Errata The following article, which was published in the January 2006 issue of The Journal of Craniofacial Surgery was missing some key information. We regret the error. A corrected version of the article is below.

MicroYComputed Tomography Evaluation of the Glenoid Fossa and Mandibular Condyle Bone After Bilateral Vertical Ramus Mandibular Distraction in a Canine Model Eduardo Franzotti Sant’Anna, DDS, MS, PhD,*12 David F. Gomez, DDS, MS,*1 Dale R. Sumner, PhD,* James M. Williams, PhD,* Alvaro A. Figueroa, DDS, MS,*1 Srdjan A. Ostric, MD,1 Spero Theodoru, MD,1 John W. Polley, MD1 Chicago, Illinois, USA

The aim of this study was to quantify bone microarchitecture within the glenoid fossa and mandibular condyle following mandibular distraction osteogenesis. Eight 6- to 9-month-old male beagle dogs underwent bilateral vertical mandibular distraction with semiburied distractors (12 days of distraction at 1 mm per day). One unoperated animal served as control. After distraction the animals were divided into two groups (N = 4) and killed after 1 or 2 months of consolidation. Threedimensional trabecular architecture was analyzed by microYcomputed tomography (mCT). At both sites the overall trends were similar. In the glenoid fossa, there was decreased bone volume, trabecular number, and connectivity density and increased trabecular separation at 1 month and decreased trabecular thickness and increased structure model index compared with the control (P G 0.05). In the mandibular condyle, there was decreased bone volume, trabecular number, and connectivity density at both 1 and 2 months, with decreased trabecular thickness and increased structure model index at 2 months only compared with the control (P G 0.05). The bone became less dense and more rodlike. These bone changes are similar to those seen by the effects of aging or impaired normal function. Thus, in the short term, changes From the *Department of Anatomy and Cell Biology, Rush Medical College, Chicago, IL; yRush Craniofacial Center, Chicago, IL; and zDepartment of Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Brazil. Address correspondence and reprint requests to Alvaro A. Figueroa, DDS, MS, Rush Craniofacial Center, 1725 W. Harrison St., Suite 425, Prof. BLDG I, Chicago, IL; E-mail: [email protected]

occur in the bone microstructure of the glenoid fossa and mandibular condyle after vertical mandibular ramus distraction in the canine model. Key Words: Mandibular ramus, hypoplasia, distraction osteogenesis, condyle, glenoid fossa, bone microarchitecture, microYcomputed tomography

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oninvasive three-dimensional imaging techniques such as computed tomography (CT) and magnetic resonance have broadened the understanding of the craniofacial skeleton macroarchitecture. They are important tools to analyze gross structural bone changes for pathologic diagnosis and after skeletal surgery. These techniques have been applied to analyze the surgical site after distraction osteogenesis of the mandible, as well as to analyze distraction effects at distant sites such as the temporomandibular joints (TMJs).1j3 Currently there is a significant interest in imaging bone at a microscopic resolution to delineate the microarchitecture of cortical and trabecular bone.4 In the articular regions the bone mainly withstands compressive forces, being entirely trabecular, with a thin subchondral shell of compact bone.5 The trabeculae of cancellous bone, though individually small, collectively provide powerful support to the surrounding compact bone.5 Trabecular architecture seems to be optimally structured for its load-bearing function, suggesting that mechanical forces govern its formation.6 Therefore, bone strength can be greatly influenced not only by bone mass but also by morphologic features such as trabecular connectivity and the architecture of trabecular elements.7 611

