Vol. 117 No. 4 April 2014
Effect of mandibular distraction osteogenesis on the temporomandibular joint: a systematic review of animal experimental studies Kristian Andersen, DDS, Thomas Klit Pedersen, DDS, PhD, Ellen Margrethe Hauge, MD, PhD, Søren Schou, DDS, PhD, and Sven Erik Nørholt, DDS, PhD Aarhus University Hospital, Aarhus, Denmark
Objective. The present systematic review aimed to test the hypothesis of no effect of mandibular distraction osteogenesis on the temporomandibular joint. Study Design. Animal experimental studies from January 1985 to August 2013 were included. Studies were searched in PubMed, Embase, Scopus, and the Cochrane Library. A total of 289 articles were identified, and 17 were included. Results. Included studies were characterized by a high risk of bias and by inhomogeneity related to animal species, experimental procedures, and evaluation methods. Mandibular distraction osteogenesis within physiologic limits may be followed by adaptive changes in bone, disk, and cartilage. Increased daily rates and total activation length may influence the severity of the adaptive changes. Conclusions. Animal experimental studies indicate that mandibular distraction osteogenesis may induce adaptive changes in the temporomandibular joint. Adaptive changes may be influenced by increased daily rates and total length of distraction osteogenesis. Well-designed studies are needed before final conclusions can be drawn. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:407-415)
During the past 20 years, distraction osteogenesis (DO) has commonly been used in the treatment of congenital or developmental abnormalities of the craniofacial skeleton. Earlier, the treatment modality was predominantly used to correct severe congenital mandibular malformations (such as Pierre Robin sequence, hemifacial microsomia, and Goldenhar syndrome), craniofacial syndromes (such as Apert, Crouzon, and Pfeiffer syndromes), and severe maxillary hypoplasia in patients with cleft lip and palate.1-5 Currently, DO is frequently used to correct severe mandibular retrognathia and mandibular asymmetry of either congenital or acquired etiology.6,7 Mandibular distraction osteogenesis (MDO) is recognized as an effective treatment procedure, but resorption of the condyle and loading of the cartilage resulting in growth disturbances in the temporomandibular joint (TMJ) have not been sufficiently studied in humans. In a number of animal studies, various aspects and mechanisms of bone formation during MDO have been evaluated.8-11 However, only limited data regarding complications have been published. Animal studies have suggested that lengthening of the mandible by MDO changes the biomechanical loading of the condyle and the articular surface of the TMJ.12,13 The effect of MDO on the TMJ has not yet been addressed in a systematic review of experimental Department of Oral and Maxillofacial Surgery, Aarhus University Hospital. Received for publication Oct 3, 2013; returned for revision Nov 20, 2013; accepted for publication Dec 17, 2013. Ó 2014 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.12.405
animal studies. The objective of the present systematic review of animal studies was therefore to test the hypothesis of no effect of MDO on the TMJ.
MATERIALS AND METHODS The inclusion criteria were as follows: 1. Animal studies evaluating the effect of MDO on the TMJ published in English from January 1, 1985, until August 13, 2013 The exclusion criteria were as follows: 1. MDO aiming to resolve alveolar defects or segmental defects 2. MDO on irradiated mandibles 3. Studies involving fewer than 5 animals The effect of MDO on the TMJ was evaluated by the following 7 outcome measures: 1) Changes in condylar cartilage 2) Changes in condylar bone metabolism
Statement of Clinical Relevance Adaptive changes may be influenced by increased daily rates and total length of mandibular distraction osteogenesis. Care must be taken not to apply increased rates and length in the planning of mandibular distraction osteogenesis in the clinical setting. 407
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Fig. 1. Search strategy for identification of studies.
3) Changes in microstructure
cortical
and
spongious
bone
4) Changes in macromorphology of the condyle 5) Changes in the articular disk 6) Changes in the glenoid fossa 7) Changes in macromorphology of the contralateral condyle The search strategy used for identification of studies is summarized in Figure 1. Computerized database search using PubMed, Scopus, and Embase was conducted with the help of a senior librarian specialized in health science database searching. A search strategy combining the following controlled vocabulary (MeSH) and free-text terms was used: (distraction osteogenesis) OR (distraction osteogeneses) OR callotaris OR callotases OR (bone lengthening) AND TMJ OR (temporomandibular joint) OR (temporomandibular joints). A thorough hand search of relevant journals published from January 1, 1985, until August 13, 2013, was performed (J Oral Maxillofac Surg (1985-2013), Int J Oral Maxillofac Surg (1986-2013), Br J Oral Maxillofac Surg (1985-2013), Oral Surg Oral Med Oral Pathol Oral Radiol Endod (1995-2011), Oral Surg Oral Med Oral Pathol Oral Radiol (2012-2013), J Craniomaxillofac Surg (1987-2013), Plast Reconstr Surg
(1985-2013), Am J Orthod Dentofacial Orthop (19862013), Int J Adult Orthodon Orthognath Surg (19862002), Orthod Craniofac Res (2002-2013), European Journal of Orthodontics (1985-2013). The search was performed by a single reviewer (K.A.). The titles of the identified articles were screened, and abstracts were evaluated if the title indicated that the study could fulfill the inclusion criteria. Full-text analysis was conducted (1) if the abstract indicated that the inclusion criteria were fulfilled or (2) if the abstract was unavailable (see Figure 1). Relevant studies were chosen by a single reviewer (K.A.). Studies were included by addressing the described outcome measures. Data were extracted by a single reviewer (K.A.) in a standardized manner into a spreadsheet to gain a systematic recording of the chosen outcome measures. Relevant information of the animal model used, surgical procedures, and distraction parameters were recorded, with focus on animal species, age of animals, distraction devices used, distracted side and site, vector applied, duration of latency, activation rate and frequency, consolidation period, and evaluation methods used (Table I). The studies found considerable variations in study design regarding animal species, distraction parameters, distraction vector, outcome measures, and methods applied; thus, metaanalyses were deemed not applicable. The search was conducted on August 13, 2013, and resulted in 707 studies (PubMed, 207; Embase, 247; Scopus, 253; Cochrane, 0), with a total of 289 unique studies (see Figure 1). After the review of titles and abstracts, full-text analysis included 60 articles, of which 17 were finally included (see Table I). No articles were added as the result of hand-searching. The quality assessment of the included studies was undertaken by 1 review author (K.A.) as part of the data extraction process (Table II). The quality assessment was performed according to the following criteria:
Estimation of sample size before study (yes/no) Randomization and statistical analysis (yes/no) Variation of outcome variable described (yes/no) Histologic evaluation involving unbiased stereologic methods (yes/no) Control group (yes/no) The studies were graded and dichotomized in 2 groups according to risk of bias: Low risk of bias (bias unlikely to alter the results) if all criteria were met High risk of bias (bias that weakens confidence in the results) if not all criteria were met
RESULTS Results of each outcome measure in the studies are presented. Animal experimental studies reporting the
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Table I. Included studies Author
Animals (study/control)
Age
Ahn et al. 2011
Rabbit (16/4)
Mature
Elgazzar et al. 2008 Harper et al. 1997 Karaharju-Suvanto et al. 1996 Kruse-Löseler et al. 2001 Kim et al. 2003 Kim et al. 2004 Liu et al. 2003 McCormick et al. 1995 Meng et al. 2010 Mihmanli et al. 2012 Rafferty et al. 2007 Sant’Anna et al. 2007 Stelnicki et al. 2000 Thurmüller et al. 2002 Thurmüller et al. 2006 Zou et al. 2001
Rabbit (16/2) Monkey (9/0) Sheep (17/0)
Distractor ForestaDent
Side
Site
