JOURNAL OF BONE AND MINERAL RESEARCH

Volume 14, Number 4, 1999

Blackwell Science, Inc.
© 1999 American Society for Bone and Mineral Research

Effects of Continuous Infusion of PTH on Experimental

Tooth Movement in Rats

S. SOMA,1 M. IWAMOTO,2 Y. HIGUCHI,3 and K. KURISU2

ABSTRACT

Development of new methods for accelerating orthodontic tooth movement has been strongly desired for short-
ening of the treatment period. The rate of orthodontic tooth movement is dependent on the rate of bone resorption
occurring in the compressed periodontium in the direction of orthodontic force applied to the tooth. In the present
study, we examined the effects of continuous infusion of parathyroid hormone (PTH) on tooth movement. Male
rats weighing 350–400 g were treated with subcutaneous infusion of vehicle or hPTH(1–84) at 1–10 µg/100 g of
body weight/day. When the upper right first molar (M1) was moved mesially for 72 h by the insertion of an elastic
band between the first and second molars, M1 movement was accelerated by PTH infusion at 10 µg. PTH infusion
caused a 2- to 3-fold increase in the number of osteoclasts in the compressed periodontium of M1, indicating that
such treatment accelerated tooth movement by enhancing bone resorptive activity induced in the compressed
periodontium. When M1 was moved mesially by an orthodontic coil spring ligated between upper incisors and M1
for 12 days, PTH(1–84) infusion at 10 µg caused a 2-fold increase in the rate of M1 movement. PTH(1–34) infusion
at 4 µg had an effect comparable to that of PTH(1–84). However, intermittent injection of PTH(1–34) did not
accelerate M1 movement. PTH infusion for 13 days did not affect either bone mineral measurements or the serum
calcium level. These findings suggest that continuous administration of PTH is applicable to accelerate orthodontic
tooth movement. (J Bone Miner Res 1999;14:546–554)

INTRODUCTION formation and bone resorption in the direction of orth-

I T IS WELL KNOWN THAT malocclusion of the teeth causes
not only an esthetic problem but also disorders in den-
tofacial function. In orthodontic therapy, it usually takes
years to complete orthodontic tooth movement. Since orth-
odontic braces and wires hinder proper oral hygiene, orth-
odontic appliances tend to cause dental caries and peri-
odontal diseases. Therefore, development of the methods
for accelerating orthodontic tooth movement would reduce
the incidence of dental diseases during orthodontic treat-
ment.
Orthodontic tooth movement is thought of as increased
alveolar bone remodeling caused by mechanical force ap-
plied to the teeth. It is generally accepted that periodontal
cells compressed between tooth root and alveolar bone se-
crete bone-resorbing cytokines, which stimulate osteoclast
odontic force vector.(1) The duration of orthodontic tooth
movement is divided into two phases.(2) When orthodontic
force is applied to a tooth, the tooth is moved immediately
by 0.2–0.3 mm as a result of compressive deformation of the
periodontal membrane (Fig. 1A). The tooth is arrested at
that position for several days. In this period, necrotic tissue
appears in the compressed periodontal membrane. Early
osteoclastic bone resorption is then initiated in the bone
marrow space adjacent to the necrotic area (undermining
bone resorption) (Fig. 1B). After elimination of the ne-
crotic tissue from the compressed periodontal membrane,
the alveolar bone is resorbed by osteoclasts in the periodon-
tal space (frontal bone resorption) (Fig. 1C). After the ini-
tiation of the frontal bone resorption, the tooth is moved
rapidly and continuously by the orthodontic force. The ve-
locity of tooth movement depends on the rate of bone re-

1
Ogo Dental Clinic, Yodogawa, Osaka, Japan.
2
Department of Oral Anatomy and Developmental Biology, Faculty of Dentistry, Osaka University, Suita, Osaka, Japan.
3
Chugai Pharmaceutical Company, Chuo-ku, Tokyo, Japan.