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Recent advances in the application of highresolution microYcomputed tomography (mCT) imaging have been instrumental in providing true quantitative and qualitative three-dimensional data on baseline bone morphology, as well as structural changes that result from load stimulation or lack thereof.8 It has been hypothesized that the magnitude of the loads imposed on bone dictates its mineralization and structural design.9 However, it is not known what the long-term effect of bone lengthening is on the articular cartilage of limbs undergoing lengthening for short stature, and whether these joints will last a lifetime.10 Because distraction osteogenesis has been applied to the mandible and this bone has two joints, it is important to elucidate the possible effects of mandibular lengthening on the TMJs. The biomechanical environment of both TMJs is altered during mandibular distraction osteogenesis. Previous studies involving unilateral linear distraction with external devices have shown temporary changes with no long-term detrimental effects on the temporomandibular joints.2 Osteoclastic activity in the TMJ has been reported, but changes seem to be partly reversible.11 There is evidence that bilateral mandibular ramus distraction with an added transverse component may induce condylar erosions similar to those observed in osteoarthritis.3 Most studies have been conducted at the histologic and macroarchitectural level,1,3,12 and changes in the three-dimensional trabecular bone microstructure of the TMJ following distraction osteogenesis have not been investigated. The aim of this pilot study was to quantify the three-dimensional trabecular bone architectural changes within the glenoid fossa and mandibular condyle in response to bilateral mandibular ramus distraction using mCT in a canine model. Our objective was to better understand the effects of distraction osteogenesis on the glenoid fossa and condylar bone structure after 1- and 2-month consolidation periods. MATERIALS

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animals were weighed preoperatively, the day following surgery, and just before sacrifice. Surgical Procedure and Distraction Osteogenesis Eight animals were operated on under intravenous pentobarbital (25 mg/kg) and general, halothaneinduced, endotracheal anesthesia. Intraoral preparation was performed using half-strength hydrogen peroxide diluted with normal saline solution. The surgical area was shaved and draped in a standard surgical fashion and cleaned with 70% isopropyl alcohol followed by 10% povidoneYiodine solution and quartered with sterile towels. The mandible was exposed on each respective side through 6- to 8-cm incisions made parallel and 0.5-cm incisions above the right and left inferior border of the mandible. The masseter muscle was reflected anteriorly, and the mandible was exposed in the supraperiosteal plane. The osteotomy was made with a reciprocating saw, copious saline irrigation, and manual tapping with an osteotome along a line below the mandibular angular process posteriorly and a point posterior to the molars on the anterior aspect of the vertical ramus (Fig 1). Special attention was paid to avoid injury of the inferior alveolar neurovascular bundle. Internal distraction devices (KLS L.P. Zurich Distractor, Cloverleaf Plate, 15 mm, Martin; Jacksonville, FL) were fixed to the mandible following a plane parallel to the canine mandibular ramus using self-tapping 1.5-mm diameter and 5- to 7-mm long screws to secure the footplates of the device above and below the line of osteotomy. The wound was closed in layers with absorbable sutures in the deep layers and nylon skin

METHODS

Animal Care

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he Institutional Animal Care and Use Committee approved the use and care of animals in this study. Nine 6- to 8-month-old male beagle dogs, weighing between 10 and 15.4 kg, were housed for a 5-day period to become acclimated to the research facility. Preoperative and postoperative care of these animals was overseen by veterinarians and husbandry staff to ensure proper humane treatment. The

Fig 1 Canine mandible with osteotomy and distractor in place.