Vector
UL
Body
Mature Custom-made Mature ND Immature ND
BL ML UL
Body Horizontal Symphysis Transversal Ramus Vertical
Rabbit (52/6)
Immature Vazquez-Diner
UL
Body
Rabbit (6/2) Rabbit (6/2) Rat (129/10) Dog (11/0) Rabbit (8/3) Rabbit (24/2) Minipig (20/8) Dog (8/1) Dog (10/6) Minipig (15/2) Minipig (15/2) Goat (8/2)
Mature Mature Mature Immature Mature Mature Mature Immature Mature Mature Immature Mature
ForestaDent UL Body ForestaDent UL Body Stryker-Leibinger UL Body ND UL Body Custom-made UL Ramus Custom-made UL Body Synthes UL Ramus KLS Martin BL Body Stryker UL/BL Angle Synthes UL Body Synthes UL Body Custom-made UL Body
Horizontal
Latency Rate Activation Total activation (d) (mm/d) per day length (mm) Consolidation (d) 5
0.5
1
3-5
14
4 7-14 5
1.5 1 0.5-1
2 2 ND
15 3-5 4.5-8.5
7-28 28 7-357
Horizontal
4
ND
1
0-13.7
4
Horizontal Horizontal Horizontal Horizontal Vertical Horizontal Oblique Horizontal Transversal Horizontal Horizontal Horizontal
7 7 3 10 7 5 1 7 5 0 0 7
0.5 0.5 0-0.6 1 0.5 0.5 1 0.5 1 1-4 1-4 0.5-1
1 1 1 1 2 2 1 2 1 2 1 2
2-5 2-5 0-5 10-20 7 5 4.2 10-12 ND 12 12 10
14 14 6-38 0-70 28-56 30-180 1-15 30-60 56 0-90 0-90 56
Evaluation methods Histology, immunohistochemistry Histomorphometric Histology Histology Histology, CT Immunohistochemistry Histology Radiography Histology, radiography Histology Histology Histology, EMG Histology, radiography Radiography Morphology Histology Histology, histomorphometry
BL, bilateral; CT, computed tomography; EMG, electromyography; ML, midline; ND, no data; PET, positron emission tomography; UL, unilateral.
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Table II. Methodologic quality assessment Study
Previous estimate of sample size
N
Ahn et al. 2011 Elgazzar et al. 2008 Harper et al. 1997 Karaharju-Suvanto et al. 1996 Kim et al. 2003 Kim et al. 2004 Kruse-Löseler et al. 2001 Liu et al. 2003 McCormick et al. 1995 Meng et al. 2010 Mihmanli et al. 2012 Rafferty et al. 2007 Sant’Anna et al. 2007 Stelnicki et al. 2000 Thurmüller et al. 2002 Thurmüller et al. 2006 Zou et al. 2001
ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND
16 16 9 17 6 6 52 129 11 8 24 20 8 10 15 15 8
Control group Randomization Yes Yes No No Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes
No No No No No No No No No Yes Yes No No No No No No
Outcome variable Unbiased variation stereologic method Risk of bias No No No No No Yes No Yes No Yes Yes Yes No No No Yes No
No No No No No No No No No No No No No No No No No
High High High High High High High High High High High High High High High High High
ND, no data.
effect of MDO on TMJ were inhomogeneous with respect to the animal model used (nonhuman primate, minipig, dog, goat, sheep, rabbit, and rat), and the number of animals in these studies varied from 8 to 129. Twelve studies used mature animals; 5, immature animals. In 13 studies, unilateral MDO was performed; 3 studies involved bilateral MDO; and a single study evaluated midline distraction. Most studies involved the mandibular body (12 studies); 4 studies involved the mandibular ramus; and 1 study involved the mandibular symphysis. A horizontal vector was applied in 12 studies, a vertical vector in 2 studies, a transversal vector in 2 studies, and an oblique vector in 1 study. Latency period varied between 0 and 14 days, and activation rate varied from 0.5 to 4.0 mm/d. Activation rate was once a day (10 studies) or twice a day (7 studies). Total activation length varied between 2 and 20 mm, and consolidation period varied between 0 and 357 days. The results are presented separately for each outcome measure in the following sections. Changes in condylar cartilage The condylar cartilage was predominantly evaluated by histologic methods (see Table I). Five studies found that a low rate of daily distraction did not induce damage to the cartilage14-18 (Table III). A thickening of the articular cartilage in the TMJ after MDO has been reported in 9 studies.13,15-22 Reversible thinning15,23-25 or reversible thickening of the cartilage after MDO was observed as well.26 An increased rate or total length of DO was associated with increased cellularity in the cartilage.15,18 Moreover, an increased rate was associated with thickening of the articular cartilage in 3 studies.15,19,20 However, thinning of the cartilage has also been found after a
high daily distraction rate,15,16 at high daily strain magnitudes,17 or at an increased total length of DO.19 A longterm, irreversible thinning of the cartilaginous zones in the bone formation after MDO has been observed in a single study.16 After mandibular midline DO, site-specific thickening of the cartilage on the surface was found.21 In conclusion, reported effects of MDO on TMJ cartilage varied, but physiologic rates may be well tolerated by the TMJ. However, increased daily rates or total lengths of MDO may induce irreversible changes in the TMJ cartilage. Changes in condylar bone metabolism Bone metabolism was predominantly assessed by semiquantitative histology, although few studies used histomorphometry (see Table I). Ten studies reported a change in bone metabolism after MDO13-16,19,20,22-25 (see Table III). Five studies reported an initial increase in bone formation,13,14,16,20,22 whereas 2 studies found an increased resorption of the subchondral bone.15,19 Three studies reported an increased remodeling of bone.23-25 Changes in bone metabolism were site-specific and located on anterior and posterior surfaces of the condyle.16,24 In conclusion, MDO was reported to induce various changes in bone metabolism, and most frequently an initial increase in bone formation was observed. Changes in cortical and spongious bone microstructure Experimental studies reporting the effect of MDO varied according to animal model and distraction parameters applied (see Table I). Condylar bone microstructure was assessed by semiquantitative histology or
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histomorphometry. Evaluation of structural parameters found a reversible thinning of trabeculae14,23(see Table III), a 10% decrease in microdensity (equivalent to bone thickness) at increased rates,12 and a decrease in trabecular connectivity.14 A single study found a reversible thickening of trabeculae.22 In conclusion, 5 studies have investigated the effect of MDO on the cortical and spongious bone microstructure, but no definitive conclusions on this outcome parameter can be drawn. Changes in macromorphology of the condyle Eight studies evaluated the condylar macromorphology after MDO.12,13,15,17,24,25,27,28 The condylar macromorphology was assessed by macroscopic examination and histologic methods (see Table I). Increased daily rates of DO were associated with a higher occurrence of changes in the condylar morphology12,15,17,25,27 (see Table III). Various morphologic changes have been connected with high daily rates of DO, including condylar size reduction in the anteroposterior dimension,12,13,27 uprighting of the condyle relative to the occlusal plane,12,15 increased convexity of the condyle’s anteroposterior dimension,13,27 and site-specific flattening of the condyle.17,24,27 Flattening, displacement of the condyle, and severe condylar erosion have been observed after transversal mandibular distraction and after displacement of the proximal segment of the mandible in relation to the distal segment.28 In conclusion, various macromorphologic changes of the mandibular condyle have been described after MDO, and changes were frequently observed after high daily distraction rates. Changes in the articular disk The articular disk was examined in 3 studies by macroscopic examination or histologic methods (see Table I). Two studies found a reversible thinning of the disk,14,27 and no change to the articular disk was observed in 1 study15 (see Table III). No studies investigated the effect of increased daily rates of DO or total activation length on the articular disk. In conclusion, no definite conclusions on the effect of MDO on the articular disk can be drawn. Changes in the glenoid fossa The glenoid fossa was assessed in 4 studies by macroscopic examination or histologic methods (see Table I). Two studies found a thinning of trabeculae in the glenoid fossa,12,23 and a single study detected erosion of the fossa after transversal mandibular DO28 (see Table III). In conclusion, no definite conclusions on the effect of MDO on the glenoid fossa can be drawn.
