Bicortical microimplant with 2 anchorage heads for mesial movement of posterior tooth in the beagle dog

ORIGINAL ARTICLE

Bicortical microimplant with 2 anchorage heads for mesial movement of posterior tooth in the beagle dog Jian-chao Wu,a Ji-na Huang,b and Shi-fang Zhaoc Hangzhou, China Introduction: The purpose of this research was to study the potential anchorage of a newly designed bicortical microimplant for mesial movement of posterior teeth in the mandibles of beagle dogs. Methods: Five adult male dogs with the third premolars in both arches extracted 1 week before the treatment were used in this study. Two bicortical microimplants were placed in the interradicular region at the center of resistance of the second premolar on each side of the mandible. One served as a loaded microimplant with 2 orthodontic nickel-titanium springs delivering 50 g of force between the bicortical microimplant and the fourth premolar. The contralateral bicortical microimplant without loading was the control. Implant-tooth measurements were made biweekly. At the end of tooth movement, the animals were killed, and the specimens with microimplants were embedded in methylmethacrylate and cut to 100 ␮m and ground to a thickness of 70 ␮m. Bone-to-implant contact was calculated. Results: All bicortical microimplants remained stable. Obvious mesial movement of the fourth premolar was observed on the loaded side, but no movement was seen on the unloaded side. No evidence of infection was seen in the histologic examination of the bone interface, and no statistical difference in the bone-to-implant contact between sides was seen. Conclusions: A bicortical microimplant with 2 anchorage units can be used for bilateral orthodontic anchorage in protraction of the posterior teeth in the mandibles of beagle dogs. (Am J Orthod Dentofacial Orthop 2007; 132:353-9)

F

irst molars are important for mastication. If they are extracted because of decay or other problems, chewing is impaired. It is now well accepted that, if the third molar is extracted or missing, the posterior molars can be moved mesially to close the space.1 It is not easy to protract a posterior molar in the mandibular arch, especially in a patient with a low facial angle. In a critical anchorage situation, the reactive anterior teeth must not be moved.2 Authors have reported various options when the dentition does not provide sufficient anchorage,3 including nontitanium implants, osseointegrated implants, onplants, biodegradable implants, mini-plates, and microimplants From the Affiliated Hospital of Stomatology, School of Medicine, Zhejiang University, Hangzhou, China. a Resident, Department of Orthodontics. b Head, Department of Orthodontics. c Dean. Partly funded by grants from the Health Bureau of Zhejiang Province (No. 491060 I20502) and the Education Bureau of Zhejiang Province (No. 20040230). Reprint requests to: Shi-fang Zhao, Affiliated Hospital of Stomatology, School of Medicine, Zhejiang University, Hangzhou 310031, China; e-mail, [email protected]. Submitted, July 2006; revised and accepted, October 2006. 0889-5406/$32.00 Copyright © 2007 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2006.10.021

and microscrews. Microimplants and microscrews have advantages over conventional implants because they can be placed not only in edentulous alveolar and midpalatal areas, but also at alveolar segments with teeth and even around root apices. Microimplants were used as stable anchorage alternatives for mesial molar displacement in critical cases.1,4,5 However, a microimplant provides only 1 anchorage unit for unilateral orthodontic anchorage, so rotation control of the tooth is needed; this increases the friction force and extends the total treatment time. Also, in patients with large spaces to be closed, the antirotation lever arm does not work well because of distortion caused by occlusal forces. In orthodontic treatment planning, the emphasis in determining the appliance design is on the ideal force system, which ensures the desired tooth movement of the active unit.6 A bilateral orthodontic force system applied to the center of resistance of the active molar is preferred to unilateral force in mesiodistal displacement of teeth. Theoretically, to obtain optimal bilateral force applied to the center of resistance of the active molar of the mandible, we can place 2 microscrews, 1 on the buccal side and another on the lingual side, but it is difficult to place the lingual one 353

354 Wu, Huang, and Zhao

American Journal of Orthodontics and Dentofacial Orthopedics September 2007

Fig 1. Schematic showing “virtual root” of P4. Fig 2. Bicortical microimplant placed in interradicular region of P2.

in the correct place because of the limitation of the anatomy of the oral cavity. We designed a new bicortical microimplant with 2 anchorage units for applying bilateral forces. It can be placed in the interradicular region horizontally with the 2 heads acting as anchorage units exposed in the oral cavity. Our purpose was to study the potential anchorage of the new bicortical microimplant in the displacement of the fourth premolar in beagle dogs from the clinical point of view. MATERIAL AND METHODS

