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Journal of Cranio-Maxillofacial Surgery (2004) 32, 140149 r 2003 European Association for Cranio-Maxillofacial Surgery. doi:10.1016/S1010-5182(03)00131-8, available online at http://www.sciencedirect.com

Biomechanical and clinical implications of distraction osteogenesis in craniofacial surgery

Ulrich Meyer, Johannes Kleinheinz, Ulrich Joos Department of Cranio-Maxillofacial Surgery (Head: Prof. Dr. Dr. Dr. h.c. U. Joos MD, DMD), University of Mu . nster, Germany
SUMMARY. Introduction: Craniofacial distraction osteogenesis is an established surgical procedure to correct

bony malformations. Force transduction through the osteotomized bone fragments elicits dened biological responses in the gap tissue, which determines the clinical success of the distraction treatment. Objective: The purpose of this investigation was to evaluate clinically a new distraction protocol based on an analysis of the biological and biomechanical parameters executing direct effects on bone regeneration during distraction. Study design: A multistep distraction protocol was used in 39 patients and the clinical outcome was monitored postoperatively. Results: All the distraction cases were successful with a single exception. Segmental displacements were stable clinically and radiologically. Conclusion: In order to improve the clinical success of distraction osteogenesis, individual treatment protocols are recommended. r 2003 European Association for Cranio-Maxillofacial Surgery. Keywords: Distraction osteogenesis; Biomechanics; Mechanical strain

INTRODUCTION Distraction osteogenesis is a widely employed surgical approach in the treatment of patients with bony malformations. The clinical success of craniofacial and alveolar distraction procedures relies on multiple factors, particularly bone anatomy and biomechanics, the distraction forces and the surgical techniques applied. This article reviews some basic principles of distraction biology and focuses on its clinical application. The implications of this treatment strategy, as described, rely on guidelines developed in our department. BONE BIOMECHANICS The biomechanical impact of distraction osteogenesis on regenerating bone tissue is a highly complex and dynamic process (Burger and Veldhuijzen, 1993). Physical and biological parameters affecting the success of distraction osteogenesis include the macroand microscopical bone anatomy, the direction and amount of the applied distraction forces, and the regenerative capacity of the tissues involved. Force transduction via adjacent structures (joints, ligaments, muscles, and soft tissue) inuences the regeneration of the tissue between the bone fragments by modulating the stress produced within the callus (Fig. 1). The reaction of bone to distraction can be analysed at least at two levels. Firstly, we can assess the material properties of bone independently of its anatomical structure and geometry by performing
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standardized mechanical tests on uniform specimens (Turner et al., 1995). Secondly, by examining the mechanical behaviour of bone as an anatomical entity, the contributions made by its structural properties can be assessed. Mechanically, these properties determine how bone responds to forces in a clinical setting. Load is a commonly used and poorly dened term. It is not dened in terms of a physical determinable condition. It is mostly used when a complex mechanically related state is meant. In contrast to load, various other terms are precisely dened. The internal resistance to an applied force is known as stress. Stress, dened as equal in magnitude but opposite in direction to the applied force, is distributed over the cross-sectional area of the bone and callus tissue. It is expressed in units of force per unit area: stress=d=force/area. In distraction osteogenesis, mechanical forces are transduced through the separated bony fragments, the regenerating tissue, and the adjacent tissues. Due to the different material properties of bone, callus, and other tissues, the force/stress relationship is more complex in distraction osteogenesis than it is in intact bone. Most stress patterns are combinations of three stress types, namely tension, compression, and shear (Einhorn, 1996). Bending, for example, produces a combination of tensile forces on the convex side of a material and compression on the concave side. Torsion or twisting produces shear stress along the entire length of a material, while tensile stress tends to elongate it and compressive stress tends to shorten it. Distraction osteogenesis can be regarded as an uniaxial elongation leading to the development of

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Biomechanical and clinical implications of distraction osteogenesis in craniofacial surgery 141

