AN OVERVIEW OF THE ROLE OF DRUGS AND

SYSTEMIC FACTORS ON ORTHODONTIC

TOOTH MOVEMENT
Authors:
Dr. Pankaj Juneja B.D.S. (M.D.S.)

,
Dr. Pllnkaj Juneja

Postgradu ate student,

Department of Orthodontics and Dentofacial Orthopedi cs,
Co ll ege of Dental Sciences,
Davangere, Karnataka.
Email : drpankaL1 23 denti st@yahoo.com
Phone: +91- 9964143808

Dr. G. Shivaprakash B.D.S., M.D.S.

Professor and Head,
Department of Orthodonti cs and Dentofacial O rthopedics,
College of Dental Sciences,
Dava ngere, Karn ataka.
Email : drshiva64 @gmail.com
Phone: +9 1- 9844041 620

Dr. Prabhuraj B. Kambalyal B.D.S., M.D.S.

Dr. Pra bhuraj

B. Kambalya l

Abstract

Assoc iate Professor,

Department of Orthodontics and Dentofacia l Orthopedics,
College of Dental Sc iences,
Davangere, Karnataka.
Email : prabhurajkambalya l@yahoo.com
Phone: +9 1- 944811 03 94

The specialty of Orthodontics is based on the fact that it is poSSible, by applying appropriate
forces, to move the teeth through the alveolar bone of the jaws. Orthodontic tooth movement
and the concomitant bone remodeling process are dependent on various local and systemic
factors like age, nutrition, consumption of drugs etc. Orthodontic patients may be affected by
systemic diseases that might need treatment with drugs that could possibly affect bone
metabolism.Patients undergOing orthodontic treatment can experience significant levels of pain .
Analgesics are commonly recommended for the control of such orthodontic pain .
This article reviews all the existing published biomedical literature on the effects of some
commonly used drugs by the patients for the relief of orthodontic pain and treatment of systemic
conditions known to affect the bone tissue and thereby influencing the rate of orthodontic tooth
movement. An attempt has been made to propose a complete picture and orient the reader for
the better understanding of some commonly used pharmaceutical products.
This is considered essential in order for the orthodontist to take into account all factors related to
the therapy and to select the best therapeutic strategy in every individual patient keeping the
mechanics as simple as possible.

Key Words

orthodontics, force, drugs, systemic, tooth movement.

36

,.

_=!n~
INTRODUCTION:

select the best therapeutic strategy in every indi vidual

patient keeping the mechanics as simp le as possible.

The aim of orthodontic trea tment in the movement of

teeth through bone is to obtain a more perfect dental
occl usion. Orthodonti c tooth movement has been
defi ned by Proffit ' as the result of a biologi ca l response
to interference in the physiologica l equilibrium in the
dentofacial complex by an externall y appli ed fo rce.

An Overview of biological basis of

orthodontic tooth movement :
In a recent review on the current concepts in the biology
of orthodonti c tooth movement Richard and Malcolm'
said th at five micro-enviro nments are altered by
O rth odo nti c for ce - ex tr ace llul ar m atri x, ce ll
membrane, cytoskeleton, nucl ea r protein matri x and
genome. Cel l membrane receptor li gand docking is an
important initi ator of signal transdu cti o n and a
discovery target for new bone enhancing drugs. Despite
progress is identifi ca tion of regul atory molecules, the
genetic mechanism of "orchestrated synthesis" between
different cell s, tissues and systems remain largely
unknown.

Nowadays, attenti on is mainly focused on the relation

of orthodonti c tooth movement to the applied force.
The contro l of pain during orthodontic treatment is of
interest to both clinicia n and pati ents. Prescription and
ove r th e co unt er ana lges ics are co mm on ly
recommended for o rth odo nti c pain. Interestingly,
despi te cli nica l evidence that pati ents experi ence pain
after orth odonti c procedures, there have been few
controlled studies that address the use of analgesics to
contro l post appointment orthodontic pain.

Ei cosa noids/A ut oco id s are bi o logical l y ac tive

derivatives of 20 ca rbon atom Polyunsaturated fatty
acids (PUFA) that are released from cell membrane
phospholipids. There are two major lipid derived
autocoids :

The objective of this review is to discuss current data

concern ing the mechani sm of action and effects of
some common ly used pharmaceutica l products and
systemic fa ctors kn own to affect bone ti ssue and thereby
influ enc ing the rat e o f tooth movement. This is
considered essentia l in order for the orthodonti st to take
into account all factors related to the therapy and to

1) Prostaglandins (PG's), and

2) Leucotrienes (LT's)

Membrane phospholipid

Phospholipase A

Arachidonic Acid

Lipo-oxygenase

..
12 HPETE

PGG,
PGH,

PGE,

PGD,

~
L TA,

..

L TB,

Prostacycl i n
synthase

5 HPETE-5 HETE

12 HPETE

I .

