safe
therapies that shorten overall orthodontic
treatment time.
What we know about cytokine effects on the
rate of tooth movement is very consistent—
blocking pro-inflammatory cytokines increases
the time needed to move teeth in different
animal models.1–6 Taken together, these studies
strongly support the conclusion that pro-
inflammatory cytokines are essential mediators
of orthodontic tooth movement. More impor-
tantly, these data clearly compel us to develop
methods to harness and titrate the pro-
inflammatory responses to safely accelerate
orthodontic tooth movement.
Accelerating tooth movement
In general, there are 2 methods to accelerate the
rate of tooth movement. The first involves
applying physical and chemical stimulants to
activate bone remodeling pathways. Importantly,
these pathways are not the pathways that are
activated during routine orthodontic tooth
movement. Rather, these stimulant-activated
pathways trigger exaggerated uncoupled activa-
tion of localized cells to resorb, or form bone in
ways that do not mimic the natural coupled cel-
lular responses to orthodontic forces. In contrast,
the second approach intensifies the naturally
coupled bone remodeling pathways that are
activated by orthodontic forces. Utilizing the
latter approach here, we present a simple and
safe method to accelerate tooth movement that
harnesses and amplifies the patient’s normal
biological response to orthodontic forces.
This novel method to accelerate tooth
movement is based on the natural inflammatory
response of the body to physical trauma. We
hypothesize that controlled micro-trauma in the
form of micro-osteoperforations (MOPs; which
maintain the integrity and architecture of hard
and soft tissue) will amplify the expression of
inflammatory markers that are normally
expressed during orthodontic treatment and that
this amplified response will accelerate both bone
resorption and tooth movement. To test our
hypothesis, we used MOPs in an animal model of
accelerated tooth movement,7 followed by
human clinical trials of the MOPs protocol.8,9
163
From rats to humans
In our study on rats, the rate of tooth movement
increased significantly, with tooth movement
occurring twice as fast in the MOP group com-
pared with the O group (Fig. 1B). Cytokine/
cytokine receptor expression increased
significantly 24 hours after force application in
the MOP and O groups compared with the C
group (Fig. 1C). Moreover, 21 cytokines were
significantly higher in the MOP group than the O
group. Histology revealed increased alveolar
bone resorption in both the MOP and O
groups compared to the C group. The MOP
group showed a significantly greater rate of
alveolar bone resorption than in the O group,
and a subsequent increase in PDL thickness
(Fig. 1D). Immunohistochemical staining of
TRAP-positive osteoclasts (Fig. 1D) revealed a
threefold increase in osteoclast number in the
MOP group compared with the O group.
Using a canine retraction model in humans,
we confirmed the results of our animal study.
After 28 days of canine retraction, we observed a
significant increase in canine retraction in the
MOP group compared with both C group and CL
side (Fig. 2B). Dental cast measurements showed
a 2.3-fold increase in canine retraction compared
with both C group and CL side (Fig. 2C). GCF
protein analysis showed increased cytokine and
chemokine expression after 24 hours of force
application compared with pre-retraction levels
for the same patients. Moreover, cytokines were
significantly higher in the MOP group than in the
C group (Fig. 2D). After 28 days, all cytokine
levels were decreased back to pre-retraction
levels with the exception of interleukin-1-beta
(IL1-β). In the MOP group, IL1-β levels at 28 days
was still significantly higher (5.0- and 3.6-fold,
respectively) than the pre-retraction levels
(Fig. 2D). In addition, we recorded pain and
discomfort levels using a self-reporting numeric
scale which ranged from 0 to 10 (0 ¼ “no pain”
and 10 ¼ “worst possible pain”) on the day of
appliance placement, the day of canine retrac-
tion, and 24 hours, 7 days, and 28 days after
retraction was initiated. All patients reported
mild to moderate discomfort compared to pre-
retraction levels (Table). Importantly, MOPs
treatment did not produce increased levels
of pain compared to conventional, non-MOPs
canine retraction treatment, with patients
164 Alikhani et al

Figure 1. MOPs accelerate tooth movement in rats. Rats were divided into 3 groups. The experimental group
(MOP) received 3 shallow MOPs (black dots) in the cortical bone 5 mm mesial to the maxillary first molar and a
spring connecting the maxillary first molar to the incisors to apply a mesial force (A). The sham group (O)
received the same mesializing spring but no MOPs. The control group (C) received passive springs and no MOPs.
(B) Magnitude of tooth movement after 28 days of orthodontic force (C, control; O, orthodontic force only; MOP,
orthodontic force þ micro-osteoperforations). The MOP group showed the greatest magnitude of movement. (C)
RT-PCR analysis of cytokine gene expression. Data presented as fold increase in cytokine expression in the O and
MOP groups compared with C group. Data shown is mean ⫾ SEM of 3 experiments. (D) Histological sections
stained with hematoxylin and eosin (top panels) show increased periodontal space (p) thickness around the
mesiopalatal root (r) of the first molar and increase in bone (b) resorption in both the O and MOP groups.
Immunohistochemical staining (bottom panels) shows an increase in osteoclast activity represented by the
increased number of TRAP-positive osteoclasts (arrowhead) in both the O and MOP groups.
 Micro-osteoperforations 165

Figure 2. MOPs treatment accelerated canine retraction in a human clinical study. In a randomized, single-center,
single-blinded study, 20 subjects were randomly divided into control and experimental groups. Both groups
received similar treatment until the initiation of canine retraction. At that time, the experimental group received 3
MOPs between the canine and the second premolar on one side only, while the contralateral side served as
additional control (CL). The control group (C) did not receive MOPs. The rate of canine retraction was
determined from dental cast analysis of impressions taken immediately before initiating canine retraction and after
28 days of retraction. (A) Diagram showing the setup during canine retraction. A power arm extending from the
vertical slot of the canine bracket to the level of the canine center of resistance (green dot) was connected by a NiTi
coil (continuous 50 cN force) to a temporary anchorage device (blue dot) placed between the second premolar and
the first molar at the level of the CR of the canine. The 3 MOPs (red dots) were placed between the canine and the
second premolar prior to retraction. (B) After 28 days of force application, the distance between the canine and
the lateral incisors was measured using a digital caliper. The canine retraction is significantly greater in the MOP
group than in the O group (orthodontic force alone or contralateral side). (C) Canine retraction in MOP group
increased 2.3-fold after 28 days of retraction compared with the control group and the contralateral side of the
experimental group. (D) Cytokine levels in the gingival crevicular fluid collected from the distobuccal crevices of
the canine before retraction and 24 hours, 7 days, and 28 days after force application cytokine protein activity was
assayed by enzyme-linked immunoassay (ELISA) and shows significantly higher levels in the MOP group than in
the C group. Data is presented as pg/uL. nSignificantly higher than control (p o 0.05). (For interpretation of the
references to colour in this figure legend, the reader is referred to the web version of this article.)
166
Table. Pain and Discomfort Assessment for Control (O) and Experimental (MOP) Groups Using a Numerical
Rating Scale (NRS)
Day of Canine Retraction
Control (O) 18 ⫾ 0.3
Experimental (MOP) 1.4 ⫾ 0.2
Pain scores in the control and experimental groups, Values represent the average for each group ⫾ SD.
reporting only moderate discomfort that was
bearable and did not require any medication.
Using the same canine retraction model in
humans, the effect of number of MOPs on the
rate of tooth movement was studied. In this study,
rate of tooth movement was compared in 3
groups: control that only received orthodontic
force (O), O þ 1 MOP group that in addition to
orthodontic force received 1 MOP between
canine and second premolar, and O þ 4 MOP
group that in addition to orthodontic force
receive 4 MOPs in the same position. At different
time points after canine retraction, the rate of
tooth movement and levels of inflammatory
marker IL1-α were evaluated as described before.
In response to 4 MOPs, IL1-α activity in the
gingival crevicular fluid increased fivefold when
compared with O group, 24 hours after MOPs
procedure and coil activation, and 3.5-fold after
28 days (Fig. 3A), which was statistically was
significant (p o 0.05). While a slight increase was
observed in the O þ 1 MOP group in comparison
to O group at all time points studied, these
changes were not statistically significant. Similar
to the results of the previous clinical trial, 4 MOPs
were able to increase the rate of tooth movement
more than 2 folds (p 4 0.05), while no
significant difference between O group and
O þ 1 MOP group was observed (Fig. 3B and
C). These results demonstrate a direct relation
between the magnitude of the trauma to the
alveolar bone and activation of inflammatory
markers, and therefore, the rate of tooth
movement.
Discussion
The demand for accelerated tooth movement is
heard from both orthodontists and their patients.
Delivering on this demand has led researchers
down varied paths, including vibration, piezo-
electricity, and light; just to name a few. We
hypothesize that harnessing and amplifying
the body’s natural inflammatory responses to
Alikhani et al
1d 7d 14 d 28 d
3.4 ⫾ 0.5 2.1 ⫾ 0.7 1.6 ⫾ 0.5 1.1 ⫾ 0.4
3.1 ⫾ 0.4 2.2 ⫾ 0.6 1.4 ⫾ 0.5 1.2 ⫾ 0.2
orthodontic tooth movement using micro-
osteoperforations in the alveolar bone would
produce a minimally invasive, safe and easily
performed protocol to accelerate tooth move-
ment. Our data from both the animal and human
studies strongly support our hypothesis. We
confidently conclude that MOPs treatment is a
viable option for orthodontists who seek to
shorten overall treatment time for their patients.
Shortening orthodontic treatment time offers
significant value to clinicians and patients alike.
Less time in fixed appliances reduces the risk for
external apical root resorption10 and deminera-
lization/caries11; patient burn-out is less likely;
young patients will miss less school; parents or
older patients will miss less work. Our MOPs
protocol not only offers these advantages by
shortening treatment time, its minimally invasive
application accelerates tooth movement without
additional discomfort for the patients.
Mechanistically, our animal studies showed
that MOPs significantly stimulated expression
of inflammatory markers and significantly
increased the number of osteoclasts and bone
resorption, as anticipated. Interestingly, we
observed that the increase in bone remodeling
was not limited to the area of the moving tooth,
but extended to the tissues surrounding the
adjacent teeth (data not shown). This most likely
contributed to the increase in the rate and
magnitude of tooth movement observed in this
study, thereby suggesting that the perforations do
not need to be very close to the tooth to be
moved to accelerate the rate of tooth movement.
The results of our human clinical trial were
similar to the rat study. Canine retraction in the
presence of MOP resulted in twice as much
distalization as observed with the orthodontic
forces alone. When compared to invasive surgical
approaches to accelerate tooth movement, it is
obvious that MOPs offers a number of advan-
tages. This procedure is minimally invasive and
flapless, allowing orthodontists to deliver care in
their offices.
 Micro-osteoperforations 167

Figure 3. Increasing the number of micro-osteoperforations increases the catabolic effect in humans. A total of 15
subjects were randomly divided into control (O) and experimental groups. Using the same canine retration model
previously described, experimental groups received either 1 (O þ 1 MOP) or 4 (O þ 4 MOP) MOPs between the
canine and the second premolar prior to retraction, on one side of maxilla. (A) Levels of IL1α in the gingival
crevicular fluid—as measured by protein activity was measured by enzyme-linked immunoassay (ELISA) before
retraction, 24 hours, 7 days, and 28 days after force application. Data show significantly higher levels in the group
that received 4 MOPs in comparison to control (O) and the O þ 1 MOP group. Data is presented as pg/uL.
n
Significantly higher than O and O þ 1 MOP groups (p o 0.05). (B) Intraoral photos showing canine retraction
after 28 days of force application. (C) Canine retraction measured in casts was significantly greater in the O þ 4
MOP group than in the O þ 1 MOP and O groups. nSignificantly different from O and O þ 1 MOP groups
(p o 0.05).
168 Alikhani et al
As it was discussed earlier osteoclast recruit-
ment depends on inflammatory marker expres-
sion. This begs the question does inflammatory
marker expression depend on the magnitude of
the trauma? Our clinical studies demonstrate
that by increasing the number of MOPs,
inflammatory maker expression, and magnitude
of tooth movement increased significantly.
Therefore, one should expect procedures such as
orthognathic surgery, corticotomies (where a
flap is raised and numerous cuts and perforations
are made in the alveolar bone), or piezocision
(where no flap is raised, and bone is accessed
through small cuts through the gingiva, followed
by bone injury by a piezoelectric device) to sig-
nificantly increase the level of inflammatory
cytokines beyond levels induced by MOPs, which
in comparison to these procedures is considered
a very conservative insult to alveolar bone.
Unfortunately, the increase in inflammatory
marker expression is not sustained for a long
time and after 2–3 months a significant decrease
in cytokine activity is observed regardless of the
type of procedure or the magnitude of injury.
Due to the need to repeat the procedures over
the course of orthodontic treatment, some of the
above procedures lose their practicality. There-
fore, based on these observations the ortho-
dontists should be able to decide which
procedure best fits the needs of their patients.
Pain and external apical root resorption
The 2 main concerns about MOPs are pain and
root resorption. MOPs are done under infiltration
of local anesthetic. Patients who received MOPs
did not demonstrate additional pain or discomfort
when compared with patients who received only
orthodontic treatment and did not require addi-
tional pain medications or additional care other
than regular oral hygiene. External apical root
resorption (EARR) is not increased following
MOPs treatment. One main reason for EARR is
high stress that produces a cell-free zone when a
tooth is pushed towards dense bone.12 In these
areas, osteoclasts are recruited from the
surrounding PDL and endosteal surfaces. The
prolonged presence of osteoclasts, rather than the
number of osteoclasts, causes EARR. While MOPs
significantly increased the number of osteoclasts,
these osteoclasts are on the adjacent endosteal
bone surface not in the PDL (data not shown).
Moreover, since MOPs decreases the density of
the adjacent alveolar bone, the cell-free zone is
smaller and cleared faster, which would prevent
prolonged osteoclast activity adjacent to tooth
roots. Thus, EARR risk decreases significantly in
MOPs treatment, even during tooth movement
over long distances.
Clinical applications
MOPs can easily be incorporated into our
orthodontic mechanics. Application of MOPs
during leveling and aligning stages should be
postponed until adequate space has been cre-
ated. While MOPs can increase the number of
osteoclasts, it will not change the side effects of
the biomechanics plan and therefore similar to
classic mechanics, the teeth without adequate
space will not be able to engage in the main
archwire. MOPs can facilitate one of the most
difficult movements to accomplish in ortho-
dontics; root movement. By activating osteoclasts
and decreasing the bone density, application of
similar bodily movement mechanics can produce
faster tooth movement and less stress on anchor
teeth, since movement occurs in less time. For
these reasons, MOPs are an excellent adjunct
technique during protraction/retraction of a
single tooth or group of teeth. MOPs between the
roots of teeth decreases the bone density while
the bone density around anchor teeth remains
unchanged. This procedure is especially useful
when a tooth is moved into an edentulous space
where alveolar bone is dense with a narrow ridge.
MOPs can significantly decrease the bone density
and allow faster and safer tooth movement while
enhancing alveolar bone remodeling in that
area. MOPs should also be considered during
segmental intrusion, during which there is a
possibility of root resorption due to high stress
area around the root apex. While keeping the
force light, MOPs application around the apex
prevents the prolonged cell-free zone that can
cause root resorption. Clinicians should take into
consideration that since the increase in cytokine
activity decreases after 2 months of MOPs
application, repeating the procedure every other
month is recommended. And if TADs are being
used to increase anchorage, application of MOPs
adjacent to the location of the TADs should be
avoided since decreased bone density around the
TADs will likely decrease their stability.
 Micro-osteoperforations
Conclusion
MOPs can be incorporated into routine ortho-
dontic mechanics and at different stages of
treatment, facilitating alignment and root
movement, reducing the possibility of root
resorption, stimulating bone remodeling in areas
of deficient alveolar bone, and reducing the
stress on anchor units. Therefore, MOPs offers a
practical, minimally invasive and safe procedure
that can be repeated as needed to maximize the
biological response to orthodontic forces.
References
1. Iwasaki LR, Haack JE, Nickel JC, et al. Human interleukin-
1 beta and interleukin-1 receptor antagonist secretion
and velocity of tooth movement. Arch Oral Biol. 2001;46
(2):185–189.
2. Yoshimatsu M, Shibata Y, Kitaura H, et al. Experimental
model of tooth movement by orthodontic force in mice and
its application to tumor necrosis factor receptor-deficient
mice. J Bone Miner Metab. 2006;24(1):20–27.
3. DeLaurier A, Allen S, deFlandre C, et al. Cytokine
expression in feline osteoclastic resorptive lesions. J Comp
Pathol. 2002;127(2-3):169–177.
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4. Chumbley AB, Tuncay OC. The effect of indomethacin
(an aspirin-like drug) on the rate of orthodontic tooth
movement. Am J Orthod. 1986;89(4):312–314.
5. Knop LA, Shintcovsk RL, Retamoso LB, et al. Non-steroidal
and steroidal anti-inflammatory use in the context of
orthodontic movement. Eur J Orthod. 2012;34(5):531–535.
6. Mohammed AH, Tatakis DN, Dziak R. Leukotrienes in
orthodontic tooth movement. Am J Orthod Dentofacial
Orthop. 1989;95(3):231–237.
7. Teixeira CC, Khoo E, Tran J, et al. Cytokine expression
and accelerated tooth movement. J Dent Res. 2010;89(10):
1135–1141.
8. Alikhani M, Raptis M, Zoldan B, et al. Effect of micro-
osteoperforations. Authors’ response. Am J Orthod Dento-
facial Orthop. 2014;145(3):273–274.
9. Alikhani M, Khoo E, Alyami B, et al. Osteogenic effect of
high-frequency acceleration on alveolar bone. J Dent Res.
2012;91(4):413–419.
10. Weltman B, Vig KW, Fields HW, et al. Root resorption
associated with orthodontic tooth movement: a systematic
review. Am J Orthod Dentofacial Orthop. 2010;137(4):
462–476[discussion 12A].
11. Benson PE, Parkin N, Dyer F, et al. Fluorides for the
prevention of early tooth decay (demineralised white
lesions) during fixed brace treatment. Cochrane Database
Syst Rev. 2013;12:Cd003809.
12. Viecilli RF, Kar-Kuri MH, Varriale J, et al. Effects of initial
stresses and time on orthodontic external root resorption.
J Dent Res. 2013;92(4):346–351.
Piezocision™-assisted orthodontics: Past,
present, and future
Serge Dibart, Elif Keser, and Donald Nelson

The past decade has seen a surge in innovations pertaining to the field of
orthodontics aimed at shortening the length of the treatment for the adult
patient. Today we are presenting an innovative, minimally invasive surgical
technique designed to help achieve such a goal and perhaps, more
importantly, help solve orthodontic challenges through timely bone density
modification. Piezocision™ is an orthodontically guided surgical procedure. It
has evolved from being initially a minimally invasive surgical alternative to
conventional corticotomies to a more sophisticated philosophy where the
orthodontist is given the tools to control the anchorage value of teeth by
selectively altering the bone density surrounding them, using the piezo-
electric knife at key time intervals, in an effort to successfully solve
orthodontic challenges. Piezocision™ gives the periodontist and the ortho-
dontist another tool to expand their scope of practice. (Semin Orthod 2015;
21:170–175.) & 2015 Elsevier Inc. All rights reserved.