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Changes in macromorphology of the contralateral condyle The contralateral condyle was examined in 4 studies by macroscopic examination or histologic methods (see Table I). Various changes in the contralateral condyle were found (e.g., deformation, reduction in the anteroposterior dimension, and increased cartilage thickness) (see Table III).15,20,27 In conclusion, no definite conclusions can be drawn on the effect of MDO on the macromorphology of the contralateral condyle. Quality assessment The results of the methodologic quality standard are shown in Table II. No studies reported a prestudy estimation of sample size, and only 2 studies contained information about randomization of animals. No studies addressed the effect of MDO on the TMJ by unbiased stereologic methods. Seven studies informed about the variation of the chosen outcome variable. In conclusion, based on these 5 criteria, all studies were considered to be at high risk of bias.
DISCUSSION The aim of the present systematic review was to test the hypothesis of no effect of MDO on TMJ as evaluated in animal experimental studies. A total of 17 studies were included. It was concluded that MDO may induce adaptive changes in the TMJ. In addition, the adaptive changes may be influenced by increased daily rates and total length of DO. In the following discussion, the obtained results for all outcome measures are discussed together to obtain an adequate overview of the influence of MDO on the TMJ. The included studies were characterized by inhomogeneity related to animal species, number of animals included, age of animals, experimental procedures, and evaluation methods; thus, meta-analyses were not applicable. The quality assessment found that all studies were considered as having high risk of bias. Therefore, the conclusions in the current systematic review may be jeopardized by the aforementioned shortcomings. A frequent observation after MDO was a change in bone metabolism, and in most studies an initial increase in bone formation or an increased remodeling of the condyle was observed. However, results regarding this outcome measure were ambiguous, which may relate to the chosen animal model, to the surgical procedure, or to increased rates or magnitudes of DO in the few studies finding resorption. According to Wolf’s law, changes in loading may trigger a tissue reaction including metabolic changes to accommodate bone to the changes in loading.29 However, few animal studies have assessed the actual loading of the TMJ after MDO,
Ahn et al. 2011
Elgazzar et al. 2008
Harper et al. 1997 Karaharju-Suvanto et al. 1996
Kim et al. 2003
Kim et al. 2004
Kruse-Löseler et al. 2001
Liu et al. 2003
McCormick et al. 1995
Condylar cartilage
Condylar bone metabolism
Thickening, hyperplasia, and cellularity at increased daily rates of DO Reversible thinning and Anterior resorption hypoplasia followed by formation Site-specific changes in the cartilage Reversible thinning of Increased formation, cartilage. No initially correlation between histologic changes and total amount of DO Thickening of cartilage Increased resorption at increased daily and reduced rates; 5 mm/d formation at high reduces thickness of daily rates cartilage Thickening of cartilage Increased formation at increased daily rates Thinning at elevated strains. Comparable bone elongation at low strain magnitude induced minor alterations in the cartilage High rate may have a traumatic effect on the cartilage Reversible thinning
Remodeling of subchondral region
Bone microstructure
Condylar macromorphology
Articular disk
Glenoid fossa
Contralateral condyle
Flattening, anterior tipping and contour irregularities initially
Reversible thickening of trabeculae
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412
Table III. Summary of results of included studies
No changes
No difference
Flattening of the anteromedial part at elevated strains
Microdensity 10% decreased after increased daily rates
Reduction and uprighting of condyle after increased daily rates Slight flattening of the posterior aspect of the condylar head
Minimal histologic changes
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Study Meng et al. 2010
Mihmanli et al. 2012 Rafferty et al. 2007
Sant’Anna et al. 2007
Condylar cartilage Reversible thinning of cartilage. Depressions and erosions in cartilage infrequently observed Reversible thickening and hyperplasia Reversible thickening of cartilage
Condylar bone metabolism Reversible increased remodeling
Bone microstructure
Thurmüller et al. 2002 Remodeling at 1 mm/d. Higher rates may have a traumatic effect on the cartilage
Glenoid fossa
Contralateral condyle
Thinner trabeculae, thin cartilage layer
Reduction in A-P dimension, Increased convexity of condyle Reversible thinning
Reversible thinning of subcortical trabecular bone
Erosion of fossa after Site-specific flattening, application of varus erosion, and displacement of vector condyle At increased daily rates: Reversible thinning of medial condylar pole Increased convexity of condyle, reduction in A-P dimension (7%-27%), and flattening of the medial condylar pole Increased steepness of No changes anterior surface of condyle after 4 mm/d
7% reduction in A-P dimension
Site-specific increase in cartilage thickness at 4 mm/d
No changes
A-P, anteroposterior; HBO, hyperbaric oxygen treatment; DO, distraction osteogenesis; MAR, mineral apposition rate.