546
PTH INFUSION ON TOOTH MOVEMENT
FIG. 1. Orthodontic tooth movement. (A) Initial tooth
movement. Tooth is moved immediately by 0.2–0.3 mm as
a result of compressive deformation of the periodontal
membrane. (B) Necrosis of compressed periodontal mem-
brane (shaded area) and undermining bone resorption.
Tooth is arrested at its position because of lack of bone
resorption in the periodontal membrane. (C) Secondary pe-
riod of tooth movement. The tooth is moved continuously
by bone resorption after the completion of undermining
bone resorption and elimination of necrotic tissue. Arrows
indicate the direction of tooth movement.
sorption proceeding in the compressed periodontal tissue.
Therefore, it is possible that administration of bone-
resorbing factors may increase bone-resorbing activity in
compressed periodontal tissue. Injections of PGE1, PGE2,
and 1␣,25(OH)2 vitamin D3 were attempted to accelerate
orthodontic tooth movement.(3–9) However, none of these
factors are applied in current orthodontic treatment.
Parathyroid hormone (PTH) is one of the potent stimu-
latory factors of osteoclast formation.(10–16) A previous re-
port demonstrated that osteoclast formation on the com-
pression side of periodontal tissue in experimental tooth
movement was completely inhibited by parathyroidectomy
and that recovery occurred after injection of parathyroid
extract,(17) indicating that PTH plays an important role in
osteoclast formation in mechanically compressed periodon-
tal tissue.
The purpose of the present study was to investigate
whether administration of PTH could be applicable to has-
ten orthodontic tooth movement. We examined the effects
of administration of human recombinant PTH(1–84) and
human synthetic PTH(1–34) on orthodontic tooth move-
ment in rats. Continuous administration of PTH was found
to be effective in accelerating orthodontic tooth movement.
MATERIALS AND METHODS
Materials
Male Wistar rats weighing 350–400 g were obtained from
Oriental Kobo Co. (Tokyo, Japan). Recombinant human
PTH(1–84) was provided by Chugai Pharmaceutical Co.
(Tokyo, Japan). Synthetic human PTH(1–34) was pur-
chased from Peptide Institute Inc. (Mino, Japan). Osmotic
pumps (Alzet 2ML1) were obtained from Alza Co. (Palo
Alto, CA, U.S.A.). Tween-80 was obtained from Wako Ju-
nyaku Co. (Tokyo, Japan). Orthodontic elastic bands
(Quik-Stik, A-1) were purchased from Unitek Co. (Mon-
rovia, CA, U.S.A.). Orthodontic super-elastic closed coil
547
springs (Sentalloy 509–21) were obtained from Tomy Inter-
national Co. (Tokyo, Japan). Dental impression materials
(Exafine, patty and injection type) were purchased from
GC Corp. (Tokyo, Japan).
Experiment I: Dose-dependent effects of PTH
infusion on separation of teeth
Twenty-four rats were divided into groups of six rats,
such that the mean body weight (BW) of each group was
comparable. PTH dissolved in citrate-buffered saline con-
taining 0.05% Tween-80 was placed in osmotic pumps,
which were then implanted in the subcutus in the dorsocer-
vical region of the rats under ether anesthesia. The rats
were given continuous infusion of PTH at 1, 3, and 10 ␮g/
100 g of BW/day and were fed a standard pellet diet (Ori-
ental Kobo Co.). For the control animals, only vehicle was
administered. Forty-eight hours after implantation, a seg-
ment of an elastic band (0.8 mm thick) was inserted be-
tween the upper first and second molars (M1 and M2) on
the right side under ether anesthesia according to the
method of Waldo and Rothblatt,(18) as shown in Fig. 2A.
This method is technically easy and causes little stress to the
animals. On day 3 after the insertion, the rats were sacri-
ficed by ether inhalation. After dissection of the upper jaws,
the interproximal distance between M1 and M2 was mea-
sured with a combination of contact gauges (Sun Dental
Co., Osaka, Japan) of 50, 100, and 150 ␮m thickness. Since
a 50 ␮m contact gauge could be inserted between M1 and
M2 on the control side, tooth separation was evaluated by
subtracting 50 ␮m from each measured datum. The jaws
were fixed in 4% paraformaldehyde, decalcified in 4% for-
mic acid, and embedded in paraffin. They were then cut
into serial mesiodistal sections of 8 ␮m thickness and
stained with hematoxylin and eosin. All of the histologic
examinations were focused on the compression side of the
interradicular septum of M1, where the number of osteo-
clasts was counted in a 300 × 700 ␮m area (Fig. 3A) in five
sections at four-section intervals for each specimen, accord-
ing to the method of Takano-Yamamoto et al.(8) Osteo-
clasts were identified as large multinucleated cells having
ruffled border, located in Howship’s lacuna, stained with
