J Oral Maxillofac Surg 65:168-176, 2007
Low-Level Laser Effect on Mandibular Distraction Osteogenesis Michael Miloro, DMD, MD,* Jason J. Miller, DDS, MD,† and Julie A. Stoner, PhD‡ Purpose: The purpose of this study was to determine whether low-level laser (LLL) application during
distraction osteogenesis could accelerate bone regeneration and decrease the length of the consolidation phase and thereby reduce potential patient morbidity. Materials and Methods: Nine adult female New Zealand white rabbits underwent bilateral mandibular corticotomies and placement of unidirectional distraction devices (KLS-Martin LP, Jacksonville, FL). Each rabbit served as its own internal control. After a latency of 1 day, distraction progressed bilaterally at 1 mm per day for 10 days. Immediately after each device activation, the experimental side, chosen randomly, was treated with real LLL (Laser Medical Systems, Hedehusene, Denmark) of 6.0 J ⫻ 6 transmucosal sites in the area of the distraction gap. Radiographs were taken presurgically, immediately postsurgically, and weekly until sacrifice, and the bone was analyzed using a semiquantitative 4-point scale (Bone Healing Score [BHS]). Three animals each were sacrificed at 2, 4, and 6 weeks postdistraction, and each hemimandible was prepared for histologic examination in a blinded fashion. Results: Ten millimeters of distraction was achieved in each rabbit bilaterally. Radiographically, the BHS was higher for the LLL-treated group at all time periods. Histologically, the area of new bone trabeculation and ossification was more advanced for the LLL-treated group, with less intervening fibrovascular intermediate zone in the bony regenerate, at all time periods. The formation of a complete inferior border occurred sooner in the treatment group than in the controls. Conclusions: LLL accelerates the process of bone regeneration during the consolidation phase after distraction osteogenesis. The adjunctive use of LLL may allow a shortened period of consolidation and therefore permit earlier device removal, with the avoidance of morbidity associated with prolonged device retention. © 2007 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 65:168-176, 2007 Distraction osteogenesis has been applied to the craniomaxillofacial skeleton to treat a variety of disorders including congenital malformations and posttraumatic defects. The distraction process involves a
latency phase, a distraction phase, and a consolidation phase. During the consolidation phase, patients are required to wear the cumbersome distraction device to allow for bony union and prevent relapse. Unfortunately, these devices are esthetically displeasing and may have psychosocial effects. Their design impairs mastication and makes articulation more difficult. These devices are also prone to infection due to their transcutaneous or transmucosal design and may lead to unsightly scarring. Finally, relapse is a consideration if there is premature removal of the device or device hardware failure. It should be noted that the specific time frame for the consolidation period varies widely by investigators and clinicians and depends upon several factors, including patient characteristics (age, general health), radiographic findings (radiodense areas occupying the distraction gap), and clinical examination of bony stability; however, there remains controversy regarding the length of the consolidation period with no firm consensus amongst surgeons and investigators.