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Resorption of Thurmüller et al. 2006 Thickening and subchondral bone hyperplasia and cellularity at increased daily rates. Reversible at reduced daily rates of distraction Zou et al. 2001 Thickening at 1 mm/d. Increased formation on the posterosuperior Thinning and surface of the degeneration at condyle 2 mm/d
Articular disk
Reversible thinning of trabecular bone
Increased formation, reversible. MAR 16% increased without consolidation Cartilage maintained Increased formation Reversible thinning of with no degenerative posterosuperiorly subcortical bone; signs Trabeculae not multiple connected
Stelnicki et al. 2000
Condylar macromorphology
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Table III. Continued
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and those that did had contradictory results.12,13 In an animal study, an immediate but short-term increase in the TMJ synovial fluid hydrostatic pressure after activation of the distraction device was found.30 The increased intra-articular pressure may increase the loading of the condyle on the TMJ after MDO. In a finite element study, higher stresses and strains on the distraction side than on the nondistraction side after unilateral vertical ramus elongation were described, implicating an increase in loading of the TMJ.31 In the current review, predominantly reversible changes in the bone metabolism were observed, and only after increased daily rates or total length activation. In a few studies, irreversible changes were observed. Based on these findings, it may be theorized that DO at physiologic rates may induce a change loading of the TMJ condyle, leading to reversible changes in the bone metabolism. Few studies assessed changes in structural parameters of bone in the contralateral condyle, and based on this review, no definite conclusions can be drawn on this outcome measure. The current review found that macromorphologic changes (e.g., condylar size reduction in the anteroposterior dimension, uprighting of the condyle relative to the occlusal plane, increased convexity of the condyle in the anteroposterior dimension, and sitespecific flattening of the condyle) were frequently observed after high daily distraction rates. The macroscopic change of the condyle after DO may be considered as an adaptation of bone to meet new functional demands and can be anticipated to be consistent with the findings of changes in bony metabolism. The animal models included in the current review predominantly applied a horizontal vector, increasing the loading on the posterior surface of the condyle. The observed changes of macroscopic appearance of the condyle may all be induced by a horizontal vector. Remodeling may induce flattening of the anterior surface and a reduction of the anteroposterior dimension of the condyle, as well as an uprighting of the condyle relative to the occlusal plane and an increased convexity of the superior surface of the condyle. A transversal vector involves rotational forces at the condyle, inducing site-specific flattening on the posterolateral and anteromedial surfaces of the condyle.21 This illustrates that the effect of DO on the TMJ is dependent on the vector applied, which is why treatments must be analyzed as separate entities according to the vector applied. Animal studies involving transversal and vertical vectors are few, and based on this review, no conclusions can be drawn on this subject. No relationship was found between changes in cartilage and macroscopic changes of the condyle. The current systematic review found a disparity regarding
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changes in the cartilage thickness after DO, which may be explained by the anatomic variation of the TMJ of the different animals studied. It has been advocated that the increased thickness of the cartilage was a reactive response to maintain functional balance and resistance to external wear in the TMJ.26 However, it has been postulated that increased thickness of the cartilage was a result of functional unloading after the surgical trauma, owing to detachment of the masseter muscle.13 Increased daily distraction rates, increased strains, or increased lengths may cause irreversible damage and degenerative changes in the cartilage, but the limit between physiologic and increased levels was not defined in the included articles, and it may be influenced by many variables, including animal species and age. Physiologic rates may be well tolerated by the TMJ cartilage, inducing only reversible changes, but increased daily distraction rates or total activation length may induce irreversible changes in the TMJ cartilage. However, as previously stated, definitive conclusions on the effect of MDO on the condylar cartilage may be hampered by the lack of unbiased animal experimental studies. Few studies assessed changes in structural parameters of bone or changes in the contralateral condyle, the glenoid fossa, and the articular disk, and based on this review, no definite conclusions can be drawn on these outcome measures. Future studies should employ power calculations, include a control group, involve randomization, and use unbiased evaluation methods to reduce the overall risk of bias of the studies. It should also be recognized that MDO is often performed in patients with a compromised TMJ of either congenital or acquired etiology. This aspect has never been addressed in an animal experimental study.
CONCLUSION Animal experimental studies have indicated that MDO may induce adaptive changes in the TMJ. In addition, the adaptive changes may be influenced by increased daily rates and total activation length of DO. Therefore, care must be taken not to apply increased rates and length in the planning of MDO. However, further welldesigned studies are needed before final conclusions can be drawn. REFERENCES 1. Figueroa AA, Polley JW. Management of the severe cleft and syndromic midface hypoplasia. Orthod Craniofac Res. 2007;10: 167-179. 2. McCarthy JG, Stelnicki EJ, Grayson BH. Distraction osteogenesis of the mandible: a ten-year experience. Semin Orthod. 1999;5:3-8. 3. Molina F. Mandibular distraction: surgical refinements and longterm results. Clin Plast Surg. 2004;31:443-462.
OOOO Volume 117, Number 4 4. Satoh K, Mitsukawa N, Tosa Y, Kadomatsu K. Le Fort III midfacial distraction using an internal distraction device for syndromic craniosynostosis: device selection, problems, indications, and a proposal for use of a parallel bar for device-setting. J Craniofac Surg. 2006;17:1050-1058. 5. Van Sickels JE. Distraction osteogenesis: advancements in the last 10 years. Oral Maxillofac Surg Clin North Am. 2007;19: 565-574. 6. Mackool RL, Shetye P, Grayson B, McCarthy JG. Distraction osteogenesis in a patient with juvenile arthritis. J Craniofac Surg. 2006;17:387-390. 7. Nørholt SE, Jensen J, Schou S, Pedersen TK. Complications after mandibular distraction osteogenesis: a retrospective study of 131 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;4:420-427. 8. Troulis MJ, Glowacki J, Perrott DH, Kaban LB. Effects of latency and rate on bone formation in a porcine mandibular distraction model. J Oral Maxillofac Surg. 2000;58:507-513. 9. Costantino PD, Shybut G, Friedman CD, et al. Segmental mandibular regeneration by distraction osteogenesis: an experimental study. Arch Otolaryngol Head Neck Surg. 1990;116: 535-545. 10. Swennen G, Dempf R, Schliephake H. Cranio-facial distraction osteogenesis: a review of the literature, part II: experimental studies. Int J Oral Maxillofac Surg. 2002;31:123-135. 11. Mehrara BJ, Rowe NM, Steinbrech DS, et al. Rat mandibular distraction osteogenesis, II: molecular analysis of transforming growth factor beta-1 and osteocalcin gene expression. Plast Reconstr Surg. 1999;103:536-547. 12. Liu ZJ, King GJ, Herring SW. Alterations of morphology and microdensity in the condyle after mandibular osteodistraction in the rat. J Oral Maxillofac Surg. 2003;61:918-927. 13. Rafferty KL, Sun Z, Egbert M, Bakko DW, Herring SW. Changes in growth and morphology of the condyle following mandibular distraction in minipigs: overloading or underloading? Arch Oral Biol. 2007;52:967-976. 14. Sant’Anna EF, Gomez DF, Polley JW, et al. Histological evaluation of the temporomandibular joint after bilateral vertical ramus mandibular distraction in a canine model. J Craniofac Surg. 2007;18:155-162. 15. Thurmüller P, Troulis MJ, Rosenberg A, Chuang SK, Kaban LB. Microscopic changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible. J Oral Maxillofac Surg. 2006;64:249-258. 16. Zou S, Hu J, Wang D, Li J, Tang Z. Changes in the temporomandibular joint after mandibular lengthening with different rates of distraction. Int J Adult Orthodon Orthognath Surg. 2001;16: 221-225. 17. Kruse-Lösler B, Meyer U, Flören C, Joos U. Influence of distraction rates on the temporomandibular joint position and cartilage morphology in a rabbit model of mandibular lengthening. J Oral Maxillofac Surg. 2001;59:1452-1459. 18. Ahn SY, Kim SG. Condylar cartilaginous changes after mandibular distraction osteogenesis in rabbits. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:191-202. 19. Kim SG, Park JC, Kang DW, et al. Correlation of immunohistochemical characteristics of the craniomandibular joint with the
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21.