eosin. Identical results were obtained from three examiners
who were not informed of which group was being counted
for osteoclast number.
Experiment II: Time course of the effects of PTH
infusion on tooth separation
Forty-eight rats were divided into two experimental
groups of 24 rats. The rats were treated with PTH infusion
at 10 ␮g/100 g of body weight/day, which was found to be
the most effective dose for tooth separation in Experiment
I. For the control animals, only the vehicle was adminis-
tered. Forty-eight hours after implantation of the osmotic
pumps, an elastic band was inserted between M1 and M2 on
the right side of each animal. The rats were sacrificed at 0,
24, 72, and 120 h of tooth separation (at 48, 72, 120, and 168
h of PTH infusion), respectively, following the procedure
performed in Experiment I.
548
FIG. 2. Effects of PTH(1–84) infusion on tooth separa-
tion. (A) To examine the effects of PTH infusion on the
separation of teeth, a piece of an elastic band (arrowheads)
was inserted between the right upper first (M1) and second
(M1) molars. (B) Dose-dependent effects of PTH infusion
on osteoclast appearance. The rats were treated with
PTH(1–84) at the indicated doses. At 72 h of separation, the
distance between M1 and M2 was measured by the insertion
of contact gauges in combination. (C) Time course of tooth
separation. The rats were treated with vehicle or PTH(1–
84) infusion at 10 ␮g/100 g of BW/day. At the indicated
time after band insertion, the distance between M1 and M2
was measured. The data shown represent the mean ± SEM
for six rats. *p < 0.05 versus the control group.
Experiment III: Effects of PTH(1–84) and
PTH(1–34) infusion on orthodontic
tooth movement
Forty rats were divided into five groups, i.e., a vehicle
infusion group of eight rats and four experimental groups
SOMA ET AL.
treated with PTH(1–84) infusion at 10 ␮g/100 g of body
weight/day, infusion of PTH(1–34) at 0.4 and 4 ␮g/100 g of
BW/day, and PTH(1–34) injection at 4 ␮g/100 g of BW/day,
respectively. The PTH injection group received a daily sub-
cutaneous injection of PTH(1–34). Twenty-four hours after
the initiation of PTH administration, M1 was moved mesi-
ally by the method of Brudvik and Rygh(19) (Figs. 5A and
5B). Briefly, an orthodontic closed coil spring was ligated
between the upper incisors and M1, the latter of which was
drawn mesially by a continuous force of 30g for 12 days.
Although the coil spring gives more stress to rats than the
elastic band inserted between molars, this appliance can
generate continuous orthodontic force for a long period.
An impression of the upper jaw was taken under ether
anesthesia for preparing plaster dental casts every third day
(Fig. 5C). The amount of orthodontic tooth movement was
evaluated by measuring the interproximal distance between
M1 and M2 on the cast under a microscope with calipers
having an accuracy of 0.05 mm. After the impression had
been taken, the coil spring was adjusted to generate a draw-
ing force at 30g. On day 12 of tooth movement, serum
samples were taken from the abdominal aorta of the rats
under ether anesthesia. Serum chemistries were measured
with an autoanalyzer (Autoanalyzer 7170; Hitachi Co., To-
kyo, Japan). The animals were sacrificed by an overdose of
anesthetic. The right femur and lumbar vertebrae L2–L5
were dissected for the measurements of bone mineral con-
tent and bone mineral density by dual-energy X-ray absorp-
tiometry (DCS-600; Aloka, Tokyo, Japan) according to the
method of Tanaka et al.(20)
Statitical analysis
Statistical differences within groups was evaluated by
analysis of variance. All results were expressed as the mean
± SEM.
Animal protocols used in the present study were ap-
proved by the Animal Care Committee at Osaka University
Dental School.
RESULTS
The effects of infusion of PTH(1–84) on tooth
separation by insertion of an elastic band
As reported in many studies regarding experimental
tooth movement in rats, the insertion of an elastic band
caused tooth separation between M1 and M2. As shown in
Fig. 2B, tooth separation was accelerated by PTH infusion.
In the group treated with PTH infusion at 10 ␮g/100 g of
BW/day, the distance between the molars was increased by
50% when compared with that of the vehicle infusion
group. There was no significant difference in tooth separa-
tion between vehicle- and PTH-treated rats 24 h after in-
sertion of the elastic band (Fig. 2C). The separation in
PTH-treated rats appeared to reach a plateau on day 5.
Since there was little friction between teeth and the inserted
elastic band on day 5 in PTH-treated rats, we discontinued
the experiment.
PTH INFUSION ON TOOTH MOVEMENT 549