The titanium bicortical microimplants used in this study were manufactured by Westlake Biomaterial, Hangzhou, China, according to the authors’ design. The microimplants were 12 to14 mm long with a diameter of 1.15 mm, in a cylindrical shape with 1 slot on each head. To study the potential anchorage of the bicortical microimplant, 5 beagle dogs were used. Their average age was 13.8 ⫾ 2.5 months, and their average weight was 10 ⫾ 1.5 kg. This protocol was approved by the Experimental Animal Committee of Zhejiang University. Full-cast metal crowns for the fourth premolars (P4) of the mandible were customized. The hook on each side of the crown looks like virtual “root,” the buccal “the third root,” the lingual “the fourth root” (Fig 1). All experimental procedures, including radiographic and surgical procedures and clinical intraoral examinations, were performed under general anesthesia by intramuscular application of a drug combining ketamine, meperidine hydrochloride, and dihydroetorphine at 0.1 mL per kilogram. Before the surgery, impressions were made of the

dogs’ mandibular dentitions with silicone impression material (Dent Silicone-V; Shofu Dental Corporation, Kyoto, Japan). Surgical templates for precise placement of the microimplants were fabricated according to the rationale reported previously.7 The interradicular region of the second premolar (P2) was selected for placement of the microimplant because there is enough space to hold it. The third premolars (P3) of each arch were removed for undisturbed mesiodistal movement of P4. After extraction of P3, the dogs were allowed to heal for 1 week. A hole perforating the mandible in the buccolingual direction was drilled with a saline-solution cooled, slow-speed, 1.1-mm drill in the interradicular region of P2 on both sides of the mandible with a the surgical template. The preferred drilling site was between the 2 roots at the level of their apical third. The bicortical microimplant was then placed with a custommade driver with the 2 heads exposed in the oral cavity. The full-cast metal crowns with 2 hooks were cemented with composite resin to P4 on both sides in each dog. One randomly selected side in each dog was the loaded side, and 2 orthodontic nickel-titanium springs (Westlake Biomaterial), each delivering 50 g of force, for a total of 100 g, were connected to the bicortical microimplant and the hooks of P4 (Fig 2). The springs were carefully calibrated biweekly for 12 weeks. The contralateral microimplant served as the unloaded control side. The dogs were given a soft diet to prevent the occlusal force from destroying the microimplants during the experiment. The appliances and the teeth were brushed and cleaned with 2% chlorhexidine digluconate every week. Distance measurements were made biweekly with calipers in each dog under general anesthesia. The

Wu, Huang, and Zhao 355

American Journal of Orthodontics and Dentofacial Orthopedics Volume 132, Number 3

Fig 3. Schematic showing measurement points: CA, canine; P2, second premolar; IB, buccal head of bicortical microimplant; P4, fourth premolar; P4B, buccal vitual “root” of P4; M1, first molar.

distances between the central cusp of the first molar (M1) and the bottom of the buccal hook of the metal crown of P4 (M1-P4B), between the central cusp of M1 and the bottom of the lingual hook of the metal crown of P4 (M1-P4L), between the central cusp of M1 and the central cusp of P4 (M1-P4), between the cusp of the canine (CA) and the center of the buccal end of the implant (CA-IB), and between the CA and the central cusp of M1 (CA-M1) were measured. Changes of M1P4B, M1-P4L, M1-P4, CA-IB, and CA-M1 indicated the displacement of the “third root,” the “fourth root,” P4, the microimplant, and M1, respectively (Fig 3). At the end of tooth movement, the animals were killed by air thrombosis administered intravenously. The specimens with microimplants were dissected, and the tissue blocks were immersed in 4% formalin for 1 week, dehydrated in a graded series of ethanol, and embedded in methylmethacrylate. Slices perpendicular to the long axis of the implant in every other 1-mm distance were cut with a diamond saw (SP1600, Leica, Wetzlar, Germany) to 100 ␮m and ground to a thickness of 70 ␮m manually. The slices were stained with van Gieson’s stain. The interface was observed for evidence of infection at 100 times magnification. The bone implant interface was also evaluated histomorphometrically for bone-to-implant contact (BIC) by using a digital camera connected to a microscope. The image at 100 times magnification was transferred to a personal computer, and BIC (expressed as a percentage) was measured around the implant surface with professional image analysis software (Image-Pro Plus 5.0, Media Cybernetics, Silver Spring, Md). The average value of BIC of each microimplant was then calculated. Statistical analysis

The mean and standard deviation were calculated for each variable. Time changes of variables were evaluated by analysis of variance (ANOVA), and ANOVA was also used to compare the displacement of M1-P4 between the test groups and the control group.

