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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 shortening 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

I

T IS WELL KNOWN THAT malocclusion of the teeth causes
not only an esthetic problem but also disorders in dentofacial function. In orthodontic therapy, it usually takes
years to complete orthodontic tooth movement. Since orthodontic braces and wires hinder proper oral hygiene, orthodontic appliances tend to cause dental caries and periodontal diseases. Therefore, development of the methods
for accelerating orthodontic tooth movement would reduce
the incidence of dental diseases during orthodontic treatment.
Orthodontic tooth movement is thought of as increased
alveolar bone remodeling caused by mechanical force applied to the teeth. It is generally accepted that periodontal
cells compressed between tooth root and alveolar bone secrete bone-resorbing cytokines, which stimulate osteoclast

formation and bone resorption in the direction of orthodontic 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 necrotic tissue from the compressed periodontal membrane,
the alveolar bone is resorbed by osteoclasts in the periodontal space (frontal bone resorption) (Fig. 1C). After the initiation of the frontal bone resorption, the tooth is moved
rapidly and continuously by the orthodontic force. The velocity of tooth movement depends on the rate of bone re-

1

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

546

(Tokyo. Recombinant human PTH(1–84) was provided by Chugai Pharmaceutical Co. Japan).S. 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.PTH INFUSION ON TOOTH MOVEMENT 547 springs (Sentalloy 509–21) were obtained from Tomy International Co. Japan).25(OH)2 vitamin D3 were attempted to accelerate orthodontic tooth movement. Injections of PGE1. Osaka. Orthodontic tooth movement. where the number of osteoclasts was counted in a 300 × 700 ␮m area (Fig. stained with eosin. Orthodontic super-elastic closed coil Twenty-four rats were divided into groups of six rats. Forty-eight hours after implantation of the osmotic pumps. and 10 ␮g/ 100 g of BW/day and were fed a standard pellet diet (Oriental Kobo Co. (Tokyo. 120.(3–9) However. On day 3 after the insertion. and 120 h of tooth separation (at 48. Arrows indicate the direction of tooth movement. The rats were treated with PTH infusion at 10 ␮g/100 g of body weight/day.). (Tokyo. Parathyroid hormone (PTH) is one of the potent stimulatory factors of osteoclast formation. patty and injection type) were purchased from GC Corp. located in Howship’s lacuna. U. Experiment I: Dose-dependent effects of PTH infusion on separation of teeth FIG. Identical results were obtained from three examiners who were not informed of which group was being counted for osteoclast number. which was found to be the most effective dose for tooth separation in Experiment I. (Tokyo.2–0. (Mino. . 72. The tooth is moved continuously by bone resorption after the completion of undermining bone resorption and elimination of necrotic tissue. (Palo Alto. 3. The rats were sacrificed at 0. For the control animals. 24.. PTH dissolved in citrate-buffered saline containing 0. tooth separation was evaluated by subtracting 50 ␮m from each measured datum. All of the histologic examinations were focused on the compression side of the interradicular septum of M1. Since a 50 ␮m contact gauge could be inserted between M1 and M2 on the control side. sorption proceeding in the compressed periodontal tissue. Dental impression materials (Exafine. an elastic band was inserted between M1 and M2 on the right side of each animal. (Tokyo.3 mm as a result of compressive deformation of the periodontal membrane.). 1. Tooth is moved immediately by 0. Synthetic human PTH(1–34) was purchased from Peptide Institute Inc. a segment of an elastic band (0. the interproximal distance between M1 and M2 was measured with a combination of contact gauges (Sun Dental Co.A. The rats were given continuous infusion of PTH at 1. such that the mean body weight (BW) of each group was comparable. Japan) of 50. This method is technically easy and causes little stress to the animals. (A) Initial tooth movement. according to the method of Takano-Yamamoto et al. 100. and 150 ␮m thickness. CA. Therefore. which were then implanted in the subcutus in the dorsocervical region of the rats under ether anesthesia. (C) Secondary period of tooth movement. After dissection of the upper jaws. respectively.S. Japan).(17) indicating that PTH plays an important role in osteoclast formation in mechanically compressed periodontal tissue.8 mm thick) was inserted between 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. only vehicle was administered.).(10–16) A previous report demonstrated that osteoclast formation on the compression side of periodontal tissue in experimental tooth movement was completely inhibited by parathyroidectomy and that recovery occurred after injection of parathyroid extract. The jaws were fixed in 4% paraformaldehyde. following the procedure performed in Experiment I. Japan). Osmotic pumps (Alzet 2ML1) were obtained from Alza Co. Tween-80 was obtained from Wako Junyaku Co.(8) Osteoclasts were identified as large multinucleated cells having ruffled border. 3A) in five sections at four-section intervals for each specimen. and embedded in paraffin. (Monrovia. decalcified in 4% formic acid. 2A.A. and 168 h of PTH infusion). only the vehicle was administered. Orthodontic elastic bands (Quik-Stik. the rats were sacrificed by ether inhalation. MATERIALS AND METHODS Materials Male Wistar rats weighing 350–400 g were obtained from Oriental Kobo Co. Japan). Continuous administration of PTH was found to be effective in accelerating orthodontic tooth movement. 72. Tooth is arrested at its position because of lack of bone resorption in the periodontal membrane. none of these factors are applied in current orthodontic treatment. We examined the effects of administration of human recombinant PTH(1–84) and human synthetic PTH(1–34) on orthodontic tooth movement in rats. (B) Necrosis of compressed periodontal membrane (shaded area) and undermining bone resorption. CA. and 1␣. The purpose of the present study was to investigate whether administration of PTH could be applicable to hasten orthodontic tooth movement. U. it is possible that administration of boneresorbing factors may increase bone-resorbing activity in compressed periodontal tissue. They were then cut into serial mesiodistal sections of 8 ␮m thickness and stained with hematoxylin and eosin. A-1) were purchased from Unitek Co.05% Tween-80 was placed in osmotic pumps. For the control animals. Japan). Forty-eight hours after implantation. PGE2.