FIG. 3. Induction of osteoclast formation and bone resorption by PTH(1–84) infusion and mechanical compression at 72
h of tooth separation. (A) Periodontal membranes were mechanically compressed (shaded area) by the insertion of an
elastic band. Histologic examination was performed in the area indicated by the rectangle. (B–I) Histologic changes in
compressed periodontal tissue. The rats of each group were continuously treated with vehicle (B, F) or PTH(1–84) infusion
at 1 (C, G), 3 (D, H), and 10 ␮g/100 g of BW/day (E, K), respectively. There was no difference in osteoclast appearance
on the left (control) side (B–E). Bone resorption by osteoclasts (arrowheads) was more extensive in rats treated with PTH
infusion on the right (tooth movement) side (F–I). n, necrotic tissue. Note the extensive bone resorption and a lack of
necrotic tissue in rats treated with PTH(1–84) at 10 ␮g (I). The bar in (F) ⳱ 100 ␮m.

The sections from control rats showed that the insertion eration was associated with the appearance of osteoclasts in
of the elastic band caused hyaline degeneration in the com- the adjacent bone marrow space (Fig. 3F). PTH(1–84) in-
pressed area of the periodontal membrane, which degen- fusion at 1, 3, and 10 ␮g (Fig. 3G, 3H, and 3I) caused
550
FIG. 4. Effects of PTH(1–84) infusion on osteoclast ap-
pearance associated with tooth separation. (A) Dose-
dependent effects of PTH(1–84) infusion on osteoclast ap-
pearance. Rats treated with PTH(1–84) at the indicated
doses were sacrificed at 72 h of tooth separation. Osteoclast
number was counted in the area indicated in Fig. 3A. (B)
Time course of tooth separation. Rats treated with vehicle
or PTH(1–84) infusion at 10 ␮g/100 g of BW/day were sac-
rificed at the indicated times after band insertion. The data
shown represent the mean ± SEM for six rats. *p < 0.05
versus the control group.
advanced bone resorption in the bone marrow space as
compared with the vehicle infusion. In contrast to the sec-
tions obtained from the rats treated with vehicle infusion or
PTH infusion at 1 or 3 ␮g, the section from the animals
infused with PTH(1–84) at 10 ␮g showed osteoclast appear-
ance in a widened periodontal membrane and a lack of
necrotic tissue (Fig. 3I), which was found in the same area
at 24 h of tooth separation (data not shown). Sections ob-
tained from the left upper molars showed that PTH infu-
sion did not increase bone resorption activity without me-
chanical compression (Figs. 3C, 3D, and 3E).
The insertion of the elastic band caused an increase in the
number of osteoclasts on the tooth separation side com-
pared with the number on the control side in vehicle-
treated animals (Fig. 4A). PTH(1–84) infusion at all con-
centrations enhanced this increase in osteoclast number. At
72 h of tooth separation, PTH infusion at 10 ␮g caused a
3-fold increase in osteoclast number as compared with ve-
hicle infusion. There was no difference in osteoclast num-
ber on the control side between these groups. As shown in
Fig. 4B, osteoclast number was significantly increased by
PTH(1–84) infusion at 24 h and 72 h after band insertion
when compared with the number for vehicle infusion.
Effects of continuous infusion of PTH(1–84) and
PTH(1–34) on orthodontic tooth movement
Since PTH(1–84) infusion accelerated tooth separation
and bone resorption only on the compression side of the
SOMA ET AL.
periodontal tissue during tooth movement, we examined
the effects of PTH infusion on continuous orthodontic
tooth movement. On day 12 of tooth movement, M1 was
moved by 0.54 ± 0.04 mm in the vehicle infusion group
(Figs. 5C and 6A). M1 in the rats treated with PTH(1–84)
infusion at 10 ␮g/100 g of BW/day was moved twice as fast
as in the rats treated with vehicle infusion. PTH(1–34) in-
fusion, an active fragment of human PTH,(16) at 4 ␮g re-
vealed an effect comparable to that of PTH(1–84) infusion
at 10 ␮g. PTH(1–34) injection at 4 g, however, did not
increase the rate of orthodontic tooth movement. As shown
in Fig. 6B, the rate of orthodontic tooth movement was
markedly accelerated both in PTH(1–84) and PTH(1–34)
infusion groups on days 6–9 of tooth movement.
Bone mineral measurements, body weight, and
serum chemistries in rats treated with PTH(1–34)
infusion or PTH(1–34) injection
At the end of PTH infusion, we examined whether PTH
affected systemic parameters of bone metabolism. PTH(1–
34) infusion did not cause decrease in the bone mineral
measurements, when compared with vehicle infusion
(Table 1). Body weight, serum calcium, and serum creati-