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sutures in an interrupted fashion. The nylon sutures were removed 7 days postoperatively. All animals were placed on a soft mechanical diet and water ad libitum beginning on the 2nd postoperative day. The dogs received intramuscular ampicillin, 250 mg/mL, twice a day for five days and antibiotic coverage and buprenorphine, 0.3 mg/mL, twice a day for 5 days postoperatively to minimize discomfort or pain. After a latency period of 7 days, distraction was initiated at a rate of 1 mm/d (0.5 mm every 12 hours) for 12 consecutive days. The animals were divided into two experimental groups (N = 4) and killed under anesthesia with intravenous KCL (5 mL; 0.3 mg/mL) after a 30- or 60-day period of consolidation. One unoperated animal served as control and was killed in a similar fashion. The length of the achieved distraction was measured postmortem with an occlusal radiograph taken of the resected hemimandible. An average of 10 mm elongation of the ramus bilaterally was recorded. The TMJs (glenoid fossa and condyle) were carefully harvested en bloc. The specimens were stored in 10% buffered formalin solution. MicroYComputed Tomographic Scanning and Analysis The TMJs were imaged at 15-mm isotropic voxels, using a Scanco Model 40 mCT scanner (Wayne, PA). In order to place the specimens consistently inside the 30-mm Perspex holder, a special jig was customized with acrylic and 0.32-inch stainless steel orthodontic wire. The device had four specially designed clasps partially embedded in an acrylic circle base that fit tightly inside the holder. The clasps were adjusted with an orthodontic plier to hold the TMJ specimens steady by the glenoid fossa and its portion of the zygomatic arch (Fig 2). The acrylic base had red ink marks that divided it equally into four segments. These marks served as reference points to position the TMJ specimens with the same orientation. Vertical

lines on the lateral side of the holder also assisted in vertically positioning the specimens. In each TMJ, two segments of orthodontic ligature wire (0.012 inch) were placed parallel to the base of the tube and around the most superior and inferior aspect of the area to be scanned. Therefore, from the mCT scout view, the volume of interest of each TMJ could be identified and standardized for all specimens. The anatomic region comprising from the superior to the medial aspect of the TMJ was chosen to be scanned as this was considered the region submitted to more pressure due to the vector of the forces applied by the distractor. Approximately 500 contiguous slices per specimen were generated. From this volume, comparable regions of interest in the condyles and the glenoid fossa were selected and approximately 200 slices were used for trabecular three-dimensional reconstruction. None of these slices included the orthodontic ligature wire. The gray-scale images were processed using a low-pass filter to remove noise, and a fixed threshold of 205 was used to separate the bone from the marrow. From the resulting binarized three-dimensional reconstruction, Scanco software was used to calculate the bone volume per tissue volume (BV/TV) ratio of cancellous bone volume in the total tissue volume (volume of interest)13; mean trabecular thickness (Tb.Th.)8; mean trabecular separation (Tb.Sp.)8; mean trabecular number (Tb.N)13; structural model index (SMI) Y varying from zero to 3 for ideal plate and rod structures, respectively8; connectivity density (Conn.D), defined as a measure of the degree to which the structure of the trabecular bone is multiply connected13; and anisotropy (DA), the degree of asymmetry in trabecular bone orientation (highly oriented 9 1 to less oriented = 1). Cortical bone thickness was visually inspected to compare differences among 1-month, 2-month, and control specimens using three mCT slices selected from each glenoid fossa and condyle.

Fig 2 Mandible hemisection with the TMJ of the control dog (A). TMJ harvested and placed in a special holder made with stainless steel clasps and an acrylic base that was adjusted to keep all TMJs with the same orientation inside the mCT scan holder (B). The white arrows represent the temporalisYzygomatic process of the temporal bone and the black arrows represent the condyle.

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Statistics Trabecular bone microarchitecture measurements included areas of interest from 36 bones (16 glenoid fossas and 16 condyles divided equally in the two experimental groups and two glenoid fossas and two condyles from an unoperated control dog). The data were analyzed using a commercially available software package (SPSS, Chicago, IL). A paired sample t- test was run to analyze differences in the trabecular bone microarchitecture between the left and right side of each dog. There was no difference between sides so the average of the two sides was calculated and is reported here. Differences in trabecular bone microarchitecture between 1 and 2 months were analyzed by using an independent sample t-test. A one-sample t-test was used to compare each experimental group with the control. P values less than 0.05 were considered significant, but exact values are given. RESULTS

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ody weight had changed slightly throughout the experiment in both groups (Table 1). Symmetric protrusion, extrusion of the molars, and open bite developed bilaterally after distraction (Fig 3). Examination of mCT slices indicated that the control group had thicker cortical bone and less prominent trabecular spaces when compared with corresponding sites of the distracted animals (Fig 4). The threedimensional reconstructions of the trabecular bone of the glenoid fossa and the condyle indicated that the control specimen had denser bone that was more platelike than the two experimental groups (Fig 5). Seven morphologic parameters were analyzed to assess bone quantity (BV/TV) and quality (Tb.Th, Tb.Sp, Tb.N., Conn.D., SMI, DA) with the use of mCT.