The separation in PTH-treated rats appeared to reach a plateau on day 5. 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. After the impression had been taken. infusion of PTH(1–34) at 0. the latter of which was drawn mesially by a continuous force of 30g for 12 days. An impression of the upper jaw was taken under ether anesthesia for preparing plaster dental casts every third day (Fig. this appliance can generate continuous orthodontic force for a long period. the coil spring was adjusted to generate a drawing force at 30g. *p < 0. . (B) Dose-dependent effects of PTH infusion on osteoclast appearance. the insertion of an elastic band caused tooth separation between M1 and M2. a vehicle infusion group of eight rats and four experimental groups 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. Japan). Effects of PTH(1–84) infusion on tooth separation. In the group treated with PTH infusion at 10 ␮g/100 g of BW/day. 2C). 5A and 5B). As shown in Fig. a piece of an elastic band (arrowheads) was inserted between the right upper first (M1) and second (M1) molars. There was no significant difference in tooth separation between vehicle. and PTH(1–34) injection at 4 ␮g/100 g of BW/day. Experiment III: Effects of PTH(1–84) and PTH(1–34) infusion on orthodontic tooth movement Forty rats were divided into five groups.. 2.(20) Statitical analysis Statistical differences within groups was evaluated by analysis of variance. treated with PTH(1–84) infusion at 10 ␮g/100 g of body weight/day. an orthodontic closed coil spring was ligated between the upper incisors and M1. 5C). The right femur and lumbar vertebrae L2–L5 were dissected for the measurements of bone mineral content and bone mineral density by dual-energy X-ray absorptiometry (DCS-600. Tokyo. Tokyo. (A) To examine the effects of PTH infusion on the separation of teeth. Since there was little friction between teeth and the inserted elastic band on day 5 in PTH-treated rats. Twenty-four hours after the initiation of PTH administration.and PTH-treated rats 24 h after insertion of the elastic band (Fig. Although the coil spring gives more stress to rats than the elastic band inserted between molars. the distance between M1 and M2 was measured. At 72 h of separation. Briefly. tooth separation was accelerated by PTH infusion. All results were expressed as the mean ± SEM. Japan) according to the method of Tanaka et al. 2B. Aloka. On day 12 of tooth movement. FIG.e. M1 was moved mesially by the method of Brudvik and Rygh(19) (Figs.4 and 4 ␮g/100 g of BW/day. The PTH injection group received a daily subcutaneous injection of PTH(1–34). serum samples were taken from the abdominal aorta of the rats under ether anesthesia. The rats were treated with PTH(1–84) at the indicated doses.548 SOMA ET AL. Animal protocols used in the present study were approved by the Animal Care Committee at Osaka University Dental School. The animals were sacrificed by an overdose of anesthetic. The rats were treated with vehicle or PTH(1– 84) infusion at 10 ␮g/100 g of BW/day. respectively. The data shown represent the mean ± SEM for six rats..05 versus the control group. we discontinued the experiment. Hitachi Co. the distance between the molars was increased by 50% when compared with that of the vehicle infusion group. At the indicated time after band insertion.05 mm. the distance between M1 and M2 was measured by the insertion of contact gauges in combination. Serum chemistries were measured with an autoanalyzer (Autoanalyzer 7170. (C) Time course of tooth separation. i.