Introduction mechanics. It is also about being an essential part

W
hat is Piezocision™-assisted orthodontics?
A minimally invasive surgical procedure
aimed to accelerate orthodontic tooth move-
ment? A tool given to the orthodontist to control
anchorage? A useful complement to treatment
with clear aligners? A way to modify/strengthen a
patient's thin biotype? Indeed, it could be used
for all of the above. Piezocision™ is a way of
seeing and treating cases differently. It has
evolved from being initially a minimally invasive
surgical alternative to conventional corticotomies
to a more sophisticated “intellectual” approach
to comprehensive orthodontic and multi-
disciplinary care. It is not just about speed any-
more; it is about the possibility for the
orthodontist to control selectively the anchorage
value of teeth at will, potentially offering a means
to successfully treating cases that until now were
beyond the scope of conventional orthodontic
Department of Periodontology, Boston University Henry M.
Goldman School of Dental Medicine, 100 East Newton st, Suite
G-217, Boston, MA 02118; Department of Orthodontics, Boston
University Henry M. Goldman School of Dental Medicine, Boston,
MA; Department of Orthodontics, Harvard School of Dental
Medicine, Boston, MA.
Corresponding author. E-mail: sdibart@bu.edu
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.003
of a multidisciplinary team, providing the
necessary space or spacings between teeth for
optimal implant placement or prosthetic reha-
bilitation. Piezocision™ can be used in a gen-
eralized, localized, or sequential manner (Fig. 1).
The technique
Piezocision™ is performed 1 week after the
placement of orthodontic appliances (fixed or
removable). A small vertical incision is made
buccally and interproximally.1,2 This mid-level
incision, between the roots of the teeth, will allow
for the insertion of the piezoelectric knife. Pie-
zocision™ has a localized and selective effect on
the teeth; only the teeth or arch(es) to be moved
need to be operated upon. The areas not surg-
erized have a higher anchorage value, since they
are not affected by the demineralization process
following Piezocision™ and can be used as such
in the global treatment plan. The tip of the
Piezotome (Satelec, Acteongroup, Merignac,
France) is inserted in the gingival openings
previously made and a 3-mm-deep piezoelectrical
corticotomy is done (Fig. 2). The decortication has
to pass the cortical layer and reach the medullary
bone to get the full effect of the regional
acceleratory phenomenon (RAP). In the areas
with thin or little gingiva (recessions) or with thin
or no cortical buccal bone (dehiscences and

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 170–175 170

 Piezocision™-assisted orthodontics 171

Figure 1. The various modes to use Piezocision™: generalized, localized, segmental, and sequential.

fenestrations), hard and/or soft tissue grafts can created by the ultrasonic handpiece at specific
be added via a tunneling procedure. The patient settings (Fig. 3). Looking at the current
is seen every week or every 2 weeks after surgery by literature, once the bone has demineralized
the orthodontist in order to change aligners following bur corticotomy, there is a 3–4-
or activate wires and take advantage of month window of opportunity to move teeth
the temporary demineralization phase created rapidly through the demineralized bone matrix
by Piezocision™. This results in faster tooth before the alveolar bone remineralizes.9 The
movement and early completion of treatment. effects of Piezocision™ on the length of this
window of opportunity are being investigated.
Our clinical experience indicates that this RAP
How does it work?
could last up to 6 months. This is best observed in
When the bone is injured, a very dynamic healing our daily practice by patients treated with
process occurs at the site of the bone injury. This Piezocision™-assisted Invisalign,10 where the
process is called the regional acceleratory phe- patient changes the aligners every 5 days
nomenon (RAP), which is proportional to the instead of every 2 weeks. After the 5th or 6th
extent of the surgical insult.3–5 There is a local- month of treatment, the tooth movement
ized surge in osteoclastic and osteoblastic activ- appears to slow down.
ities that results, in the early phases, in a decrease
in bone density with an increased bone turnover.
This transient osteoporotic condition facilitates
tooth movement. Various animal experiments6–7
have confirmed that alveolar decortication with
the bur induces a RAP response. Recently, a
similar research has been done to show the
effects of PiezocisionTM on the alveolar bone and
tooth movement.8 It has been shown that a
similar RAP effect is produced when
decortications are done with the piezotome.
Furthermore, we have found that in a
preliminary study on animals, although more
conservative as a surgical procedure,
PiezocisionTM and the use of the piezotome at
specific vibration frequency settings appeared
to induce a more extensive and diffuse
demineralization followed by increased Figure 2. After the buccal interproximal gingival
incision, the Piezotome is inserted to a depth of
remineralization effect on the bone than on approximately 3 mm to do the decortication that will
the bur. This could be due to the additive effect start the RAP. It is critical to decorticate while passing
of the osteocytes response to micro-vibrations the buccal cortex.
172 Dibart et al

Figure 3. Animal (mouse) experiment assessing the differences between bur and piezoelectric corticotomies. Left
femur is the control and right femur is the experimental site for each animal. At 8 weeks, notice the difference in
the bone response to injury. Not only is the bone responding differently to the type of injury (bur vs. piezoelectric
knife), but also to the intensity of various vibration frequencies of the piezoelectric knife (Courtesy of Dr. Robert
Gyurko).

Reduction in treatment time and more to the desired tooth movements. The ortho-
dontist, as the “chess master,” decides which
At the present time there are no well-designed
tooth or group of teeth are going to be moved
randomized controlled trials regarding Piezoci-
and where. As the strategist, s/he decides on the
sion's two tenets of piezotome-corticotomy depth
timing and extent of Piezocision™ that will allow
(3 mm into the bone, passed the cortical layer to get
for specific tooth movement to be achieved
the full RAP effect) and appointment frequency
during treatment. These challenging movements
that would give the evidence as to how much time
will be made possible, in a more “pliable” bone,
is gained by using Piezocision™-assisted ortho-
via localized alteration of the mineralization/
dontics. Our animal studies8 suggested an overall
demineralization process in various parts of the
treatment time reduction of 50%, which is
mouth. Also Piezocision™ can be repeated more
consistent with our clinical observations. A
than once in the same area(s) to re-activate the
prospective clinical study has been initiated by
RAP12 (after 5
6 months) and keep the area
our group to provide some answers. Perhaps
demineralized (depending on the difficulty of
more crucial is the realization of anchorage
the movements being performed and the
control that is now in the hands of the
morphology of the patient's bone; Fig. 5). The
orthodontist. The density of the alveolar bone
repeated procedure takes very little time and is so
and the cross-sectional area of the roots in the
conservative that it meets high patients acceptance
plan perpendicular to the direction of tooth
yet yielding great treatment outcomes.
movement are the primary considerations for
assessing anchorage potential. The volume of
osseous tissue that must be resorbed for a tooth
Periodontal biotype modifications
to move a given distance is its anchorage value.11
Piezocision™ can now be defined as another tool The orthodontic treatment of teeth beyond the
for creating differential anchorage. Since it has limits of the labial alveolar plate can lead to
been shown that the density of the bone around dehiscence formation13–15 and predispose the
the Piezocision™ cut is less,2,8 the anchorage patient to recession.16–18 Hard and/or soft tissue
values of the teeth at the decortication site would grafting can prevent such disastrous outcomes
be different. Piezocision™ can be done selec- or correct an existing recession. This is done via
tively around the teeth that are going to be a tunneling procedure without the need
moved and the anchorage values of these teeth of a conventional flap elevation (Fig. 4).
can be decreased. Therefore the need for Communication with the orthodontist is
additional anchorage devices can be eliminated paramount. She/he outlines the treatment
by designing the alveolar decortication according plan, the specific movement of teeth and their
 Piezocision™-assisted orthodontics
sequence, and the sites for Piezocision™; she/he
is responsible for the ultimate outcome. The
periodontist makes Piezocision™ cuts according
to the treatment plan devised by the
orthodontist. She/he ensures that the surgical
procedure is carried out safely and that
mucogingival defects are prevented or corrected.
Clinical applications
Piezocision™ can be used in a generalized,
localized, or sequential manner.
 Generalized: If the correction of the malocclu-
sion requires moving all of the teeth in both
maxilla and mandible at the same time.
 Localized: If the malocclusion affects only
one part of the dentition or one arch (i.e.,
an anterior crowding case with a perfect
posterior occlusion, single tooth extrusions

intrusions, etc.).
 Sequential: If the correction of the malocclu-
sion requires a “staged” approach, where
selected areas or segments of the arch are
being demineralized at different times during
orthodontic treatment to help achieve specific
results (Fig. 5).12,19
Indications
Based on our clinical experience: Class I mal-
occlusions with moderate to severe crowding
(extraction and non-extraction), selected Class II
Figure 4. Thin biotype showing underlying dehiscence and bone fenestration. Proclining these teeth without hard
and soft tissue grafting is likely to lead to severe recession during or after the orthodontic treatment.
173
malocclusions (end-on), selected Class III mal-
occlusions (dental), correction of deep bite,
correction of open bite, distalization of molars,
palatal version of root apices, rapid adult
orthodontic treatment, orthodontic treatment
with clear aligners, rapid intrusion and extrusion
of teeth, prevention or simultaneous correction
of osseous and mucogingival defects that may
occur during or after orthodontic treatment, and
multidisciplinary treatments.
Contra-indications
Medically compromised patients, patients taking
drugs modifying normal bone physiology (i.e.,
biphosphonates), any bone pathology, ankylosed
teeth, non-compliant patients, and patient and/
or operator having a pacemaker or any other
active implant.
Potential problems
Root injury, infection, and mucogingival defects.
Future directions
The direction we are moving toward now is using
Piezocision™ to help solve elegantly orthodontic
challenges. Speed, although desirable, has
become almost secondary to the greater benefits
this technique can offer. Piezocision™ may offer
a substitute for complete corticotomies in less
severe cases requiring surgically assisted rapid
174 Dibart et al

Figure 5. (A) A 60-year-old man with a skeletal Class II division 2 malocclusion characterized by a deep, impinging
anterior overbite and severely retroclined upper incisors resulting in an interincisal angle of 1791. Comprehensive
orthodontic treatment consisted of non-extraction treatment with fixed appliances in the upper and lower arches.
Piezocision™ was performed three times during treatment—twice to facilitate bite opening and especially torque
on the upper anteriors, and once to move the lower anteriors. (B) The first Piezocision™ was done to intrude
upper anteriors. The second Piezocision™ was done 6 months later on the same site (canine to canine) to torque
the upper anteriors and move the apices palatally. A third Piezocision™ was done later in the treatment to move
the lower anterior teeth (Sequential Piezocision™). (C) The pretreatment cephalometric radiograph (a) revealed
a non-coincident border of the mandible with a hypodivergent vertical pattern. The Wits and ANB indicated a
retrognathic mandible (Wits 4.3 mm; ANB 6.41, SNB 76.41). The upper anteriors to the NA line were 13.71 while
the interincisal angle was 178.21. The lower anteriors were also retroclined, with a measurement of
2.2 mm to the
NB line. The super-impositions at the end of treatment (b) displayed the significant changes in torque of the upper
anteriors and improvement in the interincisal angle. Pretreatment U1-NA-13.71, posttreatment 19.71; pretreatment
L1-NB: 5.51, posttreatment 25.61; pretreatment U1-L1 178.21, posttreatment 132.81; net change in upper incisors ¼
33.41. (D) Later The case was finished after 24 months with an ideal overjet and overbite. Rotations and crowding
as well as space of the diastema were resolved. Bite opening was achieved through a combination of intrusion of the
anteriors, extrusion of the posteriors, and a slight increase in the mandibular plane. The right and left buccal
segments were finished in Class I relationship, with canine and incisal guidance and no balancing interferences.
This illustrates perhaps the more important feature of Piezocision™—it is not just the speed anymore but the
ability to accomplish successfully challenging orthodontic movements that are very difficult or impossible with
conventional orthodontics.

palatal expansion. It helps in distalization of
molars, intrusion of molars, and correction of
open bites; it may provide a mechanism to treat
cases of alveolar insufficiency and certain Class
III malocclusions can successfully be treated
in this “unconventional” manner.19 Another
venue is integrating short orthodontics in
multidisciplinary treatments. Utilizing short
orthodontics to reposition teeth in an ideal or
more desirable position in the arch minimizes
the amount of enamel/dentin to be removed to
place a prosthetic restoration (i.e., veneer).
Finally the fear of injuring the roots during
Piezocision™ has been alleviated by using
computer-guided surgery.20 Many technical
innovations are in the process as we speak, but
truly the next page regarding the future
applications of Piezocision™ will be written by
 Piezocision™-assisted orthodontics
YOU (the orthodontists) as you become more
familiar with the potential of this technique. Your
creativity and your capability to think “outside
the box” will open the path to new ways to treat
your patient.
References
1. Dibart S, Sebaoun JD, Surmenian J. Piezocision: a
minimally invasive, periodontally accelerated orthodontic
tooth movement procedure. Compend Contin Educ Dent.
2009;30:342–350.
2. Dibart S, Surmenian J, Sebaoun JD, et al. Rapid treatment
of Class II malocclusion with piezocision: two case reports.
Int J Periodontics Restorative Dent. 2010;30(5):487–493.
3. Frost HA. The regional acceleratory phenomena: a
review. Henry Ford Hosp Med J. 1983;31:3–9.
4. Frost HM. The biology of fracture healing. An overview
for clinicians. Part I. Clin Orthop Relat Res. 1989;248:
283–293.
5. Frost HM. The biology of fracture healing. An overview
for clinicians. Part II. Clin Orthop Relat Res. 1989;248:
294–309.
6. Sebaoun JD, Kantarci A, Turner JW, et al. Modeling of
trabecular bone and lamina dura following selective
alveolar decortication in rats. J Periodontol. 2008;79:
1679–1688.
7. Baloul SS, Gerstenfeld LC, Morgan EF, et al. Mechanism
of action and morphologic changes in the alveolar bone
in response to selective alveolar decortication-facilitated
tooth movement. Am J Orthod Dentofacial Orthop. 2011;S83:
S101–1688.
8. Dibart S, Yee C, Surmenian J, et al. Tissue response during
Piezocision-assisted tooth movement: a histological study
in rats. Eur J Orthod. 2014;36(4):457–464.
175
9. Lee W, Karapetyan G, Moats R, et al. Corticotomy-/
osteotomy-assisted tooth movement microCTs differ.
J Dent Res. 2008;87(9):861–865.
10. Keser EI, Dibart S. Piezocision assisted invisalign treat-
ment. Compend Contin Educ Dent. 2011;32(2):46–51.
11. Roberts WE, Bone physiology, metabolism and biome-
chanics in orthodontic practice. In: Graber T, Vanarsdall
R, Vig K, eds. Orthodontics Current Principles and Techniques.
2015:278[Chapter 6].
12. Nelson D, Dibart S. Sequential piezocision in a challeng-
ing adult case. J Clin Orthod. 2014;48(9):555–562.
13. Wennstrom JL. Mucogingival considerations in ortho-
dontic treatment. Semin Orthod. 1996;2:46–54.
14. McComb JL. Orthodontic treatment and isolated gingival
recession: a review. Br J Orthod. 1994;21:151–159.
15. Joss-Vassalli I, Grebenstein C, Topouzelis N, et al.
Orthodontic therapy and gingival recession: a systematic
review. Orthod Craniofac Res. 2010;13:127–141.
16. Melsen B, Allais D. Factors of importance for the
development of dehiscences during labial movement of
mandibular incisors: a retrospective study of adult
orthodontic patients. Am J Orthod Dentofacial Orthop.
2005;127:552–561.
17. Zachrisson BU. Clinical implications of recent
orthodontic-periodontic research finding. Semin Orthod.
1996;2:4–12.
18. Renkema AM, Fudalej PS, Renkema A, Kiekens R,
Katsaros C. Development of labial gingival recessions in
orthodontically treated patients. Am J Orthod Dentofacial
Orthop. 2013;143(2):206–212.
19. Keser EI, Dibart S. Sequential Piezocision: a novel
approach to accelerated orthodontic treatment. Am J
Orthod Dentofacial Orthop. 2013;144:879–889.
20. Milano F, Dibart S, Montesani L, Guerra L. Computer
guided surgery using the piezocision technique. Int J
Periodontics Restorative Dent. 2014;34(4):523–529.
Scope of treatment with periodontally
accelerated osteogenic orthodontics therapy
Donald J. Ferguson, M. Thomas Wilcko, Willam M. Wilcko, and Laith Makki

Guidelines for tooth movement limits are meant to help clinicians in

treatment-planning decisions, especially for “severe” or “borderline” adult
malocclusions. The purpose of this article was to review well-accepted scope
of care beliefs and compare with suggested scope of treatment offered by
periodontally accelerated osteogenic orthodontics (PAOO). PAOO is a
surgical technique that accelerates tooth movement and expands the scope
of conventional orthodontic treatment in the adult 2–3 fold in most spatial
dimensions. (Semin Orthod 2015; 21:176–186.) & 2015 Elsevier Inc. All rights
reserved.

Introduction
everity of malocclusion is a dominant factor
S in orthodontic treatment planning. The
goals of orthodontic treatment must include
good facial esthetics, adequate function as well as
stability in the ultimate positions of the dentition
and jaws. It is the responsibility of the clinician to
offer a treatment plan that will accomplish desir-
able esthetic, functional and stable results. In the
orthodontic treatment of non-growing patients,
malocclusions viewed as “borderline” or “severe”
are filtered or sorted on the basis of two broad
possibilities for correction: (1) camouflage (ortho-
dontic positioning of the teeth to compensate for
the jaw discrepancy), and (2) orthognathic sur-
gery in conjunction with orthodontics to repo-
sition the jaws and/or dentoalveolar segments.1
The ability to resolve severe malocclusion
without surgical intervention is of great interest
to the orthodontist clinician.2 The strong
majority of clinicians who comprise the clinical
Advanced Orthodontic Program, European University College,
Dubai Healthcare City, Ibn Sina Building, Block D, 3rd Floor, Office
302, P.O. Box 53382, Dubai, United Arab Emirates; Case Western
Reserve University, Department of Periodontology, Cleveland, OH;
Private Practice in Periodontology, Erie, PA, USA; University of
Pennsylvania School of Dental Medicine, Department of Orthodon-
tics, Philadelphia, PA; Private Practice in Orthodontics, Erie, PA,
USA; Advanced Orthodontic Program, European University College,
Dubai, United Arab Emirates.
Corresponding author. E-mail: fergusonloud@gmail.com
Work was completed at European University College, Dubai
Healthcare City, United Arab Emirates.
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.004
discipline of orthodontics are conservative in
nature, and for them, avoiding surgery is the
prevailing canon. But conservative judgment
runs a-foul when compromise or camouflage
impacts too strongly upon esthetics, function
and/or stability.
Alveolar decortication with augmentation
bone grafting technique combined with ortho-
dontics is called periodontally accelerated
osteogenic orthodontics or PAOO and was first
described by Wilcko et al.3 This surgical
technique has been sufficiently described and
the main features include full thickness perio-
steal flap reflection followed by intentionally
scaring or scoring the alveolar cortical bone,
both labial and lingual, in the area of desired
tooth movement. Bone grafting is placed at the
corticotomy sites and is typically comprised of a
mixture of demineralized freeze-dried bone
allograft (DFDBA) and bovine bone. The surgi-
cal flap is sutured, and the patient is seen
every 2 weeks after the surgery for orthodontic
adjustments. It is recommended that the sur-
gical procedure be performed within 1 week of
fixed orthodontic appliance placement and
that the appliance be activated at the time of
surgery.4
PAOO accelerates orthodontic tooth move-
ment and malocclusions are resolved 3–4 times
faster; treatment times for complex cases average
6 months compared to 18–27 months.3 But
PAOO has been described as intrepid by some
and dismissed by others as unnecessary or
overreaching.5 This reaction or resistance in
the orthodontic community is understandable

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 176–186 176

 Scope of treatment with periodontally accelerated osteogenic orthodontics therapy 177

considering that the value of corticotomy plus
grafting technique and the scope of implications
are not widely recognized.6 The purpose of this
article is to compare scope of PAOO treatment
with well-accepted and prevailing scope of care
tenets with a focus on malocclusion severity.
Orthodontic tooth movement limits
Severity of the malocclusion is a dominant factor
in treatment-planning decisions but not the only
factor. Tullock et al. astutely pointed out that
relying solely on the presenting anatomic
arrangement of teeth and jaws clearly ignores
many of the factors that determine the treatment
response and thereby influence treatment plan
choice. Factors over and beyond simple pre-
senting morphological characteristics, such as
age, psychological profile, patient treatment-
planning preferences, esthetics, estimated com-
pliance, and anticipated tissue response to bio-
mechanical forces, etc. must be considered in
treatment-planning decisions.7
Maxillary and mandibular incisors
Proffit's “envelope of discrepancy,” describing
limits of orthodontic treatment in the context of