Table 1. Body Weight of Experimental Dogs Before Surgery and on the Day of Sacrifice Experimental Animals

1 Month CTSAUD CTSBAX CTUBFM CTVACX 2 Months CTSAMJ CTSAGE CTSACN CTWBAV *Day of Surgery. y Day of Sacrifice.

Weight 1* (kg)

Weight 2y (kg)

13.6 11.3 15.4 15.4

15.17 9.5 15.8 16.3

10.0 11.3 11.5 13.1

11.3 10.4 12.7 14.0

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These parameters are described first for the glenoid fossa (Fig 6) and then for the condyle (Fig 7). Control Versus 1 Month Significantly lower values were observed for BV/TV (P = 0.028), Tb.N. (P = 0.009), and Conn.D. (P = 0.002), whereas Tb.Sp. (P = 0.032) was significantly higher in the 1-month group compared with the control. DA (P = 0.05) tended to be less and SMI (P = 0.071) tended to be greater than in the control, but the differences were not statistically significant. Control Versus 2 months Tb.Th. (P = 0.008) was smaller and SMI (P = 0.033) was greater in the 2-month group than the control. BV/TV (P = 0.079) tended to be below control levels but the difference was not statistically significant. 1 Versus 2 Months No significant differences were observed in the glenoid fossa trabecular parameters between the 1- and 2-month specimens. Values for the mandibular condyles are shown in (Fig 7). Control Versus 1 Month At 1 month, there were significantly lower values for BV/TV (P = 0.04), Tb.N (P = 0.030), and Conn.D (P = 0.017) than the control, with a trend in the same direction for Tb.Th (P = 0.053). Tb.Sp. (P = 0.079) tended to be greater, but the difference was not statistically significant. Control Versus 2 Months BV/TV (P = 0.001), Tb.N (P = 0.030), Tb.Th (P = 0.00), and Conn.D (P = 0.011) had significantly lower values and SMI (P = 0.002) was significantly higher at 2 months than the control. 1 Versus 2 Months No significant differences were observed in the condylar trabecular parameters between the 1- and 2-month specimens. DISCUSSION

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n this study the trabecular architecture of the canine glenoid fossa and mandibular condyle was quantitatively evaluated with mCT after 1 and 2 months of consolidation following vertical ramus mandibular distraction osteogenesis. Following distraction osteogenesis, bone volume was decreased compared with the control. This decrease in bone density was due to decreased trabecular thickness and number, with an increase in trabecular spacing. Consequently the trabecular architecture became more rodlike. Thus, our observations indicate that distraction osteogenesis of the mandible induces changes in bone architecture at the TMJ. It is not known whether these changes are transient or permanent. It has been shown that remodeling of the TMJ, in the form of bone contour changes on both the glenoid fossa and condyle, occurs as a response to bilateral mandibular sagittal osteotomies in primates.14 Bell

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Fig 3 Control (A and B) and distracted animal from the 2-months consolidation group (C and D). Mandibular symmetric protrusion and open bite developed bilaterally after distraction. Note extrusion of the molars after mandibular distraction.

Fig 4 Representative mCT slices of the temporalisYzygomatic process of the temporal bone and condyles. Control specimen (A) and 1 (B) and 2 months (C) of consolidation. Control specimens had thicker cortical bones and less trabecular spaces when compared with corresponding sites in the distracted animals. Changes are more apparent on the condyle (lower bone) than on glenoid fossa.