F) or PTH(1–84) infusion at 1 (C. K). 3F). 3. The rats of each group were continuously treated with vehicle (B. and 3I) caused . Bone resorption by osteoclasts (arrowheads) was more extensive in rats treated with PTH infusion on the right (tooth movement) side (F–I). 3G.PTH INFUSION ON TOOTH MOVEMENT 549 FIG. Histologic examination was performed in the area indicated by the rectangle. 3. 3 (D. There was no difference in osteoclast appearance on the left (control) side (B–E). Induction of osteoclast formation and bone resorption by PTH(1–84) infusion and mechanical compression at 72 h of tooth separation. necrotic tissue. The bar in (F) ⳱ 100 ␮m. (A) Periodontal membranes were mechanically compressed (shaded area) by the insertion of an elastic band. which degen- eration was associated with the appearance of osteoclasts in the adjacent bone marrow space (Fig. 3H. Note the extensive bone resorption and a lack of necrotic tissue in rats treated with PTH(1–84) at 10 ␮g (I). and 10 ␮g/100 g of BW/day (E. (B–I) Histologic changes in compressed periodontal tissue. respectively. and 10 ␮g (Fig. n. PTH(1–84) infusion at 1. The sections from control rats showed that the insertion of the elastic band caused hyaline degeneration in the compressed area of the periodontal membrane. H). G).

however. M1 was moved by 0.550 SOMA ET AL. In contrast to the sections obtained from the rats treated with vehicle infusion or PTH infusion at 1 or 3 ␮g. however. *p < 0. and serum chemistries in rats treated with PTH(1–34) infusion or PTH(1–34) injection FIG. did not increase the rate of orthodontic tooth movement. when compared with vehicle infusion (Table 1).(16) at 4 ␮g revealed an effect comparable to that of PTH(1–84) infusion at 10 ␮g. bone mineral density and bone mineral content were significantly increased in the rats treated with PTH injection (Table 1). At 72 h of tooth separation.04 mm in the vehicle infusion group (Figs. PTH(1–34) injection at 4 g.54 ± 0. PTH injection. (B) Time course of tooth separation. patients have to wear retainers for several years after the completion of tooth movement. we examined the effects of PTH infusion on continuous orthodontic tooth movement. indicating that PTH injection had anabolic effects on bone metabolism. PTH infusion at 10 ␮g caused a 3-fold increase in osteoclast number as compared with vehicle infusion. In orthodontic treatment. On day 12 of tooth movement. PTH(1–84) infusion at all concentrations enhanced this increase in osteoclast number. PTH(1–34) infusion. 4. body weight. serum calcium. Effects of PTH(1–84) infusion on osteoclast appearance associated with tooth separation. 4A). and serum creatinine levels did not differ among these three groups (Table 2). 6B.(26. intermittent administration of PTH appears not to be effective on orthodontic tooth movement. 5C and 6A). which connects the moved teeth with surrounding tissue on . Bone mineral measurements. 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. The insertion of the elastic band caused an increase in the number of osteoclasts on the tooth separation side compared with the number on the control side in vehicletreated animals (Fig. we examined whether PTH affected systemic parameters of bone metabolism. 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. 3A. 3C.05 versus the control group. As shown in Fig. Rats treated with vehicle or PTH(1–84) infusion at 10 ␮g/100 g of BW/day were sacrificed at the indicated times after band insertion. PTH infusion activates bone remodeling without reducing bone volume. PTH(1– 34) infusion did not cause decrease in the bone mineral measurements. the section from the animals infused with PTH(1–84) at 10 ␮g showed osteoclast appearance in a widened periodontal membrane and a lack of necrotic tissue (Fig. The data shown represent the mean ± SEM for six rats. and 3E). (A) Dosedependent effects of PTH(1–84) infusion on osteoclast appearance. Many reports have demonstrated that intermittent injection of PTH into rats stimulated bone formation without causing any increase in osteoclastic bone resorption. Rats treated with PTH(1–84) at the indicated doses were sacrificed at 72 h of tooth separation. 3I). advanced bone resorption in the bone marrow space as compared with the vehicle infusion. The PTH(1–34) injection group showed a marked increase in bone mineral measurements (Table 1) and alkaline phosphatase level (Table 2) when compared with vehicle and PTH(1–34) infusion groups. 4B. Since rapid tooth movement requires an increased rate of bone resorption. Body weight.(21–30) In agreement with these studies. There was no difference in osteoclast number on the control side between these groups. Osteoclast number was counted in the area indicated in Fig. These evidences suggest that continuous administration of PTH is applicable to shortening orthodontic treatment without systemic bone loss. DISCUSSION The present study demonstrated that PTH infusion accelerates orthodontic tooth movement. As shown in Fig. periodontal tissue during tooth movement. The remaining tension of stretched periodontal fibers. showed no effect on the rate of tooth movement. 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 At the end of PTH infusion. an active fragment of human PTH. 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. However. 3D. which was found in the same area at 24 h of tooth separation (data not shown). Sections obtained from the left upper molars showed that PTH infusion did not increase bone resorption activity without mechanical compression (Figs.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).