Figure 1. Limits of orthodontic tooth movement suggested by Proffit's “envelope of discrepancy” represented by
the black inner circle and PAOO limits represented by the red circle. The two visual circles are documented also by
millimeter amounts for retraction, protraction, intrusion, and extrusion for central incisor tooth movements in the
maxilla and mandible. (Proffit's “envelope of discrepancy” is redrawn with permission.)
178 Ferguson et al
producing normal, stable occlusion, has been cited
by most authors exploring orthodontic treatment
limits and is represented in Fig. 1.8 These limits
when applied to the non-growing individual vary
by the tooth movement that would be needed if
other restraints, such as soft tissue limits, do not
apply. According to Proffit's opinion, teeth can be
moved further in some directions than others; the
range described is 7 mm (maxillary incisor
retraction) in the anteroposterior spatial plane to
2 mm (maxillary incisor protraction and some
incisor vertical dimension changes).
While limits of tooth movement are a matter of
clinical experience and opinion and are not based
in scientific fact, in general, PAOO treatment
limits for incisors exceed the envelope of dis-
crepancy described by Proffit for adult, non-
growing patients by 2–3 times in all dimension
except retraction. Corticotomy surgery is recom-
mended within 1 week of fixed orthodontic
appliance placement; alignment of incisors is
rapid after surgery, but the time it takes to align
incisors encroaches upon post corticotomy heal-
ing. Retraction movement is usually constrained
because RAP has dissipated and healing has
advanced ahead of space closure precluding
accelerated retraction. The combination of cor-
ticotomy and dental distraction9 is recommended
to facilitate retraction tooth movement.
Corticotomy surgery increases the soft and
hard tissue turnover, augmentation bone graft-
ing expands the bony alveolus and both proc-
esses expand hard and soft tissue limits and
enable teeth to be moved a greater distance.
Unlike instantaneous jaw segment movements
from orthognathic surgery constrained by soft
tissues and muscles, the augmentation bone
grafting of PAOO increases the alveolus size and
expands the soft tissue envelope gradually with
much less constraint from the craniofacial mus-
cles. The accelerated tooth movement process
involves a demineralization of alveolar bone
adjacent to the corticotomy,10,11 bone matrix
transport to a new position secondary to ortho-
dontic biomechanical forces, and remineraliza-
tion of the alveolus after active tooth movement
has been completed. It is surmised that the
remarkable stability of PAOO treatment out-
comes is the consequence of increased tissue
turnover and increased thickness of cortical
bone12 in conjunction with low constraint from
pre-existing soft tissues and muscles.
Large changes in the alveolus housing the
dentition are very amenable to PAOO technique.
Hence, PAOO is applicable to the most moderate
to severe malocclusion conditions because soft
tissue constraints are reduced and the limits of
the alveolar housing are increased. Moderate to
severe malocclusions amenable to PAOO therapy
are problems requiring alveolar extrusion or
intrusion, transverse alveolar expansion (ortho-
dontists rarely constrict), and alveolar pro-
trusion. PAOO cannot extend the limits of
alveolar retraction because this tooth movement
in severe malocclusion is typically defined by the
skeletal position of the jaw in the anteroposterior
dimension.13 For conditions of microganthia or
macrognathia accompanied by excess or
deficient overjet, only orthognathic surgery is
applicable14–17 because PAOO does not have the
capacity to move jaws in the anteroposterior
spatial plane.
Mandibular arch width
Arch expansion requires primarily the dentoal-
veolar tooth movements of tipping, up-righting
and rotation. Considering the therapeutic con-
straints offered by the mandibular dental arch,
Proffit has suggested mandibular arch expansion
limits as follows: 2 mm anterior movement of the
mandibular incisors, 0–1 mm intercanine width,
2 mm inter-first premolar expansion, 2–3 mm
inter-second premolar width, and 3 mm trans-
verse expansion of inter-molar width.8
Anteroposterior expansion greater than 2 mm
and transverse expansion by more than 4 or
5 mm will likely be unstable according to Proffit.8
Conventional wisdom suggests that orthodontic
treatment should reflect the amount of incisor
change that would occur relative to stability
because the pretreatment position likely
reflects the soft tissue influences. Moreover,
gingival recession and dehiscence of the
alveolar bone may occur with orthodontic
expansion when the attached gingiva is thin,
especially when accompanied by plaque
accumulation and inflammation.18
There is a paucity of stability studies related to
PAOO technique, but it has been recently
demonstrated that mandibular intercanine
expansion averaging 2.1 mm was stable 5 years
after active PAOO treatment. In contrast to
expected intercanine width decrease, there was a
 Scope of treatment with periodontally accelerated osteogenic orthodontics therapy
0.7 mm non-significant increase in intercanine
width during the 5 years after active treatment;
the removable retainer wear compliance was
judged “average” in a sample comprised of 33
patients with a mean age of 35.3 years.19
PAOO technique for treatment of severe
malocclusion
Several cases representing severe malocclusion
are presented all treated using PAOO technique.
The purpose of this article is to compare scope of
treatment with PAOO with Proffit's “envelope of
discrepancy” to illustrate the capacity of PAOO
therapy to resolve severe malocclusion. The goal
of demonstrating limits of tooth movement using
alveolar decortication and augmentation bone
grafting (PAOO) is achieved at the expense of a
limited amount of patient records provided.
Extrusion for open bite
Open bite treated with PAOO by extrusion of
maxillary incisors 10 mm is illustrated in Fig. 2.
Figure 2. Maxillary incisor extrusion of 10 mm following PAOO labial and lingual to maxillary incisors and canines
for correction of open bite.
179
Maxillary central incisor incisal edges were
vertically short of lower broader of upper lip
by 8 mm. Corticotomy was performed on
maxillary anterior segment between maxillary
first premolars on labial and lingual followed by
bone grafting. Active treatment time was 8
months.
Intrusion for deep bite
Deep bite treated with PAOO by intruding
mandibular incisors 7 mm is demonstrated in
Fig. 3. Mandibular incisors and right canine
represented a 7 mm deviation in the curve of
Spee. Alveolar decortication was performed
labial and lingual to all mandibular incisors
and the mandibular right canine followed by
bone augmentation grafting. Intrusion was
achieved by intruding incisors and right
canine. Active treatment time was 8 months.
Protraction for crowding
Maxillary incisors protracted 5 mm by PAOO
treatment and advancing maxillary incisors to
180 Ferguson et al
Figure 3. Mandibular incisors intruded 7 mm for correction of excess curve of Spee and deep bite malocclusion by
PAOO labial and lingual to all mandibular incisors and the right canine.
accommodate a blocked out maxillary left canine
is shown in Fig. 4. For the maxillary incisor
advancement, alveolar decortication was
performed labial and lingual to all maxillary
incisors and the maxillary left canine followed by
bone augmentation grafting. Maxillary dental
arch malocclusion was resolve in 5 months
following PAOO in preparation for mandibular
advanced orthognathic surgery; overall
treatment time including the orthognathic
surgery was 9 months. Photos with orthodontic
brackets show position of incisors prior to and
after PAOO treatment effects. Finished photos
represent 4 years following active orthodontic
treatment.
Protraction of mandibular incisor
Mandibular incisors were protracted 9 mm by
PAOO treatment in order to correct a post
trauma injury of the mandible as demonstrated
in Fig. 5. Trauma resulted in loss of the
mandibular left first premolar and ankylosis of
the canine which required extraction. Alveolar
decortication was performed labial and lingual to
all teeth anterior to the mandibular first molars
accompanied by ample augmentation grafting of
the alveolar bone. Temporary anchorage devices
(mini-screws) were place between maxillary
laterals and canines in order to protract the
mandibular incisors and correct the lower
midline deviation. Photos represent 4 months
of active treatment following the PAOO surgery.
The anatomy of the alveolar bone and soft tissues
in the area after PAOO therapy suggests that the
limit of mandibular incisor protraction is
substantially greater than without the procedure.
Expansion for posterior crossbite
Maxillary constriction was treated by expansion
of about 7 mm at intercanine width following
PAOO on both arches as illustrated in Fig. 6. The
maxillary expansion was achieved by archwire
expansion only after labial and lingual
corticotomy and augmentation bone grafting
from maxillary first molar to first molar. Active
treatment time was 6.5 months. Prior to PAOO,
free gingival grafts were placed labial to maxillary
canines and labial to mandibular second
premolar to second premolar. This case was
treated early in PAOO development; today the
free gingival grafts would not be performed.
De-crowding in the mandible
Mandibular crowding of 12 mm was resolved by
PAOO therapy as shown in Fig. 7. Maxillary
lateral incisors were missing and pretreatment
first molar occlusion was Class II. Alveolar
decortication in both arches and ample bone
 Scope of treatment with periodontally accelerated osteogenic orthodontics therapy 181

Figure 4. Maxillary incisor protraction of 5 mm by PAOO treatment surrounding maxillary incisors and left canine
to accommodate a blocked out maxillary left canine. After 4 months of PAOO therapy, the patient underwent
mandibular advancement orthognathic surgery.

grafting was performed labial and lingual to all
teeth anterior to second molars. In the
mandibular arch, fixed orthodontic appliances
were used to first tip the incisor crowns labially
followed by up-righting incisor roots into the
labial augmentation graft to achieve incisor
positions that were more up-right than at pre-
treatment. Active treatment time was 8 months.
Discussion
The benefits of PAOO therapy include the fol-
lowing: (1) increase limits of tooth movement
created by augmentation bone grafting as dem-
onstrated in the present article, (2) enhanced
stability of orthodontic treatment outcomes,19,20
(3) rapid orthodontics for severe malocclusion
averaging 6–8 months of active treatment time,21
and (4) increased robustness of the periodon-
tium.
The upper tooth movement limits considered
achievable following PAOO was represented in a
series of cases presented with limited patient
records. These cases represented maxillary inci-
sor extrusion of 10 mm, mandibular incisor
intrusion of 7 mm, maxillary incisor protrusion of
5 mm, mandibular incisor protrusion of 9 mm,
maxillary intercanine expansion of 7 mm, and
mandibular de-crowding of 12 mm. In all of these
PAOO cases, only archwires were used to achieve
the ultimate positions of the dentition.
Ackerman et al. astutely pointed out that
stability after orthodontic treatment is deter-
mined by the ability of the soft tissues to adapt to
182 Ferguson et al

Figure 5. Mandibular incisor protraction of 9 mm by PAOO therapy labial and lingual to all teeth mesial to the
first molars in an post traumatic injury patient. PAOO treatment was chosen to avoid the high risk alternate of a
multi-piece mandibular orthognathic surgery.

changes in hard tissue morphology.15 These the amount of change in tooth position that
authors and others argue that since pretreat- treatment would produce and the relationship of
ment position of the teeth already reflects soft the amount of change to stability. Evaluating soft
tissue influences, it is better to think in terms of tissue contours clinically is a critical step in
 Scope of treatment with periodontally accelerated osteogenic orthodontics therapy 183

Figure 6. Maxillary intercanine expansion of 7 mm by PAOO therapy and archwires only for correction of
maxillary arch constriction.

gathering an adequate diagnostic data base undesirable relapse-type changes.23 Moreover,

before making treatment-planning decisions.18,22
PAOO therapy influences the entire perio-
dontium, i.e., both hard and soft tissues sur-
rounding the dentition, and augmentation bone
grafting ultimately increases the size of the bony
alveolus. The influence of soft tissue on ortho-
dontic outcome stability is moderated by the
healing processes described collectively by Frost
as regional acceleratory phenomena or RAP
wherein all tissues turnover at a high rate and
likely lose the type of “memory” that result in
an increase in the thickness of the alveolar corti-
cal bone most likely contributes to enhance
orthodontic treatment outcome stability.24,25
Orthodontic problems must be solved without
causing irreversible damage to the perio-
dontium, and the greater the tooth movement,
the greater the chance of endangering the
periodontium.18 A patient with thin biotype and
little attached gingiva on the labial of mandibular
incisors may be at risk for gingival recession if the
tooth is moved facially out of its alveolar bone
184 Ferguson et al

Figure 7. Crowding of 12 mm in the mandibular dental arch was resolved by PAOO therapy labial and lingual to
all teeth in the arch.
 Scope of treatment with periodontally accelerated osteogenic orthodontics therapy 185

appears to extend the keratinized gingiva from

the gingival margin. Keratinized gingiva
increased 0.78mm in PAOO versus a decrease
of 0.38mm in non-PAOO group.29
Augmentation bone grafting increasing the size
of the alveolus28 and healing dynamics subsequent
to corticotomy,10 changes the physiologic limits of
the soft tissues and in doing so extends the limits
of tooth movement and orthodontic treatment.12
Without PAOO, the anatomic limits of tooth
movement far exceed the ability of soft tissues
to adapt to the changes in the position of the
teeth.27 When it appears that it is not possible to
achieve ideal occlusion, excellent stability, normal
function and optimal facial balance with
conventional orthodontic therapy,26 PAOO may
offer a viable alternative. When orthognathic
surgery is judged too expensive or risky, PAOO
should be considered for solving imbalances
secondary to alveolar deficiencies in the vertical
and transverse dimensions.

Summary
The purpose of this article was to compare PAOO
scope of treatment with well-accepted and pre-
vailing scope of care tenets with a focus on
malocclusion severity. In the authors opinion,
PAOO treatment expands the scope of conven-
tional orthodontic treatment in the adult 2-fold
to 3-fold in most spatial dimensions.

References
Figure 8. Increased width of keratinized gingiva 1.5
years following PAOO therapy also evident at removal
of fixed orthodontic appliances 7 months post surgery
as evident by the presence of granulation gingiva.
housing.18,22,26,27 PAOO treatment has been
demonstrated to repair cortical alveolar dehis-
cence and fenestration problems discovered at
the pretreatment stage8 and that increases in
cortical thickness from the grafting appears to be
permanent.28
During adulthood, the width of keratinized or
attached gingiva does not increase.27 It has been
revealed recently that the width of keratinized
gingiva increases as a consequence of PAOO
procedure as shown in Fig. 8. Stretching the full
thickness flap over the bulk of grafting materials
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orthodontics with alveolar reshaping: two case reports of
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6. Ferguson DJ, Malrami SB. Rapid orthodontics following
alveolar decortication: why the resistance? J Parod
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7. Tullock JFC, Lenz BE, Phillips C. Surgical versus
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8. Proffit WR, Fields HW, Sarver DM. Contemporary Ortho-
dontics. 5th ed., St. Louis, MO: Elservier; 2013.
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10. Lee W, Karapetyan G, Moats R, et al. Corticotomy-/
osteotomy-assisted tooth movement microCTs differ.
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11. Sebaoun JD, Turner JW, Kantarci A, Carvalho RS,
Van Dyke TE, Ferguson DJ. Modeling of trabecular bone
and lamina dura following selective alveolar decortication
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comparing camouflage orthodontics, dentofacial orthopedics
and orthognathic surgery—a cephalometric study to evaluate
various therapeutic effects. J Orofac Orthop. 2008;69:63–91.
15. Mihalik CA, Proffit WR, Phillips C. Long-term follow-up of
Class II adults treated with orthodontic camouflage: a
comparison with orthognathic surgery outcomes. Am J
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16. Squire D, Best AM, Lindauer SJ, Laskin DM. Determining
the limits of orthodontic treatment of overbite, overjet,
and transverse discrepancy: a pilot study. Am J Orthod
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17. Tucker MR. Orthognathic surgery versus orthodontic
camouflage in the treatment of mandibular deficiency.
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18. Ackerman JL, Proffit WR. Soft tissue limitations in ortho-
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Stability of the mandibular dental arch following
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irregularity index stability following alveolar corticotomy
and grafting: a 10 year preliminary study. (Published
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http://dx.doi.org/10.2319/061714-439.
21. Wilcko MT, Wilcko WM, Pulver JJ, Bissada NF, Bouquot
JE. Accelerated osteogenic orthodontics technique: a 1-
stage surgically facilitated rapid orthodontic technique
with alveolar augmentation. J Oral Maxillofac Surg.
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1902/jop.2015.150074 [Epub ahead of print].
Cyclic loading (vibration) accelerates tooth
movement in orthodontic patients: A
double-blind, randomized controlled trial
Dubravko Pavlin, Ravikumar Anthony, Vishnu Raj, and Peter T. Gakunga

This was a parallel, double-blind, prospective, randomized, controlled trial with

the objective to assess the effect of a defined low-level cyclic loading on the rate
of orthodontic tooth movement. Overall, 45 orthodontic patients were treated
with fixed appliances at the UTHSC San Antonio Orthodontic Department.
Inclusion criteria were extraction of maxillary first premolars, maximum
maxillary posterior anchorage, and at least 3 mm of extraction space after
initial alignment. The enrolled subjects were randomized into two groups,
vibration (n ¼ 23) and control (n ¼ 22) using a third-party computer-generated
randomization schedule. All care providers, investigators, and patients were
blinded to intervention assignment. Cyclic loading was applied to the vibration
group for 20 min/day using the AcceleDents device, which delivered a force of
0.25 N (25 g) at a frequency of 30 Hz. The control group was assigned to the same
protocol, but the device could not be activated to vibrate. The average monthly
rate of maxillary canine retraction into an extraction space was analyzed in all 45
subjects (ITT group). The mean rate of movement was significantly higher for the
AcceleDents group with 1.16 mm/month (95% CI: 0.86–1.46) compared to
0.79 mm/month (95% CI: 0.49–1.09) in the control group, with the mean
difference of 0.37 mm/month (95% CI: 0.07–0.81, P ¼ 0.05). These results showed
that low-level cyclic loading of 0.25 N at 30 Hz increases the rate of tooth
movement when applied as an adjunct to orthodontic treatment. (Semin Orthod
2015; 21:187–194.) & 2015 The Authors. Published by Elsevier Inc. This is an open
access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/bycd/4.0/).

Introduction orthodontic treatment. Physiologically, the rate of

T
he rate of tooth movement is an important
factor determining the duration of
Division of Orthodontics, Department of Developmental Dentistry,
The University of Texas Health Science Center at San Antonio, 7703
Floyd Curl Dr, San Antonio, TX 78229-3900; Private Practice, San
Antonio, TX.
Corresponding author. E-mail: pavlin@uthscsa.edu
Funding, Conflict of Interest: This study was supported by the
research grant from the OrthoAccel Technologies, Inc. [(OATI),
Bellaire, TX], which was permitted to review this manuscript, but the
right to a final decision on the content was exclusively retained by the
authors. The corresponding author (D.P.) is a consultant for OATI
and had participated in developing the study protocol approved by the
FDA. He was blinded to the group assignments and did not participate
in either data collection or treatment of any of the enrolled subjects.
& 2015 The Authors. Published by Elsevier Inc. This is an open
access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/bycd/4.0/).
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.005
tooth movement reflects the rates of bone turnover
and remodeling. Earlier approaches that have been
used in an attempt to accelerate tooth movement
include low-energy laser irradiation,1 magnetic
fields,2 as well as pharmacological interventions
with the injection of prostaglandin E23 and vitamin
D.4 However, adverse events, such as local pain and
severe root resorption,5 were associated with these
treatments. Corticotomy-facilitated orthodontics6
has limited clinical use due to the morbidity of
the surgery, cost, and insufficient clinical evidence.
Shorter treatment time decreases risk of caries,
periodontal disease, and root resorption,7 but there
has been little progress in developing new, non-
invasive approaches to accelerate tooth movement
and to reduce the duration of treatment.8
Low-level mechanical oscillatory signals
(vibrations) have been shown to increase the rate
of remodeling in mechanical loaded long bones,9

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 187–194 187

188 Pavlin et al
which is currently used in the prevention of
osteoporosis10 based on an increase in bone
metabolism and decrease in bone loss in post-
menopausal women.11 There is also compelling
evidence from animal studies using cranial suture
model12,13 and long bone periosteum14 suggesting
that dynamic loading improves bone formation and
increases orthodontic tooth movement compared
to a static force.15 While there is an emerging body
of evidence that vibration enhances orthodontic
tooth movement in animals, the effect of analogous
level vibrations on tooth movement in patients had
not been investigated. The aim of this study was to
determine whether a defined type of vibration, as
an adjunct to orthodontic treatment, increases the
rate of tooth movement in patients with fixed
orthodontic appliances.
Methods
This was a prospective, randomized, controlled,
double-blind, parallel group clinical trial con-
ducted at a single center in the United States.
Subject enrollment occurred from February 2009
through June 2010. Data analyzed included sub-
ject follow-up from the beginning of treatment
through the end of space closure. The null
hypothesis was that there was no statistically sig-
nificant difference in the rate of tooth movement
with standard orthodontic treatment alone (con-
trol group) compared with standard orthodontic
treatment plus the vibration applied for 20 min/
day (vibration group) by the AcceleDents device
(OrthoAccel Technologies, Inc., Bellaire, TX)
designed to deliver a cyclical (vibrational) force of
0.25 N (25 g) with a frequency of 30 Hz.
Sample size was determined based on an
expected movement rate of 0.24 mm/week in
the control group16 and a clinically relevant
increase over that baseline rate up to 0.35 mm/
week in the AcceleDents group, consistent with
results from an earlier pilot study.17 Using the
pilot study observed standard deviation of
0.10 mm/week, two-sided alpha (type I error)
of 0.05, and 80% power, a sample size of 16
subjects per group (total of 32) was required to
detect a statistically significant difference
between the groups. This sample yields 95%
probability to reveal at least one occurrence of all
adverse events that occur at a rate of 17.1% or
greater. The sample was increased to 45 subjects
to compensate for potentially larger number of
dropouts. The study was approved by the IRB and
written informed consent was obtained from
all subjects. Trial summary was published on
ClinicalTrials.gov. The study protocol was pre-
approved by the U.S. Food and Drug Admin-
istration (FDA) under an Investigational Device
Exemption (IDE-G080191).
Subjects inclusion criteria were age (12–40
years), required extraction of maxillary first pre-
molar(s), space closure with maximum maxillary
anchorage, 3 mm of extraction space after initial
alignment, and good oral hygiene. Subject
exclusion criteria were periodontal disease, pre-
scription medications, use of bisphosphonates,
and pregnancy. Subjects were randomly allocated
to either the AcceleDent group or the control
group that used an appliance with internally dis-
abled vibration. A third-party vendor provided a
computer-generated randomization schedule
with a block size of 4 and stratified to insure that
the number of subjects aged 12–19 years and aged
20–40 years, as well as the number of subjects with
“separate canine retraction” versus “en masse
retraction” were equally distributed between the
groups. Each subject was assigned to the next of
the 48 pre-specified numbers for four strat-
ification combinations and the allocation key was
kept locked outside the clinic. The device was
programmed to the assigned treatment by inde-
pendent site personnel and both the investigators
and the subjects remained blinded to treatment.
All subjects were treated by orthodontic resi-
dents under supervision of an investigator/faculty.
A routine set of orthodontic records was taken. A
0.022  0.028 in twin brackets (MBT, 3M Unitek,
St. Paul, MN) were bonded and the use of
AcceleDents started from the beginning of
treatment. Patient compliance with the device was
tracked using a logbook. After initial alignment, a
mini-implant was inserted18 and immediately
loaded with 180 g of force (Fig. 1), which
produced a predominantly translatory canine
movement, thus avoiding an unstable posterior
dental anchorage that would compromise
accurate measurements.19 To avoid excessive
occlusal interferences, the bite was opened
when necessary using composite build-ups. Sepa-
rate canine retraction was performed on a
0.018 in stainless steel (SS) arch wire and en masse
retraction with a 0.019  0.025 SS arch wire.
Direct measurement of space closure in
patients’ mouth precludes the analysis of intra-
 Vibration accelerates tooth movement 189