Received from the University of Nebraska Medical Center, Omaha, NE. *Leon F. Davis Professor and Section Chief, Residency Program Director, Section of Oral and Maxillofacial Surgery. †Resident, Plastic and Reconstructive Surgery; Formerly, Resident, Oral and Maxillofacial Surgery. ‡Assistant Professor, Department of Preventive and Societal Medicine. Supported by an educational grant from KLS-Martin, LP, Jacksonville, FL, and Laser Medical Systems, Hedehusene, Denmark. Address correspondence and reprint requests to Dr Miloro: Section of Oral and Maxillofacial Surgery, 985180 Nebraska Medical Center, Omaha, NE 68198-5180; e-mail:
[email protected] © 2007 American Association of Oral and Maxillofacial Surgeons
0278-2391/07/6502-0003$32.00/0 doi:10.1016/j.joms.2006.10.002
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FIGURE 1. A, Diagram of rabbit hemimandible with proposed corticotomy design in the anterior bogy region. B, Unidirectional distraction device (KLS-Martin, LP, Jacksonville, FL). Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
Low-level laser (LLL) treatment was first used to treat nonhealing and slow healing ulcers in 1971.1 Since then, LLL has been used to treat a variety of disorders including ankle sprains, rheumatoid arthritis, temporomandibular disorders, and numerous other conditions. In 1995, Barushka et al2 reported the use of LLL to promote bone repair. He showed that LLL could induce osteoblastic activity and bone repair at the site of injury. The exact mechanism of action of LLL therapy is unknown, but several theories exist that describe an association with NF-kappa-B, as well as other growth factors. More recently, LLL therapy has been shown to improve wound healing of both hard1-4 and soft tissues5 and fibroblasts,6 as well as specialized tissues7-10 and vascular endothelium11 and blood cell components.12 Additionally, LLL may induce osteoblastic activity and bone repair at the site of injury. The hypothesis of this study is that LLL will accelerate the process of bone healing during the consolidation period of distraction osteogenesis and permit a decreased length of the consolidation period for earlier device removal and reduced morbidity. While this is an animal study, further studies are warranted to determine clinical extrapolation.
169 underwent a midline submental incision with bilateral mandibular body corticotomies (just posterior to the mental foramina), and placement of unidirectional distraction devices (KLS-Martin LP, Jacksonville, FL) (Fig 1). The activation devices existed transcutaneously near the posterior border of the mandible bilaterally. Each rabbit served as its own internal control. After a latency of 1 day, distraction progressed once bilaterally at 1 mm per day for 10 days. Immediately after each device activation, the experimental side, chosen randomly, was treated with real LLL using a gallium-aluminum-arsenide (Ga-Al-As) laser of 820 nm and an output of 400 mW (Laser Medical Systems, Hedehusene, Denmark) of 6.0 Joules ⫻ 6 transmucosal sites on the buccal and lingual aspects of the area of the distraction gap (Fig 2). The control sides were treated with placebo by placement of the laser probe on the same 6 transmucosal sites as the laser-treated sides. Therefore, LLL and placebo treatment occurred for 10 days during distraction, and not after the end of the distraction period. Lateral oblique radiographs of the right and left mandibles were taken presurgically, immediately postsurgically, and at weekly intervals thereafter until sacrifice. Three animals each were sacrificed at 2, 4, and 6 weeks postdistraction (Fig 3). In a blinded fashion, the ex vivo clinical appearance of the distracted mandibles was analyzed using a semiquantitative 4-point scale or Bone Healing Score (BHS), which assessed the percentage of radioopacity that occupied the 1-cm distraction gap according to the following scale: 1 ⫽ 0%-25% opacity, osteotomy site clearly visible; 2 ⫽ 25%-50% opacity; 3 ⫽ 50%-75%
Materials and Methods After approval was obtained from the Institutional Animal Care and Use Committee (IACUC# 01-091-01), 9 adult female Harlan Sprague-Dawley rabbits were selected for the study. After general anesthesia was induced with ketamine 45 mg/kg intramuscularly, each of 9 adult female New Zealand white rabbits
FIGURE 2. Low-level laser unit gallium-aluminum, arsenide at 820 nm (Laser Medical Systems, Hedehusene, Denmark). Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
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FIGURE 3. Rabbit mandible at harvest with distraction devices in place. Note bone fill on the lingual aspect of the mandible in this 6-week specimen. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
of osteotomy site filled with radiopaque bone; and 4 ⫽ 75%-100% opacity, osteotomy site nearly not visible (ie, bone fills almost the entire gap). Also, stability was rated on a 4-point subjective scale (Bone Stability Scale [BSS]): 1 ⫽ unstable (nonunion); 2 ⫽ mobility in 2 planes (vertical and horizontal); 3 ⫽ mobility in 1 plane (horizontal or vertical); 4 ⫽ no mobility (ie, clinical union). Each hemimandible was then fixed in 2% formaldehyde and 0.1 mol/L cacodylate buffer, decalcified with 10% formic acid, embedded in paraffin, and sectioned into 6 micron sections, then examined histologically by light microscope in a blinded fashion. A nonparametric paired Wilcoxon test was used to compare differences between LLL and control groups of animals.