Fig. 1 Different biomechanical parameters involved in the distraction osteogenesis.

tensile stress. The measurement of deformation normalized to the original length of the specimen is called strain: strain E change in length=original length deformed length-orig: length=orig: length: Strain is expressed as a percentage change. At low levels of stress, there is a linear relationship between the stress applied and the resultant deformation (in bone) in terms of strain (Curey, 1962). This proportionality is called the modulus of elasticity or Youngs modulus. It is a measured from the slope of the linear portion of the curve and is calculated by dividing the stress by the strain at any point along this linear portion of the curve. If the stress/strain area were to be generated by testing a whole bone as opposed to a uniform specimen, this measurement of the linear slope would give the stiffness or rigidity of the bony or callus tissue. With respect to distraction osteogenesis, it is important to recognize that Youngs modulus is nearly stable in the separated bony fragments, but varies in the regenerating tissue depending on its maturation stage. Thus, the modulus of elasticity of the elongated gap tissue alters during the distraction treatment. Energy put into deformation of an elastic material just prior to reaching the yield point can be recovered by removing the stress (Chamay, 1970). The energy recovered is known as resilience and is a measure of the ability of the material to store energy. Although this energy is not always recoverable in a useful form, it will not be lost as long as the material does not undergo permanent deformation. The ability to store energy highlights the need to stabilize an elongated specimen at the end of the distraction treatment in order to prevent an immediate relapse (Mc Tavish et al., 2000). The relation between force application and resultant bone deformation is crucial for the outcome of craniofacial distraction. A variety of powerful approaches has generated a comprehensive picture of how the gap tissue responses to deformation. Loaddependent deformation of bones can be evaluated by various approaches. Indirect measurements of defor-

mation are measured indirectly by means of intraoral devices (Ahmad et al., 1982; Mosley et al., 1997) or strain gauges (Ahrendts and Sigolotto, 1989, 1990). Additionally, holographic interferometry has been performed to assess the impact of mechanical forces on bone deformation (Ferre et al., 1985). One major disadvantage of all experimental studies using either strain gauges or holographic interferometry is the inability to determine strains at dened positions within the specimen. Biomechanical research by these methods is limited to surface deformations and neither stresses nor dislocations within the gap tissue can be measured directly. Computer-aided simulation based on nite element analysis (FEA) has addressed the adequacy of mathematical models to relate mechanical factors such as load transfer to the biomechanical behaviour of tissue specimens. Given a high correlation between the calculated FEA and the measured experimental data, various biomechanical parameters can be determined within the distracted tissue (Meyer et al., 2000; Vollmer et al., 2000). The accuracy of FEA in describing the biomechanical behaviour of non-living bony specimens has been demonstrated by various authors (Hart et al., 1992; Voo et al., 1996; Korioth and Verslius, 1997). In contrast to explanted tissue, living bone has a very different structure. This is due to the high dynamics of tissue remodelling. Intact bone as well as separated bony fragments bridged by callus tissue undergo deformation in a changing mechanical environment and react biologically when a force is applied (Aronson, 1994). If the bone or the fragments are xed so that they cannot move, or if equal and opposing forces are applied to them, deformation will occur, resulting in the generation of internal resistance to the applied force (Brown and Ferguson, 1978). Whereas a number of in vitro studies have investigated the relationship between the applied forces and the resulting bone deformation, much less is known about the in vivo behaviour of intact or osteotomized bones. Because of the technical problems involved, it is difcult to measure directly the force required to distract the various skull bones and there is only one recent report on this subject in the literature (Robinson et al., 2001). On account of their more simplied geometry, the distraction forces have mainly been measured in long bones. However, this has yielded a better insight into the mechanical properties of callus tissue. PRINCIPLES OF LOAD-RELATED BONE REGENERATION The purpose of bone is to provide structural strength corresponding to its mechanical use (Brown and Ferguson, 1978). This means that bones provide enough strength to keep voluntary physical loads from causing pain or damage as a result of fractures. However, recent research has suggested that bones also display an extraordinary adaptive behaviour