Figure 1. (A) Orthodontic appliance for separate canine retraction: C, canine being retracted; T, TAD (Tomas-
pin, Dentaurum, Ispringen, Germany) with a diameter of 1.6 mm and a length of 9 mm was inserted between the
maxillary second premolar and the first molar, under local anesthetic and was immediately loaded; F, retraction
force of 180 g (measured by Dontrixs gauge, American Orthodontics, Sheboygan, Wisconsin) was applied with a
nickel-titanium coil spring between the TAD and the canine bracket; d, distance measured parallel to the occlusal
plane using a digital caliper prior to each coil spring activation or reactivation. An average value from two
measurements was entered at each visit, which were approximately 4 weeks apart. The spring was truncated as
needed and re-tied to deliver 180 g of force. (B) Representative example of retraction mechanics for space closure.
(a) Activated coil spring in place at the beginning of space closure. (b) One month later, the space opened mesial
to the canine.

rater error at the same appointment. Thus, the
intra-rater and inter-rater reliability was tested by
making measurements on 12 different quadrants of
typodonts with mounted mini screws and bonded
brackets. The intra-rater reliability was tested for
each rater 1 and rater 2 by comparing repeated
measurements with a 1-week interval between them,
and the inter-rater reliability was tested by com-
paring the average of the assessments of two
independent raters who each conducted two
assessments of each quadrant. Intraclass correlation
coefficients (ICCs) were calculated with ICC model
2.1 for intra-rater reliability and ICC model 2.2 for
inter-rater reliability.
As a primary outcome measure, the average
monthly rates of tooth movement in the Acce-
leDent and control groups were analyzed for the
intent-to-treat (ITT) and the per-protocol (PP)
treatment populations, using a general linear
model that accounted for age (12–19 versus 20–
40 years), gender, and type of retraction. The
monthly rate of tooth movement was calculated
for each subject and each quadrant by calculating
the total distance the cuspid moved, while the
TAD was stable and dividing it by the total length
of time that the TAD was stable during the space
closure. If any level of TAD mobility was
observed, it was considered loose and the last
month’s measurement was excluded. If a TAD
continued to fail after two attempts of re-
insertion in the proximity of the original site,
the measurements were discontinued (Fig. 2).
The subject’s data were included in the analysis if
there were at least three consecutive stable TAD
measurements recorded.
Results
Baseline demographic and clinical characteristics
analysis showed that there was no difference
between the AcceleDent and control groups with
respect to age, ethnicity, or weight. Of 45 subjects
enrolled in the study (ITT group), 39 were
represented in the PP group (Fig. 2). Six subjects
were excluded from the PP group for the
following reasons: pregnancy (n ¼ 1),
extraction space less than 3 mm after initial
alignment (n ¼ 1), and no stable TAD
distance measurements [TAD failure due to
poor oral hygiene (n ¼ 4)]. The retraction was
190 Pavlin et al

Figure 2. Patient flow diagram (CONSORT format) describing subjects enrolled and included in analyses.
The number of subjects excluded from analysis in each group (listed in the Analysis—PP boxes) does not
correspond to the total number of lost to follow-up and discontinued intervention subjects (listed in the Follow-
Up boxes). This is because some of the subjects with discontinued intervention had fulfilled the requirement of
at least three consecutive measurements being taken prior to discontinuation, thus remaining in the
analysis group.

bilateral in 35 patients, and an average rate was
calculated for each subject. The canine moved by
translation, as demonstrated by the reversal lines
in bone and mathematical analysis (Fig. 3). The
results of the error analysis showed that the ICC
was 0.98 for rater 1 (95% CI: 0.93–0.99), 0.96 for
rater 2 (95% CI: 0.87–0.99), and the ICC for the
average assessments between the two raters was
0.94 (95% CI: 0.80–0.98), indicating that there
was no significant intra-rater and inter-rater dif-
ferences that biased the tooth movement
measurements.
The ITT analysis of the primary outcome is
presented in the Table. The average monthly
rate of tooth movement in the AcceleDent group
was 1.16 mm/month (95% CI: 0.86–1.46), which
was significantly faster (48.1 ⫾ 7.1%) compared
to 0.79 mm/month (95% CI: 0.49–1.09) in the
control group, with the mean difference of
0.37 mm/month (95% CI: 0.07–0.81, P ¼
0.05). The PP analysis also demonstrated
significantly faster movement of the retracting
cuspids when vibration was applied (P ¼ 0.02,
Table). The emphasis in interpretation of the
 Vibration accelerates tooth movement 191

Figure 3. Representative panoramic radiograph during space closure. R, the reversal lines at the mesial aspects of
distally moved canines. These lines, which indicate the onset of new bone formation on the tension side of the
periodontium, are parallel with the outline of the root surface, indicating predominantly translational movement.
With the difference of 0.004 in between the slot size and wire diameter and the mesio-distal bracket width 0.125 in,
the tipping component during closing of 5.3 mm (the average extraction space size in this study) was minimal and
clinically insignificant, resulting in almost pure translational movement with the center of rotation at 9.48 m above
the canine root apex. Translational tooth movement resulted in uniform, non-traumatic stress levels across the
periodontium, thus eliminating excessive stresses in the apical and coronal regions.

results is placed on the ITT analysis to minimize Discussion

bias in assessing the primary outcome. After
enrollment and randomization, some subjects
were withdrawn from the ITT group for various
reasons and excluding these subjects could
introduce a bias in statistical analysis.
The most common adverse side effect in both
groups was loosening of TADs, which was
reported in three subjects in the AcceleDent
group and two subjects in the control group. A
TAD was considered loose if any detectable level
of mobility was observed clinically. Additional
harms/safety-related outcomes analyzed in this
study included the effect of vibration on root
resorption and other potential harmful effects
(such as pain, discomfort, and headache), as
well as subjects’ perception of the ease of use of
the device. Because of space limitations, the
results of these outcomes will be reported
elsewhere (manuscript in preparation). These
outcomes generally indicated that the Accele-
Dents is safe and convenient for patients’
daily use.
The design of this study and the mechanics used
maximized the reproducibility of orthodontic
force application and measurement of tooth
movement, while minimizing the variables asso-
ciated with the loss of posterior anchorage. A
recent systematic review20 revealed lack of quality
randomized clinical trials that would allow for an
evidence-based approach in clinical use of
techniques for accelerated tooth movement. The
present study fully adheres to the CONSORT
guidelines and CONSORT 2010 checklist21 for
conducting and reporting randomized clinical
trials and provides evidence for the positive effect
of cyclic loading on the rate of orthodontic tooth
movement.
Relatively constant and reproducible retrac-
tion force of 180 g was used, reported to be
within an optimal range for canine retraction.22
The sliding mechanics produced a translatory
canine movement23 with a negligible component
of tipping (Fig. 3). The applied force level of

Table. Average rate (mm/month) of tooth movement during space closure.

ITTa PPa
Treatment Mean (SE) 95% CI P value Treatment Mean (SE) 95% CI P value

AcceleDent (N ¼ 23) 1.16 (0.153) 0.86–1.46 AcceleDent (N ¼ 21) 1.25 (0.117) 1.01–1.49
Control (N ¼ 22) 0.79 (0.150) 0.49–1.09 Control (N ¼ 18) 0.89 (0.118) 0.63–1.15
Mean difference 0.37 (0.217) 0.07 to 0.81 0.05 Mean difference 0.36 (0.181) 0.01 to 0.73 0.02
a
P values for the individual covariates included in the general linear model for ITT were 0.97 (age), 0.28 (type of retraction), and
0.093 (gender). Corresponding P values for PP were 0.88 (age), 0.02 (type of retraction), and 0.03 (gender).
192 Pavlin et al
0.25 N represents an approximately 70-fold
reduction of the level of 18 N used in clinical
trials in patients with osteoporosis,24 and it is
based on the difference in the mass of the maxilla
compared to the whole skeleton (since no similar
studies applying pre-defined levels of cyclic force
to the alveolar bone have been reported). The
0.25 N force imposes peak to peak accelerations
of less than 0.003 g (1 g ¼ earth’s gravitational
field), which is over 300 times lower than the
level of 1 g demonstrated to be safe and not
produce any detrimental skeletal resonances.24
This extremely low force did not produce any
significant discomfort or adverse effects for the
patients. The monthly rate of canine retraction
for the control group was 0.79 mm/month,
which compares favorably with earlier
reports.16,25 The effect of vibrations in the
AcceleDent group was 48.1% above this estab-
lished baseline value, which demonstrates a sig-
nificant clinical benefit. The results from analysis
of harms and safety-related outcomes showed
that the AcceleDents is safe and convenient for
patient’s use.
A recent study using the Tooth Masseuse
device in orthodontic patients26 reported no
effect on the rate of tooth movement. This is
contrary to our results, and those from medical
clinical trials and animal models, most likely
because the Tooth Masseuse was never
intended or designed to accelerate tooth
movement: its output frequency is four times
higher compared to our study, while the force is
about four times lower. Another study reported
that micro-osteoperforation increased the tooth
movement by 2.3-fold, measured during the
period of initial 28 days of canine retraction
into a first bicuspid extraction space.27 These
results are consistent with studies using other
invasive procedures, such as corticotomy6 and
similar surgical interventions. A recent
systematic review and meta-analysis (which
did not include vibration) revealed some evi-
dence for effectiveness of low laser therapy and
corticotomy and only a weak or no evidence for
the effectiveness of interseptal bone reduction,
photobiomodulation, and pulsed electro-
magnetic fields.28
While loosening or potential drift of some
TADs cannot be excluded, it is important to note
that only a relatively small number of subjects
had TAD failures, which were distributed
similarly between the groups (three in the
AcceleDent, two in the control), with an overall
failure rate of 11.1% that is smaller than the
reported average TAD failure rate of 13.5%.29
Furthermore, the loading conditions in the
present study were markedly different from the
single study where a total average drift of 0.4 mm
(0.044 mm/month) was reported in seven out of
16 patients over the course of 9 months of space
closure, using an excessive retraction force of
400 g per side.30 The accuracy of our technique,
using a TAD as a reference point, has advantage
over most other techniques (e.g., using the
palatal rugae or an adjacent tooth that can
move being pulled by trans-septal fibers), since
it avoids several intermediate steps in making a
cast and its 2-D image and overlying a grid or
drawing lines, with each step introducing addi-
tional errors. Measuring space closure from lat-
eral cephalograms can introduce considerable
magnification, angulation, and landmark recog-
nition errors. Using casts and custom reference
templates is more accurate method for measur-
ing 3-D tooth movement31,32 that is particularly
suitable for space closure by segmented arch
technique where canine is not engaged into an
arch wire, and its side effects are difficult to
control. Employing sliding mechanics with a tight
bracket-wire interface in this study minimized a
chance for the second order tipping, rotational,
and vertical displacements. This allowed us to use
a direct, highly reproducible, and accurate one-
step measuring technique and focus on the effect
of vibration on a single, reproducible type of
tooth movement—the translation of canine
during space closure.
Vibrational loading stimulates bone remod-
eling,9,10 but the biological mechanism under-
lying this effect is not understood. Mechanical
loading initiates signaling pathways in bone33,34
and osteocytes were identified as mechano-
responsive cells during orthodontic tooth
movement,35 in which signals can be triggered by
fluid shear stress, bone microfractures, or bone
bending, all of which occur during vibrations.
Early responses in osteocytes are followed by
differentiation of osteoblasts36 and stimulation of
other bone genes.37 Future studies should
address the question whether cyclic loading, as
an adjunct to orthodontic stress, activates known
or new signaling pathways underlying the faster
tooth movement.
 Vibration accelerates tooth movement
Conclusion
The application of cyclic loading (vibration) of
0.25 N (25 g) at the frequency of 30 Hz, as an
adjunct to treatment with a fixed orthodontic
appliance, significantly increases the rate of
orthodontic tooth movement.
Acknowledgments
The authors would like to thank the orthodontic
residents at the UTHSCSA for providing orthodontic
treatment for the subjects in this study: Drs: April Brown,
Jonathan Collette, Jason Frasier, Mathew Kriewaldt,
Cameron Martin, Jared Oliver, Vishnu Raj, Raoul Santos,
and Kelly Wray.
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Kyung HM. Comparison and measurement of the
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the use of implant anchorage during canine retraction.
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Photobiostimulation as a modality to accelerate
orthodontic tooth movement
Sean Chung, Melissa Milligan, and Siew-Ging Gong

Photobiostimulation refers to the alterations, produced by relatively low

levels of irradiation, in chemical, physical, and metabolic processes in target
tissues with little or no temperature changes. A number of investigations
have focused attention on the use of two photobiostimulation modalities,
low-level laser therapy (LLLT) and light-emitting diodes (LED), to accelerate
orthodontic tooth movement (OTM). Many of these studies have been
performed on animal models and patients, often with mixed results. The
increase in tooth movement in studies that showed positive effects of laser
therapy was about 0.5 mm/month in humans. However, no statistically
significant changes in tooth movement rates were observed in some other
studies. Conflicting results from different studies are attributed to the
variability in parameters and lack of rigorous research design and statistical
analyses. We conclude, upon review of the available literature, that the
apparent increase in tooth movement obtained from use of LLLT can be of
significant benefit in the clinic provided that more rigorous research, in both
animal models and humans, is conducted to improve the consistency and
predictability of laser and LED therapy usage. (Semin Orthod 2015; 21:195–
202.) & 2015 Elsevier Inc. All rights reserved.

Introduction Of interest to this article are the non-thermal

effects, termed collectively as photobiostimulation,
instein first described the manipulation of
E light in 1917 with the concept of laser
(“Light Amplification by Stimulated Emission of
produced by the application of relatively low
levels of irradiation from monochromatic light to
tissues.1 Used interchangeably with terms such as
Radiation”). Light has since then been shown to
biostimulation, photostimulation, and biopho-
interact with tissues via various means such as
tomodulation, photobiostimulation refers to the
absorption, reflection, scattering, and trans-
alterations in chemical, physical, and metabolic
mission of energy.1 The resultant effects of such
processes and any associated downstream effects
interactions can be photochemical (via chemical
when energy is absorbed by a target tissue with
reactions), photothermal (resulting in heat,
little or no temperature change.1 Photo-
ablation, and/or coagulation), and photo-
biostimulation has been widely used in
mechanical or photoionizing (resulting in
medicine and dentistry to reduce pain and
destruction of cell membranes, proteins, or
inflammation, accelerate wound healing and
DNA).2 The ability of light to interact with
hair growth, prevent cell death and tissue
tissues is based on the wavelength being used
damage, improve blood circulation, and during
and the incident photons in the beam of light.
orthodontic tooth movement (OTM).1,3
OTM is a physiologic process in response to an
externally applied force to a tooth.4 Macro-
Private Practice, Toronto, Ontario, Canada; Department of
Orthodontics, Faculty of Dentistry, University of Toronto, Toronto, scopically, force application induces bone
Ontario, Canada; Dental Research Institute, Faculty of Dentistry, bending and is associated with variations in
University of Toronto, 124 Edward St, Toronto, Ontatrio, Canada. blood supply and the recruitment of
Corresponding author at: Dental Research Institute, Faculty of multinuclear giant cells, osteoblasts, osteoclasts,
Dentistry, University of Toronto, 124 Edward St, Toronto, Ontatrio,
Canada. E-mail: sg.gong@dentistry.utoronto.ca
and fibroblasts. Microscopically, an application
of force alters cellular metabolism and gene
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0 expression, changing the amount of cytokine and
http://dx.doi.org/10.1053/j.sodo.2015.06.006 protein production such as TNF-α, IL-1/6, PGE2,

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 195–202 195

196 Chung et al
substance-P, MMPs 8/13, BMP, and TIMPs.
Upon force application, a physical link
between the nucleus and cell-surface adhesion
receptors allows the propagation of specific sig-
naling pathways, e.g., those involved in inflam-
mation. In fact, OTM is a state of aseptic
inflammation and tissue repair resulting in the
modulation of the RANK-RANKL-osteoprotegrin
(OPG) pathway such that in an area of com-
pression, bone is resorbed and in an area of
tension, bone is deposited.
Various methods to increase the rate of OTM
via an influence on bone metabolism have
included the application of vitamin D, prosta-
glandin E2, osteocalcin, parathyroid hormone,
corticosteroid hormones, thyroxin, corticotomy,
and photobiostimulation.5–7 The purpose of this
article is to review the use of two major photo-
biostimulatory modalities, as a means of altering
the rate of OTM and assess their appropriateness
for use in clinical practice.
Photobiostimulation modalities
Photobiostimulation may be therapeutically
applied in the form of lasers (low-level/intensity/
energy laser therapy or LLLT) and light-emitting
diodes (LEDs). Both types of applications utilize
a near-infrared wavelength of approximately
600–1000 nm, with a range of 730–850 nm being
viewed as most appropriate for photo-
biostimulatory effects. The relatively narrow
wavelength range allows for greater absorption
by target tissues.8–11 Although both laser and
LED are capable of delivering specific wave-
lengths at specific energy levels, they differ in
several ways (Table 1). Lasers are spatially and
temporally coherent, i.e., the light waves are
identical in shape and size and travel together in
the same space and time, thus permitting light to
be focused. In contrast, LEDs are incoherent in
Table 1. Differences between Laser and LED
LASER LED
Cost ▲ ▼
Safety ▼ ▲
Heat ▲ ▼
Focus Narrow Wide
# Clinic visits ▲ ¼
Beam Coherent Incoherent
Energy use ▲ ▼
Device size Large Small
nature allowing for a modality that is cheaper to
produce and potentially safer if applied in a non-
clinical environment.12
Cellular and molecular mechanisms of
photobiostimulation
Increased cellular metabolism has been pro-
posed to be the major photobiostimulatory effect
of infrared light. Photobiostimulation has been
proposed to stimulate mitochondrial cytochrome
c oxidase, the primary photo-acceptor in the
wavelength range of 600–950 nm, resulting in
increased cell metabolism (via ATP, cAMP, and
Ca2þ).3,10,13,14 Another proposed mechanism is
the “singlet-oxygen hypothesis,” where molecules
like porphyrins and some flavoproteins can
become activated and interact with oxygen to
create reactive singlet oxygen that removes
energy deficits and increases overall cell metab-
olism.3 A complementing hypothesis is the
“redox properties alteration hypothesis” where
photobiostimulation changes the overall cell
redox potential toward that of greater
oxidation, thereby encouraging cells with a
lower resting intracellular state toward an up-
regulation of transcription factors.3 Finally, it has
been proposed that photobiostimulation can
directly augment RNA and DNA synthesis and
replication, protein synthesis and overall cell
metabolism by increases in Naþ/Kþ pump
activity and intracellular Ca2þ.13,15 Although
described as distinct mechanisms of action, it is
conceivable that all the above hypotheses refer to
a change of state where several levels of cellular
activity are affected during photobiostimulation.
Photobiostimulation and orthodontic tooth
movement
In the past two decades, a number of inves-
tigations have focused attention on the use of
photobiostimulation to accelerate the rate of
OTM. Most of these studies were performed on
animal models of OTM. More recently, a number
of clinical trials have also been conducted. These
studies will be summarized and discussed in the
following subsections.
Animal studies
Several animal studies have been performed with
diode lasers (which utilize a semiconductor, most
Table 2. Summary of studies assessing effects of photostimulation on orthodontic tooth movement in rats and dogs
References N Day Rx Day Laser λ (nm) Power (mV) Energy Density Time app Force Level AT AP Op Mode Results

Rats—LLLT
Kawasaki and Shimizu18 12 13 Daily 830 100 6366 540 10 g Direct 3 CW ↑
Yamaguchi19 25 7 Daily 810 100 6366 540 10 g Direct 3 CW ↑
Fujita et al.17 25 8 Daily 810 100 6366 540 10 g Direct 3 CW ↑
Yoshida et al. 20099 30 20 Daily D0–6, 810 100 4821 540 10 g Direct 4 CW ↑
D13, and
D20
Gama et al.25 15 19 Every other day 790 40 4.5 (11 buccal EO) 15.7 (8.6 EO) 40 g NS 3 NS ↓ D7, NC
after
Marquezan et al.24 18 7 Daily 830 100 6000 540 41 g Direct 3 CW NC

Photobiostimulation
Yamaguchi et al.16 25 7 Daily 810 100 6366 540 10 g Direct 3 CW ↑
Abi-Ramia et al.20 20 7 Daily 830 100 18 12 41 g Direct 3 NS ↑
Duan et al.21 40 14a Daily 830 180b 3.6 (CW) 12 (CW) 10 g Direct 3 CW and ↑
PW
Rats—LED
Fujita et al.17 25 8 Daily 850 75 NA 720 10 g Direct 3 NA NC
Ekizer et al.28 8 21 Daily D0–10 618 20 mW/cm2 NA 1200 51 g EO Cheek NA ↑
Dogs—LLLT
Goulart et al.27 18 63 Every 7 days 780 70 5.25 3 85 g Direct 1 CW ↑↓
35 20
Kim et al.26 12 56 Every 3 days 808 763 mW 41.7 160 (72 active 150 g 3 mm 8 PW ↑
(75 mJ laser) from
/pulse) gingiva

Rx: treatment; CW: continuous wave; PW: pulse wave; direct: direct contact; AT: application technique; AP: application point; Op mode: operating mode; LLLT: low-level laser therapy;
LED: light-emitting diode; EO: extraoral; NC: no change; NA: not applicable; NS: not stated.
a
Three laser treatments.
b
50% Duty cycle for PW; ↑Increase and ↓Decrease in tooth movement.

