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Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats
Injury, Int. J. Care Injured 40 (2009) 831–834
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats Jie Long a,1, Wei Tang a,1, Yu-bo Fan b,*, Wei-dong Tian a, Fan Feng a, Lei Liu a, Xiao-hui Zheng a, Wei Jing a, Ling Wu b a b
Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, PR China Key Lab of Biomechanics, Sichuan University, Chengdu 610065, PR China
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 24 September 2008
Objective: Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. Use of a rapid distraction rate in craniofacial distraction osteogenesis to shorten the distraction period is possible owing to the unique characteristics of craniofacial bones, including an abundant blood supply and rapid bone healing compared with long bones. The effects of using a rapid distraction rate in the treatment of craniofacial deformities are currently unclear, however. The objective of this study was to investigate the effects of a rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats. Methods: Sixteen goats were randomly divided into four groups consisting of four goats each. In Groups A, B, and C, the right mandible of each goat was distracted at a rate of 0.8 mm/d, 1.6 mm/d, and 2.0 mm/d, respectively; Group D was the control group and did not undergo distraction. Six weeks after the conclusion of distraction, bone densitometry and three-point bending testing were performed in all groups. Results: The mean bone density value of goats in Group A was significantly higher than those of all the other groups (p < 0.05), and the mean bone density value of goats in Group C was significantly lower than those of all the other groups (p < 0.05). The mean curve slope, peak stress, bending modulus, and energy to failure values of Groups A, B, and C were all significantly lower than those of the control group (p < 0.05). As the distraction rate increased, the curve slope and peak stress values gradually declined (p < 0.05). Conclusions: Use of a rapid distraction rate in mandibular distraction osteogenesis may have detrimental effects on the quality of new bone, despite the abundant blood supply of craniofacial bones. ß 2008 Elsevier Ltd. All rights reserved.
Keywords: Distraction osteogenesis Distraction rate Bone densitometry Biomechanical strength
Introduction Patients with craniofacial deformities usually require skeletal expansion. Traditional treatment methods involve autogenous bone grafting, which often results in problems including graft resorption, infection, and donor site morbidity. A newer technique for skeletal expansion, distraction osteogenesis, can help overcome these problems.2,6,11 In addition to avoiding bone grafting and donor site morbidity, this technique allows the concurrent expansion of the soft-tissue envelope.3 The first use of distraction osteogenesis for lengthening of the mandible was reported by McCarthy et al. in 1992.8 Since then, distraction osteogenesis has
* Corresponding author. E-mail address: [email protected] (Y.-b. Fan). 1 These two authors equally contributed to this work. 0020–1383/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2008.09.011
become a widely used technique in the treatment of craniofacial deformities. In recent years, studies have been conducted on the factors that influence the quality and quantity of new bone generated during distraction osteogenesis. It is generally accepted that the biomechanical properties of the distraction force have an important effects on stress distribution in the distraction gap, which determines the quality and quantity of the newly generated bone.12,13 One important biomechanical factor of the distraction force is the rate of distraction: different distraction rates may have different effects on the newly generated bone according to the tension-stress effect. For long bones, it has been found that the most effective distraction rate is 1.0 mm/d; a slower rate can result in premature bone formation, and a more rapid rate may lead to fibrous union.6,7 These findings have been applied to distraction of other skeletal areas as well. The craniofacial bones, however, have unique characteristics including an abundant blood supply and a
J. Long et al. / Injury, Int. J. Care Injured 40 (2009) 831–834
832
rapid rate of bone healing compared with long bones. Therefore, a rapid distraction rate might be considered in the treatment of craniofacial deformities.5 Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. By shortening the distraction period, the use of a rapid distraction rate in craniofacial distraction osteogenesis may be a way of overcoming these problems. In this study we evaluated the effects of different distraction rates in a large-animal model on the quality of the new bone generated during mandibular distraction osteogenesis, including biomechanical strength and bone density values. The primary objective was to assess the feasibility of using a rapid distraction rate in mandibular distraction osteogenesis.
immediately anterior to the first premolar with a pneumatic fissure-cutting bur. During the surgical procedure, care was taken to maintain the continuity of the periosteum. The distractor was placed along the plane perpendicular to the corticotomy cut fissure and fixed with 3-mm-diameter titanium screws. Finally, the periosteum, subcutaneous tissue, and skin were repositioned and closed in layers with 3–0 silk sutures, and the activation rod was placed submandibularly. After the surgical procedure, an antibiotic (300 mg cefoperazone sodium) was administered to every animal by intramuscular injection twice daily for 2 weeks, and the skin wound was thoroughly cleaned daily to prevent infection.