22.
23.
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26.
27.
28.
29.
30.
31.
degree of mandibular lengthening in rabbits. J Oral Maxillofac Surg. 2003;61:1189-1197. Kim SG, Ha JW, Park JC. Histological changes in the temporomandibular joint in rabbits depending on the extent of mandibular lengthening by osteodistraction. Br J Oral Maxillofac Surg. 2004;42:559-565. Harper RP, Bell WH, Hinton RJ, Browne R, Cherkashin AM, Samchukov ML. Reactive changes in the temporomandibular joint after mandibular midline osteodistraction. Br J Oral Maxillofac Surg. 1997;35:20-25. Karaharju-Suvanto T, Peltonen J, Laitinen O, Kahri A. The effect of gradual distraction of the mandible on the sheep temporomandibular joint. Int J Oral Maxillofac Surg. 1996;25:152-156. Meng Q, Chen G, Long X, Deng M, Cai H, Li J. Histological evaluation of condylar hyperplasia model of rabbit following distraction osteogenesis of the condylar neck. J Oral Rehabil. 2011;38:27-33. Elgazzar RF, El-Bialy TH, Megahed E. Effect of bilateral mandibular osteodistraction on the condylar cartilage: an experimental study on rabbits. Open Dent J. 2008;2:103-108. McCormick SU, McCarthy JG, Grayson BH, Staffenberg D, McCormick SA. Effect of mandibular distraction on the temporomandibular joint, part 1: canine study. J Craniofac Surg. 1995;6:358-363. Mihmanli A, Dolanmaz D, Tüz H, Pampu A, Dönmez HH. Histomorphometric examination of long-term changes in temporomandibular joints after mandibular lengthening by distraction osteogenesis in rabbits. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:600-603. Thurmüller P, Troulis MJ, Rosenberg A, Kaban LB. Changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible. J Oral Maxillofac Surg. 2002;60:1327-1333. Stelnicki EJ, Stucki-McCormick SU, Rowe N, McCarthy JG. Remodeling of the temporomandibular joint following mandibular distraction osteogenesis in the transverse dimension. Plast Reconstr Surg. 2001;107:647-658. Wolff J. The classic: on the inner architecture of bones and its importance for bone growth. 1870. Clin Orthop Relat Res. 2010;468:1056-1065. Herford AS, Hoffman R, Demirdji S, et al. A comparison of synovial fluid pressure after immediate versus gradual mandibular advancement in the miniature pig. J Oral Maxillofac Surg. 2005;63:775-785. Kofod T, Cattaneo PM, Dalstra M, Melsen B. Three-dimensional finite element analysis of the mandible and temporomandibular joint during vertical ramus elongation by distraction osteogenesis. J Craniofac Surg. 2005;16:586-593.
Reprint requests: Kristian Andersen, DDS Department of Oral and Maxillofacial Surgery Aarhus University Hospital Nørrebrogade 44 8000 Aarhus C Denmark [email protected]
Effect of mandibular distraction osteogenesis on the temporomandibular joint: a systematic review of animal experimental studies Kristian Andersen, DDS, Thomas Klit Pedersen, DDS, PhD, Ellen Margrethe Hauge, MD, PhD, Søren Schou, DDS, PhD, and Sven Erik Nørholt, DDS, PhD Aarhus University Hospital, Aarhus, Denmark
Objective. The present systematic review aimed to test the hypothesis of no effect of mandibular distraction osteogenesis on the temporomandibular joint. Study Design. Animal experimental studies from January 1985 to August 2013 were included. Studies were searched in PubMed, Embase, Scopus, and the Cochrane Library. A total of 289 articles were identified, and 17 were included. Results. Included studies were characterized by a high risk of bias and by inhomogeneity related to animal species, experimental procedures, and evaluation methods. Mandibular distraction osteogenesis within physiologic limits may be followed by adaptive changes in bone, disk, and cartilage. Increased daily rates and total activation length may influence the severity of the adaptive changes. Conclusions. Animal experimental studies indicate that mandibular distraction osteogenesis may induce adaptive changes in the temporomandibular joint. Adaptive changes may be influenced by increased daily rates and total length of distraction osteogenesis. Well-designed studies are needed before final conclusions can be drawn. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:407-415)
During the past 20 years, distraction osteogenesis (DO) has commonly been used in the treatment of congenital or developmental abnormalities of the craniofacial skeleton. Earlier, the treatment modality was predominantly used to correct severe congenital mandibular malformations (such as Pierre Robin sequence, hemifacial microsomia, and Goldenhar syndrome), craniofacial syndromes (such as Apert, Crouzon, and Pfeiffer syndromes), and severe maxillary hypoplasia in patients with cleft lip and palate.1-5 Currently, DO is frequently used to correct severe mandibular retrognathia and mandibular asymmetry of either congenital or acquired etiology.6,7 Mandibular distraction osteogenesis (MDO) is recognized as an effective treatment procedure, but resorption of the condyle and loading of the cartilage resulting in growth disturbances in the temporomandibular joint (TMJ) have not been sufficiently studied in humans. In a number of animal studies, various aspects and mechanisms of bone formation during MDO have been evaluated.8-11 However, only limited data regarding complications have been published. Animal studies have suggested that lengthening of the mandible by MDO changes the biomechanical loading of the condyle and the articular surface of the TMJ.12,13 The effect of MDO on the TMJ has not yet been addressed in a systematic review of experimental Department of Oral and Maxillofacial Surgery, Aarhus University Hospital. Received for publication Oct 3, 2013; returned for revision Nov 20, 2013; accepted for publication Dec 17, 2013. Ó 2014 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.12.405
animal studies. The objective of the present systematic review of animal studies was therefore to test the hypothesis of no effect of MDO on the TMJ.
MATERIALS AND METHODS The inclusion criteria were as follows: 1. Animal studies evaluating the effect of MDO on the TMJ published in English from January 1, 1985, until August 13, 2013 The exclusion criteria were as follows: 1. MDO aiming to resolve alveolar defects or segmental defects 2. MDO on irradiated mandibles 3. Studies involving fewer than 5 animals The effect of MDO on the TMJ was evaluated by the following 7 outcome measures: 1) Changes in condylar cartilage 2) Changes in condylar bone metabolism
Statement of Clinical Relevance Adaptive changes may be influenced by increased daily rates and total length of mandibular distraction osteogenesis. Care must be taken not to apply increased rates and length in the planning of mandibular distraction osteogenesis in the clinical setting. 407
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Fig. 1. Search strategy for identification of studies.