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towards a changing mechanical environment, which is often regarded as phenotype plasticity (Aegerter and Kirkpatrick, 1973; Frost, 2000a, 2000b; Losos, 2001; Frost et al., 2002). Specic strain-dependent signals are thought to control this adaptive mode of bony tissue modelling (Meyer et al., 1997b). The adaptive mechanisms include basic multicellular units (BMUs) of bone remodelling. Effector cells within BMUs have been shown to function in an interdependent manner. While hormones may bring about as much as 10% of the postnatal changes in bone strength and mass, 40% are determined by mechanical effects. This has been shown by the loss of extremity bone mass in patients with paraplegia (more than 40%). Modelling occurs by separate formation and resorption drifts to reshape, thicken, and strengthen a bone or trabecula by moving its surfaces around in tissue space (Frost, 1964a, 1964b, 1983, 1986; Takahashi, 1995). Remodelling also involves both resorption and formation of bone. BMUs turn bone over in small packets through a process in which an activating event causes some bone resorption and bone formation is following (Frost, 1964a, 1964b; Martin et al., 1998; Jee, 1999). This BMU-based remodelling operates in two modes: conservation mode and disuse mode (Frost and Schonau , 2000). . A specic strain threshold range controls which of these two modes is active at any given time (Martin et al., 1998). MECHANOTRANSDUCTION OF OSTEOBLASTS As distraction healing is a highly dynamic cellular process, tensile strains are the leading stimuli for bone regeneration (Frost, 1992). It is generally suggested that distraction forces leading to cellular deformation are signalled to the cellular genome through mechanotransduction. Mechanotransduction, or the conversion of a biophysical force into a cellular response, is an essential mechanism in bone biology (Meyer et al., 1997a). It allows bone cells to respond to a changing mechanical environment. Mechanotransduction can be categorized in an idealized manner into (1) mechanocoupling, which means the transduction of mechanical force applied to the tissue into a local mechanical signal perceived by a bone cell; (2) biochemical coupling, the transduction of a local mechanical signal into biochemical signal cascades altering gene expression or protein activation; (3) transmission of signals from the sensor cells to effector cells, which actually form or remove bone; and ultimately (4) the effector cell response. When loads are applied to bone, the tissue begins to deform causing local strains (typically reported in units of microstrain; 10,000 microstrain=1% change in length). It is well known that osteoblasts and osteocytes act as the sensors of local bone strains and that they are appropriately located in the bone for this function.

Fig. 2 Load-related cellular responses as assessed in cell cultures. High strains (>3000 mstrain) lead to a broblastic, whereas lower strains (3003000 mstrain) result in an osteoblastic differentiation.

Various investigators have revealed that reactive loads give rise to relatively high strains at frequencies that extend from 1 to 10 Hz. It was found that peak strain magnitudes measured in a wide variety of species are remarkably similar, ranging from 2000 to 3500 microstrain. Lanyon et al. (1975) showed that, within a single period of loading, the remodelling process seemed to be saturated after only a few (o50) loading cycles. Further strain repetitions then produced no extra effect. There have been many suggestions for biophysical transduction mechanisms on a cellular level (Ando et al., 1988; Binderman et al., 1988; Jones et al., 1991; Takei et al., 1998). Most studies have suggested that mechanical strain transduction might be directly related to mechanical deformation of ultrastructural organelles or proteins, thereby converting the mechanical information into a biochemical signal. Although hydrostatic compression has been proposed as being analogous to physiological strain and re-creates physiological strain effects, no signicant distortion or compression of the uid-lled cell can occur until very high pressures are attained (Bogi and Burger, 1989). Cell elongation seems to be the driving force for signal transduction. Studies of cell elongation in vitro have demonstrated that physiological loading of osteoblast-like cells induces the differentiation of osteoblasts, whereas hyperphysiological load tends to dedifferentiate cells towards a broblastic phenotype (Meyer et al., 2001c; Fig. 2). It is assumed that the strain sensor is linked to the cytoskeleton, although other hypotheses have been suggested. If the strain sensor is located in the cytoskeleton, then deformations of this structure would tend not to be homogeneous because different compartments would have different mechanical properties and the weakest link would deform the most. In this model, elongation of bone cells appears to inuence subsequent transcriptional events. LOAD-RELATED DISTRACTION HEALING In clinical terms, gradual distraction of bones mechanically elongates the gap tissue. Because the