Thromboxane
synthase

Isomerase

Chemical or
mechanical st imuli

-------,~

Cyclo-oxygenase

LTC,

LTD,

TXA,

PGL

LTE,

TXB,

6 KetoPGF,..

LTF,

PGF,.
Biosynthesis of PG 's and LT's'
37

Cyclooxygenase is known to exist in two isoforms CoxI and Cox-2 . While both isoforms catalyses the same
reactions, cox-1 is constitu ti ve enzyme in most cells.
O n the other hand cox-2 is normall y present in
insignifi cant amou nts but is inducible by cytokines,
grow th fa c tor s and o th er sti mul i during the
inil ammatory response. It is believed that eicosa noids
produced by cox- 1, participate in physiological (house
keeping) fun ction such as secretion of mucous for
protection of gastri c mucosa etc. while those produced
by cox-2 lead to inflammatory and other pathological
changes.

in the alveolar bone. Force application disrupts the

equilibrium that ex ists between bone formation on the
pressure side and more bone form ation than resorpti on
on tension side. Resorption of bone by osteoclasts is
c o upl ed with subsequ ent bon e formation by
osteobl asts. Loca l and systemic fa ctors' (Table I )
including cytokin es, hormo nes, growth factors and
mechanica l stimulation activate osteoblasts to produce
the receptor activator of NF-a~ ligand (RANKL) which
is vital for osteoclasts differentiation and activit y.
RANKL is expressed on the surface of osteoblastic cell s
and bone marrow stromal cell s and binds to the RANK
receptor on the surface of osteoclastic precursors,
thereby stimulating the differentiation and activation
of osteoclasts.

Tooth movement during orthodontic treatment requires

remodeling of periodontal ligament tissues, especia ll y

Table I
Faclors affecling bone remodeling process
Hormones and systemic faclors

PTH
Ca lcitosi n
Insulin
Growth hormone
Vitamin 0
Glucocorti coids
Sex steroids
Thyroid hormones

TGF~

Fibroblast growth factor

Platelet derived growth factor

IL-1,4,6, 11, 13, 18

TN F
Osteoclast differentiating factor
Interferon y
Osteoprotegrin

M-CSF
G-CSF
GM-CSF

Prostaglandins
Leukotri enes
Nitric ox ide

Growth factors

Insulin like GF I and II

Cytokines

Colony stimulating factors

Others

It is now clear that O TM is influenced both by drug

Intracellular secondary messengers play an important

role in the differentiation of osteoclasts from monocytes
in b o ne resorption during force app li catio n .
Davidovitch et ai' measured cGMP and cAMP levels
in the alveolar bone of cats under orthodontic treatment
and reported that Ca" , cGM P and cAMP acts as a key
mediators or seconda ry messengers in the function of
many drugs and hormones.

and the systemi c factors. An attempt has been made to

review the past and present literature published in
various articl es in different journals on the factors that
tend to influence the OTM, and same wi ll be discussed
as presented in Tab le II and Table III.

38

Table II
Effec ts of drugs on tooth movement
Effects on bone tissue

Drug
1)

NSAIDS
Aspirin
Aceta minophen
Ibuprofen
Rofecox ib
Valdecoxib
Celecoxib

Ecosanoids I Au tocoids
Prostaglandins

2)

3)

Decreased bone
resorption

Increased bone
resorption

Effects on tooth

Mechanism of

movement

action

- Inhibition of
cyclooxygenase
enzyme.

Decreased rate of
tooth movement

Increased rate of
tooth movement

Leukotrienes

Bishosphonates

Decreased bone
resorption

Increases cAMP and

cGMP levels.

Activates osteoclasts.

Decreased rate of
tooth movement

Decreases root

Increases bone
mineral density

Decreased rate of
tooth movement.

Increases bone
mass/density

Increa sed rate of

Inhibit osteoblastic
function.
Decreases bone
Formation.

resorption

4)

Fluorides

Inhibit bone
turnover.

Increased bone mass

and mineral denSity
Decreased bone
resorpti on

I ncreased bone
resorption

Decreased bone
formati on

Greater potentia l for

relapse as movement
is less stable.

Epidermal growth factor

(EGF)

Increased bone
resorption

Increased rate of
tooth movement.

Osteoprotegrin gene
transfer

Decreased bone
resorption

Decreased rate of

Inhibits RANKL
mediated
osteoclastogenesis.

8)

Echistatin (RGD peptide)

Decresed bone
resorpti on

Decreased rate of
tooth movement

Inhibits Integrin
receptors.

9)

Tezosentan

Increased bone
resorpti on

Increased rate of
tooth movement

Enhances bone
resorpti on via ETA
receptors.

5)

6)
7)

Corti costeroids

tooth movement

Enhances osteoclats
recruitment.

tooth moveme nt

Table III
Effects of systemic factors on tooth movement
Effects on bone tissue

H ormo ne

Effects on tooth movement

Mechanism of action

1)

Estrogen

Decreased bone resorpti on

Decreased rate of tooth movement

2)
3)

Androgen

- Decreased bone resorption

- Enhances DNA transcription.

- Increased bone resorpti on

Decreased rate of tooth movement.

Vitamin D

Increased rate of tooth movement.