3) Changes in microstructure
cortical
and
spongious
bone
4) Changes in macromorphology of the condyle 5) Changes in the articular disk 6) Changes in the glenoid fossa 7) Changes in macromorphology of the contralateral condyle The search strategy used for identification of studies is summarized in Figure 1. Computerized database search using PubMed, Scopus, and Embase was conducted with the help of a senior librarian specialized in health science database searching. A search strategy combining the following controlled vocabulary (MeSH) and free-text terms was used: (distraction osteogenesis) OR (distraction osteogeneses) OR callotaris OR callotases OR (bone lengthening) AND TMJ OR (temporomandibular joint) OR (temporomandibular joints). A thorough hand search of relevant journals published from January 1, 1985, until August 13, 2013, was performed (J Oral Maxillofac Surg (1985-2013), Int J Oral Maxillofac Surg (1986-2013), Br J Oral Maxillofac Surg (1985-2013), Oral Surg Oral Med Oral Pathol Oral Radiol Endod (1995-2011), Oral Surg Oral Med Oral Pathol Oral Radiol (2012-2013), J Craniomaxillofac Surg (1987-2013), Plast Reconstr Surg
(1985-2013), Am J Orthod Dentofacial Orthop (19862013), Int J Adult Orthodon Orthognath Surg (19862002), Orthod Craniofac Res (2002-2013), European Journal of Orthodontics (1985-2013). The search was performed by a single reviewer (K.A.). The titles of the identified articles were screened, and abstracts were evaluated if the title indicated that the study could fulfill the inclusion criteria. Full-text analysis was conducted (1) if the abstract indicated that the inclusion criteria were fulfilled or (2) if the abstract was unavailable (see Figure 1). Relevant studies were chosen by a single reviewer (K.A.). Studies were included by addressing the described outcome measures. Data were extracted by a single reviewer (K.A.) in a standardized manner into a spreadsheet to gain a systematic recording of the chosen outcome measures. Relevant information of the animal model used, surgical procedures, and distraction parameters were recorded, with focus on animal species, age of animals, distraction devices used, distracted side and site, vector applied, duration of latency, activation rate and frequency, consolidation period, and evaluation methods used (Table I). The studies found considerable variations in study design regarding animal species, distraction parameters, distraction vector, outcome measures, and methods applied; thus, metaanalyses were deemed not applicable. The search was conducted on August 13, 2013, and resulted in 707 studies (PubMed, 207; Embase, 247; Scopus, 253; Cochrane, 0), with a total of 289 unique studies (see Figure 1). After the review of titles and abstracts, full-text analysis included 60 articles, of which 17 were finally included (see Table I). No articles were added as the result of hand-searching. The quality assessment of the included studies was undertaken by 1 review author (K.A.) as part of the data extraction process (Table II). The quality assessment was performed according to the following criteria:
Estimation of sample size before study (yes/no) Randomization and statistical analysis (yes/no) Variation of outcome variable described (yes/no) Histologic evaluation involving unbiased stereologic methods (yes/no) Control group (yes/no) The studies were graded and dichotomized in 2 groups according to risk of bias: Low risk of bias (bias unlikely to alter the results) if all criteria were met High risk of bias (bias that weakens confidence in the results) if not all criteria were met
RESULTS Results of each outcome measure in the studies are presented. Animal experimental studies reporting the
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Table I. Included studies Author
Animals (study/control)
Age
Ahn et al. 2011
Rabbit (16/4)
Mature
Elgazzar et al. 2008 Harper et al. 1997 Karaharju-Suvanto et al. 1996 Kruse-Löseler et al. 2001 Kim et al. 2003 Kim et al. 2004 Liu et al. 2003 McCormick et al. 1995 Meng et al. 2010 Mihmanli et al. 2012 Rafferty et al. 2007 Sant’Anna et al. 2007 Stelnicki et al. 2000 Thurmüller et al. 2002 Thurmüller et al. 2006 Zou et al. 2001
Rabbit (16/2) Monkey (9/0) Sheep (17/0)
Distractor ForestaDent
Side
Site
Vector
UL
Body
Mature Custom-made Mature ND Immature ND
BL ML UL
Body Horizontal Symphysis Transversal Ramus Vertical
Rabbit (52/6)
Immature Vazquez-Diner
UL
Body
Rabbit (6/2) Rabbit (6/2) Rat (129/10) Dog (11/0) Rabbit (8/3) Rabbit (24/2) Minipig (20/8) Dog (8/1) Dog (10/6) Minipig (15/2) Minipig (15/2) Goat (8/2)
Mature Mature Mature Immature Mature Mature Mature Immature Mature Mature Immature Mature
ForestaDent UL Body ForestaDent UL Body Stryker-Leibinger UL Body ND UL Body Custom-made UL Ramus Custom-made UL Body Synthes UL Ramus KLS Martin BL Body Stryker UL/BL Angle Synthes UL Body Synthes UL Body Custom-made UL Body
Horizontal
Latency Rate Activation Total activation (d) (mm/d) per day length (mm) Consolidation (d) 5
0.5
1
3-5
14
4 7-14 5
1.5 1 0.5-1
2 2 ND
15 3-5 4.5-8.5
7-28 28 7-357
Horizontal
4
ND
1
0-13.7
4
Horizontal Horizontal Horizontal Horizontal Vertical Horizontal Oblique Horizontal Transversal Horizontal Horizontal Horizontal
7 7 3 10 7 5 1 7 5 0 0 7
0.5 0.5 0-0.6 1 0.5 0.5 1 0.5 1 1-4 1-4 0.5-1
1 1 1 1 2 2 1 2 1 2 1 2
2-5 2-5 0-5 10-20 7 5 4.2 10-12 ND 12 12 10
14 14 6-38 0-70 28-56 30-180 1-15 30-60 56 0-90 0-90 56
Evaluation methods Histology, immunohistochemistry Histomorphometric Histology Histology Histology, CT Immunohistochemistry Histology Radiography Histology, radiography Histology Histology Histology, EMG Histology, radiography Radiography Morphology Histology Histology, histomorphometry
BL, bilateral; CT, computed tomography; EMG, electromyography; ML, midline; ND, no data; PET, positron emission tomography; UL, unilateral.
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Table II. Methodologic quality assessment Study
Previous estimate of sample size
N
Ahn et al. 2011 Elgazzar et al. 2008 Harper et al. 1997 Karaharju-Suvanto et al. 1996 Kim et al. 2003 Kim et al. 2004 Kruse-Löseler et al. 2001 Liu et al. 2003 McCormick et al. 1995 Meng et al. 2010 Mihmanli et al. 2012 Rafferty et al. 2007 Sant’Anna et al. 2007 Stelnicki et al. 2000 Thurmüller et al. 2002 Thurmüller et al. 2006 Zou et al. 2001
ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND
16 16 9 17 6 6 52 129 11 8 24 20 8 10 15 15 8
Control group Randomization Yes Yes No No Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes
No No No No No No No No No Yes Yes No No No No No No
Outcome variable Unbiased variation stereologic method Risk of bias No No No No No Yes No Yes No Yes Yes Yes No No No Yes No
No No No No No No No No No No No No No No No No No
High High High High High High High High High High High High High High High High High
ND, no data.