197
198 Chung et al
commonly gallium–aluminum–arsenide, as the
lasing medium).9,16–21 The rat model is the most
commonly utilized animal, but studies have also
included monkeys, dogs, and cats.8,22 Compar-
ison among these studies has been rendered
difficult due to the use of numerous different
parameters between the studies (Table 2): (a)
Sample size—from 8 to 40 animals; (b) Energy
output—wattage ranges from 40 to 763 mW; (c)
Wavelength—aries within the infrared region
from 780 to 850 nm; (d) Orthodontic force levels
—in rats, range from 10 to 40.78 g; in dogs from
85.05 to 150 g, and (e) Method of LLLT application
—varies in the number of application points and
use of either pulsed or continuous wave
operating modes.
On the whole, the majority of the studies
showed a positive effect of LLLT application
(Table 2). Fold change appeared to be the most
commonly used method for quantitating and
comparing the amount of tooth movement. For
example, 1.34-fold9 and 1.5-fold17 increases were
observed in LLLT-exposed groups over a period
of 21 and 7 days, respectively. However, while
these findings were statistically significant, actual
numbers were often absent, and the actual dif-
ference in tooth movement between exper-
imental and control groups was o0.2 mm in
many cases.9,16–18 Interestingly, some studies
have shown that the benefit to OTM in irradiated
groups versus controls decreased over time.16,17
For example, Yamaguchi et al.16 showed
differences of 2.0-fold increase at day 3, but by
days 4 and 7, the increases had slipped to 1.9- and
1.3-folds, respectively.
Three other separate studies, using different
methodologies (e.g., fewer laser applications,
extra-oral application of laser, and higher
orthodontic forces) found no significant differ-
ence between photobiostimulation and controls
in affecting the rate of OTM.23–25 Similar benefits
of increased OTM were not seen in beagle dogs
at 2 months of LLLT despite histological evi-
dence suggestive of increased osteoclastic
activity.26
With regard to the use of LED, conclusions
from the limited number of LED studies suggest
that it does not have an effect on tooth move-
ment.27 However, a study reported a statistically
significant benefit of extra-orally applied LED for
accelerating OTM in the rat, albeit using
parameters that were very different from that of
other studies (e.g., shorter wavelengths 618 nm
as opposed to 790–810 nm) and high force levels
( 50 g in the rat).28
Clinical studies
Of the documented LLLT studies in patients
undergoing orthodontic treatment, seven5–7,29–32
were considered in our analysis, with one study29
ultimately being excluded due to an inadequate
description of a biomechanical protocol and lack
of discrete OTM values (Table 3). In all studies, a
split-mouth design was used whereby photo-
biostimulation was applied to only one side of the
dental arch. A split-mouth design is intended to
limit confounding influences of interpersonal
factors such as biological variation between
patients, but has been challenged by some
because of a potential for a systemic effect of
LLLT.33 The sample sizes in the seven cited
studies ranged from 11 to 30 cases. Tooth
movement was usually assessed during bilateral
single tooth (usually canine) distalization via a
relatively predictable and controllable
application of a constant force between the
retracted tooth and the anchorage segment in
a straight line and on a rigid arch wire. There
were, however, some studies that used thinner,
segmented wires in larger slot sizes during
extraction space closure, a method that might
affect the precision of tooth movement
quantitation.5
Similar to animal studies, the parameters
(laser characteristics, force levels, etc.) in the
clinical trials also varied dramatically (Table 3).
Not surprisingly, the range in LLLT parameters
led to conflicting data. Of the two studies30,31 that
reported no difference in the amount of tooth
movement with LLLT, one had inadequate
description of the quantitation of tooth move-
ment over a period that was considered very short
(7 days).30 The second study,31 cited in a meta-
analysis of LLLT and OTM studies as being of
“high quality,”34 showed a lack of difference in
tooth movement change between control and
teeth subject to laser therapy at three different
time points (Table 3). The lack of difference was
hypothesized to result from an inappropriate
energy density of the laser.
The four remaining studies reported a stat-
istically significant increase in the amount/rate
tooth movement following LLLT (Table 3).5–7,32
Table 3. Human studies assessing effects of photobiostimulation (LLLT) on OTMa
LT Grp distance (mm) Control Grp distance (mm)
References Mos N Rx days λ (nm) Freq (Hz) Power (W) ED (J/cm2) Dose /apt (J) LT time (s) Rate (mm/mos) Rate (mm/mos)

NO difference in tooth movement

Kocoglu-Altan and Socuku30 0.25 14 1, 2, 3, and 7 1064 10 1/3.94 cm2 40 NA 40 1.15 0.94
NA NA
Limpanichkul et al. 31
1 12 0, 1, and 2 860 CW 0.1/0.09 cm 2
25 2.3 184 0.32 ⫾ 0.08 0.38 ⫾ 0.08
0.32b 0.38b
2 0.73 ⫾ 0.13 0.74 ⫾ 0.13
0.365b 0.37b
3 1.29 ⫾ 0.21 1.24 ⫾ 0.21
0.43b 0.41b

Photobiostimulation
Difference in tooth movement
Youssef et al. 20086c NA 30 0, 3, 7, and 14 809 NA 0.1/1.00 cm2 8 8 80 NA NA
2.027 1.109
Cruz et al. 20047 2 11 0, 3, 7, and 14 780 CW 0.02/0.4 mm2 5 NA 100 4.39 ⫾ 0.27d 3.3 ⫾ 0.24
2.195b 1.65b
da Silva Sousa et al. 2009 5
1 13 0, 3, and 7 780 CW 0.02/0.04 cm 2
5 2 100 1.16 ⫾ 0.51 0.42 ⫾ 0.29
1.16b 0.42b
2 2.05 ⫾ 0.93 0.8 ⫾ 0.49
1.025b 0.4b
3 3.09 ⫾ 1.06d 1.6 ⫾ 0.63
1.03b 0.53b
Doshi-Mehta and Bhad-Patil 201132 3 30 0, 3, 7, and 14 800 CW 0.00025/ NA 8 40 2.3 ⫾ 0.45d 1.98 ⫾ 0.46
4 mm2 0.77b 0.66b
4.5 Total/apt: 0.1 5.49 ⫾ 0.99d 3.96 ⫾ 0.98
1.22b 0.88b
Mos: months; Rx: treatment; Freq: frequency; ED: energy density; apt: appointment; SS: stainless steel; NiTi: nickel titanium; Grp: group; LT: laser therapy; CW: continuous wave; NA:
not applicable; mos: months.
a
Studies were mostly on bilaterally symmertic extraction space closure using 150 g force.
b
Extrapolated OTM rates using velocity ¼ distance/time.
c
Intermittent force system (Ricketts spring).
d
Significantly different, o0.05.

199
200 Chung et al
However, the presence of a relatively high degree
of bias regarding concealment and blinding
makes it difficult to draw definite conclusions.
For example, although Youssef et al.6 reported
higher velocities of OTM, the length of the
analysis of OTM was unspecified. da Silva Sousa
et al.5 showed higher canine distalization after
2 months of treatment; however, their biomech-
anical system (segmented 0.016" stainless steel
arch wire, 0.022  0.028" slot, 150 g retraction
force) represented an arrangement that was
more susceptible to arch wire distortions
during retraction than systems where larger
unsegmented multidimensional arch wires were
used.7,32 Inadequate description of the different
LLLT power levels was found in the reportedly
positive findings of another study32 that has
since been attacked for an improper statistical
analysis.35 Overlooking the deficiencies in design
and methodologies, the reported average benefit
to tooth movement in general was of
approximately 0.5 mm/month (range: 0.11–
0.918 mm/month) change when LLLT was
applied (Table 3).
Conflicting conclusions were reached in two
systematic reviews on clinical trials of LLLT
therapy in OTM, depending on which original
studies were included in the review analyses.34,36
Long et al.34 reviewed four clinical studies and
found no appreciable effect of LLLT on OTM.
Conversely, Ge et al.36 included an additional five
studies and found an overall benefit from LLLT,
albeit with a caveat that many of the reviewed
studies contained moderate to high bias. An
interesting observation that was made after the
analysis of the different studies was a pattern
where lower energy densities (2–5 J/cm2) may be
associated with increased OTM, whereas higher
energy densities (420–25 J/cm2) may not. The
biphasic dose–response curve may be explained
by the Arndt–Schultz Law, which states that lower
photobiostimulatory exposures can elicit
stimulatory tissue response, whereas at higher
exposures, there is an inhibitory effect.30,37
Summary and conclusion of animal and
clinical studies
Taken together, animal and clinical studies
illustrate the ambiguity that currently exists
regarding the effect of LLLT phototherapy on
OTM (Tables 2 and 3). Accompanying this
ambiguity of tooth movement effects, however, is
the relatively clear message that photo-
biostimulation is not associated with any harmful
effects on the periodontium and teeth (as
assessed by radiographic and clinical assess-
ments) and even that it has the potential to
reduce pain during OTM.5–7,10,29,32
The findings from both animal and human
studies so far reveal conflicting results that
showed both positive and negative effects of
LLLT on the amount and/or rate of OTM. The
extensive variability in the experimental param-
eters used between studies is a major contributor
to the existing conflicting results and conclusions
in the field. A second contributor to the con-
fusion is the fact that a number of these studies
were conducted with a less than rigorous design,
e.g., inadequate and improper statistical analysis,
variable laser exposure, and less than ideal bio-
mechanical arrangements. Even with the animal
and clinical studies that did show positive effects
of photobiostimulatory therapy, the change of
tooth movement lies in the order of no more
than 0.5 mm/month. Furthermore, the apparent
benefit to OTM appeared to taper off with time,
being greatest at the initiation of OTM and
subsequently decreasing. Another finding of
interest is that higher dosage of laser therapy
appeared to be inhibitory compared to lower
dosages.
Clinical applications of photobiostimulation
Given that the amount of tooth movement
needed in orthodontics to achieve functionally
and esthetically pleasing results are often in the
range of 0–1 mm per appointment, we conclude,
upon review of the available literature, that the
apparent increase of no more than about
0.5 mm/month benefit of LLLT, although lim-
ited, does have the potential to be clinically
significant. However, before the use of photo-
biostimulatory therapies can be offered in a
clinical setting, more research is needed. Rig-
orous research designs and efforts, both in ani-
mal models and humans, have to be invested to
test in a methodical and systematic way the
optimal photobiostimulation parameters (e.g.,
wavelengths, power densities, application modes,
and target tissues) needed to move teeth in a
controlled and consistent manner. The current
absence of available optical standards upon
 Photobiostimulation
which future studies in photobiostimulation can
be conducted presents a challenge that should be
addressed. Future studies should also attempt to
elucidate an effective dose–response relation-
ship, optimal energy densities, preferred photo-
biostimulation wavelength, and to clearly test
these variables at the clinical level. Concurrent to
these research endeavors, attention toward
describing the mechanisms of action of photo-
biostimulation at the cellular and molecular levels
will permit an understanding of the pathways
influenced by photobiostimulation and provide
insights into how this therapeutic approach can be
best applied to orthodontics and healthcare in
general. The knowledge generated from all these
research studies will place orthodontists in a much
better position to make decisions as to whether to
utilize LLLT and/or LED to modulate and aug-
ment OTM in their practices.
Conclusions
 Photobiostimulation is not associated with any
harmful effects on the periodontium and
teeth.
 The apparent increase in tooth movement can
be significant in the clinic provided that more
rigorous research, in both animal models and
humans, is conducted to improve the consis-
tency and predictability of laser and LED
therapy usage.
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Molecular effects of low-energy laser irradiation
during orthodontic tooth movement
Kazutaka Kasai, Michelle Yuching Chou, and Masaru Yamaguchi

Since orthodontic treatments usually take around 2–3 years, it can be a great
burden for both patients and providers. Therefore, shortening the duration of
treatment is both desirable and beneficial to the orthodontists as long
treatment duration is associated with increased risks of gingival inflamma-
tion, decalcification, dental caries, and root resorption. Several novel
modalities have been reported to accelerate orthodontic tooth movement
including low-level laser therapy, pulsed electromagnetic fields, electrical
currents, corticotomy, distraction osteogenesis, and mechanical vibration.
Low-level laser therapy (LLLT) is an effective method to prompt wound
healing, bone repair, and modeling after surgery. These biostimulatory
effects of LLLT have been related to increased fibroblast and osteoblast
activities. Similarly, LLLT has been suggested to play a role in accelerated
tooth movement. In vivo rat studies have demonstrated that low-level laser
irradiation (LLLI) increases osteoclastogenesis on the compression side via
stimulation of the receptor activator of nuclear factor-κB (RANK)/RANK
ligand (RANKL) and the c-fms/macrophage colony-stimulating factor (M-CSF)
during experimental tooth movement. On the tension side, LLLI stimulates
bone formation and has been associated with increased expression of type I
collagen (COL1), fibronectin (FN), and osteopontin (OPN). Furthermore,
In vivo studies have shown that LLLI induces differentiation and activation
of osteoblasts and osteoclasts. Therefore, LLLI facilitates the turnover of
connective tissues and accelerates the bone remodeling process by
stimulating osteoblast and osteoclast proliferation and function during
orthodontic tooth movement. This article reviews the current knowledge
of the biological effects of laser irradiation and its molecular effect on
orthodontic tooth movement. (Semin Orthod 2015; 21:203–209.) & 2015
Elsevier Inc. All rights reserved.

Introduction In an effort to achieve efficient tooth move-

P
rolonged orthodontic treatment may lead to
root resorption, caries, and reduced patient
compliance. Thus, accelerating orthodontic
treatment would be beneficial for both ortho-
dontists and patients.
Department of Orthodontics, Nihon University School of Dentistry
at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587,
Japan; Department of Developmental Biology, Harvard School of
Dental Medicine, Boston, MA.
Corresponding author. E-mail: yamaguchi.masaru@nihon-u.ac.jp
This research was supported in part by Grants-in-Aid for Scientific
Research from the Japan Society for the Promotion of Science, Japan
(24890261 and 25463200).
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.007
ment, many researchers have employed bio-
chemical agents such as prostaglandin E2,1 1,25-
dihydroxyvitamin D3 [1,25-(OH)2D3],2 and
parathyroid hormone.3 However, these agents
have systemic effects on body metabolism, and as
a consequence their application in orthodontics
is very limited.4
Other methods have been reported to accel-
erate orthodontic tooth movement such as pulsed
electromagnetic fields, electrical currents, corti-
cotomy, distraction osteogenesis, mechanical
vibration, and low-level laser irradiation (LLLI).
Various biostimulatory effects of LLLI have
been reported including fibroblast proliferation,5
collagen synthesis,6 and nerve regeneration.7 In
particular, the acceleration of bone regeneration
by laser treatment has been the focus of recent

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 203–209 203

204 Kasai et al

studies.8 In dentistry, low-level laser therapy
(LLLT) has been used to accelerate wound
healing and to reduce inflammation.9 Lim et al.10
showed that LLLT is an effective tool to manage
orthodontic pain.
Recently LLLT has drawn attention as a non-
invasive method to accelerate orthodontic tooth
movement,11 although some studies have
demonstrated no significant increase in the
rate of orthodontic tooth movement after
LLLT.12 The goal of this review is to survey the
existing literature on applying LLLT during
orthodontic treatment, and its molecular effect
on accelerating tooth movement.
Low-level lasers
Laser irradiation has a variety of effects on tis-
sues.13 Its effects on tissues depend on the
wavelength of the laser. The “biostimulating
effects” of laser irradiation on tissues are
accompanied by no more than 11C increase in
local temperature. Treatments that utilize the
biostimulation potency of laser irradiation are
called “low-level laser therapy.”14
The low-level laser lights from the red and near-
infrared regions correspond with the characteristic
energy and absorption levels of the respiratory
chain in mitochondria. The laser functions by
stimulating antenna pigments, the primary photo
acceptors of the respiratory chain, thus increasing
the mitochondrial ATP production.15 The primary
reaction occurring in the respiratory chain
increases the cellular metabolism and as a result
increases DNA synthesis and cell proliferation.16
These events are the basis of the beneficial and
therapeutic actions of laser irradiation.17
LLLI, also known as “soft laser,” stimulates
molecules and atoms of cells but does not cause a
rapid or significant increase in tissue temper-
ature.18 Lasers with different wavelengths can
penetrate into human tissues at different depths.
Red laser penetrates deeper compared with
violet, blue, green, or yellow lasers. Infrared
and near-infrared lights are invisible but have
been demonstrated to penetrate human tissues
deeper than the visible red light.19 While LLLI
produces stimulatory effects on cells, high-energy
laser irradiation produces inhibitory effects. For
this reason, LLLI has been recommended to
stimulate wound healing in non-healing ulcers.20
LLLT in dentistry and orthodontics
It has been suggested that application of LLLT in
dentistry is an effective method to prompt wound
healing,21 nerve regeneration, bone repair, and
modeling after surgery.22 These effects have been
attributed to the biostimulatory effect of LLLT
on collagen synthesis, as well as osteoblast and
fibroblast proliferation and differentiation.23
Given this, laser therapy has been suggested
for treatment of aphthous ulcers24 and dentinal
hypersensitivity, and for use as an oral analgesic.
In addition, laser therapy has been used to treat
periodontitis as it renders anti-inflammatory
effects25 and has been shown to accelerate
osseointegration after implant placement.26
In terms of the application of LLLT in
orthodontics, current evidence suggests that

Table 1. Literature survey of effect of LLLT on tooth movement in humans

Wavelength Power
References Laser type (nm) (mW) Duration Acceleration

Cruz et al.11 GaAlAs 780 20 100 s On days 0, 3, 7, and 14 for 2 monthly Yes
spring activations
Doshi-Mehta and AlGaAr 800 0.25 100 s For days 0, 3, 7, and 14 in the first month Yes
Bhad-Patil32 and thereafter on every 15th day until space is closed
37
Limpanichukul et al. GaAlAs 860 100 25 J/cm2/site; 184 s On days 0, 1, and 2 for 4 No
monthly activations
Yousssef et al.38 GaAlAs 809 100 80 s On days 0, 3, 7, and 14 after every activation Yes
(per 21 days) until space is closed
39
Sousa et al. Diode laser 780 20 10 s For 3 days per month for 3 months Yes
Dominguez et al.40 Diode laser 670 200 9 min On days 0, 1, 2, 3, 4, and 7 Yes
Heravi et al.41 GaAlAs 810 200 21.4 J/cm2/point On days 0, 3, 7, 11, and No
15 and repeated after re-activations at the 28th day

GaAlAs, a gallium-aluminum-arsenide laser; AlGaAr, an aluminum-gallium-arsenide laser.

 Laser accelerates tooth movement 205

Table 2. Literature survey of effect of LLLT on experimental tooth movement in animals

References Laser type Wavelength (nm) Power (mW) Duration Animal Acceleration

Seifi et al.12 Diode laser 805 5 3 min/day for 9 days Rabbit No

Fujita et al.42 GaAlAs 630 10 9 min/day for 7 days Rat Yes
810
Yamaguchi et al.43 GaAlAs 810 100 9 min/day for 7 days Rat Yes
Marquezan et al.44 GaAlAs 830 100 6000 J/cm2 for 7 days Rat No
Altan et al.45 GaAlAs 820 100 108 s/day for 3 days Rat Yes
Duan et al.46 GaAlAs 830 180 4 s/day for 3 days Rat Yes
Shirazi et al.47 InGaAlP 660 25 5 min/day for 14 days Rat Yes
Yoshida et al.48 GaAlAs 810 100 9 min/day for 7 days Rat Yes
Kim et al.49 GaAlAs 808 96 10 s/day for 7 days Rat No
Ohashi et al.50 GaAlAs 810 100 9 min/day for 7 days Rat Yes

InGaAlP, an indium-gallium-aluminum-phosphide laser.