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osteoblast is the principal cell for bone growth and regeneration, straining of osteoblasts seems to be the major determinant inuencing the subsequent tissue responses in distraction osteogenesis. Several investigations have been performed to evaluate basic mechanisms of bone formation following distraction of the mandible (Karp et al., 1992; Stewart et al., 1998). Treatment protocols differed substantially among the various authors, thus making it nearly impossible to directly compare the effects of tissue strains. The chosen schedules of daily bone lengthening in these studies were based mainly on clinical experience. In rabbits, mandibular osteotomies were subjected to dened daily strains using an implanted mechanical distractor. This animal model allowed the application of dened strain magnitudes (Frost, 1996). These studies demonstrated that bone regeneration is primarily strain related (Meyer et al., 1999c). It appeared that differentiation and matrix production in the bone cell, are inuenced by the applied peak strain magnitudes. Different histological patterns corresponding to various stages of bone healing were distinguished. Woven and, in some areas, lamellar ossication predominated at physiologic strain magnitudes (B2000 microstrain). At higher strain magnitudes (B20,000 microstrain) trabecular bone formation is detected, and brous tissue formation is observed at hyperphysiological strain magnitudes (200,000 and 300,000 microstrain, respectively). Interestingly, the application of multiple increments of distraction (10 cycles per day vs. 1 cycle per day) does not change the histological pattern of bone regeneration, but leads to an overall greater extent of bone deposition (Meyer et al., 1999a; Fig. 3). In specimens distracted at higher strain magnitudes (B20,000 microstrain), areas containing chondroid tissue are often observed in the osteotomy gap. Micromovements within the osteotomy gap may also lead to the development of cartilage (Klotch et al., 1995; Meyer et al., 2001b). Growth factors are likely to play an important role in distraction osteogenesis. Mechanical strain has been shown to increase the expression of transform-

ing growth factor beta in mandibular lengthening (Farhadieh et al., 1999). It was demonstrated that, in response to cyclical strain, human osteoblasts released transforming growth factor beta into the conditioned culture medium (Neidlinger-Wilke et al., 1995). Furthermore, insulin-like growth factor I and basic broblast growth factor have both been identied in the distracted region of osteotomized mandibles suggesting that these proteins promote osteoblast proliferation and formation from mesenchymal precursor cells (Farhadieh et al., 1999). It has been shown that the oestrogen receptor is involved in the adaptive response of osteoblasts to mechanical strain (Damien et al., 1998, 2000). Stress in mechanically loaded bone may activate the mitogen-mediated protein kinase (MAPK) pathway, nally leading to phosphorylation and activation of transcription factors such as c-Jun N-terminal kinase (Matsuda et al., 1998). Recent evidence suggests that mechanical loading of bones induces immediate early gene expression such as Egr-1 and nuclear translocation of NF-kappa B (Dolce et al., 1996: Granet et al., 2001). Other modulators of mechanotransduction in bone are parathyroid hormone, prostanoids, and extracellular calcium (Mikuni-Takagaki, 1999). Bone cells are assumed to act in vivo by secreting cytokines in a strain-related manner. Different cytokines are involved in paracrine and autocrine signalling cascades (Cheal et al., 1991; Meyer et al., 2001a; Bouletreau et al., 2002; Fig. 4). A reduced vascular supply with diminished oxygen tension might be an additional factor controlling the clinical outcome of distraction osteogenesis. Some studies indicated that vascular formation was not prominent in the regenerated tissue and that angiogenesis was not found until later stages of tissue regeneration (Sawaki et al., 1996). In contrast, Rowe et al. (1999) described an intense vascular response associated with mandibular distraction in the early stages of osteogenesis. Numerous studies have recently demonstrated that both the collagen microarchitecture and the mineralization process of bone are inuenced by

Fig. 3 The histological appearance of the elongated mandibular tissue critically depends on the applied strain magnitude and frequency.