Methods
A total of 16 goats were divided into four groups consisting of four animals each. Group A underwent distraction at a rate of 0.8 mm/d for 12 days, Group B underwent distraction at a rate of 1.6 mm/d for 6 days, Group C underwent distraction at a rate of 2.0 mm/d for 5 days, and Group D was the control group, which underwent surgery involving the skin incision and periosteum but not corticotomy or fixation of a distraction device. In the distraction groups, distraction was performed four times daily after a 7-d latency period, with a total elongation of about 10 mm in all animals. All of the animals were killed 6 weeks after the conclusion of distraction, and the distracted mandibles in the three distraction groups and the operative side mandibles of the control group were harvested for further analysis.
Animal models Sixteen male goats, each weighing about 20–24 kg, were used in this study. All of the animals were approved by the Chinese Academy of Agricultural Science (CAAS). All of the animals were kept in a recognised animal holding facility under veterinary supervision in the Laboratory Animal Center of West China Hospital, SiChuan University. Design of the distraction device A customised unilateral distraction device was designed for this study. The distraction device was made of titanium alloys and consisted of a retention plate, an activation rod, and a guide rod. The activation rod was positioned extraorally; one clockwise full turn of the activation rod resulted in a 0.4-mm separation between the two fixation arms. The maximum elongation capacity allowed by this distraction device was about 20 mm (Fig. 1). Anaesthesia, surgical procedure, and postoperative care All 16 animals underwent the same surgical procedure. The animal was positioned supine and anaesthetised by intramuscular injection of xylazine (5 mg/kg), acepromazine (1.5 mg/kg), and ketamine (20 mg/kg), and 2 mL of 2% lidocaine was injected subcutaneously in the right submandibular area. A submandibular skin incision was made longitudinally to expose the edentulous mandibular body between the anterior teeth and the first premolar. After carefully raising the periosteum, the mental blood vessel bundle was ligated, and corticotomy was performed
Subject groups and distraction procedure
Assessment methods Bone densitometry Density of the newly generated bone in the distraction gap was assessed using dual-energy X-ray bone densitometry (CHALLENGER, France). The harvested mandibles were placed horizontally on the densitometer, and the area of the bone tissue between the first premolar and the anterior teeth was projected by dual X-ray from buccal to lingual, and then the mean bone density value of newly generated bone was obtained. The bone density values of the control group were obtained using the same method. Biomechanical testing (three-point bending test) Soft-tissue was excised from the dissected mandibles. Bone tissue of the distraction gap in the three distraction groups and the mental foramen region of the control group was machined into 15mm 2-mm 1.5-mm standard specimens. During the cutting process, the specimens were moistened continuously with 0.145 M NaCl solution. The specimens were then stored frozen at 20 8C and were thawed to room temperature immediately before testing. All of the specimens underwent three-point bending testing with a WD10A electronic materials testing machine (Guangzhou City, China). The specimens were positioned and fixed on the base plate, and the three-point bending load was applied at a rate of 1 mm/min until the specimen ruptured. During the test, the displacement and load data of every specimen were recorded, and material mechanical testing parameters including slope of the stress–strain curve, peak stress, bending modulus, and energy to failure were obtained and analysed using a personal computer. Statistical tests
Fig. 1. Custom-made distraction devices.
Groups were compared by one-way analysis of variance and SNK-q test with SPSS version 11.0 software (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as p < 0.05.
J. Long et al. / Injury, Int. J. Care Injured 40 (2009) 831–834
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Table 1 Densitometry outcomes. Group Group Group Group Group
A B C D (control)
Number of animals
Bone density (g/cm2)
4 4 4 4
0.6112 0.0917* 0.4338 0.0409# 0.3075 0.0540* 0.4312 0.0517
Note: Data are expressed as mean S.D. * Significant differences were found between this group and the other three groups (p < 0.05). # No significant difference was found between this group and the control group (p > 0.05).
Biomechanical testing (three-point bending test) Fig. 2. The newly generated bone in the distraction gap.