LLLT reduces post-adjustment pain,27 stimulates
bone regeneration in midpalatal suture area
after rapid maxillary expansion,28 enhances the
stability of orthodontic mini-implants, and
accelerates tooth movement.29
Pain from orthodontic treatment is mostly
local and therefore may be controlled more
efficiently by locally administered analgesics.
Several studies have reported the analgesic effect
of tissue-penetrating type lasers, such as He:Ne,30
CO2,31 and semi-conductor lasers.32 These lasers
are reported to reduce orthodontic pain by
irradiating the teeth and gingiva.
Saito and Shimizu33 observed that LLLT
accelerated bone regeneration in the midpalatal
suture after rapid maxillary expansion (RME) in
rats. Several other studies have demonstrated that
LLLT can accelerate bone formation by increasing
osteoblastic activity, vascularization, and
organization of collagen fibers.34,35 Omasa
et al.29 reported that LLLT enhanced the stability
of mini-implants placed in rat tibiae and accel-
erated peri-implant bone formation by increasing
the gene expression of BMP-2 in surrounding cells.
Effect of LLLT on the rate of tooth
movement
In physiological bone remodeling, the amounts
of bone resorption and formation are almost

Table 3. Literature survey of effect of LLLI on cell function in vitro

Wavelength Power Up-regulated
References Laser type (nm) (mW) Duration Cell factors

Ozawa GaAlAs 830 500 1, 3, 6, and 10 min/day MC3T3-E1 ALP

et al.34 for 21 days Osteocalcin
Hamajima GaAlAs 830 500 1, 3, 6, and 10 min/day MC3T3-E1 Osteoglycin
et al.35 for 21 days
Stein He-Ne 632 10 1, 3, 6, and 10 min/day Human osteoblasts Proliferation
et al.58 Differentiation
Renno He-Ne 670 50 3 days Murine osteoblasts (MC3T3) ALP
et al.59 780 and human osteosarcoma
830 (MG63)
Hirata GaAlAs 830 500 20 min/day Rat osteoblasts (C2C12 cells) BMP
et al.60 ALP
Kiyosaki GaAlAs 830 500 5–20 min MC3T3-E1 Mineralization
et al.61
Fujimoto GaAlAs 830 500 5–20 min MC3T3-E1 BMP
et al.62
Aihara GaAlAs 810 50 1, 3, 6, and 10 min/day Rat osteoclasts RANK
et al.63 for 8 days
Coombe GaAlAs 830 90 0.3–4 J for 10 days Human osteosarcoma (SAOS-2) No
et al.64
ALP, alkaline phosphatase; BMP, bone morphogenic protein; RANK, the receptor activator of nuclear factor κB.
206 Kasai et al

Figure. The schematic diagram shows the molecular effects of LLLT on accelerated tooth movement. Low-level
laser irradiation (LLLI) has been suggested to accelerate tooth movement by stimulating osteoclastogenesis on the
compression side via stimulating the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) and
the c-fms/macrophage colony-stimulating factor (M-CSF) during orthodontic tooth movement. On the tension
side, LLLI also stimulates the bone formation and increases the expression of COL1, FN, and OPN. ALP, alkaline
phosphatase; BMP, bone morphogenic protein; RANK, the receptor activator of nuclear factor κB; RANKL, RANK
ligand; M-CSF, the c-fms/macrophage colony-stimulating factor; COLI, type I collagen; FN, fibronectin; OPN,
osteopontin; MMP-9, matrix metalloproteinase-9.

equal, and the total bone mass does not change.5
This so called “coupling” of bone resorption and
formation is the basis for bone remodeling. On
the other hand, when orthodontic force is applied
to a tooth, osteoclastogenesis is induced on the
compression side, while osteogenesis is induced
on the tension side. These reactions disrupt the
coupling balance resulting in more bone
resorption on the compression side, opposing
more bone formation on the tension side. This
alveolar bone remodeling taking place around the
root is the underlying mechanism of tooth
movement.36
Recent studies have suggested that LLLT may
accelerate orthodontic tooth movement in
humans (Table 1)11,32,37–41 and animals
(Table 2).12,42–50 Fujita et al.42 and Yamaguchi
et al.43 demonstrated that LLLI facilitated
osteoclastogenesis on the compression side by
stimulating the receptor activator of nuclear
factor-κB (RANK)/RANK ligand (RANKL), and
the c-fms/macrophage colony-stimulating factor
(M-CSF) during experimental tooth movement.
In response to orthodontic force, RANK,
RANKL, and osteoprotegerin (OPG) facilitate
the coordination of bone remodeling. An increase
in concentration of RANKL in gingival crevicular
fluid (GCF) during orthodontic tooth movement
has been reported.51,52 Moreover, Yamaguchi
et al.53 reported that in the rat experimental tooth
movement, LLLI stimulated the expression of
matrix metalloproteinase-9, cathepsin K, and α(v)
β3 integrin, indicating that LLLI may accelerate
the rate of tooth movement by stimulating
osteoclastogenesis.
On the tension side, LLLI stimulates bone
formation48 and has been associated with
increased expressions of type I collagen
(COL1), fibronectin (FN),49 and osteopontin
(OPN)50 during experimental tooth movement.
Type I collagen is abundant in the periodontal
ligament, and fibronectin is apparent throughout
the mesenchyme.54 Fibronectins bind to collagen
fibers and support the proliferation and
 Laser accelerates tooth movement
chemotaxis of the fibroblasts in the periodontal
ligament.55 OPN, a major member of the
noncollagenous extracellular matrix secreted by
osteoblasts, has been implicated in bone
remodeling upon mechanical stress.56 Kim
et al.57 reported localization of OPN in
periodontal tissue during orthodontic tooth
movement in rats, suggesting that LLLI may
also stimulate osteogenesis during orthodontic
tooth movement.
In vitro studies have shown the effects of LLLI
on cell proliferation and osteogenesis as shown in
Table 3. Hamajima et al.35 reported that the
increased expression of OGN (osteoglycin) gene
induced by LLLI in the early proliferation stage
of cultured osteoblastic cells might play an
important role in the stimulation of bone
formation. Ozawa et al.34 reported that LLLI
administered during the early stages of formation
of osteoblast-like cells isolated from fetal rat
calvariae significantly stimulated cellular pro-
liferation, alkaline phosphatase (ALP) activity,
and osteocalcin gene expression. Furthermore,
in the earlier stages of cell cultures, LLLI was
shown to significantly stimulate the proliferation
of osteoblasts, resulting in a greater number (1.7-
fold) and larger area (3.4-fold) of bone nodules
developing in culture over 21 days. LLLI was also
shown to promote proliferation and maturation
of human osteoblasts,58,59 stimulate mineraliza-
tion, and increase bone morphogenic protein
(BMP) expression.60–62 Meanwhile, Aihara
et al.63 reported that LLLI stimulated osteoclast
activity in vitro.
Fig. shows a schematic acceleration of tooth
movement induced by LLLT. LLLI facilitates the
turnover of connective tissues and accelerates the
bone remodeling process by stimulating osteoblast
and osteoclast proliferation and function during
orthodontic tooth movement.38 However, many
studies have shown no significant increase in the
rate of tooth movement after LLLT.49,64 There-
fore, more studies are needed to identify the
optimum energy, wavelength, and duration of
usage for laser therapeutics.
Conclusion
According to the findings of this review, LLLT
may accelerate orthodontic tooth movement by
stimulating the functions of osteoblasts and
osteoclasts. However, some studies demonstrate
207
no significant clinical effects on the rate of tooth
movement. Therefore, further studies should be
carried out to investigate how to optimize the
biological stimuli of LLLI to increase the rate of
tooth movement.
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Effect of low-level laser on the rate of tooth
movement
Su Jung Kim, DMD, MSD, PhD, Michelle Yuching Chou, DDS, MPH, and
Young Guk Park, DMD, MS, PhD, MBA

Low-level laser therapy (LLLT) has been introduced in orthodontic procedures

with its initial purpose to alleviate the pain after adjustment of the appliances
and to enhance healing of the sore spot caused by appliance impingement.
Recent studies have shown that LLLT may increase the differentiation and
proliferation of the cells associated with bone remodeling machinery and
therefore affect the rate of orthodontic tooth movement. The effects of LLLT in
regards to orthodontic tooth movement have been controversial. This article
reviews the previous studies on the biological effects of LLLT on orthodontic
tooth movement in animals and human subjects, and thereby aims to set the
optimal protocol to accelerate tooth movement in orthodontic avenue. (Semin
Orthod 2015; 21:210–218.) & 2015 Elsevier Inc. All rights reserved.

Introduction the only mean to stimulate such cellular reactions.

T
Other stimuli such as osteotomy and corticotomy
he biological cascades along with the con-
are among the first procedures suggested to
ventional biomechanics allow tooth move-
increase the rate of tooth movement. Nonetheless,
ment for less than 1 mm per month; therefore,
these procedures involve relatively invasive surgi-
the orthodontic treatment usually takes approxi-
cal interventions such as full thickness flap and
mately 2–3 years. Most orthodontists have long
extensive alveolar bone decortication.
yearned for shorter treatment period since the
Recently, wide diversity of clinical trials to
extended treatment duration may increase the
accelerate orthodontic tooth movement by non-
risk of dental caries and/or root resorption.
invasive approaches such as electromagnetic
In addition, the actual treatment duration occa-
provisions, cytokine administration, or endocrine/
sionally surpasses the estimated treatment period,
paracrine regimens has been suggested. The low-
leading to the attrition of patients' cooperation.
level (energy) laser therapy (LLLT) has been
The orthodontic mechano-therapeutic systems
suggested to accelerate turnover of periodontal
presently in use apply mechanical force to the
tissue through its biostimulatory effect, which in
teeth in order to derive tooth movement by
turn is postulated to accelerate tooth movement.
remodeling the periodontal tissues surrounding
Low-level laser may also be known as low-power
the teeth. Cellular and molecular studies on the
laser, soft laser, cold laser, biostimulation laser,
biological mechanism of tooth movement con-
therapeutic laser, and laser acupuncture.
ducted to date signify that mechanical force is not
The present article reviews the existing liter-
ature on the effects of LLLT at the cellular level
and the experimental tooth movement in animal
Department of Orthodontics, Kyung Hee University School of
Dentistry, Seoul, Korea; Department of Developmental Biology,
models to provide the basis for clinical applica-
Harvard School of Dental Medicine, Boston, MA. tions on human subjects.
Address correspondence to Young Guk Park, DMD, MS, PhD,
MBA, Department of Orthodontics, Kyung Hee University School of
Dentistry, Kyung Hee Dae Ro 26, Seoul 130-701, Korea. E-mail:
ygpark@khu.ac.kr Biostimulatory effect of the low-level
This work was supported in part by a grant from Kyung Hee laser therapy (LLLT)
University, South Korea KHU-20131081: “Development of
Interdisciplinary Orthodontic Theragnosis for Bone Defect Disease.” The laser has diverse mechanisms for application
& 2015 Elsevier Inc. All rights reserved.
in the biomedical domain. It is primarily used for
1073-8746/12/1801-$30.00/0 optical instruments such as fluoroscopy or high
http://dx.doi.org/10.1053/j.sodo.2015.06.008 definition coherence tomography. Laser causes

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 210–218 210

 Effect of low-level laser
Table 1. Laser–tissue Interactions According to Intensity and Irradiation Time
High-level laser therapy (HLLT) Plasma-induced ablation
Photomechanical interactions
Photoablation
Photothermal interactions
LLLT Photochemical and photobiostimulatory
interactions
receptive cells and tissues to initiate light-induced
chemical reactions such as photobiostimulation
or photobiomodulation. The interaction with
target tissues converts light energy of the laser
into heat energy (photothermal reaction), result-
ing in photoablation and consequent breakdown
of the tissue. The high-power laser triggers
photomechanical interaction which then gives
rise to rupture of the tissue; therefore, high-level
laser is used for photoablation, photothermal,
and photomechanical interaction (Table 1). In
contrast, the low-level laser is used for photo-
chemical effects on the tissues. LLLT employs
red and infrared light to promote wound healing
process of soft tissues, as well as to reduce
inflammatory response and associated pain by its
photochemical effects on cells (Table 2).1
The cellular effect of LLLT
The cellular mechanism of LLLT
The main cellular effects of LLLT are dependent
upon the absorption of wavelengths of red and
infrared light that activates the electron respi-
ratory chain in mitochondrial membranes. The
photon of the laser is absorbed in cytochrome,
generating single oxygen free radicals which
increase its cellular energy by elevating ATP
synthesis. These responses from nitric oxide
(NO) leads to the alteration of cell activity by
Table 2. Physical Characteristics of the Low-level Laser
Therapy (LLLT)
Light source Visible (generally red) or near-infrared
light generated from a laser or light
emitting diode (LED) system
Wave length 600–1000 nm
Power 10–500 mW
Intensity (power 5–50 mW/cm2 (for stimulation and
density) healing)
Dose (energy 1–20 J/cm2
density)
211
Intensity (W/cm2) Irradiation Time (s)
1012 – 1014 10 13 – 10 10
1012 – 1015 10 12 – 10 9
108 – 1011 10 9 – 10 7
102 – 107 10 5 – 100
10 3 – 100 101 – 103
increasing cell membrane permeability to cal-
cium and other ions.
Furthermore, this laser may also affect RNA
and DNA synthesis and therefore have an effect
on cell proliferation, release of the growth fac-
tors, an increase in collagen synthesis by fibro-
blast, change in nerve conduction, and release of
the neurotransmitter.2
The effects of the LLLT particularly on
osteoblasts, osteoclasts, and fibroblasts are more
of interest in regards to orthodontic tooth
movement (Table 3).
Osteoblast
Dörtbudak et al.3 described the biostimulatory effect
of LLLT on osteoblasts in vitro while reporting an
increased bone matrix production by irradiation of
a pulsed diode soft laser. While some studies
demonstrated an increase in DNA replication and
proliferation of the osteoblasts in vitro in response to
LLLT stimulation,4,5 others demonstrated tempo-
rarily triggered G2/M arrest on the cell cycle of the
osteoblast and promoted osteoblast differentiation
and osteogenesis.6 Furthermore, Grassi et al.7
reported that LLLT augmented the osteogenic
potential of growth-induced cells and further
stimulated the rate of growth and differentiation of
the human osteoblast-like cells.
Osteoclast
Unlike the effects of LLLT on osteoblasts, its
effects on osteoclasts are not clear. Aihara et al.8
applied Ga–Al–As semiconductor laser on rat
osteoclast precursor cells in vitro, and demon-
strated that LLLT facilitated differentiation and
activation of osteoclasts via RANK expression.
Macrophage colony-stimulating factor (M-CSF)
is essential for osteoclastogenesis to stimulate not
only osteoclast precursor cells but also mature
osteoclasts. Yamaguchi et al.9 presented that LLLT
increased the velocity of tooth movement via
212 Kim et al

Table 3. Summary of the Studies on the Cellular Effects of LLLT In Vitro

First Author Laser
(Publication
No. Year) Cell Culture Laser Type Wave Length Power, Time Dose (J/cm2) Result

Osteoblast
1 Dörtbudak3 Rat femora Diode laser 690 nm 21 mW, 60 s 1.6 Increase cell growth
(2000)
2 Yamamoto4 Mouse Diode laser 830 nm 500 mW, 20 min 7.64 Increase DNA replication
(2001) calvaria and gene expression
3 Fukuhara6 (2006) Rat calvaria Diode laser 905 nm 150 s 1.25 Arrest G2/M of cell cycle
4 Pires Mouse bone Diode laser 830 nm 50 mW, 36 s 3 Increase mitochondrial
Oliveira5(2008) activity
Osteoclast
5 Aihara8 (2006) Rat bone Diode laser 810 nm 50 mW 1 min 9.33 Stimulate osteoclast
3 min 27.99 formation
6 min 55.98
10 min 93.30
6 Yamaguchi9 Rat bone Diode laser 810 nm 50 mW, 3 min 27.99 Increase M-CSF, c-fms
(2007), expression
Fujita11 (2008)
7 Xu12 (2008) Rat calvaria Diode laser 650 nm 2 mW 1 min 0.23 Downregulate RANKL:OPG
5 min 1.14 mRNA ratio
10 min 2.28
Fibroblast
8 Soudry13 (1998) Human Helium–neon 632.8 nm 10 mW, 10 min 1.2 Growth acceleration
gingival laser Increase of cell division
fibroblasts
9 Saygun14 (2008) Human Diode laser 685 nm 25 mW, 140 s 24 Increased the proliferation
gingival 1 cm2 of human gingival
fibroblasts fibroblasts and release of
bFGF, IGF-1, and IGFBP3
10 Frozanfar15 Human Diode laser 810 nm 50 mW, 32 s 4 Increase in proliferation and
(2013) gingival 0.4 cm2 collagen I gene expression
fibroblasts

stimulating the expression of M-CSF and its
receptor system (colony stimulating factor-1
receptor; c-fms) in the Wistar rats. The follow-
up study10 in the same specie asserted that the
expression of MMP-9, cathepsin K, and integrin α
(v)β3 increased with application of LLLT which
may help to increase the rate of tooth movement.
Fujita et al.11 observed, as well, that LLLT in vitro
promoted the differentiation and activation of
osteoclasts due to increased c-fms gene expression
and RANK/RANKL. However, Xu et al.12 have
shown that LLLT indirectly inhibited osteoclast
differentiation by downregulating the RANKL:
OPG mRNA ratio in osteoblasts and promoting
proliferation and differentiation of osteoblasts,
thus contributing to bone remodeling.
Fibroblast
It has been shown that LLLT in vitro increases the
proliferation of human gingival fibroblast
(HGF), and the expression of collagen type I,
basic fibroblast growth factor (bFGF), insulin-like
growth factor-1 (IGF-1), and receptor of IGF-1
(IGFBP3) in HGF.13–15
Animal studies of LLLT
There are various animal studies on the effects of
LLLT on orthodontic tooth movement. Among
these studies, nine studies were conducted in
rats9–11,16–21 and two studies in dogs.22,23 The
studies that did not offer data on the velocity of
tooth movement with control and/or placebo
group were excluded. The animal studies offer
vast arrays of evidence on the effect of laser on
orthodontic tooth movement (Table 4).
In 2000, Kawasaki and Shimizu16 published
the first investigation ever conducted to find the
effect of LLLT on tooth movement in animals in
2000. They described the effect of LLLT on tooth
movement by applying a mesial force of 10 g with
a closed coil spring on the upper left first molar
in rats. Ga–Al–As diode laser with a wavelength of
Table 4. Summary of the Studies on Effect of LLLT on the Tooth Movement in Animal Subjects
First Author Laser Application
(Publication Year) Result
2
No Animal Laser type Wave Length Power, Time Dose (J/cm ) Total Energy (J) Irradiation Interval Applied Tooth Force (g) Velocity

1 Kawasaki16 24 Rats Diode 830 nm 100 mW, 3 min6000/Point 18/Point Once a day Upper 1st molar (3 10 Increase
(2000) 6 Weeks old laser CW 18,000/Session 54/Session Total 13 days points) 1.3 fold
0.0028 cm2 234,000/13 702/13 Days
Days
2 Yamaguchi9 50 Rats Diode 810 nm 100 mW, 3 min 6000/Point 18/Point Once a day Upper 1st molar (3 10 Increase
(2007) 6 Weeks old laser CW 0.0028 cm2 18,000/Session 54/session Total 8 days points)
144,000/8 432/8 Days
Days
3 Fujita11 (2008) 75 Rats Diode 810 nm 100 mW, 3 min 6000/Point 18/Point Once a day Upper 1st molar (3 10 Increase
6 Weeks old laser CW 0.0028 cm2 18,000/Session 54/Session Total 8 days points)
144,000/8 432/8 Days
Days
Yoshida17 (2009) 60 Rats

Effect of low-level laser

4 Diode 810 nm CW 100 mW, 2.5 min 4500/Point 13.5/Point Once a day for 7, 13, Upper 1st molar (4 10 Increase
6 Weeks old laser 0.0028 cm2 18,000/Session 54/Session and 20 days points)
162,000/9 486/9 Days
Days
5 Gama19 (2010) 30 Rats Diode 790 nm 40 mW, 2.5min 20/Session 0.6/Session 2 Day interval for Upper 1st molar (4 points, 40 No effect
12 Weeks laser CW 0.03 cm2 total 19 days 3 intra, 1 extra)
old
6 Marquezan20 36 Rats Diode 830 nm 100 mW, 3min 6000 Point 18/Point Once a day Upper 1st molar (4 41 No effect
(2010) 12 Weeks laser CW 0.003 ncm2 18,000/Session 54/Session Total 7 days points)
old
7 Yamaguchi10 50 Rats Diode 810 nm 100 mW, 3 min 6000/Point 18/Point Once a day Upper 1st molar (3 10 Increase
(2010) laser 18,000/Session 54/Session Total 8 days points)
2
6 Weeks old CW 0.0028 cm 144,000/8 432/8Days
Days
8 Duan21 (2012) 44 Rats Diode 830 nm 180 mW, 4 s 3.6/Point 18/Point Days 0,1,2 Upper 1st molar (3 10 Increase
laser CW 0.2 cm2 54/Session points)
6 Weeks old 830 nm 90 mW, 8 s 10.8/Session 162/3 Days Total 3 days
PW 0.2 cm2 32.4/3 Days
9 Altan18 (2012) 38 Rats10 Diode 820 nm 100 mW, 30 s, 343.9/Point 3/Point Days 0,1,2 Upper incisors (5 points) 20 No effect
Weeks laser 108 s 1717.2/Session 15/Session
old
CW 0.03 cm2 95.5/Point 10.8/Point Total 9 days
477/Session 54/Session
23
10 Goulart (2006) 18 Dogs Diode 780 nm 70 mW, 3 s 5.25/Session 0.21/Session Every 7 days 1st Molar (1 point) 85 Increase
laser CW 0.04 cm2 35/Session 1.4/Session Total 9 weeks
11 Kim22 (2009) 12 Dogs Diode 808 nm 76.3 mW, 20 s 41.7/Point 0.052/Point Every 3 days Upper 2nd premolar (8 150 Increase
laser PW 0.0013 cm2 333.6/Session 0.42/Session Total 8 weeks points)