nine levels did not differ among these three groups (Table
2). The PTH(1–34) injection group showed a marked in-
crease in bone mineral measurements (Table 1) and alka-
line phosphatase level (Table 2) when compared with ve-
hicle and PTH(1–34) infusion groups, indicating that PTH
injection had anabolic effects on bone metabolism.
DISCUSSION
The present study demonstrated that PTH infusion ac-
celerates orthodontic tooth movement. PTH injection,
however, showed no effect on the rate of tooth movement.
Many reports have demonstrated that intermittent injection
of PTH into rats stimulated bone formation without causing
any increase in osteoclastic bone resorption.(21–30) In agree-
ment with these studies, bone mineral density and bone
mineral content were significantly increased in the rats
treated with PTH injection (Table 1). Since rapid tooth
movement requires an increased rate of bone resorption,
intermittent administration of PTH appears not to be ef-
fective on orthodontic tooth movement. However, PTH in-
fusion activates bone remodeling without reducing bone
volume.(26,31–34) The present study also demonstrated that
PTH infusion at 4 ␮g/100 g of BW/day resulted in neither a
decrease in bone mineral measurements nor an increase in
the serum calcium level (Table 2). These evidences suggest
that continuous administration of PTH is applicable to
shortening orthodontic treatment without systemic bone
loss.
In orthodontic treatment, patients have to wear retainers
for several years after the completion of tooth movement.
The remaining tension of stretched periodontal fibers,
which connects the moved teeth with surrounding tissue on
PTH INFUSION ON TOOTH MOVEMENT
FIG. 5. Procedure and measurement of orthodontic tooth
movement. (A) M1 was moved mesially by a closed coil
spring ligated between M1 and incisors (Is). (B) Oral pho-
tograph of the rat at the initiation of orthodontic tooth
movement. (C–E) Photographs of the plaster dental casts.
The rats were treated with vehicle infusion (C), PTH(1–34)
infusion at 4 ␮g/100 g of BW/day (D), and PTH(1–34) in-
jection at 4 ␮g/100 g of BW/day (E), respectively. On day 12
of tooth movement, impression of the upper jaw was taken
for preparing the dental cast. Note that the widest inter-
proximal space between M1 and M2 was seen in the PTH(1–
34) infusion group.
the tension side, is one of the major causes of relapse after
orthodontic tooth movement. To prevent the relapse, re-
tainers should be worn until periodontal tissue of the
551
FIG. 6. Effects of PTH infusion on orthodontic tooth
movement. (A) Effects of PTH infusion and injection on
orthodontic tooth movement. The animals were treated
with vehicle, PTH(1–84) infusion at 10 ␮g/100 g of BW/day,
PTH(1–34) infusion at 0.4 or 4 ␮g/100 g of BW/day, and
PTH(1–34) injection at 4 ␮g/100 g of BW/day, respectively.
The distance between M1 and M2 was measured on day 12
of tooth movement. (B) Time course of orthodontic tooth
movement in the rats treated with vehicle infusion, PTH(1–
84) infusion at 10 ␮g/100 g of BW/day, and PTH(1–34)
infusion at 4 ␮g/100 g of BW/day, respectively. The distance
between M1 and M2 was measured on the indicated days of
tooth movement. The data shown represent the mean ±
SEM for eight rats. ap < 0.05, bp < 0.01 versus the control
group.
moved teeth is reorganized in their new position.(35) At the
end of orthodontic tooth movement, periodontal space is
still widened on the tension side. This widened space be-
comes narrow to be a physiologically normal width as a
result of bone apposition during retention. It is clinically
well known that the tendency of the moved teeth to get
back to their original position is often observed in an early
period of retention. This suggests that bone apposition on
the tension side is important for stabilizing tooth position.
As described in many reports, both PTH injection and in-
fusion stimulate bone formation.(21–28,30–33) Therefore,
PTH may increase the bone apposition rate on the tension
side of the moved teeth. PTH administration may also be
applicable in improving retention after orthodontic tooth
movement.
The present study has demonstrated that continuous in-
fusion of PTH(1–84) increased osteoclast number and ad-
vanced bone resorption on the tooth movement side (Figs.
3 and 4). In contrast to its effect on the tooth movement
side, PTH(1–84) infusion did not increase either osteoclast
number or bone resorption on the control side. Therefore,
PTH(1–84) infusion at 10 ␮g/100 g of BW/day appears not
552 SOMA ET AL.