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Fig 5 Cancellous bone three-dimensional mCT reconstructions of the glenoid fossa and mandibular condyle. Control specimen (A) and 1 (B) and 2 months (C) of consolidation. A decline in bone density, thinning of the trabeculae, and a change in microstructure of cancellous bone from predominantly platelike to more rodlike were observed between control and specimens from the distracted groups.

and Kennedy14 indicated that the vessels that perfuse the condyle emerge from the lateral pterygoid muscle and the joint capsule. These structures were not disturbed by the surgical procedure in this study. However, the masseter muscle was detached from the mandible to allow fixation of the semiburied distractor device. It has been demonstrated that detachment of the rat masseter muscle alone can lead to significant changes in the morphology of the condyle.15 In addition, Liu et al16 have demonstrated that relative loss of masseter function could happen as a result of overstretching after excessive distraction, possibly leading to a decrease in density and size of the condyle in rats. Although the difference between trabecular architecture at 1 and 2 months was not statistically significant, the values after 2 months of consolidation tended to be closer to control values than after 1 month of consolidation. This was especially true for

the glenoid fossa. This trend was much less evident in the mandibular condyle. This apparent difference in dynamic changes on the two sides of the temporal mandible joint may be explained by the fact that the temporal bone was not directly affected by surgery (e.g., osteotomy, muscle detachment, alteration in blood supply) and the distraction process, whereas the mandible was directly affected. Conn.D and SMI indexes are known to be helpful in the assessment of the three-dimensional nature of bone structures and architectural features indicative of bone quality as they influence the strength of bone similar to what the strategic placement of beams and rafters does for building a structure.8 With the exception of the glenoid fossa at 2 months, Conn. D. was below the control value. Kinney and Ladd17 have suggested that recovery of mechanical function might depend on the preservation or restoration of trabecular connectivity. However, it has also been

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MICROYCOMPUTED TOMOGRAPHY IN A CANINE MODEL / Sant’Anna et al

Fig 6 Comparison of mCT parameters for glenoid fossae. Bars represent the mean and error bars the standard deviations for 1 and 2 months of consolidation. The dashed line represents the value for the one intact control animal. Significant differences between group means and the single control are indicated with asterisks (! P G 0.05, !! P G 0.01).

suggested that loss of structural connectivity appears to be an irreversible process.18 Longer-term studies are needed to determine whether this aspect of trabecular architecture returns to normal. SMI in both glenoid fossa and condyle specimens demonstrated trends of change from platelike toward a rodlike structure. Trabecular structural changes from platelike to rodlike gradually occur with aging.19 Previous studies have demonstrated a positive correlation between bone strength and parameters such as bone volume, trabecular number, trabecular thickness, and connectivity.17,20Y22 Thus, although the mechanical properties of the specimens were not measured in our study, the observed changes in cancellous bone structure imply a decrease in bone strength. In this study, the cancellous bone in the control mandibular condyle and glenoid fossa specimens was anisotropic. Giesen et al23 observed that the trabecular bone in human mandibular condyles is also somewhat anisotropic where trabecular orientation consists of parallel plates perpendicular to the mediolateral aspect of the condylar axis. Such a trabecular structure is optimally adapted to sustain

loads in directions that coincide with the majority of joint forces applied to the condyle during mastication and also to supply nutrition to the avascular cartilage. Despite limited masticatory function after surgery and distraction, the degree of anisotropy did not change in the current study. Thus, despite changes in bone volume and other parameters, anisotropy was not affected by distraction osteogenesis. Similarly, Giesen et al25 have shown that the degree of trabecular anisotropy did not differ among loaded and less loaded human mandibular condyles, although decreased mechanical load was associated with reduced density, stiffness, and strength. In the current study, most of the indices analyzed suggested trends in trabecular architecture and volume similar to what has been observed in experiments in which bone was aging19,26,27 or normal function impaired.28 Due to the short time frame of the study and the use of skeletally immature animals, aging probably had no influence on the bone changes. Therefore, it is likely that distraction osteogenesisYinduced changes explain the observations. 617

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Fig 7 Comparison of mCT parameters for the mandibular condyle. Bars represent the mean and error bars the standard deviations for 1 month and 2 months of consolidation. The dashed line represents the value for the one intact control animal. Significant differences between group means and the single control are indicated with asterisks (! P G 0.05, !! P G 0.01, !!! P G 0.001).