Results Clinical outcome All of the animals completed the experimental process. The right mandibles of goats in Groups A, B, and C were lengthened to about 10 mm. Osteogenesis was achieved between the two bone fragments in all of the groups (Fig. 2), with no cases of osteonecrosis or nonunion observed. The distraction devices were stable until the day of killing, and obvious crossbite and malocclusion of the lower incisor were observed (Fig. 3). Bone densitometry The mean bone density values of the animals in all four groups are shown in Table 1. The mean bone density value of animals in Group A was significantly higher than those in the other three groups (p < 0.05). The mean bone density value of animals in Group C was significantly lower than those in the other three groups (p < 0.05). No statistically significant difference in bone density was found between Group B and Group D (p > 0.05).
The results for the three-point bending test are shown in Table 2. For curve slope, statistically significant differences were found between every two groups (p < 0.05). The mean curve slopes of Groups A, B, and C were all lower than that of the control group (p < 0.05), and as the distraction rate increased, the curve slope gradually declined significantly (p < 0.05). For peak stress, the mean values of Groups A, B, and C were all significantly lower than that of the control group (p < 0.05). Statistically significant differences were found between Groups A, B, and C (p < 0.05), and as the distraction rate increased, the peak stress value gradually decreased significantly (p < 0.05). For bending modulus and energy to failure, the mean values of Groups A, B, and C were all significantly lower than that of the control group (p < 0.05). The mean values for Group A were significantly higher than those for Groups B and C (p < 0.05), but no statistically significant differences were detected between Group B and Group C (p > 0.05). Discussion The main disadvantage of mandibular distraction osteogenesis is the long period required for bone distraction and consolidation.1,4,10 Reducing the overall treatment time would alleviate patient discomfort and inconvenience during the process, and this
Fig. 3. Obvious crossbite and malocclusion in distraction group (left). Normal in control (right). Table 2 Three-point bending test results. Group A Curve slope (N/mm) Peak stress (MPa) Bending modulus (GPa) Energy to failure (N mm)
333.75 51.25 51.75 4.64* 6.25 0.85* 1.42 0.24*
Group B *
Group C *
225.00 19.15 42.25 4.03* 4.85 0.31** 1.07 0.18**
Note: Data are expressed as mean S.D. * Significant differences were found between this group and the other three groups (p < 0.05). ** A significant difference was found between this group and the control group (p < 0.05).
Group D (control) *
171.25 27.80 31.00 4.76* 4.40 0.32** 0.85 0.13**
630.00 16.30 132.50 22.17 13.48 0.42 3.25 0.29
834
J. Long et al. / Injury, Int. J. Care Injured 40 (2009) 831–834
could be accomplished by using a rapid rate of distraction. As previously mentioned, the abundant blood supply of the craniofacial bones makes the use of a rapid distraction rate possible.5,9 To determine the feasibility of a rapid distraction rate to decrease the overall treatment time during mandibular distraction osteogenesis, we used a goat model to evaluate the quality of new bone generated during mandibular distraction osteogenesis at different distraction rates. Radiological and histological techniques are the two main traditional methods of assessing the maturity of bone tissue. Although these techniques can provide some information about the quality of the bone tissue, they cannot provide quantitative data on bone density and other biomechanical parameters. Bone is one kind of anisotropic and nonlinearly elastic material; thus density and biomechanical properties are more accurate measures of the maturity of bone tissue. In this study, dual-energy X-ray densitometry was used to investigate the density of the newly generated bone, and the three-point bending test was used to measure the bone’s biomechanical properties. Dual-energy X-ray densitometry has been regarded as a useful tool for assessing bone density because of its precise results and reasonable cost. The bone density value reflects the degree of mineralisation of the bone tissue and is closely related to the quantity and diameter of bone trabeculae per unit area. The conventional wisdom is that the higher the bone density, the greater the maturity of the bone tissue. The results of this study show that the distraction rate of 0.8 mm/d resulted in the highest bone density value and thus the greatest maturity of new bone. As the distraction rate increased, the bone density of the newly generated bone decreased, indicating an inverse correlation between distraction rate and bone maturity. Although the mean bone density values of Groups A and B were higher than that of the control group, this did not indicate that mineralisation of the newly