Results All animals were eating an adequate daily oral intake by postoperative day 3, and there were no
FIGURE 5. LLL and placebo (no LLL) hemimandible comparison at 2 weeks after distraction. Note less bony trabeculation in the placebo group, and immature bone completely occupying the distraction gap in the LLL group as opposed to a discontinuity in the placebo group. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
wound infections in any animal. Ten millimeters of distraction was achieved in each rabbit bilaterally, to achieve a Class III malocclusion (Fig 4). Radiographically, the BHS was higher for the LLL-treated group at all time periods. Histologically, the area of new bone trabeculation and ossification was more advanced for the LLL-treated group, with less intervening fibrovascular intermediate zone in the bony regenerate, at all time periods (Figs 5-7). The formation of a complete inferior border occurred sooner in the treatment group than in the controls. Results showed that LLL-treated mandibles displayed increased BHSs and increased BSSs. In the 2-week group, the LLL-treated mandibles displayed an average BHS of 2.3 and BSS of 2.3 compared with 1.3
FIGURE 4. Rabbit facial skeletal pattern after 10 mm of distraction. Note the Class III malocclusion. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
MILORO, MILLER, AND STONER
171 erence line indicate an increase with LLL treatment. These plots display the increase associated with LLL treatment, and also provide the raw measurements and, by week 6, all measurements of the percent gap occupied with bone are greater than 80% with both control and LLL therapy. In summary, based on the data from all 9 animals at the 3 time periods, the following findings were made: The median distraction area did not differ significantly between the LLL and control sides (P ⫽ .2). There was a statistically significant increase in bone area associated with the LLL treatment (P ⫽ .008). There was a statistically significant increase in the percentage of the gap occupied with bone associated with the LLL treatment (P ⫽ .01).
FIGURE 6. LLL and placebo (no LLL) hemimandible comparison at 4 weeks after distraction. Note more mature bone trabeculation in the LLL group. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
and 1.7, respectively, for nontreated mandibles. At 4 weeks, the LLL mandibles had an average BHS of 2.3 and BSS of 3.0 compared with nontreated values of 2 and 2.3, respectively. And at 6 weeks, the LLL mandibles showed an average BHS of 2.7 and BSS of 3.0, whereas nontreated mandibles showed values of 2.3 and 3.0, respectively. Histologically, LLL-treated mandibles showed improved bone formation, trabeculation, and consolidation most noticeable at the 4-week time point. The median distraction area measurement, bone area measurement, and percent gap occupied with bone assessed radiographically were compared between the LLL-treated sites and the control sites using a nonparametric paired Wilcoxon test. The median bone healing scores were compared between the LLL-treated sites and the control sites using a nonparametric paired Wilcoxon test. Paired data (LLL and control measurements) were collected on 9 animals. The 9 animals were divided evenly into 3 follow-up groups. The mean and standard deviation for the difference between the laser and control sides in distraction area, bone area, and percent gap occupied with bone are summarized in Table 1 according to the follow-up periods of 2, 4, and 6 weeks. The radiographic measures of distraction area, bone area, and percent gap occupied with bone are graphically displayed for each animal in Figures 8, 9, and 10. The horizontal axis corresponds to the control measurement and the vertical axis corresponds to the LLL measurement. Values above the diagonal ref-
Note that the effect of the LLL appeared to be greatest at the 4-week time period, after which the control side basically coincides with the LLL-treated side, although more data on more animals is needed to more definitively ascertain the differences in the effect of LLL therapy over time. Figure 11 displays the changes in the BHS over time. Separate figures are drawn for each animal and separate time trend curves are drawn for the LLL and control measurements. At all but a few time points, the bone healing measure with the LLL treatment was greater than the bone healing measure with the control treatment.