TABLE 1. EFFECT OF PTH (1–34) INFUSION OR INJECTION ON BONE MINERAL MEASUREMENTS ON DAY 12 OF TOOTH
MOVEMENT (ON DAY 13 OF PTH ADMINISTRATION)

Bone mineral content (mg) Bone mineral density (mg/cm2)

Femur L2–L5 Femur L2–L5
Vehicle 256 ± 13 261 ± 25 115.7 ± 2.7 122.6 ± 5.6
PTH infusion at 4 ␮g 274 ± 8 245 ± 16 123.4 ± 8.5 118.6 ± 4.9
PTH injection at 4 ␮g 327 ± 13*† 327 ± 13*† 141.9 ± 1.4*† 144.2 ± 2.9*†
Data are expressed as the mean ± SEM.
* Significantly different from vehicle group at p < 0.05 level.
† Significantly different from PTH infusion group at p < 0.05 level.

TABLE 2. EFFECTS OF PTH (1–34) INFUSION OR INJECTION ON BLOOD CHEMISTRIES ON DAY 12 OF TOOTH MOVEMENT
(ON DAY 13 OF PTH ADMINISTRATION)

Serum chemistries
Body weight Total protein Calcium Phosphorus Creatinine ALP
(g) (g/dl) (mg/dl) (mg/dl) (mg/dl) (IU/l)
Vehicle 420 ± 18 6.06 ± 0.14 10.1 ± 0.3 7.43 ± 0.24 0.52 ± 0.02 836 ± 162
PTH infusion at 4 ␮g 425 ± 39 5.41 ± 0.52 10.3 ± 0.6 6.40 ± 0.25* 0.53 ± 0.01 1062 ± 299
PTH injection at 4 ␮g 417 ± 34 6.27 ± 0.12 10.2 ± 0.1 6.93 ± 0.59 0.55 ± 0.03 1388 ± 140*†
Data are expressed as the mean ± SEM.
* Significantly different from vehicle group at p < 0.05 level.
† Significantly different from PTH infusion group at p < 0.05 level.