generated bone in the 6th week after distraction was greater than that in normal bone tissue. Dual-energy X-ray densitometry measures bone mineralisation per unit area but not per unit volume. A large amount of callus was generated in the distraction gap according to the tension-stress effect, which led to the formation of thicker bone from buccal to lingual in the distraction gap. Therefore, although the mineralisation of the newly generated bone in the 6th week after distraction was not very advanced, dualenergy X-ray densitometry showed higher bone density than in normal bone tissue. The newly generated bone in the distraction gap will ultimately bear the repeated loads of mastication; therefore, biomechanical strength of the bone tissue is the most reliable parameter of bone maturity. In this study, the three-point bending test was used to evaluate the mechanical strength of the newly generated bone at various rates of distraction in order to determine the best mandibular distraction rate. The results showed that as the distraction rate increased, the curve slope, peak stress, bending modulus, and energy to failure values of newly generated bone decreased. Animals in Group A, the group with the slowest distraction rate of 0.8 mm/d, had the highest biomechanical strength of all three-distraction groups. The results demonstrated that as the distraction rate increases, the quality of the newly generated bone decreases. Overall test results showed that bone density and biomechanical strength of the newly generated bone were highest in the 0.8mm/d distraction group. Clearly, despite the abundant blood supply of craniofacial bones, use of a rapid distraction rate does not
improve the outcome. A distraction rate of about 0.8 mm/d may be optimal for achieving relatively efficient new bone formation whilst maintaining the quality and quantity of the newly generated bone. This study did not address distraction rates slower than 0.8 mm/d because an excessively slow distraction rate may cause premature bone healing and lead to a much longer treatment time, thus resulting in increased patient discomfort. Conclusions The results of this study indicate that rapid distraction may lead to formation of poor-quality new bone during mandibular distraction osteogenesis, despite the abundant blood supply of craniofacial bones. Therefore, the issue of how to shorten the distraction period remains a challenge. A new approach is local gene therapy using osteogenic growth factor, such as BMP-2, which may compensate for the detrimental effects of a rapid distraction rate on new bone formation. Our future work will focus on this new approach. Conflict of interest None declared. Acknowledgement This work was supported by research grants from the National Natural Science Foundation of China (No. 10502037), which are gratefully acknowledged. References 1. Antoci V, Ono CM, Antoci Jr V, Raney EM. Axial correction in children via distraction osteogenesis. Int Orthop 2006;30(4):278–83. 2. Carls FR, Sailer HF. Seven years clinical experience with mandibular distraction in children. J Craniomaxillofac Surg 1998;26(4):197–208. 3. Cope JB, Samchukov ML, Cherkashin AM. Mandibular distraction osteogenesis: a historic perspective and future direction. Am J Orthod Dento facial Orthop 1999;115(4):448–60. 4. Corcoran J, Hubli EH, Salyer KE. Distraction osteogenesis of costochondral neomandibles: a clinical experience. Plast Reconstr Surg 1997;100(2):311–5. 5. Hollier Jr LH, Higuera S, Stal S, Taylor TD. Distraction rate and latency: factors in the outcome of pediatric mandibular distraction. Plast Reconstr Surg 2006;117(7):2333–6. 6. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part 1. The influence of stability of fixation and soft-tissue preservation. Clin Orthop 1998;238:249–81. 7. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part 2. The influence of the rate and frequency of distraction. Clin Orthop 1989;239: 263–85. 8. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH. Lengthening the human mandible by gradual distraction. Plast Reconstr Surg 1992;89(1):1–10. 9. Mofid MM, Manson PN, Robertson BC, Tufaro AP, Elias JJ, Vander Kolk CA. Craniofacial distraction osteogenesis: a review of 3278 cases. Plast Reconstr Surg 2001;108(5):1103–14. 10. Molina F, Ortiz Monasterio F. Mandibular elongation and remodeling by distraction: a farewell to major osteotomies. Plast Reconstr Surg 1995;96(4):825– 40. discussion 841–2. 11. Morovic CG, Monasterio L. Distraction osteogenesis for obstructive apneas in patients with congenital craniofacial malformations. Plast Reconstr Surg 2000;105(7):2324–30. 12. Samchukov ML, Cope JB, Harper RP, Ross JD. Biomechanical considerations for mandibular lengthening and widening by gradual distraction. J Oral Maxillofac Surg 1998;56(1):51–9. 13. Waanders NA, Richards M, Steen H, Kuhn JL, Goldstein SA, Goulet JA. Evaluation of the mechanical environment during distraction osteogenesis. Clin Orthop 1998;349:225–34.