- Acti va tes DNA and RNA

Enhances reestabli shment of

supporti ng tissues

Inhibits cy tokine involved in

bone resorpti on.

w ithin target cell s.

4)

Thyroid

Increased rate of bone

remodeling

5)

Parathyroid

Increased rate of bone

resorpti on

- Increased rate of tooth movemen t.

Increased rate of tooth movement

Decreases root resorption

39

Activates a spec ific DNA

sequence ca lled Thyroid
hormone response element.

- Increases cAMP formation and

intracellular Ca in ta rget cells

1. EFFECT OF DRUGS ON TOOTH

MOVEMENT;

bone resorption process. O ne approach to dea l with

thi s is the use of selecti ve cox-2 inh ibitors, also cal led
as cox ibs, which are replacing conventiona l NSAIO's,
In compari son to NSAIO's, Cox-2 inhibitors have longer
dose interva ls, different side effect profile, similar onset
of action and similar analgesic effect.

NSAID'S:
All drugs gro uped in this class have analgesic ,
antipyreti c and anti -i nflammatory actions in different
mea sures. They are also ca ll ed no n narcoti c, non
opioi d, or aspiri n li ke analgesics . They act primaril y
on periph eral pain mechanisms but also in CNS to raise
pain threshold, by inhibition of cyclo-oxygenase, w hich
modulates the transforma ti on of PG's from arachidonic
acid in the cellular plasma membrane.

Sari et al" showed that the inhibition effect of aspirin

on PGE, was more than that of Rofecoxib, In another
study Young et al " concl uded th at va ldecoxib may be
a better approac h to prevent discomfort of initi al
archwire placement. In a previous study by Carl os et
al " found no substanti al adva ntage in using a selective
cox-2 inhibitor co mpared wi th non specific cox
inhibitors. But in a recent study Ca rl os et al' evaluated
orthodontic tooth movement after different coxib
therapies and concluded that celecoxib and parecox ib,
but not rofecoxib, seem appropri ate for discomfort and
pain relief while avo iding interference during tooth
movement.

They are the most common group of medica ti ons used

in orth odontics for relief of pai n.b" . Numerous studi es
eva luated the pain reducing effects of va riou s NSAIO's.
Then drugs have become the focus of recent research
in orthodontics.
Amongst the earli est studies ca rri ed out Chumbley et
ai" eva luated the effect of indomethacin (an aspirin like
drug) and recommended that aspirin like drugs not to
be admi ni stered to patients undergoing orthodontic
treatmen t as it may extend the treatment time. W alker
et al '" eva luated the impairment of O.T.M. ca used by
NSAIO's and results showed that th ey ca n impair O,T.M
and until long term human data are obtain ed ,
acetam inophen remains an appropriate altern ative to
NSAIO's. Similar results were found by Arias et al"
who compared aspirin, acetaminophen and ibuprofen
and found that acetaminophen did not affect OTM,
Even Roche et al" concluded that acetaminophen has
no effect on rate of O TM, Kehoe et al" also suggested
acetaminophen as the analgesic of cho ice for minor
di scomiort associated w ith orthodonti c treatment. But
in a recen t contrasting stud y Brad ley et al" compared
Ibuprofen and paracetamol for the con trol of pain and
iOlll1d that pre-operative and post-operati ve Ibuprofen
to be more effecti ve than paracetamol. In another study
by Polat et al1' , Naproxem sodium was found to have
lower levels of pa in than patients taking ibuprofen,

Gameiro et al" eva lauted the effects of short and long

term celecoxi b on orthodontic tooth movement and
concluded that although celecox ib administration did
not affect the number of osteoclasts, the osteoclasts
activity might be reduced, w hi ch could explain the
inhibition of tooth movement observed,
However the effect of th ese drugs on ort hodontic root
resorption is not well understood. Gameiro et al" did
histologi ca l analysis of orthodontic root resorpti on
treated with celecoxib and found that short and long
term celecox ib did not suppress the root resorption,
Therefore, it is recommended th at patients undergoing
orthodontic treatment should be advised not to take
these over the counter drugs w ithout the dentist' s prior
knowledge,

EICOSANOIDS / AUTOCOIDS :
Prostaglandins:
Arachidonic acid is metaboli zed by cyclooxygena se
resulting in prostaglandin production ." Experiments
have show n that PG' s are an important medi ators of
mechani ca l stress during OTM,

Moreover the use of over the counter drugs have also

shown abe rr ant remodeling of th e periodontal
vasculature affecting the tooth movement, Kyrkanides
et al '" investigated the effects of indometh ac in on
co ll age nase acti vity and proco ll age n sy nth esis.
Cyclooxygenase inhibit ion resulted in exacerbation of
IL-l beta mediated collagenase B (MMP-9l producti on
and acti vity, as well as alterati on oftype IV procollagen
synt hesis levels by endotheli al cells in vi tro.