FIGURE 7. LLL and placebo (no LLL) hemimandible comparison at 6 weeks after distraction. Note formation of inferior border in the LLLtreated mandible with incomplete formation in the placebo mandible. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
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Table 1. AVERAGE DIFFERENCE BETWEEN THE LLL AND CONTROL GROUPS*
Follow-Up Period Difference in Outcome Measure Laser – Control Mean (SD)
2 Weeks (n ⫽ 3)
4 Weeks (n ⫽ 3)
Distraction area (mm2) Bone area (mm2) Percent gap occupied with bone
1.13 (1.96) 8.83 (0.12) 16.13 (1.88)
0.27 (6.59) 18.80 (4.57) 35.66 (9.59)
All Animals (n ⫽ 9)
6 Weeks (n ⫽ 3)
1.53 (0.35) 5.17 (3.69) 7.34 (7.15)
0.98 (3.49) 10.93 (6.78) 19.71 (13.94)
*For example, on average among animals sacrificed at 4 weeks, the bone area was 18.80 mm2 greater for the LLL group than the control group. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
A difference may be calculated in the BHS with LLL treatment and control treatment for each animal at each time point with the following statements:
At 1 week, there was no significant difference in the BHS associated with LLL treatment (P ⬎ .9). At 2 weeks, there is a significant increase in BHS associated with LLL treatment (P ⫽ .008). At 3 weeks, there was a marginally significant increase in BHS associated with LLL treatment (P ⫽ .06). At 4 weeks, there is a significant increase in BHS associated with LLL treatment (P ⫽ .02). At 5 weeks, there is no significant difference in the BHS associated with LLL treatment (P ⫽ .1). At 6 weeks, there is no significant difference in the BHS associated with laser treatment (P ⫽ .2).
Discussion While the mechanism of action of LLL treatment remains unknown,13 this study showed that LLL treatment significantly accelerated bone healing, based upon BSS, BHS, and histologic analysis, in the distraction gap of the rabbit mandible, when applied during the distraction process. Clinical healing of the distraction site using BSSs were noted to reach optimal levels
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At 1 week, all BHS were 1. At 2 weeks, 2 (22%) animals had a 2-unit increase, 6 (67%) animals had a 1-unit increase, and 1 (11%) animal had a 0-unit increase in the BHS with LLL treatment relative to control treatment. At 3 weeks, 1 (17%) animal had a 2-unit increase, 3 (50%) animals had a 1-unit increase, and 2 (33%) animals had a 0-unit increase in the BHS with LLL treatment relative to control treatment. At 4 weeks, 2 (33%) animals had a 2-unit increase and 4 (67%) animals had a 1-unit increase in the BHS with LLL treatment relative to control treatment. At 5 weeks, 1 (33%) animal had a 2-unit increase and 2 (67%) animals had a 1-unit increase in the BHS with LLL treatment relative to control treatment. At 6 weeks, 2 (67%) animals had a 1-unit increase and 1 (33%) animal had a 0-unit increase in the BHS with LLL treatment relative to control treatment. At each of the time points, the median increase in BHS with LLL treatment relative to control treatment was 1 unit.
These observations yield the following hypothesis testing results:
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FIGURE 8. Distraction area comparison for LLL versus control groups at end time period. Note: values above the diagonal line indicate an increase with LLL treatment.
FIGURE 9. Bone area comparison for LLL versus control groups at end time period. Note: values above the diagonal line indicate an increase with LLL treatment.
Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
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FIGURE 10. Percentage of distraction gap occupied with bone comparison for LLL versus control groups at end time period. Note: values above the diagonal line indicate an increase with LLL treatment. Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
earlier in the consolidation phase in the mandibles treated with LLL than in control animals. These differences became less significant at the end of the consolidation phase, perhaps due to normal bone maturation and healing. In the LLL-treated group, “optimal” level of bone stability of 3.0 was reached at 4 weeks, while in the placebo group, it was not reached until 6 weeks. At 4 weeks, the BSS was 3.0 for the LLL group and only 2.3 for the placebo group, indicating a more rapid progression to bony healing with the use of LLL. Also, a significantly higher amount (percentage) of bone was seen in the distraction gap of the LLL-treated animals than in the placebo group. In fact, all BSS scores for all animals were at 3.0, indicating movement in only one plane of space, which would indicate, at the very minimum, functional stability that would go on to complete bony union considering the progression over the previous 6 weeks; but further studies would be necessary to assess this hypothesis adequately. LLL may prove efficacious in allowing a shorter consolidation period phase of distraction osteogenesis. This would provide great benefit to patients, allowing them to avoid the burdens of a prolonged period of bony fixation. Future studies are warranted with larger numbers of animals. Also, further research is needed to determine the precise cellular and biochemical effects of LLL treatment on both hard and soft tissues. Other studies indicate that the use of LLL therapy (830 nm, 30 mW) had no effect on postoperative pain and swelling after third molar removal, although it should be recognized that LLL effects may be dose dependent.14 LLL therapy
has become popular in the management of many localized, painful, musculoskeletal disorders (osteoarthritis, rheumatoid arthritis), as well as peripheral nerve disorders, temporomandibular joint disease, and wound healing, and laser energy may produce both thermal and nonthermal effects. Most “low level” lasers operate with an average output power of between 1 and 50 mW, and therefore do not produce any thermal effects. The biological effects may include cell membrane stabilization and endogenous endorphin release. With regard to LLL effects on bone healing, it has been shown that LLL treatment has biostimulatory effects on bone marrow cells.15 Improvement in bone formation has been found in rat calverial defects,16 and in the area of dental implant osseointegration.17,18 Again, future studies are necessary to examine the timing, dosage, and frequency of LLL to maximize its effect on bone healing.19 The use of lasers at low energy has been shown to be an effective therapy for postsurgical edema and pain, as well as accelerated wound healing. LLL therapy has been applied extensively in the medical and dental specialties to treat both hard and soft tissue injuries, yet the biostimulatory effects are not completely understood, although many theories exist. The use of a galliumaluminum-arsenide laser at 820-830 nm wavelength in the near infrared spectrum can be used in the 70-, 150-, or 400-mW output ranges. The laser used in this study has a spot size of 0.13 cm2 with a probe diameter of 18 mm. Current theories suggest that transcription of certain nuclear proteins, such as a rhodopsin-kinase enzyme may be photosensitive at certain wavelengths and this may be responsible for the accelerated wound healing capabilities of the LLL. Another theory proposes that nuclear factor kappa-B (NF-B), a transcription factor, helps to induce certain gene transcription and, as a result, the LLL-treated hard and soft tissues allow translocation of NF-B into the nucleus to exert its effect on tissue protein repair elements. Despite these theories, there are few large, detailed, prospective randomized clinical trials of the biostimulatory effects of LLL in human subjects. In this small group of rabbits, the use of LLL therapy during distraction osteogenesis of the mandible resulted in a statistically significant accelerated process of normal bone healing compared with a placebo group of animals. While it may be true that the placebo-treated group would eventually go on to bony union, as in the LLL-treated group, a more rapid response was found in the laser-treated animals in terms of bone turnover and consolidation. Clinical studies are warranted to determine whether the use of LLL may accelerate the process of bony consolidation in human subjects, and the results presented here can-
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FIGURE 11. Raw data on Bone Healing Scores (BHS) for each animal at each time point. Note: at all but a few time points, the BHS with LLL group was greater than the control group. (Figure 11 continued on next page.) Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
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FIGURE 11 (cont’d). Miloro, Miller, and Stoner. Low-Level Laser Effect on Mandibular Distraction Osteogenesis. J Oral Maxillofac Surg 2007.
not be extrapolated clinically without further evidence-based studies.