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats Jie Long a,1, Wei Tang a,1, Yu-bo Fan b,*, Wei-dong Tian a, Fan Feng a, Lei Liu a, Xiao-hui Zheng a, Wei Jing a, Ling Wu b a b
Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, PR China Key Lab of Biomechanics, Sichuan University, Chengdu 610065, PR China
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 24 September 2008
Objective: Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. Use of a rapid distraction rate in craniofacial distraction osteogenesis to shorten the distraction period is possible owing to the unique characteristics of craniofacial bones, including an abundant blood supply and rapid bone healing compared with long bones. The effects of using a rapid distraction rate in the treatment of craniofacial deformities are currently unclear, however. The objective of this study was to investigate the effects of a rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats. Methods: Sixteen goats were randomly divided into four groups consisting of four goats each. In Groups A, B, and C, the right mandible of each goat was distracted at a rate of 0.8 mm/d, 1.6 mm/d, and 2.0 mm/d, respectively; Group D was the control group and did not undergo distraction. Six weeks after the conclusion of distraction, bone densitometry and three-point bending testing were performed in all groups. Results: The mean bone density value of goats in Group A was significantly higher than those of all the other groups (p < 0.05), and the mean bone density value of goats in Group C was significantly lower than those of all the other groups (p < 0.05). The mean curve slope, peak stress, bending modulus, and energy to failure values of Groups A, B, and C were all significantly lower than those of the control group (p < 0.05). As the distraction rate increased, the curve slope and peak stress values gradually declined (p < 0.05). Conclusions: Use of a rapid distraction rate in mandibular distraction osteogenesis may have detrimental effects on the quality of new bone, despite the abundant blood supply of craniofacial bones. ß 2008 Elsevier Ltd. All rights reserved.
Keywords: Distraction osteogenesis Distraction rate Bone densitometry Biomechanical strength
Introduction Patients with craniofacial deformities usually require skeletal expansion. Traditional treatment methods involve autogenous bone grafting, which often results in problems including graft resorption, infection, and donor site morbidity. A newer technique for skeletal expansion, distraction osteogenesis, can help overcome these problems.2,6,11 In addition to avoiding bone grafting and donor site morbidity, this technique allows the concurrent expansion of the soft-tissue envelope.3 The first use of distraction osteogenesis for lengthening of the mandible was reported by McCarthy et al. in 1992.8 Since then, distraction osteogenesis has
* Corresponding author. E-mail address: [email protected] (Y.-b. Fan). 1 These two authors equally contributed to this work. 0020–1383/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2008.09.011
become a widely used technique in the treatment of craniofacial deformities. In recent years, studies have been conducted on the factors that influence the quality and quantity of new bone generated during distraction osteogenesis. It is generally accepted that the biomechanical properties of the distraction force have an important effects on stress distribution in the distraction gap, which determines the quality and quantity of the newly generated bone.12,13 One important biomechanical factor of the distraction force is the rate of distraction: different distraction rates may have different effects on the newly generated bone according to the tension-stress effect. For long bones, it has been found that the most effective distraction rate is 1.0 mm/d; a slower rate can result in premature bone formation, and a more rapid rate may lead to fibrous union.6,7 These findings have been applied to distraction of other skeletal areas as well. The craniofacial bones, however, have unique characteristics including an abundant blood supply and a
J. Long et al. / Injury, Int. J. Care Injured 40 (2009) 831–834
832
rapid rate of bone healing compared with long bones. Therefore, a rapid distraction rate might be considered in the treatment of craniofacial deformities.5 Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. By shortening the distraction period, the use of a rapid distraction rate in craniofacial distraction osteogenesis may be a way of overcoming these problems. In this study we evaluated the effects of different distraction rates in a large-animal model on the quality of the new bone generated during mandibular distraction osteogenesis, including biomechanical strength and bone density values. The primary objective was to assess the feasibility of using a rapid distraction rate in mandibular distraction osteogenesis.
immediately anterior to the first premolar with a pneumatic fissure-cutting bur. During the surgical procedure, care was taken to maintain the continuity of the periosteum. The distractor was placed along the plane perpendicular to the corticotomy cut fissure and fixed with 3-mm-diameter titanium screws. Finally, the periosteum, subcutaneous tissue, and skin were repositioned and closed in layers with 3–0 silk sutures, and the activation rod was placed submandibularly. After the surgical procedure, an antibiotic (300 mg cefoperazone sodium) was administered to every animal by intramuscular injection twice daily for 2 weeks, and the skin wound was thoroughly cleaned daily to prevent infection.