Nga n et al" observed that PG 's cause hyperalgesia by

facilitating pai n stimulu s and increasing the effects of
hi sta mine and bradykinin , Chao et al" observed that
PGE , injection increased the number of osteoclasts in
pdl membrane. Oavidovitch et ai' demonstrated in vitro
direct effect of PG's on bone resorption along with
increase in cAMP and cGMP levels. Sandy et al" fou nd
that inhibition of PG synthes is by flurbiprofen, a PG
inh ibitor, showed inhibition of osteoclast activity and
bone resorption. In another study by Gurton et al"
found that PGI, and TXA, analogs increase the number

The studies mentioned above showed that NSAIO's

effecti vely reduce the pain and discomfort caused by
orthodontic tooth movement but th ese drugs may also
aiiect the sequence of tooth movement by inhibiting
or at least by reducing the associated inflammatory and

40

Sato Y et al 15 did a study to clarify th e effects of

Bi sph osphonate administration o n stru c ture and
function of osteoclasts in alveolar bone resorption
during experim ental tooth movement and found that
BP Signifi ca nt ly impair th e osteoclast structure and
reduces express ion of both vacuo lar type H(+) ATPase
and ca thepsin K in osteoclasts during tooth movement.
Liu et al'6 also suggested th e inhibitory effect of
clodronate on tooth movement and osteoclasts ma y
b e due to inhibition of cox-2 d epe nd ent PGE ,
production and RANKL expression in pdl cell s.

of multinuclea r osteoclasts, osteoclastic bone resorption

and rate of OTM. Si mil ar results were also shown by
Yamasaki et al. "
Studi es were also conducted in order to eva luate the
effect of PG's on root resorption. Leiker et al" found
that the amount o f root resorption did increase w ith
th e use of PG inj ec tion s, spec ifi ca ll y PGE, . In a
contrasting study by Boekenoogen et al '" conc l uded
that PGE, appea red to have no effect on the number or
depth of resorption lacunae. In a simi lar stud y Brudvick
et al " found no significa nt difference in root resorption
but trend towards more root resorption was seen on
teeth w here PGE, inj ecti on had been perform ed . In a
recent stud y Seifi et al" showed the importance of Ca"
ions worki ng in association wi th PGE, in stabili zi ng root
resorption w hil e signifi ca ntl y increased OTM .

Root resorption associated with tooth movement in an

un so lved probl em in orthodontics. If suc h root
resorption could be prevented, it would be an important
co ntribution to wa rd s redu ci n g risk factors in
orthodonti c treatment. The use of BP to reduce the
amount of inflammator y root reso rp tion has been
investigated and were found to be effecti ve in thi s
regard.

Leuco tr ienes :
Th ey are also metabolites of arac hid o ni c ac id ,
produced by lipo-oxygenase enzymes" They are also
important medi ators of OTM. Their rol e in OTM is
clearly demon strated when inhibitors of leucotrienes
are used in different experim ents.

Liu et al 37 found that local clodronate inhibited root

resorption incident to tooth movement and suggested
it to be a usefu l therapeuti c adjunct in orthodontic
tre atme n t. Igarashi et al " eva lu ated topi ca l
administration of residronate on roo t resorption and
found that it did not appea r to inhibit the repair process
of roo t resorption .

It is a well known observation that inhibition of one

pathway of arachidonic ac id will shunt the effect into
an increase in the conversion via the other pathway .
Mohammed et al]) inves tigated rol e of a LT inhibitor
AA861 in OTM and found that it ca used signifi ca nt
LTB, inhibition and simultaneous increase in PGE,
production, suggesting LT role in medi ating OTM.
However inspite of - PG levels, a selective inhibiti on
of LT synthes is ca used a Signifi ca nt reduction in tooth

The clinical utility of Bi sphosphonates resides in their

ability to inhibit bone resorpti on. In Orthodontics,
undes irable movement of anchor teet h during tooth
movement and rela pse of moved teeth after treatment
are the main ca use of unsuccessful results. If these tooth
movements could be prevented with pharm acologica l
agents, a less complex orthodontic force system and
less extensive retention wou ld be required.

movement.
Consequ entl y leu cot ri ene inhibitors ca n d el ay
orthodont ic trea tm ent, whereas leuco tri enes and
prostaglandins ca n have future appli ca tions that could
result in enhanced tooth movement. 11

Iga rash i et al" eva luated the anchorage and retentive

effects of a BP (AHBuBP) on tooth movement in rats
and concluded that it could be useful in enhanci ng
anchorage or retaining teeth . Kim et al'" eva luated the
effect of Bisphosphonate administratio n on osteoclastic
bon e resorpti on during relapse and found th at it
decrease the extent of initi al relapse via mechani sm
invol ving impai rm ent of the structure and resorption
functions of osteoclasts.

BISPHOSPHONATES:
Th e ph arm aco logic age nt bisphosphonates are
analogues of pyroph osphate. Recentl y" they have
received mu c h a tt enti o n in d ent a l l it era ture.
Bisphosphonates in oral or IV forms are used to that
va ri ous diseases suc h as certain ca ncer, bone and
cal c ium related disorders, osteoporosis e tc.
Bisphosphonate inhibit bone turnover and res ult in
increased bone mineral densi ty. The most serious side
effect o f Bisphosphonate treatment is osteonecrosis of
the mandib le or the maxilla represented by exposed
non hea li ng bone. O ther related comp lications include
dec reased bone h ea ling and an inhibition of
orthodontic tooth movement.