Fig 4. Mesial movement of P4 with tipping after 12 weeks of 50 g bilateral orthodontic force.

The difference of BIC in 2 groups was evaluated by paired Student t test. P ⬍.05 was considered statistically significant. RESULTS

All bicortical microimplants healed uneventfully and remained stable during the treatment time. Slight mucositis was found at peri-implant mucosal tissues in both groups. There were no ulcers on the tongues in either side. Obvious mesialization of P4 was observed on the loaded side, with no displacement on the unloaded side after orthodontic loading. The active P4 showed mesial tipping to some extent (Fig 4). The Table shows the values of the parameters before and after orthodontic treatment in each dog including the distances between M1 and the buccal hook of the metal crown of P4 (M1-P4B), between M1 and the lingual hook of the metal crown of P4 (M1-P4L), between M1 and P4 (M1-P4), between CA and the buccal end of the implant (CA-IB), and between CA and M1 (CA-M1). Figure 5, A and B, shows that the values of CA-M1 and CA-IB in both groups were almost unchanged during treatment; this indicates that the position of the bicortical microimplant did not change after 12 weeks of treatment. Significant differences were found in the change of M1-P4 between the loaded side at 4 weeks and thereafter (Fig 5, C). As shown in Figure 5, D, the values of M1-P4B minus M1-P4L were almost the same during treatment; this indicates no rotation of P4 in both sides. In Figure 6, significant differences were found between the changes of M1-P4B and M1-P4 on the loaded side at 10 weeks and thereafter—ie, displacement of the “crown” of P4 was significantly greater than that of the “root” at these

356 Wu, Huang, and Zhao

Table.

American Journal of Orthodontics and Dentofacial Orthopedics September 2007

Distance and difference of each measuring parameter before and after orthodontic force application Dog 1

M1-P4B (mm) Initial Final Initial–final M1-P4L (mm) Initial Final Initial–final M1-P4 (mm) Initial Final Initial–final CA-M1 (mm) Initial Final Initial–final CA-1B (mm) Initial Final Initial–final

Dog 2

Dog 3

Dog 4

Dog 5

Loaded

Unloaded

Loaded

Unloaded

Loaded

Unloaded

Loaded

Unloaded

Loaded

Unloaded

21 24.1 3.1

21.1 21 –0.1

20.5 23.3 2.8

20.7 20.5 –0.2

19.8 22.2 2.4

19.7 19.8 0.1

18.5 21.5 3

18.7 18.5 –0.2

19.8 23 3.2

19.7 19.5 –0.2

19.5 22.5 3

19.5 19.4 –0.1

19 21.8 2.8

19 18.8 –0.2

18.3 20.7 2.4

18.2 18.2 0

17 20 3

17.1 17 –0.1

18.2 21.7 3.5

18 17.7 –0.3

9.5 13.8 4.3

9.6 9.5 –0.1

10.1 13.9 3.8

10.5 10.4 –0.1

9.8 13.7 3.9

9.5 9.6 0.1

10.5 14.3 3.8

10.2 10.1 –0.1

10.6 14.4 3.8

9.95 10 0.05

56.5 56.8 0.3

57 57 0

58 57.5 –0.5

58.5 58.4 –0.1

57.7 57.9 0.2

57.5 57.4 –0.1

58.6 58.5 –0.1

58.1 58.3 0.2

54 54 0

61 60.5 –0.5

22 22.5 0.5

22 21.8 –0.2

22 22.5 0.5

24 23.7 –0.3

24.5 24.1 –0.4

21.7 21.5 –0.2

21.6 21.5 –0.1

20.8 20.5 –0.3

20.5 21 0.5

21.5 22 0.5

times; this means that the bilateral orthodontic force caused tipping of P4 rather than translation after 12 weeks of loading. The histologic examination showed no evidence of infection in the bicortical microimplant-bone interface. The bicortical microimplant showed that the average BICs were 23.3% on the unloaded side and 24.9% on the loaded side after 12 weeks of horizontal bilateral orthodontic loading. No statistical difference in BIC between the 2 sides was seen (Figs 7 and 8). DISCUSSION