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References 1. Mester E, Spiry T, Szende B, et al: Effect of lasers on wound healing. Am J Surg 122:532, 1971 2. Barushka O, Yaakobi T, Oron U: Effect of low-energy laser irradiation on the process of bone repair in the rat tibia. Bone 16:47, 1995 3. Khadra M, Kasem N, Haanes HR, et al: Enhancement of bone formation in rat calvarial bone defects using low-level laser therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:693, 2004 4. Khadra M, Ronold HJ, Lyngstadaas SP, et al: Low-level laser therapy stimulates bone-implant interaction: An experimental study in rabbits. Clin Oral Implants Res 15:325, 2004 5. Yaakobi T, Maltz L, Oron U: Promotion of bone repair in the cortical bone of the tibia in rats by low energy laser (He-Ne) irradiation. Calcif Tissue Int 59:297, 1996 6. Stadler I, Lanzafamee RJ, Evans R, et al: 830-nm irradiation increases the wound tensile strength in a diabetic murine model. Lasers Surg Med 28:220, 2001 7. Webb C, Dyson M, Lewis WHP: Stimulatory effect of 660 nm low level laser energy on hypertrophic scar-derived fibroblasts:
9.
10.
11.
12.
13.
14.
Possible mechanisms for increased cell counts. Lasers Surg Med 22:294, 1998 Fernando S, Hill CM, Walker R: A randomised double blind comparative study of low level laser therapy following surgical extraction of lower third molar teeth. Br J Oral Maxillofac Surg 31:170, 1993 Miloro M, Halkias, LE, Mallery S, et al: Low-level laser effect on neural regeneration in gore-tex tubes. Oral Surg Oral Med Oral Pathol 93:27, 2002 Rosner M, Caplan M, Cohen S, et al: Dose and temporal parameters in delaying injured optic nerve degeneration by lowenergy laser irradiation. Lasers Med Surg 13:611, 1993 Rochkind S, Nissan M, Barr-Nea L, et al: Response of peripheral nerve to He-Ne laser: Experimental studies. Lasers Med Surg 7:441, 1987 Gal D, Chokshi SK, Mosseri M, et al: Percutaneous delivery of low-level laser energy reverses histamine-induced spasm in atherosclerotic Yucatan microswine. Circulation 86:756, 1992 Stadler I, Evans R, Kolb B, et al: In vitro effects of low-level laser irradiation at 660 nm on peripheral blood lymphocytes. Lasers Surg Med 27:255, 2000 Fernando S, Hill CM, Walker R: A randomized double blind comparative study of low level laser therapy following surgical extraction of lower third molar teeth. Br J Oral Maxillofac Surg 31:170, 1993
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15. Dortbudak O, Haas R, Mailath-Pokorny G: Biostimulation of bone marrow cells with a diode soft laser. Clin Oral Implants Res 11:540, 2000 16. Khadra M, Kasem N, Haanes HR, et al: Enhancement of bone formation in rat calverial bone defects using low-level laser therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:693, 2004 17. Dortbudak O, Haas R, Mailath-Pokorny G: Effect of low-power
laser irradiation on bony implant sites. Clin Oral Implants Res 13:288, 2002 18. Khadra M, Ronald HJ, Lyngstadaas SP, et al: Low-level laser therapy stimulates bone-implant interaction: An experimental study in rabbits. Clin Oral Implants Res 15:325, 2004 19. Saito S, Shimizu N: Stimulatory effects of low-power laser irradiation on bone regeneration in midpalatal suture during expansion in the rat. Am J Orthod Dentofac Orthop 111:525, 1997