In another stud y by Adachi et al", found that the top ica l

admini stration of resid ro nate ma y be helpful in
an c horing and retai ning teeth under orth odo nti c
treatment.
Therefore it is imperative that Bisphosphonate medica l
screening, pat ient counseling, informed con cent, and
changes in treatment planning shou ld be considered
for every pati ent by the orthodontist."
41

FLOURIDE:

Because acute corticosteroid ingestion reduces bone

turnover, in these patients orthodonti c treatment might
best be postponed until a time the patient is free of the
drug. 50 Chronic stero id ingestion leads to an increased
bi o log ica l reac ti o n to mec hani ca l perturbat io n
indica ting that the Orthodonti c force level should be
reduced and controlled more frequently in patients on
chronic steroid treatment. 50 Moreover specific attention
must be paid to the retention protocol as the tooth
movement is less stable. As a consequence, carefu l
mo nitor ing of pati ents undergoi ng cort icos tero id
treatment is suggested .

The effect of flu oride on bone metabolism has been

well reported in the medica l fi eld, because it has been
used as a drug by itself or as an adjunct in the treatment
of osteoporosis. Fluoride treatment results in an increase
in bone mass beca use of the stimul ati on of bo ne
form ation .
Hell sing et al" eva luated the effect of flu oride on OTM
and found that the veloc ity of TM is influenced by
hormones as well as trace elements. In another study
use of F' as a vari able was found to increase the mea n
osteocalcin concentration" (a bone protein that has
been used to mark bone turnover). Foom et al"
eva luated the effect of systemic F' in take o n root
reso rpt ion and fo un d that F' redu ces th e size of
resorption craters, but the effect is va riable.

MISCELLANEOUS:
1)

Epidermal growth factor :

Recently the use of epidermal growth factor (EG F) to

develop a suitable environment and stimulate selective
d ifferentiation and proli feration has been proposed . It
has also been suggested that it may be involved in
responses of osteobl asti c cell li ves to mechanica l
stimuli. Saddi et al" found that loca l admini stration of
EGF located w ith in liposomes had an additive effect
on the rate of osteoclasts recruitment, produci ng faster
bone resorption and tooth movement.

The clin ical util ity of F' agents incl udes cari es preventive
treatment protocols such as fo llowing oral prophylax is,
proxima l strippi ng/ sli ci ng etc . may in crease the
orthodont ic treatment time due to its anabo lic effects
on bone, as fl uoride increase both bone mass and
density.

Biological agents - Relaxin:

CORTICOSTEROIDS:

2)

Orthodontic pat ients may be affected by systemi c

diseases that might need treatment w ith drugs that could
po ss ibly affec t bo ne metabo li sm. Sy nth et i c
corticosteroids have been used in therapeutic regimens
for the treatment of a w ide variety of ailments ranging
from arthri tis to renal, collagen, allergic and neopl astic
diseases. Supra-phys iologic doses of these drugs w hen
administered induce the sa me osteoporosis fo und in
naturall y occ urr i ng statu s of hypercorti so li sm."
Co rti c ost ero id s inh ib it osteobl as ti c fun cti o n by
mediating its effects on osteoblast and its precursors
resulting in decreased bone formation. The latter may
be due to elevated PTH leve ls ca used by direct
inhibition of Cal< absorpti on by the steroi ds. End result
being increase in bone resorption. Aschroft et al" found
th at rabbi ts subjected to cor ti cos tero ids indu ced
os teoporosis un derwent more rapid O .T.M and
subsequent relapse. M avraga ni et al" found that low
dose doxyc yl ine may have an inhibitory effect o n
orthodont ica lly induced resorptive activity.

Using biologica l agents to modify the rate of tooth

movement have been shown to be effecti ve in animals.
Relaxin main action is to increase the turnover of fib rous
connecti ve ti ssue. M ada n et al" eva luated effect of
human relax in on OTM and found that it does not
acce lerate O TM , it ca n redu ce th e leve l of Pdl
orga ni za tion and mechanica l strength and increase
tooth mobility at ea rl y time peri ods.
3)

Osteoprotegrin gene transfer:

It has been reported that osteocl astogenesis is primarily

acti va ted by the receptor acti va tor of nuclear factor
Ka pp a b li ga nd (RAN KL) and i n hi bi ted by
osteoprotegrin (OPG). Pdl cell s w hich ex ists between
teeth and alveo lar bone, induce osteoclastogenes is in
vitro th rough the up regulati on of RANKL expression
via PGE, synthesis w hen subj ected to mec han ical
compress ive force.
Kanzaki et al" fo und significa ntly d imin ished tooth
movement on loca l O PG gene transfer to pd l ti ssue as
it inhibited RAN KL mediated osteoclastogensis and
inhibited experimental tooth movement.