Edentulous areas are common in adults because of molar extractions or agenesis of premolars. Molar mesialization is often used in these situations to close the space. In critical anchorage cases, the anterior unit should not be loaded with horizontal forces. The preferred biomechanics of molar mesialization is balanced bilateral loading.8 New anchorage modalities have focused on a system with high efficiency. The bicortical microimplant with 2 anchorage units designed by the authors appears to meet this criterion. Furthermore, intrusion of an overgrown tooth is often a desirable orthodontic movement limited principally by inadequate dental anchorage. Forces from an intrusion arch can cause an adverse tip-back action of the anchor molar.9 Bicortical microimplants with bilateral anchorage units might also be an effective alternative for absolute intrusion of the teeth because of the optimized biomechanics in tooth movement.

Repeatable periapical radiographs could help to better define the exact location for implants and enhance the visualization of the displacement of P4. Furthermore, it could help to detect bone changes around the implant.10 However, lingual appliances limit the use of customized x-ray jigs needed for repeatable radiographs. Radiographs with x-ray jigs also have limitations, including projection error.9 To measure the displacement of the root of P4, we measured only the “virtual roots.” The 2 hooks of the full-cast crown were set to the level of the apex of the roots of P4, so they looked like 2 “virtual roots.” It was readily apparent that the “virtual roots” have a strong relationship with the real roots. We postulated that displacement of the “virtual roots” of P4 was approximately equal to the displacement of the real roots. In this way, the displacement of the root of P4 can be measured easily. An important finding of this study is that P4 moved mesially without rotation by bilateral orthodontic loading. It was confirmed by clinical measurement of the relative displacement of the 2 “virtual roots” of P4 (Fig 5, D). In the study by Saito et al,11 although segmented edgewise rectangular archwires with a loop were placed between the implants and P4 to control the mesial displacement of P4, tipping and rotation of P4 were still observed. The bilateral force system was an easy way to control the rotation of P4. If the line of action of an applied force passes through the center of resistance of a tooth, the tooth will respond with translation in the direction of the line of action of the applied force.8

American Journal of Orthodontics and Dentofacial Orthopedics Volume 132, Number 3

Wu, Huang, and Zhao 357

Fig 5. Distances measured in both groups during treatment period. A, CA-M1 distances were almost unchanged; B, CA-IB distances were almost unchanged; C, M1-P4 distance remained unchanged on unloaded side but increased significantly on loaded side; D, no significant relative displacement of 2 “virtual roots” of P4. Degree of rotation of P4 expressed as value of M1-P4B minus M1-P4L.

Fig 6. Displacement of “crown” of P4 was significantly greater than that of “ root” at 10 weeks and thereafter on loaded side; this meant mesial tipping of P4 at end of tooth movement.

However, in our study, P4 moved bodily at the beginning of bilateral loading, but with tipping to some extent at the end of treatment (Fig 4). The reasons for the tipping of P4 include (1) the dogs’ mandibles were so compact that the tooth could not easily move even with bilaterally applied orthodontic force, and (2) the

Fig 7. Average BIC in both groups after 12 weeks of treatment. No statistical difference in BIC between groups.

center of resistance varied with alveolar bone height8— ie, when P4 moved into the possible resorption site of alveolar bone in the edentulous area, the center of resistance of P4 went deeply into the apical part of the tooth. The unexpected tipping of the teeth, from a clinical point of view, can be controlled or corrected by an archwire with a T or an L loop, or by a microimplant placed in the retromolar area.2

358 Wu, Huang, and Zhao

American Journal of Orthodontics and Dentofacial Orthopedics September 2007

Fig 8. Stained (van Gieson stain) images of slices perpendicular to long axis of implant. Average BIC was A, 24.9% on loaded side and B, 23.3% on unloaded side after 12 weeks of treatment.