effect of MDO on TMJ were inhomogeneous with respect to the animal model used (nonhuman primate, minipig, dog, goat, sheep, rabbit, and rat), and the number of animals in these studies varied from 8 to 129. Twelve studies used mature animals; 5, immature animals. In 13 studies, unilateral MDO was performed; 3 studies involved bilateral MDO; and a single study evaluated midline distraction. Most studies involved the mandibular body (12 studies); 4 studies involved the mandibular ramus; and 1 study involved the mandibular symphysis. A horizontal vector was applied in 12 studies, a vertical vector in 2 studies, a transversal vector in 2 studies, and an oblique vector in 1 study. Latency period varied between 0 and 14 days, and activation rate varied from 0.5 to 4.0 mm/d. Activation rate was once a day (10 studies) or twice a day (7 studies). Total activation length varied between 2 and 20 mm, and consolidation period varied between 0 and 357 days. The results are presented separately for each outcome measure in the following sections. Changes in condylar cartilage The condylar cartilage was predominantly evaluated by histologic methods (see Table I). Five studies found that a low rate of daily distraction did not induce damage to the cartilage14-18 (Table III). A thickening of the articular cartilage in the TMJ after MDO has been reported in 9 studies.13,15-22 Reversible thinning15,23-25 or reversible thickening of the cartilage after MDO was observed as well.26 An increased rate or total length of DO was associated with increased cellularity in the cartilage.15,18 Moreover, an increased rate was associated with thickening of the articular cartilage in 3 studies.15,19,20 However, thinning of the cartilage has also been found after a
high daily distraction rate,15,16 at high daily strain magnitudes,17 or at an increased total length of DO.19 A longterm, irreversible thinning of the cartilaginous zones in the bone formation after MDO has been observed in a single study.16 After mandibular midline DO, site-specific thickening of the cartilage on the surface was found.21 In conclusion, reported effects of MDO on TMJ cartilage varied, but physiologic rates may be well tolerated by the TMJ. However, increased daily rates or total lengths of MDO may induce irreversible changes in the TMJ cartilage. Changes in condylar bone metabolism Bone metabolism was predominantly assessed by semiquantitative histology, although few studies used histomorphometry (see Table I). Ten studies reported a change in bone metabolism after MDO13-16,19,20,22-25 (see Table III). Five studies reported an initial increase in bone formation,13,14,16,20,22 whereas 2 studies found an increased resorption of the subchondral bone.15,19 Three studies reported an increased remodeling of bone.23-25 Changes in bone metabolism were site-specific and located on anterior and posterior surfaces of the condyle.16,24 In conclusion, MDO was reported to induce various changes in bone metabolism, and most frequently an initial increase in bone formation was observed. Changes in cortical and spongious bone microstructure Experimental studies reporting the effect of MDO varied according to animal model and distraction parameters applied (see Table I). Condylar bone microstructure was assessed by semiquantitative histology or
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histomorphometry. Evaluation of structural parameters found a reversible thinning of trabeculae14,23(see Table III), a 10% decrease in microdensity (equivalent to bone thickness) at increased rates,12 and a decrease in trabecular connectivity.14 A single study found a reversible thickening of trabeculae.22 In conclusion, 5 studies have investigated the effect of MDO on the cortical and spongious bone microstructure, but no definitive conclusions on this outcome parameter can be drawn. Changes in macromorphology of the condyle Eight studies evaluated the condylar macromorphology after MDO.12,13,15,17,24,25,27,28 The condylar macromorphology was assessed by macroscopic examination and histologic methods (see Table I). Increased daily rates of DO were associated with a higher occurrence of changes in the condylar morphology12,15,17,25,27 (see Table III). Various morphologic changes have been connected with high daily rates of DO, including condylar size reduction in the anteroposterior dimension,12,13,27 uprighting of the condyle relative to the occlusal plane,12,15 increased convexity of the condyle’s anteroposterior dimension,13,27 and site-specific flattening of the condyle.17,24,27 Flattening, displacement of the condyle, and severe condylar erosion have been observed after transversal mandibular distraction and after displacement of the proximal segment of the mandible in relation to the distal segment.28 In conclusion, various macromorphologic changes of the mandibular condyle have been described after MDO, and changes were frequently observed after high daily distraction rates. Changes in the articular disk The articular disk was examined in 3 studies by macroscopic examination or histologic methods (see Table I). Two studies found a reversible thinning of the disk,14,27 and no change to the articular disk was observed in 1 study15 (see Table III). No studies investigated the effect of increased daily rates of DO or total activation length on the articular disk. In conclusion, no definite conclusions on the effect of MDO on the articular disk can be drawn. Changes in the glenoid fossa The glenoid fossa was assessed in 4 studies by macroscopic examination or histologic methods (see Table I). Two studies found a thinning of trabeculae in the glenoid fossa,12,23 and a single study detected erosion of the fossa after transversal mandibular DO28 (see Table III). In conclusion, no definite conclusions on the effect of MDO on the glenoid fossa can be drawn.
ORIGINAL ARTICLE Andersen et al. 411
Changes in macromorphology of the contralateral condyle The contralateral condyle was examined in 4 studies by macroscopic examination or histologic methods (see Table I). Various changes in the contralateral condyle were found (e.g., deformation, reduction in the anteroposterior dimension, and increased cartilage thickness) (see Table III).15,20,27 In conclusion, no definite conclusions can be drawn on the effect of MDO on the macromorphology of the contralateral condyle. Quality assessment The results of the methodologic quality standard are shown in Table II. No studies reported a prestudy estimation of sample size, and only 2 studies contained information about randomization of animals. No studies addressed the effect of MDO on the TMJ by unbiased stereologic methods. Seven studies informed about the variation of the chosen outcome variable. In conclusion, based on these 5 criteria, all studies were considered to be at high risk of bias.