In a recent study Verna et al" investi gated the effect of

ac ute and c hro n ic cor ti cos tero id trea tm ent o n
orthodont ica ll y induced root resorpti on and fo und
more root resorption in acute group. When compared
to chronic group and suggested that it may be due to
lack of ba lance between blastic and clastic acti viti es
during initia l phase of drug admini stration.

4) Echistatin and RGD peptide :

Recentl y a stud y done o n effect of ec hi statin, an
Arginine-glyci ne-aspartic aci d peptide by Dolce C et
al" showed that ELVAX loaded w ith RGD peptide
w hi ch was surgica ll y impl anted next to max illary

42

mo lars inhibited O TM. The RG D peptide also redu ced

mo lar drifts, therefore it shows the feas ibility of using
them to deliver integrin inhibitors adjacent to teeth to
limit loca l tooth movement in response to orthodo nti c
force.

th y roxine in rats has been shown to increase bo ne

resorption , in contrast to low dose admini strati o n,
w hich was fo und to reduce peri ostea l resorpti o n."
Po umpro s et a l " al so found th at th y rox in e
administratio n seems to lower the frequency of root
resorpti on in rats. Shi raz i et alb' eva luated the effect of
th y rOid horm o ne o n OTM in rats and fo und th at
admini stratio n o f 20/mym/kg i.p . I day L-thyrox ine
Significa ntl y increased the amount of O TM and the
ex tent of root resorpti o n decreased w ith th yro xine
administration.

In another recent study Talic et al" evaluated the effect

of echistatin on orth odontica lly induced root resorpti on
and concluded that targeting av~3 integrin receptor
expressed by odo ntocl asts ca n be effecti ve in reducing
root resorpti on during tooth movement.
5) Endothelin Antagonist: Tezosentan

Endothelin is a cytokine peptide present in the pdl in

physio logica l condit ions. Its concentratio n in the pdl
doubl es after 3 hors of ax ial loading of a tooth .

PTH is secreted by parath yrOid glands, regul ated by

pl asma Ca" concentration; there is no trophi c hormone
for it. The PTH recepto r is a G protein coupled receptor
w hi ch on acti va tion increases cAMP formatio n and
intracellular Ca" in target cells. In bo ne the target cells
appears to be the osteoblasts beca use PTH receptors
are not expressed o n the surface of osteoclasts. It has
been proposed that PTH-osteoblast complex some how
inc reases the acti vity of osteocl asts as well as the birth
rate of bone remod eling units in w hi ch osteoclasts
precursors are recruited.

In a recent study by Sproga r et al", eva luated the effects

of TBC 32 14, a se lecti ve endothelin ETA receptor
antagonist on OTM in rats and found that H , is involved
in OTM probabl y by enhanci ng bo ne resorptio n via
ETA receptors . In another study Drevensek M et al57
fo und that Tezosentan, an e ndo thelin antagoni st,
enhanced o rthodonti c tooth movement in rats.

EFFECT OF SYSTEMIC FACTORS ON

ORTHODONTIC TOOTH MOVEMENT:

Experim ents have shown that PTH ca n induce bone

resorpti on that w ould increase the rate of OTM. So ma
et al""" eva luated th e effect of loca l and chro ni c
appl ica tion of PTH on tooth movement and found that
loca l inj ectio n of PTH in a slow release formul atio n is
appli cabl e to orthod ontic therapy.

THYROID AND PARATHYROID HORMONE:

The movement of teeth during orth odo nti c trea tment
requires bo n e rem o d e lin g. Th e ro le o f bo ne
metabo lism, however, in contro lling tooth movement
have been considered secondary to the force applied.
This is largely a result of the difficulty in altering bone
metabo li sm systemi ca ll y, in addition to the fac t that
th e for ce is th e most ea sil y manipul ated fac tor .
Co nsequently, several pa pers have focused o n the
changes in bo ne remodeling in relation to the applied
force. In additi on to applied force, tooth movement
seems to depend o n ca lcium metaboli sm is alveolar
bone.

It is suggested that th yroid and parath yro id fun ction is

an important clini ca l factor in patients undergoing
orthodo nti c trea tm ent. Orth odo nti st should take a
thorough history of the patients to determin e w hether
they are on any hormonal supp lementa ti on drugs as it
might adversely affect the treatment. A dmini stration of
th y rox in e ca n be co nsid ered in so m e pati ent s,
especiall y in those who show beginning root resorption,
or those who have low th yroid fun ctio n.

A stud y by Midgetts" et al indi cated that animals w ith

hyperparath yroidi sm had signifi ca ntl y decreased bo ne
density, as well as increased bone remodeling changes.
Engstrom et al" demonstrated that although the level
of PTH in serum pl ays an important rol e in th e
regulatio n of the resorptive acti v ity in bone, a change
in serum ca lci um level is determining fac tor fo r root
resorption . This indi ca tes that fo rce- indu ced root
resorption is dependent o n more than o ne endocrine
system.