Methods
A total of 16 goats were divided into four groups consisting of four animals each. Group A underwent distraction at a rate of 0.8 mm/d for 12 days, Group B underwent distraction at a rate of 1.6 mm/d for 6 days, Group C underwent distraction at a rate of 2.0 mm/d for 5 days, and Group D was the control group, which underwent surgery involving the skin incision and periosteum but not corticotomy or fixation of a distraction device. In the distraction groups, distraction was performed four times daily after a 7-d latency period, with a total elongation of about 10 mm in all animals. All of the animals were killed 6 weeks after the conclusion of distraction, and the distracted mandibles in the three distraction groups and the operative side mandibles of the control group were harvested for further analysis.
Animal models Sixteen male goats, each weighing about 20–24 kg, were used in this study. All of the animals were approved by the Chinese Academy of Agricultural Science (CAAS). All of the animals were kept in a recognised animal holding facility under veterinary supervision in the Laboratory Animal Center of West China Hospital, SiChuan University. Design of the distraction device A customised unilateral distraction device was designed for this study. The distraction device was made of titanium alloys and consisted of a retention plate, an activation rod, and a guide rod. The activation rod was positioned extraorally; one clockwise full turn of the activation rod resulted in a 0.4-mm separation between the two fixation arms. The maximum elongation capacity allowed by this distraction device was about 20 mm (Fig. 1). Anaesthesia, surgical procedure, and postoperative care All 16 animals underwent the same surgical procedure. The animal was positioned supine and anaesthetised by intramuscular injection of xylazine (5 mg/kg), acepromazine (1.5 mg/kg), and ketamine (20 mg/kg), and 2 mL of 2% lidocaine was injected subcutaneously in the right submandibular area. A submandibular skin incision was made longitudinally to expose the edentulous mandibular body between the anterior teeth and the first premolar. After carefully raising the periosteum, the mental blood vessel bundle was ligated, and corticotomy was performed
Subject groups and distraction procedure
Assessment methods Bone densitometry Density of the newly generated bone in the distraction gap was assessed using dual-energy X-ray bone densitometry (CHALLENGER, France). The harvested mandibles were placed horizontally on the densitometer, and the area of the bone tissue between the first premolar and the anterior teeth was projected by dual X-ray from buccal to lingual, and then the mean bone density value of newly generated bone was obtained. The bone density values of the control group were obtained using the same method. Biomechanical testing (three-point bending test) Soft-tissue was excised from the dissected mandibles. Bone tissue of the distraction gap in the three distraction groups and the mental foramen region of the control group was machined into 15mm 2-mm 1.5-mm standard specimens. During the cutting process, the specimens were moistened continuously with 0.145 M NaCl solution. The specimens were then stored frozen at 20 8C and were thawed to room temperature immediately before testing. All of the specimens underwent three-point bending testing with a WD10A electronic materials testing machine (Guangzhou City, China). The specimens were positioned and fixed on the base plate, and the three-point bending load was applied at a rate of 1 mm/min until the specimen ruptured. During the test, the displacement and load data of every specimen were recorded, and material mechanical testing parameters including slope of the stress–strain curve, peak stress, bending modulus, and energy to failure were obtained and analysed using a personal computer. Statistical tests
Fig. 1. Custom-made distraction devices.
Groups were compared by one-way analysis of variance and SNK-q test with SPSS version 11.0 software (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as p < 0.05.
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Table 1 Densitometry outcomes. Group Group Group Group Group
A B C D (control)
Number of animals
Bone density (g/cm2)
4 4 4 4
0.6112 0.0917* 0.4338 0.0409# 0.3075 0.0540* 0.4312 0.0517
Note: Data are expressed as mean S.D. * Significant differences were found between this group and the other three groups (p < 0.05). # No significant difference was found between this group and the control group (p > 0.05).
Biomechanical testing (three-point bending test) Fig. 2. The newly generated bone in the distraction gap.