to induce bone resorption by itself. These evidences
indicate that PTH enhances osteoclastic bone resorp-
tion only in periodontal tissue under mechanical com-
pression without undesired bone loss in another area of
alveolar bone. Our previous report demonstrated that con-
ditioned medium obtained from mechanically deformed
bone cells enhanced PTH-dependent osteoclast forma-
tion from bone marrow cultures,(36) suggesting that respon-
siveness of bone marrow cells to PTH is enhanced by hu-
moral factors secreted from mechanically stressed bone
cells. An earlier study demonstrated that the levels of bone
resorptive factors such as interleukin-1, interleukin-6, and
tumor necrosis factor-␣ were rapidly increased in periodon-
tal tissue at the initiation of orthodontic tooth move-
ment.(37) PTH may stimulate osteoclast formation in the
compressed periodontal tissue synergistically with these
factors.
Regarding the histologic findings, necrotic tissue in com-
pressed periodontal membrane in the group treated with
PTH(1–84) infusion at 10 ␮g/100 g of BW/day was elimi-
nated by 72 h of tooth separation, whereas it was still ob-
served in the group treated with vehicle or PTH infusion at
1 or 3 ␮g/100 g of BW/day (Figs. 3F–3I). Thus, PTH infu-
sion seems to stimulate removal of necrotic tissue from the
compressed periodontal membrane. Many reports have
demonstrated that PTH stimulated bone cells to secrete
proteolytic enzymes such as collagenase,(38–42) cathepsin
B,(43) or cathepsin L.(44) PTH may cause rapid removal of
necrotic tissue by stimulating bone cells to secrete these
proteolytic enzymes. It is well known that root resorption
is one of the major side effects in orthodontic tooth
movement. When severe root resorption is observed dur-
ing orthodontic therapy, the orthodontist has no choice but
to discontinue the treatment. An earlier study demon-
strated that root resorption initiated beneath the necrotic
tissue in the compressed periodontal membrane.(19) Thus,
continuous administration of PTH may reduce the inci-
dence of unfavorable root resorption during orthodontic
therapy.
The present study has demonstrated that systemic infu-
sion of PTH accelerated orthodontic tooth movement with-
out reducing systemic bone mineral measurements. How-
ever, our results cannot rule out the possibility that PTH
might enhance undesired bone resorption in weight-bearing
bones such as vertebrae. An earlier study showed that PTH
locally injected into bone marrow space was effective at
inducing local bone resorption.(45) Therefore, it seems to be
more appropriate to give PTH locally into the circumfer-
ential tissue of the moved tooth than to give it systemically
in orthodontic therapy. Local administration would be ad-
vantageous in reducing the dose of PTH as well. Moreover,
local application of PTH would be beneficial for treating
orthodontic patients in whom selected teeth have to be
moved rapidly while other teeth should be kept in their
original position. For the local application of PTH, it is
necessary to develop a slow-release vehicle that keeps
the local concentration of PTH at a certain level for a long
period. Since PTH(1–34) can be manufactured by chem-
ical synthesis, PTH(1–34) seems to have more potential
in being applied to larger animals or for clinical use in
orthodontic treatment than PTH(1–84). On this point, we
are now examining the effects of local injection of PTH(1–
34) in a slow-release system on orthodontic tooth move-
ment.
PTH INFUSION ON TOOTH MOVEMENT
ACKNOWLEDGMENTS
We thank Dr. R. Cederquist, Dr. H.-D. Nah-Cederquist
(University of Pennsylvania), and Dr. T. Takano-
Yamamoto (Okayama University, Japan) for critical read-
ing of this manuscript and helpful suggestions. This work
was supported by a Research Grant from the Ministry of
Education, Science, and Culture of Japan and by supports
from Chugai Pharmaceutical Co., Ltd.
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Address reprint requests to:
Masahiro Iwamoto
Department of Oral Anatomy and Developmental Biology
Faculty of Dentistry
Osaka University
1-8 Yamadaoka, Suita
Osaka 565-0871, Japan
Received in original form April 24, 1998; in revised form Novem-
ber 13, 1998; accepted December 16, 1998.