VITAMIN D:
Vitamin D is the co llecti ve name given to anti rachiti c
substances synthes ized in the body and fou nd in foods
acti va ted by UV radi atio n. The ro le of Vit. D in the
maintenance of Ca homeostasis in human bei ngs has
been well documented. It is a steroid hormone Ihat
has spec ific receptors in many target o rga ns and ti ssues.
It exerts its actions by activating DNA and RNA w ithin
the target cell to produce proteins and enzymes that
ca n be used in bone resorption process. In parti cul ar,
the acti ve form of Vi t. O, 1,25 dihydroxy choleca lcifero l
is the most potent stimulu s of osteoclasti c acti vi ty
known. It is also involved in the formati on of osteoclasts
from precursor mo nocytes .

In addition to parath yroid hormo ne, bone resorpti ve

acti vity is also regul ated by L th yroxine. Patient w ith
untrea ted hyp erth yro id is m sh ow in creased b o ne
reso rpti o n .'" Th e admini strati o n of hi gh dose o f
43

Calcitriol enhances resorption of calcium and

phosphate from bone by promoting recru itment and
differentiation of osteoclast prec ursors in bon e
remodeling un its. but mature osteoclasts lack Vit.D
receptor. Though osteoblastic cells express ViI. 0
receptor and respond to it. calcitriol appears to help
bone mineral ization indirect ly by maintai ning norm al
plasma calc ium and phosphate concentra tion. Its action
is independent of but fac ilitated by PTH.

are more fema le patients tha n male patients. Also there

is an increase in the number of adult female patients
seeking orthodontic treatment worldw ide. Orthodontist
shou ld pay specia l attenti on and should take this fac tor
into cons ideration as then drugs have shown to reduce
the velocity of O.T.M by inh ibiting bone resorption.

ANDROGENS:
Androgens are the sub stan ces which cause
development of secondary sex characters in the
castrated men. Anabol ic steroids are used by the
at hletes during th e period of training w hich are
supposed to hav e high er anabolic and lo w er
androgeni c acti vity. As then drugs also inhibit bone
resorption, it may affect the duration of the orthodontic
treatment. Therefore a thorough history regard ing the
use of such drugs should be taken from the adult males.

Collins et al"" found on histologic levels an increase in

the number of mononuclear osteoclasts recruitment and
activation result ing in bone resorption on pressure side
upon injection of Vit.D metaboli te 1.2 50 into Pd !.
Yamamoto et al' found that injections of 1,25fOH),D,
did not change serum Ca, PO, and ALPase activity and
there were no apparent cli nica l or microscop ic sideeffects. Nevertheless Vit. 0 (1 ,2S(OH),D,l enhances
the re-establ ishment of supporting tissues, especially
alveolar bone of teeth, after orthodontic treatmenl.'"

CONCLUSION:
Since orthodon tist plays a pivotal role in cl inical
pharmacology in the dental practice, they should have
an understanding of the fundamentals of drug therapy.
Orthodontist should be able to converse with patients
about medi ca tions prescr ibed for them, includ ing
rev iewing potentia l adverse effects, drug interact ions .
and how to take the med ication . A thorough medica l
history should be reviewed with the patient, including
any prescription, and over the counter products. as
many patients use drugs on dail y basis wh ich have
therapeutic as well as adverse effects.

ESTORGEN :
It has become increasingly evi dent hat estrogen is the
most important hormone to affect bone metabolism in
women. The various cytokin es invo lved in bone
reso rpt i o n are inhibited by est rogen . Since
mechanically induced bone modeling and remodel ing
are essential for orthodontic tooth movement. the
response to orthodontic force may va ry depending
upon the phase of menstrual cycle.
ZhaoQ et al" explored the iniluence ofOTM on estrous
cycle and estrogen and found that estrou s was the
appropria te time for orthodont ic force. In another study
j in Z et al '" suggested that estrogen promoted the
alveolar bone forming and inh ibited bone resorption.
Haruya man et al " also concluded that cycl ic changes
in the estrad iol level may be associated with the estrous
cycle dependent va ri ation in tooth movement through
its effect on bone resorption.

Drugs like NSAID 's, Bi sphosphona tes, vitam in 0

metabolites, fluor ides can decrease the velocity of tooth
movement. On the contrary drugs and systemic fa ctors
l ike eicosano i ds, cor ti coste roids. th yroid and
parathyroid hormones can increase the veloci ty of tooth
movemenl. Orthodontist should be awa re of such
medications so that treatment pl an best suited for the
individual pati ent could be made and keep ing the
mec han ics as simple as possible.

Osteoporosis is commonly seen in the postmenopausal

women due to the defi ciency of estrogen. In order to
evalua te the two most co mmonly used drugs for
osteoporosis Wagle et al " determined the effects of
FOSAMAX and EVISTA on OTM . Fosamax
(alendronate) and Evi sta (ralaxifenel showed evidence
of preventing bone resorption. Alendronate inh ib its
orthodontic activity but not osteoclast recrui tment.
w hi le ralox ifene regulates osteoclastic act ivity by
binding and modu lating estrogen receptors to affect
osteoclast number and acti vity. The author concluded
that orthodo nti c treatment may be contraindi ca ted
when taking these drugs.