DISCUSSION The aim of the present systematic review was to test the hypothesis of no effect of MDO on TMJ as evaluated in animal experimental studies. A total of 17 studies were included. It was concluded that MDO may induce adaptive changes in the TMJ. In addition, the adaptive changes may be influenced by increased daily rates and total length of DO. In the following discussion, the obtained results for all outcome measures are discussed together to obtain an adequate overview of the influence of MDO on the TMJ. The included studies were characterized by inhomogeneity related to animal species, number of animals included, age of animals, experimental procedures, and evaluation methods; thus, meta-analyses were not applicable. The quality assessment found that all studies were considered as having high risk of bias. Therefore, the conclusions in the current systematic review may be jeopardized by the aforementioned shortcomings. A frequent observation after MDO was a change in bone metabolism, and in most studies an initial increase in bone formation or an increased remodeling of the condyle was observed. However, results regarding this outcome measure were ambiguous, which may relate to the chosen animal model, to the surgical procedure, or to increased rates or magnitudes of DO in the few studies finding resorption. According to Wolf’s law, changes in loading may trigger a tissue reaction including metabolic changes to accommodate bone to the changes in loading.29 However, few animal studies have assessed the actual loading of the TMJ after MDO,
Ahn et al. 2011
Elgazzar et al. 2008
Harper et al. 1997 Karaharju-Suvanto et al. 1996
Kim et al. 2003
Kim et al. 2004
Kruse-Löseler et al. 2001
Liu et al. 2003
McCormick et al. 1995
Condylar cartilage
Condylar bone metabolism
Thickening, hyperplasia, and cellularity at increased daily rates of DO Reversible thinning and Anterior resorption hypoplasia followed by formation Site-specific changes in the cartilage Reversible thinning of Increased formation, cartilage. No initially correlation between histologic changes and total amount of DO Thickening of cartilage Increased resorption at increased daily and reduced rates; 5 mm/d formation at high reduces thickness of daily rates cartilage Thickening of cartilage Increased formation at increased daily rates Thinning at elevated strains. Comparable bone elongation at low strain magnitude induced minor alterations in the cartilage High rate may have a traumatic effect on the cartilage Reversible thinning
Remodeling of subchondral region
Bone microstructure
Condylar macromorphology
Articular disk
Glenoid fossa
Contralateral condyle
Flattening, anterior tipping and contour irregularities initially
Reversible thickening of trabeculae
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Study
412
Table III. Summary of results of included studies
No changes
No difference
Flattening of the anteromedial part at elevated strains
Microdensity 10% decreased after increased daily rates
Reduction and uprighting of condyle after increased daily rates Slight flattening of the posterior aspect of the condylar head
Minimal histologic changes
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Study Meng et al. 2010
Mihmanli et al. 2012 Rafferty et al. 2007
Sant’Anna et al. 2007
Condylar cartilage Reversible thinning of cartilage. Depressions and erosions in cartilage infrequently observed Reversible thickening and hyperplasia Reversible thickening of cartilage
Condylar bone metabolism Reversible increased remodeling
Bone microstructure
Thurmüller et al. 2002 Remodeling at 1 mm/d. Higher rates may have a traumatic effect on the cartilage
Glenoid fossa
Contralateral condyle
Thinner trabeculae, thin cartilage layer
Reduction in A-P dimension, Increased convexity of condyle Reversible thinning
Reversible thinning of subcortical trabecular bone
Erosion of fossa after Site-specific flattening, application of varus erosion, and displacement of vector condyle At increased daily rates: Reversible thinning of medial condylar pole Increased convexity of condyle, reduction in A-P dimension (7%-27%), and flattening of the medial condylar pole Increased steepness of No changes anterior surface of condyle after 4 mm/d
7% reduction in A-P dimension
Site-specific increase in cartilage thickness at 4 mm/d
No changes
A-P, anteroposterior; HBO, hyperbaric oxygen treatment; DO, distraction osteogenesis; MAR, mineral apposition rate.
ORIGINAL ARTICLE Andersen et al. 413
Resorption of Thurmüller et al. 2006 Thickening and subchondral bone hyperplasia and cellularity at increased daily rates. Reversible at reduced daily rates of distraction Zou et al. 2001 Thickening at 1 mm/d. Increased formation on the posterosuperior Thinning and surface of the degeneration at condyle 2 mm/d
Articular disk
Reversible thinning of trabecular bone
Increased formation, reversible. MAR 16% increased without consolidation Cartilage maintained Increased formation Reversible thinning of with no degenerative posterosuperiorly subcortical bone; signs Trabeculae not multiple connected
Stelnicki et al. 2000
Condylar macromorphology
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Table III. Continued
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and those that did had contradictory results.12,13 In an animal study, an immediate but short-term increase in the TMJ synovial fluid hydrostatic pressure after activation of the distraction device was found.30 The increased intra-articular pressure may increase the loading of the condyle on the TMJ after MDO. In a finite element study, higher stresses and strains on the distraction side than on the nondistraction side after unilateral vertical ramus elongation were described, implicating an increase in loading of the TMJ.31 In the current review, predominantly reversible changes in the bone metabolism were observed, and only after increased daily rates or total length activation. In a few studies, irreversible changes were observed. Based on these findings, it may be theorized that DO at physiologic rates may induce a change loading of the TMJ condyle, leading to reversible changes in the bone metabolism. Few studies assessed changes in structural parameters of bone in the contralateral condyle, and based on this review, no definite conclusions can be drawn on this outcome measure. The current review found that macromorphologic changes (e.g., condylar size reduction in the anteroposterior dimension, uprighting of the condyle relative to the occlusal plane, increased convexity of the condyle in the anteroposterior dimension, and sitespecific flattening of the condyle) were frequently observed after high daily distraction rates. The macroscopic change of the condyle after DO may be considered as an adaptation of bone to meet new functional demands and can be anticipated to be consistent with the findings of changes in bony metabolism. The animal models included in the current review predominantly applied a horizontal vector, increasing the loading on the posterior surface of the condyle. The observed changes of macroscopic appearance of the condyle may all be induced by a horizontal vector. Remodeling may induce flattening of the anterior surface and a reduction of the anteroposterior dimension of the condyle, as well as an uprighting of the condyle relative to the occlusal plane and an increased convexity of the superior surface of the condyle. A transversal vector involves rotational forces at the condyle, inducing site-specific flattening on the posterolateral and anteromedial surfaces of the condyle.21 This illustrates that the effect of DO on the TMJ is dependent on the vector applied, which is why treatments must be analyzed as separate entities according to the vector applied. Animal studies involving transversal and vertical vectors are few, and based on this review, no conclusions can be drawn on this subject. No relationship was found between changes in cartilage and macroscopic changes of the condyle. The current systematic review found a disparity regarding
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changes in the cartilage thickness after DO, which may be explained by the anatomic variation of the TMJ of the different animals studied. It has been advocated that the increased thickness of the cartilage was a reactive response to maintain functional balance and resistance to external wear in the TMJ.26 However, it has been postulated that increased thickness of the cartilage was a result of functional unloading after the surgical trauma, owing to detachment of the masseter muscle.13 Increased daily distraction rates, increased strains, or increased lengths may cause irreversible damage and degenerative changes in the cartilage, but the limit between physiologic and increased levels was not defined in the included articles, and it may be influenced by many variables, including animal species and age. Physiologic rates may be well tolerated by the TMJ cartilage, inducing only reversible changes, but increased daily distraction rates or total activation length may induce irreversible changes in the TMJ cartilage. However, as previously stated, definitive conclusions on the effect of MDO on the condylar cartilage may be hampered by the lack of unbiased animal experimental studies. Few studies assessed changes in structural parameters of bone or changes in the contralateral condyle, the glenoid fossa, and the articular disk, and based on this review, no definite conclusions can be drawn on these outcome measures. Future studies should employ power calculations, include a control group, involve randomization, and use unbiased evaluation methods to reduce the overall risk of bias of the studies. It should also be recognized that MDO is often performed in patients with a compromised TMJ of either congenital or acquired etiology. This aspect has never been addressed in an animal experimental study.
CONCLUSION Animal experimental studies have indicated that MDO may induce adaptive changes in the TMJ. In addition, the adaptive changes may be influenced by increased daily rates and total activation length of DO. Therefore, care must be taken not to apply increased rates and length in the planning of MDO. However, further welldesigned studies are needed before final conclusions can be drawn. REFERENCES 1. Figueroa AA, Polley JW. Management of the severe cleft and syndromic midface hypoplasia. Orthod Craniofac Res. 2007;10: 167-179. 2. McCarthy JG, Stelnicki EJ, Grayson BH. Distraction osteogenesis of the mandible: a ten-year experience. Semin Orthod. 1999;5:3-8. 3. Molina F. Mandibular distraction: surgical refinements and longterm results. Clin Plast Surg. 2004;31:443-462.
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Reprint requests: Kristian Andersen, DDS Department of Oral and Maxillofacial Surgery Aarhus University Hospital Nørrebrogade 44 8000 Aarhus C Denmark [email protected]