(C–E) Photographs of the plaster dental casts. This widened space becomes 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. retainers should be worn until periodontal tissue of the moved teeth is reorganized in their new position. bp < 0. On day 12 of tooth movement. Procedure and measurement of orthodontic tooth movement.01 versus the control group. both PTH injection and infusion stimulate bone formation. The distance between M1 and M2 was measured on the indicated days of tooth movement. respectively. PTH(1–84) infusion did not increase either osteoclast number or bone resorption on the control side. the tension side. As described in many reports.(35) At the end of orthodontic tooth movement. The present study has demonstrated that continuous infusion of PTH(1–84) increased osteoclast number and advanced bone resorption on the tooth movement side (Figs. respectively.30–33) Therefore. PTH(1–34) infusion at 0. (A) Effects of PTH infusion and injection on orthodontic tooth movement. The distance between M1 and M2 was measured on day 12 of tooth movement. (A) M1 was moved mesially by a closed coil spring ligated between M1 and incisors (Is). is one of the major causes of relapse after orthodontic tooth movement. This suggests that bone apposition on the tension side is important for stabilizing tooth position. (B) Oral photograph of the rat at the initiation of orthodontic tooth movement. (B) Time course of orthodontic tooth movement in the rats treated with vehicle infusion. respectively. To prevent the relapse. FIG.4 or 4 ␮g/100 g of BW/day. Effects of PTH infusion on orthodontic tooth movement. The data shown represent the mean ± SEM for eight rats. PTH(1–84) infusion at 10 ␮g/100 g of BW/day appears not . impression of the upper jaw was taken for preparing the dental cast. 6. periodontal space is still widened on the tension side. ap < 0. and PTH(1–34) injection at 4 ␮g/100 g of BW/day. The rats were treated with vehicle infusion (C).PTH INFUSION ON TOOTH MOVEMENT 551 FIG. PTH may increase the bone apposition rate on the tension side of the moved teeth. Therefore. PTH(1–34) infusion at 4 ␮g/100 g of BW/day (D). Note that the widest interproximal space between M1 and M2 was seen in the PTH(1– 34) infusion group. The animals were treated with vehicle. PTH(1–84) infusion at 10 ␮g/100 g of BW/day.05. In contrast to its effect on the tooth movement side. and PTH(1–34) injection at 4 ␮g/100 g of BW/day (E). 3 and 4). 5.(21–28. and PTH(1–34) infusion at 4 ␮g/100 g of BW/day. PTH administration may also be applicable in improving retention after orthodontic tooth movement. PTH(1– 84) infusion at 10 ␮g/100 g of BW/day.