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47

REVIEWS
(Compiled by Dr. Sridevi Padmanabhan)

Near-end of Treatment Panoromic Radiogrph

in the Assessment of Mesiodistal Root
Angulation

7.5 of torsion and at 15 for the passive self- ligati ng

brackets. The torqu e expressi on was higher for the
active self-li gating brackets at cl inica lly usa ble torsio n
angles (0-35). The pass ive self-ligating brackets started
produci ng moments at high torsion that cannot be used
clini ca lly.

Ann Marie Owens; Ama Johal, Angle Orthodontist,

Vol. 78, No.3, 2008.

Thus the cl inica lly applicable range of torque acti vation

and torque control was greater for the acti ve self- ligating
brackets.

This study aimed to test the hypothes is that there is no

difference between the mesiodistal root angulation and
the mesiodistal root angul ation as measured on the
panoramic radiograph . Thi s was eva luated using a
typodont dentition set into Class I occl usio n.

Botulinum toxin type A (Botox) for the

neuromuscular correction of excessive
gingival display on smiling (gummy smile)

Wire strust were pl aced on the bucca l surface of each

tooth to represent their long axes and the each the
denti tion was fixed into a natural skull for imaging.
The radiographic and true mesio-di stal angul ati on of
eac h too th to th e horizontal reference pl ane was
meas ured . Th e measurements were repeated after
alteri ng the mes iodistal root pos itions to a more mesia l
and more di stal positi on.

Introduction: Prev io usly, botulinum tox in type A

(BTX-A) (Botox; All ergan, Irvine, Ca li f) was shown to
be effecti ve in reducing excess ive gingiva l di spl ay in 5
pati ents with gummy smiles. This study was conducted
to determin e w heth er the doses and the prim ary
injection sites used in the pilot study for the correcti on
o f gumm y smil es prov ide consistent, stati sti ca ll y
significant, and esthetica lly pleasing results.

O nl y 26.7% of the root angulations were w ithin the

clinica lly acceptable angul ar vari ation range of 2.5.
The greatest va ri ati on in the upper arch was in the
ca nine premo lar region w here the roots were proj ected
as being more divergent. The greatest vari ation in the
lower arch occurred in the lateral incisor-canine region
w here th ese roo ts appea red m o re co nve rge nt.
Radiographic distorti on was stati stica ll y more in the
lower than in the upper arch.

Methods: Thirty patients received BTX-A injections to

reduce excessive gingiva l display. G ingiva l display was
defin ed as the differe nce between the lower margin of
the upper lip and the superior margin of the right incisor.
Patients were fo llowed at 2,4, 8,12,16,20, and 24 weeks
pos t i nj ec ti o n, w ith c h anges d oc um ent ed by
photograph s and videos. At week 2, the patients rated
the effects of BTX-A. A group of specia lity cl inicia ns
also evaluated the effects of BTX-A.

Concl usion: There is a cl ini ca lly signifi ca nt vari ation

between the radiographic and the true root angulations
recorded and ca utio n is advi sed w hen interpreting
mes io-d istal root angul ati on using O PG.

Results: Prei nj ecti o n g in g ival di spl ay ave raged

5.2 1.4mm in the 30 patients. At 2 weeks post injection,
m ea n g ing iva l di spl ay had dec lin ed to 0.0 9mm
(1.06mm) in 30 pati ents (1=26.01 , P<.OOOOl ). The
average lip-drop at 2 weeks was 5. 1mm for 30 patients.
Gingiva l di splay gradu all y increased fro m 2 weeks
postinj ectin through 24 weeks, but, at 24 weeks,
average gingival di sp lay had not returned to baseli ne
va lu es. Based o n predi cti o ns fro m a th i rd-o rder
polynomial equati on, the baseline average of 5.2 mm
wo uld
no t
be
reac hed
until
30 to 32 weeks postinjection. Patients and specia lty
eva luators rated the effects of BTX-A as highly favorable.

Torque expression of self-ligating brackets

Hi sham M. Badawi , Roger W. Toogood, Jason
P.R.Carey, Giseon Heo and Paul W. Major.
Th is stu dy meas ured the difference in third-order
mo m ents th at ca n b e d e l ive red by engag in g
0.0 19xO.025 - in stainless steel archwires to 2 acti ve
self- ligating brackets (I n-ovati on and Speed) and two
passive self- ligating brackets (Damon 2 and Smart Clip)
using a novel torque measurement device.

Conclusions: BTX-A inj ectio ns for the nueromuscular

correction of gummy smil es caused by hyperfun ctional
upper lip elevator muscles was effecti ve and statistica lly
superi o r to ba selin e smi les, altbo ucl1 the. effect is
transitory.

There was a signi fica nt di fference in the engagement

angle between the two types of brackets. For the active
self- ligat ing brackets, torqu e started to be expressed at
48