All loaded bicortical microimplants with 2 heads exposed in the oral cavity remained stable during orthodontic force application; this was shown by the clinical measurements of the implant position and by the results of the histologic and histomorphometric examinations. Good primary stability is crucial for immediate loading and thus the success of a microimplant.2 It depends on the surgical technique, the geometry of the implant (its length, diameter, and type), and the local amount of bone and its density.12 Compared with a microimplant, a bicortical microimplant is longer in length and similar in diameter. Better implant stability can also be achieved through bicortical stabilization. Ivanoff et al13 demonstrated that removal torques for bicortically stabilized implants were twice the values for implants with monocortical engagement in a study using rabbit tibiae. The usefulness of bicortical implants for orthodontic anchorage was also proven in a clinical study. Freudenthaler et al6 showed that some load-distributing advantages can be achieved through bicortical stabilization of implants in the mandible by engagement of the lingual cortical plate. It is well known that high stress concentration is an important factor for implant failure. Orthodontic force loading on microimplants can be divided into 2 forces perpendicular to each other,8 one of which is parallel to the implant’s long axis. The parallel force is responsible for the out-pulling of the implant, which is thought to be detrimental to its stability. It is reasonable to adjust the orientation of the loading force to enlarge the force division perpendicular to the long axis of microimplant, resulting in better primary stability for immediate loading.14 However, the increased perpendicular force division increases the compressive stress in the bone interface. Until now, the physiologic stress in orthodontic microimplant-bone interface was unknown, but it is recommended that orthodontists use light forces in loading microimplants. In their nonanimal

implant models, Pierrisnard et al15 and Jeong et al16 found that engagement of lingual cortical plate changed maximum stress in the crestal cortical bone compared with nonengagement. It is likely that the orthodontic force can be efficiently shared by the bicortical bone; this decreases the stress at the microimplant-bone interface. Mesialization of posterior tooth with a bicortical microimplant might have several advantages: (1) 2 anchorage units for bilateral force, (2) dissipating orthodontic force with bicortical bone, (3) no rotation of tooth, and (4) better primary stability and immediate loading. The disadvantages might include complicated placement of the bicortical microimplant and a possible intense tongue reaction. From a clinical point of view, in the case of tongue soreness, a patient with limited lingual sulcus is not recommended for this bicortical microimplant, and the springs delivering the force should be covered with a soft rubber tube. BIC was used as an index of osseointegration in the literature.17,18 Osseointegration with as little as 5% bone contact at the bone-implant interface successfully resisted about 200 to 300 g of orthodontic force in the mandibles of beagles.17 The osseointegration of the bicortical microimplant was 24.9% on average; this was strong enough for orthodontic loading. As we know, a temporary microimplant must be extracted after functional loading. Ohmae et al19 showed that even 40% to 50% partial osseointegrated microimplant, in screw shape, could be removed by a screw driver easily. So 24.9% osseointegrated bicortical microimplant could be removed easily, if in screw shape. Early loading had been thought to decrease osseointegration,20 but a recent study by Nkenke et al21 showed that immediate loading does not affect the bone-mineral apposition rate when compared with unloaded implants with good primary stability.21 The osseointegration of loaded and unloaded bicortical microimplants in our

American Journal of Orthodontics and Dentofacial Orthopedics Volume 132, Number 3

study did not show differences; this meant that early orthodontic loading did not affect osseointegration of bicortical microimplants. In case of the possible bone damage, lowering the osseointegration of the bicortical microimplant is preferred. The smooth surface of the implant, thought to be detrimental to osseointegration,22,23 might be beneficial to bicortical microimplants. In addition, if our bicortical microimplant had been made in the shape of a screw, it might be removed easily by a screw driver. Improvements in the design and the fabrication of bicortical microimplants are needed. Moreover, a new generation of bicortical microimplant, made of degradable materials, without the difficulty of removal, is also under research. CONCLUSIONS

We focused on the usefulness of the bicortical microimplant with 2 anchorage units for bilateral orthodontic anchorage from the clinical viewpoint. The results showed that all loaded and unloaded bicortical microimplants remained stable during 12 weeks of treatment. Mesial displacement of posterior teeth without rotation in beagle dogs was achieved by bilateral orthodontic force. Bicortical microimplants with 2 anchorage units can function as anchors for mesial movement of posterior teeth. REFERENCES 1. Kyung SH, Choi JH, Park YC. Miniscrew anchorage used to protract lower second molars into first molar extraction sites. J Clin Orthod 2003;37:575-9. 2. Kyung HM, Park HS, Bae SM, Sung JH, Kim IB. Development of orthodontic micro-implants for intraoral anchorage. J Clin Orthod 2003;37:321-8. 3. Favero L, Brollo P, Bressan E. Orthodontic anchorage with specific fixtures: related study analysis. Am J Orthod Dentofacial Orthop 2002;122:84-94. 4. Bae SM, Park HS, Kyung HM, Kwon OW, Sung JH. Clinical application of micro-implant anchorage. J Clin Orthod 2002;36: 298-302. 5. Maino BG, Bednar J, Pagin P, Mura P. The spider screw for skeletal anchorage. J Clin Orthod 2003;37:90-7. 6. Freudenthaler JW, Haas R, Bantleon HP. Bicortical titanium screws for critical orthodontic anchorage in the mandible: a preliminary report on clinical applications. Clin Oral Implants Res 2001;12:358-63. 7. Wu JC, Huang JN, Zhao SF, Xu XJ, Xie ZJ. Radiographic and surgical template for placement of orthodontic microimplants in interradicular areas: a technical note. Int J Oral Maxillofac Implants 2006;21:629-34.