Results Clinical outcome All of the animals completed the experimental process. The right mandibles of goats in Groups A, B, and C were lengthened to about 10 mm. Osteogenesis was achieved between the two bone fragments in all of the groups (Fig. 2), with no cases of osteonecrosis or nonunion observed. The distraction devices were stable until the day of killing, and obvious crossbite and malocclusion of the lower incisor were observed (Fig. 3). Bone densitometry The mean bone density values of the animals in all four groups are shown in Table 1. The mean bone density value of animals in Group A was significantly higher than those in the other three groups (p < 0.05). The mean bone density value of animals in Group C was significantly lower than those in the other three groups (p < 0.05). No statistically significant difference in bone density was found between Group B and Group D (p > 0.05).
The results for the three-point bending test are shown in Table 2. For curve slope, statistically significant differences were found between every two groups (p < 0.05). The mean curve slopes of Groups A, B, and C were all lower than that of the control group (p < 0.05), and as the distraction rate increased, the curve slope gradually declined significantly (p < 0.05). For peak stress, the mean values of Groups A, B, and C were all significantly lower than that of the control group (p < 0.05). Statistically significant differences were found between Groups A, B, and C (p < 0.05), and as the distraction rate increased, the peak stress value gradually decreased significantly (p < 0.05). For bending modulus and energy to failure, the mean values of Groups A, B, and C were all significantly lower than that of the control group (p < 0.05). The mean values for Group A were significantly higher than those for Groups B and C (p < 0.05), but no statistically significant differences were detected between Group B and Group C (p > 0.05). Discussion The main disadvantage of mandibular distraction osteogenesis is the long period required for bone distraction and consolidation.1,4,10 Reducing the overall treatment time would alleviate patient discomfort and inconvenience during the process, and this
Fig. 3. Obvious crossbite and malocclusion in distraction group (left). Normal in control (right). Table 2 Three-point bending test results. Group A Curve slope (N/mm) Peak stress (MPa) Bending modulus (GPa) Energy to failure (N mm)
333.75 51.25 51.75 4.64* 6.25 0.85* 1.42 0.24*
Group B *
Group C *
225.00 19.15 42.25 4.03* 4.85 0.31** 1.07 0.18**
Note: Data are expressed as mean S.D. * Significant differences were found between this group and the other three groups (p < 0.05). ** A significant difference was found between this group and the control group (p < 0.05).
Group D (control) *
171.25 27.80 31.00 4.76* 4.40 0.32** 0.85 0.13**
630.00 16.30 132.50 22.17 13.48 0.42 3.25 0.29
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could be accomplished by using a rapid rate of distraction. As previously mentioned, the abundant blood supply of the craniofacial bones makes the use of a rapid distraction rate possible.5,9 To determine the feasibility of a rapid distraction rate to decrease the overall treatment time during mandibular distraction osteogenesis, we used a goat model to evaluate the quality of new bone generated during mandibular distraction osteogenesis at different distraction rates. Radiological and histological techniques are the two main traditional methods of assessing the maturity of bone tissue. Although these techniques can provide some information about the quality of the bone tissue, they cannot provide quantitative data on bone density and other biomechanical parameters. Bone is one kind of anisotropic and nonlinearly elastic material; thus density and biomechanical properties are more accurate measures of the maturity of bone tissue. In this study, dual-energy X-ray densitometry was used to investigate the density of the newly generated bone, and the three-point bending test was used to measure the bone’s biomechanical properties. Dual-energy X-ray densitometry has been regarded as a useful tool for assessing bone density because of its precise results and reasonable cost. The bone density value reflects the degree of mineralisation of the bone tissue and is closely related to the quantity and diameter of bone trabeculae per unit area. The conventional wisdom is that the higher the bone density, the greater the maturity of the bone tissue. The results of this study show that the distraction rate of 0.8 mm/d resulted in the highest bone density value and thus the greatest maturity of new bone. As the distraction rate increased, the bone density of the newly generated bone decreased, indicating an inverse correlation between distraction rate and bone maturity. Although the mean bone density values of Groups A and B were higher than that of the control group, this did not indicate that mineralisation of the newly