Without baseline controls, it is not possible to know whether altered growth or remodeling kinetics, or both, account for the structural differences found between the experimental animals and the intact control. Significant variation in animal weight before and after surgery was not detected, suggesting that growth of the animals was not impaired, and all animals, including the control, had a similar soft diet. Thus, it is likely that either the surgery, its consequences on the blood supply, or distraction osteogenesisYinduced alterations in the biomechanical environment of the TMJ led to the observed changes in bone architecture. A limitation of an animal model is that the surgical procedure is tested in healthy individuals, as opposed to the clinical situation of treating a disease. Biomechanically, mandibular distraction osteogenesis in a previously normally functioning animal probably generates abnormally high forces and pressures at the TMJ. In addition, experimental mandibular distraction osteogenesis induces changes in normal masticatory function, as opposed to the

clinical situation, in which distraction osteogenesis leads to more normal mastication. Despite these limitations, the present data indicate that normal loading of the TMJ and normal physical function are critical to maintaining trabecular microarchitecture and bone volume. A second limitation of our study is that we did not include analysis of the soft tissues, including TMJ ligaments, articular capsule, and disk. Changes in these structures following distraction osteogenesis need to be explored as it is possible that patients may be more likely to suffer clinical symptoms if changes occur in the soft tissue components of the joint than in the bone itself. As a consequence of the surgery itself or because of alterations in the biomechanics of the TMJ following distraction osteogenesis, there was decreased bone quantity and quality of the skeletal TMJ structures in the current study. Thus, deterioration of trabecular bone microarchitecture could occur clinically as distraction osteogenesis would induce change in function, even if it is a change toward

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more normal function. Whether these changes in bone microarchitecture are reversible, have influence on long-term stability of distracted cases, or cause TMJ disorders was not addressed in this study but merit attention clinically. Healthy subchondral trabecular bone is important not only because it deforms during loading, absorbing forces that could destroy the cartilage layer,29 but also because the vascularization of this area serves, along with synovial fluid, as a source of nutrition for the avascular cartilage.24 It has been shown that mandibular condylar resorption and condylar atrophy can be a potential undesirable outcome of acute mandibular advancement, leading to relapse after conventional orthognatic surgery. 30 Although gradual increase of mandibular length with distraction could, theoretically, minimize these deleterious effects on the TMJ, the current study demonstrates that distraction osteogenesis at a clinically used rate did affect bone microarchitecture in the TMJ. Therefore, long-term experiments and clinical follow-up are needed for patients who have had distraction osteogenesis to determine whether change in bone microarchitecture is an adaptive response without significant structural and functional complications. Dr. Sant’Anna is a recipient of a scholarship from Capes Agency, Ministry of Education, Brazil. KLS-Martin, Jacksonville, FL. Research grant to Drs. Polley and Figueroa. Grainger Foundation and NIH RR16631 support for Dr. Sumner.

REFERENCES 1. McCormick SU, McCarthy JG, Grayson BH, et al. Effect of mandibular distraction on the temporomandibular joint: part 1, canine study. J Craniofac Surg 1995;6:358Y363 2. McCormick SU, Grayson BH, McCarthy JG, Staffenberg D, et al. Effect of mandibular distraction on the temporomandibular joint: part 2, clinical study. J Craniofac Surg 1995;6: 364Y367 3. Stelnicki EJ, Stucki-McCormick SU, Rowe N, McCarthy JG, et al. Remodeling of the temporomandibular joint following mandibular distraction osteogenesis in the transverse dimension. Plast Reconstr Surg 2001;107:647Y658 4. Majumdar S. Advances in imaging: impact on studying craniofacial bone structure. Orthod Craniofac Res 2003;6:48Y51 5. Soames RW. Skeletal system. In: Soames RW, ed. Gray’s anatomy. London: Churchill Livingstone, 1999:425Y712. 6. Huiskes R. If bone is the answer, then what is the question? J Anat 2000;197(part 2):145Y156 7. Zysset PK. A review of morphology-elasticity relationships in human trabecular bone: theories and experiments. J Biomech 2003;36:1469Y1485 8. Judex S, Boyd S, Qin Y-X, et al. Combining high-resoloution micro-computed tomography with material composition to define the quality of bone tissue. Curr Osteoporos Rep 2003;1:11Y19