Wu, Huang, and Zhao 359

8. Smith RJ, Burstone CJ. Mechanics of tooth movement. Am J Orthod 1984;85:294-307. 9. Southard TE, Buckley MJ, Spivey JD, Krizan KE, Casko JS. Intrusion anchorage potential of teeth versus rigid endosseous implants: a clinical and radiographic evaluation. Am J Orthod Dentofacial Orthop 1995;107:115-20. 10. Hermann JS, Schoolfield JD, Nummikoski PV, Buser D, Schenk RK, Cochran DL. Crestal bone changes around titanium implants: a methodologic study comparing linear radiographic with histometric measurements. Int J Oral Maxillofac Implants 2001; 16:475-85. 11. Saito S, Sugimoto N, Morohashi T, Ozeki M, Kurabayashi H, Shimizu H, et al. Endosseous titanium implants as anchors for mesiodistal tooth movement in the beagle dog. Am J Orthod Dentofacial Orthop 2000;118:601-7. 12. Nkenke E, Hahn M, Weinzierl K, Radespiel-Troger M, Neukam FW, Engelke K. Implant stability and histomorphometry: a correlation study in human cadavers using stepped cylinder implants. Clin Oral Implants Res 2003;14:601-9. 13. Ivanoff CJ, Sennerby L, Lekholm U. Influence of mono- and bicortical anchorage on the integration of titanium implants. A study in the rabbit tibia. Int J Oral Maxillofac Surg 1996;25:229-35. 14. Costa A, Raffainl M, Melsen B. Miniscrews as orthodontic anchorage: a preliminary report. Int J Adult Orthod Orthognath Surg 1998;13:201-9. 15. Pierrisnard L, Renouard F, Renault P, Barquins M. Influence of implant length and bicortical anchorage on implant stress distribution. Clin Implant Dent Relat Res 2003;5:254-62. 16. Jeong CM, Caputo AA, Wylie RS, Son SC, Jeon YC. Bicortically stabilized implant load transfer. Int J Oral Maxillofac Implants 2003;18:59-65. 17. Deguchi T, Takano-Yamamoto T, Kanomi R, Hartsfield JK Jr, Roberts WE, Garetto LP. The use of small titanium screws for orthodontic anchorage. J Dent Res 2003;82:377-81. 18. Wehrbein H, Merz BR, Hammerle CH, Lang NP. Bone-toimplant contact of orthodontic implants in humans subjected to horizontal loading. Clin Oral Implants Res 1998;9:348-53. 19. Ohmae M, Saito S, Morohashi T, Seki K, Qu H, Kanomi R, et al. A clinical and histological evaluation of titanium mini-implants as anchors for orthodontic intrusion in the beagle dog. Am J Orthod Dentofacial Orthop 2001;119:489-97. 20. Ohashi E, Pecho OE, Moron M, Lagravere MO. Implant vs screw loading protocols in orthodontics. Angle Orthod 2006;76: 721-7. 21. Nkenke E, Lehner B, Weinzierl K, Thams U, Neugebauer J, Steveling H, et al. Bone contact, growth, and density around immediately loaded implants in the mandible of mini pigs. Clin Oral Implants Res 2003;14:312-21. 22. Lossdorfer S, Schwartz Z, Wang L, Lohmann CH, Turner JD, Wieland M, et al. Microrough implant surface topographies increase osteogenesis by reducing osteoclast formation and activity. J Biomed Mater Res A 2004;70:361-9. 23. Grizon F, Aguado E, Hure G, Basle MF, Chappard D. Enhanced bone integration of implants with increased surface roughness: a long term study in the sheep. J Dent 2002;30:195-203.