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). to induce bone resorption by itself.(37) PTH may stimulate osteoclast formation in the compressed periodontal tissue synergistically with these factors.5 141. PTH infusion seems to stimulate removal of necrotic tissue from the compressed periodontal membrane. Local administration would be advantageous in reducing the dose of PTH as well.05 level.41 ± 0. the orthodontist has no choice but to discontinue the treatment.03 836 ± 162 1062 ± 299 1388 ± 140*† Data are expressed as the mean ± SEM. it seems to be more appropriate to give PTH locally into the circumferential tissue of the moved tooth than to give it systemically in orthodontic therapy. it is necessary to develop a slow-release vehicle that keeps the local concentration of PTH at a certain level for a long period.3 ± 0.7 ± 2. The present study has demonstrated that systemic infusion of PTH accelerated orthodontic tooth movement without reducing systemic bone mineral measurements. However.24 6. EFFECT SOMA ET AL.6 ± 4.(44) PTH may cause rapid removal of necrotic tissue by stimulating bone cells to secrete these proteolytic enzymes.7 123.06 ± 0.40 ± 0.552 TABLE 1. * Significantly different from vehicle group at p < 0. * Significantly different from vehicle group at p < 0.05 level. For the local application of PTH. EFFECTS OF PTH (1–34) INFUSION OR INJECTION ON BLOOD CHEMISTRIES (ON DAY 13 OF PTH ADMINISTRATION) ON DAY 12 OF TOOTH MOVEMENT Serum chemistries Vehicle PTH infusion at 4 ␮g PTH injection at 4 ␮g Body weight (g) Total protein (g/dl) Calcium (mg/dl) Phosphorus (mg/dl) Creatinine (mg/dl) ALP (IU/l) 420 ± 18 425 ± 39 417 ± 34 6.93 ± 0.05 level.25* 6.14 5.9*† Data are expressed as the mean ± SEM.52 6.(38–42) cathepsin B.(43) or cathepsin L. An earlier study showed that PTH locally injected into bone marrow space was effective at inducing local bone resorption.1 ± 0. continuous administration of PTH may reduce the incidence of unfavorable root resorption during orthodontic therapy.4 ± 8.3 10. Moreover. TABLE 2.6 10.1 7.9 ± 1. 3F–3I).(36) suggesting that responsiveness of bone marrow cells to PTH is enhanced by humoral factors secreted from mechanically stressed bone cells.05 level.2 ± 0.53 ± 0. Thus. whereas it was still observed in the group treated with vehicle or PTH infusion at 1 or 3 ␮g/100 g of BW/day (Figs.01 0. interleukin-6.6 ± 5. An earlier study demonstrated that root resorption initiated beneath the necrotic tissue in the compressed periodontal membrane.59 0. An earlier study demonstrated that the levels of bone resorptive factors such as interleukin-1.9 144.(45) Therefore. OF PTH (1–34) INFUSION OR INJECTION ON BONE MINERAL MEASUREMENTS MOVEMENT (ON DAY 13 OF PTH ADMINISTRATION) DAY 12 OF TOOTH Bone mineral density (mg/cm2) Bone mineral content (mg) Vehicle PTH infusion at 4 ␮g PTH injection at 4 ␮g ON Femur L2–L5 Femur L2–L5 256 ± 13 274 ± 8 327 ± 13*† 261 ± 25 245 ± 16 327 ± 13*† 115.43 ± 0.52 ± 0. 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. When severe root resorption is observed dur- ing orthodontic therapy. necrotic tissue in compressed periodontal membrane in the group treated with PTH(1–84) infusion at 10 ␮g/100 g of BW/day was eliminated by 72 h of tooth separation.55 ± 0.27 ± 0.(19) Thus. It is well known that root resorption is one of the major side effects in orthodontic tooth movement.6 118. † Significantly different from PTH infusion group at p < 0. . Regarding the histologic findings.12 10. These evidences indicate that PTH enhances osteoclastic bone resorption only in periodontal tissue under mechanical compression without undesired bone loss in another area of alveolar bone.4*† 122. Many reports have demonstrated that PTH stimulated bone cells to secrete proteolytic enzymes such as collagenase. we are now examining the effects of local injection of PTH(1– 34) in a slow-release system on orthodontic tooth movement. Our previous report demonstrated that conditioned medium obtained from mechanically deformed bone cells enhanced PTH-dependent osteoclast formation from bone marrow cultures.2 ± 2. and tumor necrosis factor-␣ were rapidly increased in periodontal tissue at the initiation of orthodontic tooth movement. On this point. our results cannot rule out the possibility that PTH might enhance undesired bone resorption in weight-bearing bones such as vertebrae. † Significantly different from PTH infusion group at p < 0. Since PTH(1–34) can be manufactured by chemical synthesis.02 0.

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