9. Frost HM. Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff’s law: the bone modeling problem. Anat Rec 1990;226:403Y413 10. Gross RH. Limb lengthening for stature: another view. J Pediatr Orthop 2005;25:128Y129 11. Karaharju-Suvanto T, Peltonen J, Laitinen O, Kahri A, et al. The effect of gradual distraction of the mandible on the sheep temporomandibular joint. Int J Oral Maxillofac Surg 1996;25: 152Y156 12. Thurmuller P, Troulis MJ, Rosenberg A, Kaban LB, et al. Changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible. J Oral Maxillofac Surg 2002;60:1327Y1333 13. Fanuscu Ml, Chang TL. Three-dimensional morphometric analysis of human cadaver bone: microstructural data from maxilla and mandible. Clin Oral Implants Res 2004;15:213Y218 14. Bell WH, Kennedy JW 3rd. Biological basis for vertical ramus osteotomies: a study of bone healing and revascularization in adult rhesus monkeys. J Oral Surg 1976;34:215Y224 15. Ghafari J, Heeley JD. Condylar adaptation to muscle alteration in the rat. Angle Orthod 1982;52:26Y37 16. 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;61:918Y927 17. Kinney JH, Ladd AJ. The relationship between threedimensional connectivity and the elastic properties of trabecular bone. J Bone Miner Res 1998;13:839Y845 18. Parfitt AM. Trabecular bone architecture in the pathogenesis and prevention of fracture. Am J Med 1987;82:68Y72 19. Halloran BP, Ferguson VL, Simske SJ, et al. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res 2002;17:1044Y1050 20. Joo Yl, Sone T, Fukunaga M, et al. Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats. Bone 2003;33:485Y493 21. Weinstein RS, Hutson MS. Decreased trabecular width and increased trabecular spacing contribute to bone loss with aging. Bone 1987;8:137Y142 22. Kleerekoper M, Villanueva AR, Stanciu J, et al. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int 1985; 37:594Y597 23. Giesen EB, Ding M, Dalstra M, van Eijden TM, et al. Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic. J Biomech 2001;34:799Y803 24. Malinin T, Ouellette EA. Articular cartilage nutrition is mediated by subchondral bone: a long-term autograft study in baboons. Osteoarthr Cartil 2000;8:483Y491 25. Giesen EB, Ding M, Dalstra M, van Eijden TM, et al. Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle. Clin Biomech (Bristol, Avon) 2003;18:358Y363 26. Ruegsegger P, Koller B, Muller R. A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 1996;58:24Y29 27. Ding M, Odgaard A, Linde F, Hvid I, et al. Age-related variations in the microstructure of human tibial cancellous bone. J Orthop Res 2002;20:615Y621 28. Modlesky CM, Majumdar S, Narasimhan A, Dudley GA, et al. Trabecular bone microarchitecture is deteriorated in men with spinal cord injury. J Bone Miner Res 2004;19:48Y55 29. Giesen EB, van Eijden TM. The three-dimensional cancellous bone architecture of the human mandibular condyle. J Dent Res 2000;79:957Y963 30. Arnett GW, Milam SB, Gottesman L. Progressive mandibular retrusion-idiopathic condylar resorption: part I. Am J Orthod Dentofacial Orthop 1996;110:8Y15

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