213
214 Kim et al
830 nm at power of 100 mW was applied in the
manner of continuous wave by placing the
optical fiber tip in contact with the mesial,
buccal, palatal side of the gingiva of the tooth
for three minutes respectively (9 min in total,
35.3 W/cm2) for 12 days. The irradiation
protocol was based on previous studies that
demonstrated osteogenic effects of the laser on
rats after maxillary expansion16 and during bone
healing process in tooth extraction socket.24 The
study reported a 1.3-fold increase in tooth
movement in the irradiation group, as well as a
significant increase of bone formation on the
tension side, and an increase in the number of
osteoclasts on the pressure side.
Majority of studies9,10,17–21 conducted after-
wards were on rats within the age of 6–12 weeks.
All of the studies targeted on the upper first
molars, except for one study, which focused on
maxillary incisors.18 While 10 g of force is applied
with closed coil springs in majority of these
studies, a larger force of 20–41 g was applied on
others.18–20 In most cases, Ga–Al–As diode laser
emitting a wavelength of 780–830 nm in the
infrared light domain was commonly used.
Most of these studies conducted on ani-
mals9–11,16–20 used continuous wave laser. A
recent study by Duan et al.21 in 2012 aimed to
look at the differences in the rate of tooth
movement when using the continuous wave laser
compared to the pulsed wave laser. The study
announced that there were no significant
differences between both types of lasers. Both
lasers led to faster tooth movement in comparison
to the control group. Later on, the study conducted
by Kim et al.23 employed pulsed wave laser on
beagle dogs which demonstrated an accelerated
effect on the rate of tooth movement.
Unlike most studies9–11,16,17,21 that demon-
strate an accelerated speed of tooth movement in
rats by laser irradiation, the investigations by
Altan et al.,18 Gama et al.,19 and Marquezans
et al.20 announced that there were no significant
differences in the rate of tooth movement against
the control group. Two main differences in these
investigations were the application of laser on
older aged (70–120 days old) rats and application
of heavier orthodontic forces. This demonstrated
the possibility that response to laser irradiation
could differ depending on the age and force.
The split-mouth double-blind study in dogs
conducted by Goulart et al.23 looked at the effect
of laser on the speed of orthodontic movement
in accordance with the dosage of irradiation
(5.25 J/cm2 and 35.0 J/cm2 irradiation groups).
The 5.25 J/cm2 dosage group showed an accele-
rated orthodontic movement while the 35.0 J/cm2
group retarded it. They hypothesized that the
lower dosage has an anti-inflammatory effect
while higher dosage retarded orthodontic move-
ment as a result of intensifying repair process in
the tissues. Such postulation signals that there is a
possibility to control the rate of tooth movement
by regulating the modality of laser treatment.
In our previous investigation22 with beagle
dogs, animals were exposed to surgically assisted
stimulation (corticision) and/or LLLT. The
results of this study demonstrated a 2.08-fold
increase in the LLLT group associated with
cellular activation (Figs. 1 and 2) when com-
pared to a 2.23-fold increase in the rate of tooth
movement in the group exposed to corticision.
However, in the group where LLLT was com-
bined with corticision, the movement was rather
inhibited when compared with the control. We
concluded that LLLT may predominantly acti-
vate healing process of surgical defect rather
than facilitate tooth movement.
Clinical studies of LLLT
The results of the animal studies implied that the
rate of tooth movement would be enhanced with a
proper amount of energy whereas inhibitory effect
appeared with overdose and the tooth movement
would receive no effect from an insufficient
amount of energy.24,25 Table 5 illustrates the
human studies that (1) used the suitable type
and wavelength of laser for biostimulation, (2)
suggested a clear LLLT application protocol, (3)
presented a difference in tooth movement rate,
and (4) met the conditions set forth for rando-
mized controlled trial (RCT)/split-mouse design
including control and/or placebo group.
Cruz et al.26 carried out the first investigation
to examine the effect of LLLT on orthodontic
tooth movement in humans. Extraction of the
upper first premolar was followed by retraction of
the canine with 150 g of force in eleven patients
of both genders from ages 12 to 18 years. It was a
split-mouth study applying Ga–Al–As diode laser
with a wavelength of 780 nm in a continuous
wave form, and the irradiation totaled up to 2.0 J
(5 J/cm2, irradiated 10 times for 10 s). The study
 Effect of low-level laser 215

Figure 1. Effects of LLLT on multinucleated cells at 8th week in Beagle dogs [Tartrate resistant acid phosphatase
(TRAP) staining, 400]. (A) In the LLLT group, there is an increase in numbers of TRAP-positive multinucleated
osteoclasts lining the resorbed alveolar bone surface on the compression side. (B) Control group. (Color version of
figure is available online.)

was conducted in reference to the animal performed comparative measurements through

experiment by Luger et al.27 which aimed to
determine the optimum dose of laser, expecting
10 times of 5 J/cm2 of laser irradiation to deliver
a more uniform energy to tooth, rather than
60 J/cm2 which is the dosage for healing a
fractured tibia in rats. The study reported that
the rate of tooth movement was accelerated by
34% in the experimental group.
More researches followed thereafter to
examine the effect of laser on tooth movement
on human subjects.28–31 Most of the studies
adopted Ga–Al–As diode laser emitting a wave-
length of 780–810 nm of infrared light, and
split-mouth study with 150 g of retraction force
on the canine after extracting of the upper first
premolar. All the studies demonstrated that the
application of laser accelerated the velocity of
tooth movement; however, there appeared to be
no significant difference between the laser and
the control group in the study conducted by
Limpanichkul et al.28 The design of the study was
identical to the study by Cruz et al.,26 with the
only difference of adopting 18.4 J (25 J/cm2,
eight times of irradiation for 23 s). The authors
proclaimed that such a result sprung from insuffi-
cient laser dose to accelerate the tooth move-

Figure 2. Effects of LLLT on PCNA-positive cells at 8th week in beagles [Proliferating cell nuclear antigen (PCNA)
staining, 400]. (A) In the LLLT group, there is an increase in numbers of hyperchromatic proliferative PCNA-
positive cells on the tension side: osteoblasts lining the newly formed bone surface and fibroblasts in the
periodontal ligament. (B) Control group. (Color version of figure is available online.)
216 Kim et al

ment. Upon considering the results of previous

2 Increase (6 mo)

2 Increase (4 mo)
investigations, the “18.4 J” of energy that

No effect (3 mo)

20–40% Increase
Limpanichkul et al.28 applied was found to be

Increase 34%
Velocity
Result
higher than the “2.0–8.0 J” range of energy levels

(2 mo)

(1 mo)
other studies had applied to demonstrate an
enhanced tooth movement in human subjects.
In the study by Youssef et al.,29 a double-fold
Force (g)

increase in the rate of tooth movement was

150
150

150

150

80
observed when 8.0 J Ga–Al–As diode laser was
irradiated while reducing 70% of accompanying
pain during tooth movement. Unlike the designs

Upper lateral
Applied Tooth

in other previous studies, Genc et al.31 measured

incisors
Application

Canine
Canine

Canine

Canine
the velocity of orthodontic tooth movement and
nitric oxide levels in the gingival crevicular fluid
(GCF) when retracting the maxillary lateral
First 3 days of each

incisor with 80 g of orthodontic force. This

0,3,7,14,21,28 Days
0,3,7 Days of each
Total Energy (J) Irradiation Interval

study applied 2.0 J (0.71 J/cm2, 10 times of

4 Days of each

0,3,7,14 Days

irradiation, for 10 s each) laser, and observed a

month

month

month

20–40% significant acceleration of orthodontic

tooth movement. However, they reported no
statistically significant changes in the nitric oxide
level of GCF during orthodontic treatment.
18.4/Session
8.0/Session
2.0/Session

2.0/session

2.0/session

Putting together the previous clinical studies,

0.2/Point

2.3/Point

0.2/Point

0.2/Point

Ga–Al–As diode laser of 780–810 nm wavelength

Table 5. Summary of the Effect of LLLT on the Tooth Movement in Human Subjects

irradiation was found to accelerate the velocity of

orthodontic tooth movement when a continuous
No information

wave of 5–20 J/cm2, 2.0–8.0 J was applied by

200/Session

7.1/Session
Dose (J/cm )

50/Session

50/Session

contacting the tip of the laser to the gingival

0.71/Point
2

25/Point
5/Point

5/Point

surface (Fig. 3). The optimum dose of laser energy

required to facilitate the tooth movement in
human subject appeared to be different against
100 mW, 10/20/

the dose recommended in animal subjects.

Laser

100 mW, 23 s
20 mW, 10 s

20 mW, 10 s

20 mW, 10 s
Wave length Power, Time

0.04 cm2

0.09 cm2

0.04 cm2

0.28 cm2
10 s
780 nm

860 nm

809 nm

780 nm

808 nm
11 Diode laser

12 Diode laser

15 Diode laser

13 Diode laser

20 Diode laser
N Laser type

Youssef29 (2008)
No (Publication Year)

Limpanichkul28

Figure 3. Clinical application of low-level laser therapy

Sousa30 (2011)

(2013)
Cruz26 (2004)

around the target tooth to be moved. Four irradiation

First Author

points at the labial surface, two points on the mesial

(2006)

32

and two points on the distal, and another four points at

Genc

the lingual surface turned out to be effective in

accelerating tooth movement. (Color version of figure
is available online.)
1

5
 Effect of low-level laser
Discussion
The effect of LLLT on accelerating tooth
movement is still controversial in animal studies
as well as in clinical trials for human subjects.
Although a majority of the findings demon-
strated positive effects in expediting tooth
movement,9–11,16,17,21–23,26,29–31 several other
reports announced a zero effect or even an
inhibitory effect.18–20,28
The effects of the laser poses variant results
depending upon the wavelength, power, spectral
area, dose, application frequency, and exposure
time of the laser. The wavelength is presumably not
the decisive factor of facilitating tooth movement
amongst the physical configurations of the laser32;
however, it is rather predominantly attributable to
the total energy dose exposed to the subject.
The Arndt–Schulz rule is a claimed law con-
cerning the effects of drugs or poisons in various
concentrations. It states that for every substance
small doses stimulate, moderate doses inhibit, and
large doses kill. It is relevant to set up the optimal
level of the laser dosage towards the therapeutic
window, since an excessive dosage may inhibit the
effect of tooth movement with insufficient amount
leading to no effect. Both animal studies and
clinical trials for human subjects which employ the
laser approach may imply such a rule to be valid
regarding the energy density and dose.
Several issues of LLLT usage still need to be
resolved such as high cost laser equipment of
which the burden could be imposed on patients,
a long duration of time consumed while applying
the laser leading to a lengthy chair time, and a
requirement for trained human resources. It is
imperative for further well conducted pro-
spective clinical trials to determine a “gold
standard” for clinical application of LLLT.
Conclusion
Understanding the characteristics and limi-
tations of the biostimulation caused by LLLT
would lead to broader clinical implications in
orthodontics in addition to the control of tooth
movement rate.
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The effects of low-intensity pulsed ultrasound
on the rate of orthodontic tooth movement
Hui Xue1, Jun Zheng1, Michelle Yuching Chou1, Hong Zhou, and
Yinzhong Duan

Accelerating alveolar bone remodeling and thus accelerating the velocity of

orthodontic tooth movement is highly desirable by orthodontists and
patients. Low-intensity pulsed ultrasound (LIPUS) stimulation has been
reported to promote fracture healing to treat bone nonunion, and to
accelerate bone maturation and remodeling during the consolidation stage
of distraction osteogenesis. Low-intensity pulsed ultrasound (LIPUS) is a
safe, non-invasive approach, which has demonstrated the potential to
increase the rate of tooth movement. The purpose of this review article is
to help readers understand the science behind this technology and to discuss
the different potential applications of LIPUS in orthodontics. (Semin Orthod
2015; 21:219–223.) & 2015 Elsevier Inc. All rights reserved.

Introduction hormone,4 and dihydroxyvitamin D3 [1,25-

(OH)2D3].5 However, due to systemic effects,
O rthodontic treatment is a process to achieve
appropriate esthetics and masticatory
function through movement of teeth by applying
their application in orthodontics has not been
justified.1 Therefore, recent studies have focused
on exploring the potential use of non-invasive
an external physical force. In this regard, stim-
physical methods to achieve faster orthodontic
ulating proper physiological reactions in the
tooth movement.2,6,7 One of the potential
surrounding tissue is the main focus of ortho-
physical approaches suggested in these studies is
dontic treatment.1,2 Optimizing proper bio-
low-intensity pulsed ultrasound (LIPUS). To
logical responses may not only accelerate tooth
validate the use of LIPUS in orthodontics, a
movement, but also decrease side effects. In
search of the current literature was conducted
order to improve the velocity of orthodontic
using ISI Web of Knowledge, Science Direct, and
treatment, previous studies have utilized differ-
PubMed search engines.
ent biochemical agents, such as osteocalcin and
prostaglandin E2 (PGE2),3 parathyroid

Department of Orthodontics, School of Stomatology, Fourth Biological effects of LIPUS

Military Medical University, Xi’an, 710031 PR China; Department
of Dentistry, Hegang People’s Hospital, Hegang, 310006 PR China;
Department of Oral and Maxillofacial Surgery, Stomatological
Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR China;
Department of Developmental Biology, Harvard School of Dental
Medicine, Boston, 02138 MA; Department of Orthodontics, Stoma-
tological Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR
China.
Corresponding authors. E-mail: zhouhong@mail.xjtu.edu.cn;
duanyz@fmmu.edu.cn
1
These authors contributed equally to this work.
Funding: This study was supported by grants from The Scientific
and Technological Project of Shaanxi Province of China, PR China
(2008K14-03 to Dr. Duan), who had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.009
LIPUS (30–100 mW/cm2) is a form of mechan-
ical energy that is transmitted through living
tissues as acoustic pressure waves, resulting in
biochemical changes at the cellular and molec-
ular levels.8 These biochemical changes may have
several therapeutic benefits, one of which
includes an increase in rate of soft and hard
tissue healing.9,10 Therefore, LIPUS is widely
used in the field of physical therapy, and has
been approved by the U.S. Food and Drug
Administration (FDA) as a modality of treatment.
Since LIPUS can improve the rate of bone
healing after trauma, a number of studies have
tried to understand its biostimulatory effects,
especially in regard to the osteoblastic and
osteoclastic responses. It has been reported that

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 219–223 219

220 Xue et al
in response to LIPUS, there is up-regulation of
osteogenic markers, such as IL-8, bFGF, VEGF,
TGF-β, alkaline phosphatase, and non-
collagenous bone proteins, as well as con-
comitant down-regulation of the osteoclastic
markers.4,11–14 It has also been reported that the
biostimulatory effects of LIPUS are derived from
the induction of micro-stream signals and
mechanical stresses. These signals directly stim-
ulate cell membranes, cytoskeletal structures,
and focal adhesion molecules, which result in
signal transduction and subsequent gene
transcription.15
Previous studies16,17 have shown that the
periodontal ligament contains precursor cells of
cementoblasts and osteoblasts in the perivascu-
lar area. Cyclic mechanical stimulation of the
PDL, via the regulation of EGF/EGFR system,
would induce the differentiation of these pre-
cursor cells toward either the osteoblastic or
cementoblastic pathway.16,18 This biological
effect of LIPUS may help with repair of root
resorption.19,20
Similarly, LIPUS has been reported to upre-
gulate fibroblast growth factors (from a
macrophage-like cell line) and angiogenic factor
(CD31).21,22 It also has been demonstrated that
applying LIPUS on human gingival fibroblasts
(5 min per day for 3 weeks) upregulates ALP and
OPN expressions in these cells, which indicates
the possibility of osteogenic differentiation.23
LIPUS is distinguished by being non-invasive
and easy to use, and the signal is considered
neither thermal nor destructive.24 Compared with
other types of ultrasound, LIPUS has a better
biological effect in promoting tissue healing.25–27
Therefore, LIPUS has been used to promote the
healing of various types of hard and soft tissues,
such as fractured bone, intervertebral disc, and
cartilage.28 It has also been used to enhance
mandibular growth in children with hemifacial
microsomia.29 In addition, LIPUS induces a
significant increase in the amount of predentin,
cementum, and the number of cells in the PDL
and the sub-odontoblast layer29–33; which indi-
cates that LIPUS is a potential method to prevent
root resorption during orthodontic tooth move-
ment.30 LIPUS is generally utilized in 1.5 MHz
frequency pulses with a pulse width of 200 ms,
repeated at 1 kHz at an intensity of 30 mW/cm2
for 20 min per day as recommended by the
FDA.34–36
While the clinical applications of LIPUS in the
medical field are well-studied, there are very few
studies on LIPUS stimulation for orthodontic
tooth movement.34,37
LIPUS treatment and orthodontic tooth
movement
There is a narrowing of the PDL in the pre-
ssure side of the tooth immediately upon
orthodontic forces on the periodontium. Sho-
rtly after, osteoclasts differentiate along the
wall of alveolar bone, initiating bone reso-
rption, which is considered the initial stage of
the tooth movement. Regions of bone resor-
ption are seen as an increase in the width of
the PDL.
In the later stage of tooth movement, there is
an increase in the proliferation and differ-
entiation of local cells into fibroblasts and
osteoclasts, followed by the deposition of osteoid
tissue on the tension side of the tooth. The
original periodontal fibers are gradually
embedded in the new layers of osteoid until the
PDL has returned to its original width.38
There is no difference observed between the
tissue reactions in orthodontic tooth movement
with or without LIPUS stimulation.37,39 However,
the changes observed in tissue upon LIPUS
stimulation are more extensive, resulting in the
rapid movement of teeth during the orthodontic
treatment.37,40
A list of previous studies on the application of
LIPUS during orthodontic treatment is shown in
the Table. These studies illustrated that LIPUS
can be used in orthodontics to reduce the risk of
root resorption, increase the rate of tooth
movement, or modify mandibular growth. In
addition, LIPUS promotes the proliferation of
cells in PDL and alveolar bone, which improves
the quality of the periodontium and reduces
the possiblity of relapse after orthodontic
treatment.41,42
Discussion
The ultimate aim of orthodontic tooth move-
ment is to move teeth in the most effective way
with minimal side effects such as root resorption.
Recent studies have provided evidence of the
beneficial effects of LIPUS on the rate of
orthodontic tooth movement37; however, the
 Use of LIPUS in orthodontics
Table. Summary of studies assessing effects of LIPUS on orthodontic tooth movement
Study LIPUS Parameter Duration
el-Bialy et al.32 200 ms (1.5 MHz) 1 kHz 20 min/day
30 mW/cm2 4 weeks
El-Bialy et al.30
El-Bialy et al.29
Dalla-Bona et al.33 2 ms (1 MHz) 100 Hz 30 15 min/day
(150) mW/cm2
El-Bialy et al.31
200 ms (1.5 MHz) 1 kHz 5 (10) min/day
30 mW/cm2
Xue et al. 37
200 ms (1.5 MHz) 1 kHz 20 min/day
30 mW/cm2
Hu et al. 51
200 ms (1.5 MHz) 1 kHz 20 min/day
90 mW/cm2
mechanisms of these biochemical effects still
remain unclear. In El-Bialy et al.’s31 study of
mandibular organ culture, they suggested that
LIPUS might promote tooth movement by
enhancing alveolar bone remodeling.
Using a rat orthodontic model, Xue et al.37
showed that LIPUS may promote alveolar bone
remodeling via increasing the gene expression of
the HGF/Runx2/BMP-2 signaling pathway; as
a result, the velocity of orthodontic tooth
movement was increased. Furthermore, in the
in vitro study of human PDL cells (hPDL), it was
confirmed that in response to LIPUS stimulation,
the expression of BMP-2 mRNA and protein
was enhanced via Runx2 expression.37 These
findings are in agreement with previous studies
and confirm that BMP expression is significantly
increased upon mechanical stimulation, such as
compressive and shear stress.43,44 The BMP-2
activation induced by orthodontic forces plays a
significant role in increasing the rate of bone
remodeling by enhancing osteoblast pro-
liferation and indirectly supporting osteoclast
differentiation,45,46 which in turn increases the
rate of tooth movement.
Another benefit of LIPUS application in
orthodontics comes from the preventive effect of
LIPUS on root resorption. As root resorption
may present as a complication during or after
orthodontic tooth movement, some therapeutic
approaches have been proposed to either inhibit
root resorption or to induce periodontal
regeneration after root resorption has
occured.47–50 However, the effectiveness of these
approaches still remains controversial. el-Bialy
et al.31 suggested that LIPUS might minimize
orthodontically-induced root resorption by
enhancing cementum and dentine deposition,
221
Study Type Results
In vivo Enhanced the mandibular incisors
eruption and incisor apical ends growth
In vivo Decreased orthodontic root resorption
In vivo Modified the growth pattern of mandible
In vitro LIPUS protected against root resorption
Ex vivo Enhanced cementum and predentin
formation
In vivo Accelerated orthodontic tooth movement
In Vitro Facilitated osteogenic differentiation
of hPDLCs
which provides a preventive layer against root
resorption.
Considering the benefits of LIPUS, which
include its safety, non-invasive nature, and the
ability to be reapplied over the course of the
orthodontic treatment, it can serve as a great
option to accelerate orthodontic tooth move-
ment. However, further studies are required to
fully validate the biological effects of LIPUS.
Conclusion
In orthodontics, seeking non-invasive techniques
to accelerate the rate of tooth movement has
been a continuous effort. To our knowledge,
LIPUS is a potentially useful tool in clinical
orthodontics. While many studies have explored
the effects of LIPUS on the periodontal tissue,
very few studies have assessed its effects on tooth
movement. Therefore, further studies are
needed to fully understand the use of LIPUS in
orthodontics.
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 Use of LIPUS in orthodontics
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41. Singh G, Batra P. The orthodontic periodontal inter-
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Accelerated tooth movement: Do we need a new
systematic review?
Daniel Rozen, Edmund Khoo, Hend El Sayed, Richard Niederman,
Richard McGowan, Mani Alikhani, and Cristina C. Teixeira