generated bone in the 6th week after distraction was greater than that in normal bone tissue. Dual-energy X-ray densitometry measures bone mineralisation per unit area but not per unit volume. A large amount of callus was generated in the distraction gap according to the tension-stress effect, which led to the formation of thicker bone from buccal to lingual in the distraction gap. Therefore, although the mineralisation of the newly generated bone in the 6th week after distraction was not very advanced, dualenergy X-ray densitometry showed higher bone density than in normal bone tissue. The newly generated bone in the distraction gap will ultimately bear the repeated loads of mastication; therefore, biomechanical strength of the bone tissue is the most reliable parameter of bone maturity. In this study, the three-point bending test was used to evaluate the mechanical strength of the newly generated bone at various rates of distraction in order to determine the best mandibular distraction rate. The results showed that as the distraction rate increased, the curve slope, peak stress, bending modulus, and energy to failure values of newly generated bone decreased. Animals in Group A, the group with the slowest distraction rate of 0.8 mm/d, had the highest biomechanical strength of all three-distraction groups. The results demonstrated that as the distraction rate increases, the quality of the newly generated bone decreases. Overall test results showed that bone density and biomechanical strength of the newly generated bone were highest in the 0.8mm/d distraction group. Clearly, despite the abundant blood supply of craniofacial bones, use of a rapid distraction rate does not
improve the outcome. A distraction rate of about 0.8 mm/d may be optimal for achieving relatively efficient new bone formation whilst maintaining the quality and quantity of the newly generated bone. This study did not address distraction rates slower than 0.8 mm/d because an excessively slow distraction rate may cause premature bone healing and lead to a much longer treatment time, thus resulting in increased patient discomfort. Conclusions The results of this study indicate that rapid distraction may lead to formation of poor-quality new bone during mandibular distraction osteogenesis, despite the abundant blood supply of craniofacial bones. Therefore, the issue of how to shorten the distraction period remains a challenge. A new approach is local gene therapy using osteogenic growth factor, such as BMP-2, which may compensate for the detrimental effects of a rapid distraction rate on new bone formation. Our future work will focus on this new approach. Conflict of interest None declared. Acknowledgement This work was supported by research grants from the National Natural Science Foundation of China (No. 10502037), which are gratefully acknowledged. References 1. Antoci V, Ono CM, Antoci Jr V, Raney EM. Axial correction in children via distraction osteogenesis. Int Orthop 2006;30(4):278–83. 2. Carls FR, Sailer HF. Seven years clinical experience with mandibular distraction in children. J Craniomaxillofac Surg 1998;26(4):197–208. 3. Cope JB, Samchukov ML, Cherkashin AM. Mandibular distraction osteogenesis: a historic perspective and future direction. Am J Orthod Dento facial Orthop 1999;115(4):448–60. 4. Corcoran J, Hubli EH, Salyer KE. Distraction osteogenesis of costochondral neomandibles: a clinical experience. Plast Reconstr Surg 1997;100(2):311–5. 5. Hollier Jr LH, Higuera S, Stal S, Taylor TD. Distraction rate and latency: factors in the outcome of pediatric mandibular distraction. Plast Reconstr Surg 2006;117(7):2333–6. 6. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part 1. The influence of stability of fixation and soft-tissue preservation. Clin Orthop 1998;238:249–81. 7. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part 2. The influence of the rate and frequency of distraction. Clin Orthop 1989;239: 263–85. 8. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH. Lengthening the human mandible by gradual distraction. Plast Reconstr Surg 1992;89(1):1–10. 9. Mofid MM, Manson PN, Robertson BC, Tufaro AP, Elias JJ, Vander Kolk CA. Craniofacial distraction osteogenesis: a review of 3278 cases. Plast Reconstr Surg 2001;108(5):1103–14. 10. Molina F, Ortiz Monasterio F. Mandibular elongation and remodeling by distraction: a farewell to major osteotomies. Plast Reconstr Surg 1995;96(4):825– 40. discussion 841–2. 11. Morovic CG, Monasterio L. Distraction osteogenesis for obstructive apneas in patients with congenital craniofacial malformations. Plast Reconstr Surg 2000;105(7):2324–30. 12. Samchukov ML, Cope JB, Harper RP, Ross JD. Biomechanical considerations for mandibular lengthening and widening by gradual distraction. J Oral Maxillofac Surg 1998;56(1):51–9. 13. Waanders NA, Richards M, Steen H, Kuhn JL, Goldstein SA, Goulet JA. Evaluation of the mechanical environment during distraction osteogenesis. Clin Orthop 1998;349:225–34.