Current systematic reviews are important for health care providers in

supporting their evidence-based practice decisions. Equally important is
the ability to determine when a new systematic review is needed in view of
the rapid publication output. The current best evidence from a 2013
systematic review suggests that certain treatments may accelerate ortho-
dontic tooth movement. Our aim was to determine if an updated systematic
review is needed on this topic by applying the modified Ottawa method. A
systematic search of Pubmed, Embase, CENTRAL, and Web of Science
databases, identical to the previous systematic review, was executed. Two
authors performed screening for inclusion/exclusion of studies and selected
full-text articles were reviewed. Qualitative and quantitative criteria were
applied to assess studies describing the following types of interventions to
accelerate tooth movement: electrical, photobiomodulation, micro-osteo-
perforations, vibration, corticotomy, and low-level laser therapy. The Ottawa
method showed that studies produced since 2011 have (1) potentially
invalidating evidence and description of new methods and (2) combined new
data that would enhance the precision of the existing evidence on low-level
laser therapy. These collectively indicate the need for a new systematic
review on adjunct procedures to accelerate orthodontic tooth movement,
which may offer new evidence and techniques not previously mentioned.
(Semin Orthod 2015; 21:224–230.) & 2015 Elsevier Inc. All rights reserved.

Introduction and has not yet been established in the ortho-

C
urrent systematic reviews are of consid-
erable importance to the health care and
the orthodontic community in making evidence-
based practice decisions. With new evidence
published frequently in peer review journals, the
necessity for an objective method to establish the
need to update a systematic review is imperative
Department of Orthodontics, New York University College of
Dentistry, 345 E 24th St, New York, NY 10010; Department of
Epidemiology and Health Promotion, New York University College of
Dentistry, New York, NY; New York University College of Dentistry,
New York, NY; Consortium for Translational Orthodontic Research,
New York University College of Dentistry, New York, NY; Department
of Developmental Biology, Harvard School of Dental Medicine,
Boston, MA.
Corresponding author at: Department of Orthodontics, New York
University College of Dentistry, 345 E 24th St, New York, NY 10010.
E-mail: ct40@nyu.edu
& 2015 Elsevier Inc. All rights reserved.
1073-8746/12/1801-$30.00/0
http://dx.doi.org/10.1053/j.sodo.2015.06.010
dontic literature.
The Cochrane Collaboration recommends a
time-based approach in maintaining and updating
systematic reviews at least every 2 years.1 In a study
to determine when to update high-quality sys-
tematic reviews, it was concluded that indicators
for updating occurred often and in a short period
of time.2 Therefore, a priority-setting approach
has been suggested as more appropriate than a
time-based approach.3 The Agency for Healthcare
Research and Quality (AHRQ) Evidence-Based
Practice Center (EPC) has been developing
methods to appraise the need to update evidence
reviews.4 Ultimately two methods have been
proposed, the RAND and Ottawa methods, both
found to provide similar indicators for the need to
update systematic reviews.4 In 2014 we sought to
evaluate the need for an update to the most recent
systematic review on the effectiveness of
interventions that accelerate orthodontic tooth
movement, which was published in 2013.5 For
simplicity we will refer to the aforementioned

Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 224–230 224

 Accelerated tooth movement 225

Table 1. Search terms and databases used to identify studies assessing methods of accelerating tooth movement
Database Limit to Search terms Number of
publication date citations

Pubmed 2010/01/01 to (orthodontics[Mesh] OR orthodontic*) AND (Tooth Movement[Mesh] OR 405 results (382
2014/07/31 mov* OR retract*) AND (rapid OR accelerat* OR short* OR speed OR rate) in English)
Embase 2010–2014 (orthodontics OR orthodontic*) AND (Tooth Movement OR mov* OR 251 results (241
retract*) AND (rapid OR accelerat* OR short* OR speed OR rate) in English)
CENTRAL 2010–2014 (orthodontics OR orthodontic*) AND (Tooth Movement OR mov* OR 31 results (30 in
retract*) AND (rapid OR accelerat* OR short* OR speed OR rate) English)
Web of 2010–2014 (orthodontics OR orthodontic*) AND (Tooth Movement OR mov* OR 305 results (302
Science retract*) AND (rapid OR accelerat* OR short* OR speed OR rate) in English)
OpenSIGLE (orthodontics OR orthodontic*) AND (Tooth Movement OR mov* OR 1 result
retract*) AND (rapid OR accelerat* OR short* OR speed OR rate)

Five databases were searched using the terms listed in the middle column, yielding different number of published articles.

review as Long et al., which evaluated and
compared interventions adjunct to orthodontic
treatment for accelerating tooth movement, such
as laser irradiation, corticotomy, and pulsed
electromagnetic fields. Long et al. included
nine studies in the final systematic review and
three were included in a meta-analysis for low-level
laser therapy. They concluded that low-level laser
therapy is safe, but not able to accelerate tooth
movement; corticotomies are safe and able to
accelerate tooth movement; and electrical current
and pulsed electromagnetic fields are effective in
accelerating orthodontic tooth movement.
A year later, we decided to use an objective
approach to appraise the need for an update of
Long et al. using the modified Ottawa method.
The modified Ottawa method has been shown
to be an effective tool in previous applications
in dentistry.6 The aim of this study was to assess the
current evidence on accelerated tooth movement
published since the last systematic review and
apply the principles from the modified Ottawa
method to determine if an update is needed.
Search strategy
A systematic search was first conducted for the
clinical question: which methods adjunct to
orthodontic treatment will accelerate orthodontic
tooth movement? Upon review of the search
results, the recent systematic review by Long et al.
was found to address the same clinical question.
Long et al. included search dates from January 1990
to August 2011 and was published in January 2013.
A literature search was performed on April 28,
2014 employing the same search strategy as Long
et al. The search terms and databases are
displayed in Table 1. For completeness, our
search was performed from January 2010 to
April 2014 utilizing the following databases:
Pubmed, Embase, CENTRAL, Web of Science,
and OpenSIGLE. Inclusion criteria were limited
to randomized control trials or quasi-randomized
control trials that evaluated or compared meth-
ods to accelerate orthodontic tooth movement.
Systematic reviews related to the topic of accel-
erated tooth movement were also included. After
primary selection, full-text articles were retrieved
and analyzed further for inclusion.
The modified Ottawa method
The modified Ottawa method was proposed to
assess whether an updated systematic review is
required. The method applies qualitative, quan-
titative, and “other” indicators to newly published
studies after the search date of the previous sys-
tematic review. A new systematic literature search
was employed to identify new studies assessing
interventions for accelerating orthodontic tooth
movement. If a previous meta-analysis was per-
formed then quantitative indicators were sought.
Quantitative indicators (B1 and B2) were eval-
uated, merging of new data with the original data
in a fixed-effects meta-analysis. If no previous
meta-analysis were performed then qualitative or
“other” indicators were sought. The appraisal of
these indicators was initiated after analysis of the
full-text articles. The types and description of
these indicators are shown in Table 2.
Literature search and data collection
The database search returned 992 articles and
after removal of duplicates, 533 citations were
included for provisional screening. Two authors
226
Table 2. Types of signals used to appraise new publications
Type of indicators (signals)
Qualitative Qualitative signals: studies without meta-
analysis—potentially invalidating changes in
evidence
Qualitative signals: studies without
meta-analysis—major changes in evidence
Quantitative Quantitative signals: studies with
meta-analysis
Other Other Signals
In order to demonstrate the need to update a systematic review on a given topic, the Ottawa method applies qualitative,
quantitative, and “other” indicators to newly published studies after the search date of the latest systematic review. The definitions
of these signals are summarized on the last column on the right.
scanned the titles and abstracts for the inclusion
criteria. A total of 14 articles were assessed in full-
text for eligibility in the final analysis. Sub-
sequently, eight articles were included in the
final analysis and six articles were not included
based on violations of the inclusion criteria
(Fig. 1). Articles were excluded due to not
qualifying for true randomized control trial or
quasi-randomized control trial.7–9 Three articles
were not included because they were already
included in the previous systematic review.10–12
Indicator results
The following types of interventions to accelerate
orthodontic tooth movement were analyzed in
the final review: electrical, photobiomodulation,
micro-osteoperforations, vibration, corticotomy,
and low-level laser therapy. Six articles were
analyzed for qualitative indicators A1–A7, a total
of two qualitative indicators were detected. One
article received indicator code A1 (opposing
findings13) and one received A3 (superior new
Rozen et al
Signal Operational definitions
code
A1 Opposing findings: a pivotal trial,1 meta-analysis, or
guidelines that opposed the findings from the original
review
A2 Substantial harm: a pivotal trial,1 meta-analysis, or guidelines
whose results called into question the use of the treatment
based on evidence of harm or that did not proscribe use
entirely but did potentially affect clinical decision making
A3 A superior new treatment: a pivotal trial, meta-analysis, or
guidelines whose results identified another treatment as
superior to the one evaluated in the original review, based
on efficacy or harm
A4 Important changes in effectiveness short of “opposing findings”
A5 Clinically important expansion of treatment
A6 Clinically important caveat
A7 Opposing findings from discordant meta-analysis or
nonpivotal trial
B1 A change in statistical significance (from nonsignificant to
significant)
B2 A change in relative effect size of at least 50%
n/a “Other” signals were sought for key questions for which
there was no prior meta-analyses or RCTs, for example,
questions for which only large cohort or case control studies
were identified
The criteria included a major increase in the number of new
studies or a new study with at least three times the number of
participants as in previous studies
treatment14). Two articles were analyzed for
quantitative indicators B1 (change in statistical
significance) and B2 (change in relative effect
size). The data from Long et al. on low-level laser
therapy was pooled with the new data in a
“random effects model.” The quantitative anal-
ysis revealed an increase in the total effect from
0.32 to 0.36 and the p value went from non-
significant (p o 0.08) in Long et al. to significant
(p o 0.008) when combined with the new data. A
signal code of B1 was subsequently applied to two
articles.15,16 Two articles received “other” sig-
nals.17,18 No further signals were identified from
the remaining articles.19,20 Signal summaries with
explanations can be found in Table 3.
Orthodontic impact
Several key findings were identified through our
systematic search and data analysis. The article on
electrical stimulation13 had greater than three times
the number of participants than the study included
in Long et al. and indicated an opposing outcome
 Accelerated tooth movement 227

Idenficaon
Records idenfied through Addional records idenfied
database searching through other sources
(n = 992) (n = 0)

Records aer duplicates removed

(n = 533)
Screening

Records screened Records excluded

(n = 533) (n = 519)
Eligibility

Full-text arcles assessed Full-text arcles excluded,

for eligibility with reasons
(n = 14) (n = 6)

Studies included in
qualitave synthesis
(n = 8)
Included

Studies included in
quantave synthesis
(meta-analysis)
(n = 2)

Figure 1. Flow chart of database search strategy. A total of 992 articles were identified after a systematic search and
533 articles were screened after removal of duplicates. Of those 14 articles were assessed for eligibility but only eight
articles were included in final analysis.

(indicator code A1, opposing findings), suggesting
potentially invalidating evidence from the review
performed by Long et al. One new method of accel-
erating tooth movement (micro-osteoperforations)
was not mentioned in Long et al. and was published
in a pivotal journal (signal code A3, superior new
treatment). The two major journals in orthodontics
the American Journal of Orthodontics and the
Journal of Clinical Orthodontics were considered
pivotal journals. Two new treatments identified on
the effect of vibration and photobiomodulation on
tooth movement were not reported in Long et al.
and received an “other” signal code. An article on
corticotomy and a systematic review on corticotomies
did not receive a signal code because it agreed with
the previous findings from Long et al. Change in
statistical significance (signal code B1) was found
when data was combined from Long et al. and new
data from the articles on low-level laser therapy. This
indicates that a new review would improve the
precision of the original review as demonstrated in
Fig. 2 and provide orthodontists with new evidence
on methods to accelerate tooth movement.
Discussion
The goal of this study was to determine if an
update was necessary for the recent systematic
review on methods used to accelerate tooth
movement. Employing the principles of the
modified Ottawa method, we have demonstrated
that an updated systematic review on accelerated
tooth movement is warranted. Systematic reviews
are constantly produced in orthodontic literature
with little emphasis on whether an update is
actually needed or how the requirement for an
update was derived. In this study we showed the
application of the modified Ottawa method
through a systematic search, data analysis,
and assignment of focused signal criteria. The
228 Rozen et al

Table 3. Overview of articles used in the Ottawa method analysis

Article Level of Type of intervention Explanation Signal
evidence

Falkensammer RCT Electrical Falkensammer et al. conducted an RCT with A1; opposing findings
et al.13 greater than 3
the number of participants
(n ¼ 26), found no significant difference in tooth
movement rate. In Long et al. detected a significant
difference indicating opposing findings
Kau et al.17 RCT Photobiomodulation No previous meta-analysis or RCT Other
Alikhani et al.14 Quasi-RCT Micro- A significant difference detected in the rate of A3; superior new
osteoperforations canine retraction, treatment group was 2.3
faster treatment, published
compared to control. Published in pivotal journal in pivotal journal
Miles et al.18 RCT Vibration No previous meta-analysis or RCT Other
Shoreibah RCT Corticotomy Results agreed with Long et al. No signal
et al.19
Hoogeveen Systematic Corticotomy Systematic review indicating similar conclusions No signal
et al.20 review to Long et al.
Doshi-Mehta RCT Low-level laser In Long et al., p ¼ 0.08. After pooling with B1; change in statistical
et al.15 therapy new data p ¼ 0.008 significance
Dominguez Quasi-RCT Low-level laser In Long et al., p¼ 0.08. After pooling with B1; change in statistical
et al.16 therapy new data p ¼ 0.008 significance

Table summarizes articles reviewed and includes type of study, intervention evaluated, and findings when qualitative, quantitative,
and “other” indicators were applied, with a brief explanation.

orthodontic community should consider inves-
ting a small amount of time to determine whether
a new update is needed prior to investing
countless hours into a review that would
not advance our understanding on important
topics.
The application of the modified Ottawa
method in evaluating new evidence on the effect
of different procedures to accelerate tooth
movement resulted in interesting and exciting
new findings. We found that the amount of lit-
erature produced on the topic during our search

Figure 2. Quantitative analysis of studies on the effect of low laser therapy in accelerating tooth movement. Meta-
analysis from the original systematic review displaying the pooled mean difference for low-level laser therapy vs.
control (A). Data from newly published studies on low-level laser therapy was combined with data from the original
systematic review, displaying the increased precision in results with the combined new data (B).
 Accelerated tooth movement 229

New York University Checklist:

Based on Modified Ottawa Method

Employ search methodology of previous systematic review

Primary selection: Scan Titles and Abstracts

Final selection: Full-text Analysis

Studies with meta analysis Studies without meta analysis

Quantitative signals: B1-B2

Qualitative signals: A1-A7
or
“Other Signals”
Perform meta-analysis1

Application of signals

Develop conclusion for update need analysis

Figure 3. Flow chart displaying the steps for the application of the modified Ottawa method. We created a
checklist to guide researchers on the application of this method to newly published studies after the search date of
the previous systematic review, to help determine need for an updated review. 1Obtained by pooling data extracted
from new trials with data from the original systematic review and performing a fixed-effects analysis meta-analysis.6

(4 years from January 1, 2010 to July 31, 2014)
produced as many papers as Long et al. identified
(11 years from January 1990 to August 2011) in a
much shorter time span. This indicates the
popularity of accelerated tooth movement in
recent years and the drive in our field to find ways
to shorten treatment duration. The Ottawa
method has shown that the studies produced
since 2011 have potentially invalidating evidence
and description of new methods. Furthermore,
our meta-analysis on low-level laser therapy
demonstrates that the combined new data
increases the precision of the results. These
collectively indicate the need for a new systematic
review on adjunct procedures to accelerate
orthodontic tooth movement.
Conclusion
The results of this study indicate that based on
the modified Ottawa method, there is a need for
an updated systematic review on accelerated
230 Rozen et al
tooth movement. These signals identified in this
study suggest an updated systematic review would
be beneficial in identifying new and superior
treatments and would increase the precision of
the previous meta-analysis. This method could be
applied to further investigations within the
orthodontic field. To assist in this endeavor we
have created a worksheet for orthodontic
researchers, residents, educators, and practi-
tioners (Fig. 3) to facilitate the application of the
modified Ottawa method to other important
questions in orthodontics.
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 Seminars in Orthodontics
Future Issues
Vol 21 No 4 (December 2015)
ADVANCES IN CBCT DIAGNOSTICS WITH ORTHODONTIC TREATMENT: INTERPRETATION AND MANIPULATION
Onur Kadioglu, DDS, MS, Guest Editor

Recent Issues
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JUVENILE IDIOPATHIC ARTHRITIS AND TEMPOROMANDIBULAR JOINT INVOLVEMENT: AN INTERDISCIPLINARY APPROACH
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INTERDISCIPLINARY MANAGEMENT OF THE ORTHODONTIC PATIENT
Pratik Kumar Sharma, BDS(Hons), MFDS, MSc, MOrth, FDSOrth, Guest Editor
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ALL ROADS LEAD TO ROME: NEW DIRECTIONS FOR CLASS II
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PERIODONTAL-ORTHODONTIC INTERACTIONS
Ramzi V. Abou-Arraj, DDS, MS, Guest Editor
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AGE-APPROPRIATE ORTHODONTIC TREATMENT, PART II
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Vol 19 No 2 (June 2013)
PROGRESSIVE CONDYLAR RESORPTION AND DENTOFACIAL DEFORMITIES
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INTERDISCIPLINARY TREATMENT OF ADOLESCENTS WITH MISSING ANTERIOR TEETH
Mark R. Yanosky, DMD, MS, Guest Editor
Vol 18 No 4 (December 2012)
UPDATES ON THE BIOLOGICAL FOUNDATIONS OF ORTHODONTIC TOOTH MOVEMENT
Vinod Krishnan, BDS, MDS, M Orth RCS D, PhD, and Ze’ev Davidovitch, DMD, Cert Ortho, Guest Editors
Vol 18 No 3 (September 2012)
AN OVERVIEW OF FACIAL ATTRACTIVENESS FOR ORTHODONTISTS
Margaret Collins, BDS, FDSRCPS, DOrth, MSc, MOrthRCS, MA, Guest Editor
Vol 18 No 2 (June 2012)
MAXILLARY EXPANSION AND MANDIBULAR WIDENING: TREATMENT METHODS AND STABILITY
Haluk İ şeri, DDS, PhD, Guest Editor
Vol 18 No 1 (March 2012)
FUNCTION AND DYSFUNCTION OF THE TEMPOROMANDIBULAR JOINT
Rakesh Koul, MDS (Orthodontics), Guest Editor
Vol 17 No 4 (December 2011)
PRACTICE MANAGEMENT AND MARKETING
Peter M. Sinclair, DDS, MSD, and Ellen M. Grady, BA, Guest Editors