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Fig. 4 Feedback regulation of tissue development. Osteoblasts synthesize the extracellular matrix that mineralizes according to the strain history. The newly developing tissue inuences subsequent osteoblast reactions depending on the applied load and the stability of the regenerate.

mechanical stress. Tensile strains were found to be associated with an increased tissue anisotropy. Collagens have been identied as important structural proteins, which are sensitive to the application of mechanical strains. Fratzl et al. (1998) have shown that low strains lead to a straightening of collagen bres, whereas higher strains induce a molecular gliding within the brils, resulting ultimately in the disruption of the brillar organization. Ultrastructural data from various studies support the hypothesis of a structural alteration of collagen assembly under tension stress (Farrar et al., 1978; Mosley et al., 1997; Fratzl et al., 1998; Meyer et al., 2001d). The spatial orientation of collagen bres appears to be associated with different modes of mineralization, as judged by electron microscopy, diffraction analysis, and element determination by analysis of X-rays. In rabbit mandibles distracted at low strains (2000 microstrain), electron diffraction analysis demonstrated mature crystal formation, as indicated by the appearance of multiple reection patterns. In contrast, even moderately elevated strain applications (20,000 microstrain) result in immature crystal formation, containing predominantly developing apatite crystals. The stimulating effect of mechanical distraction on osteoblast proliferation and extracellular matrix synthesis is well characterized (Karp et al., 1992; Stewart et al., 1998). However, little is known about the involvement of apoptosis in bone regeneration and distraction osteogenesis. Using light microscopy to detect apoptotic bodies in injured rat tibia, Landry co-workers (1997) have suggested that osteoblasts are removed from the injury site via apoptosis. Recent investigations into distraction osteogenesis have revealed that incremental traction of osteotomized mandibles results in an enhanced rate of apoptosis (Fig. 5). As a result of hyperphysiological strain application, some osteoblastic cells in the newly formed tissue at osteotomy sites undergo apoptosis. In contrast, mandibles exposed to low magnitudes of strain display only minimal, if any, evidence of

Distraction healing
Strain magnitude

<0,3%

0,3-3%

>3%

Mineralized tissue

Callus tissue

Soft tissue/Apoptosis

Fig. 5 Strain-related distraction healing. Physiological strain leads to callus formation, maximum strains (>20,000 mstrain) to nonunion.

programmed cell death (Meyer et al., 1999b). Recent ndings have implied that in human osteoblasts the small G-protein H-Ras induces apoptosis and inhibits integrin-mediated adhesion (Tanaka et al., 2002). MULTISTEP DISTRACTION PROTOCOL The fact that large gaps between bone fragments impair bone healing (Watson-Jones, 1943) has been well documented. However, with the Ilizarov procedure, healing is possible even in very large gaps if they commence as small gaps and increase in size very slowly (Ilizarov, 1989). This contradicts the former view that micromotion between fracture or osteotomy fragments impair bone healing (Watson-Jones, 1943). While excessive motion can obviously prevent healing, the extent to which small strains actually help to guide the remodelling in bone healing is, at present, unclear (Carter et al., 1988; Kenwright and Goodship, 1989; Hanafusa et al., 1995; Buckwalter and Grodzinshy, 1999; Meyer et al., 1999a, 1999c). It should be noted that fracture and distraction repairs proceed by the same cellular healing process, although the strain rate as related to ossication is

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different. Ossication does not occur in fracture repair when the mobility of the distracted fragment is excessive. Non-union of bone is more likely to occur when the critical gap widens and fragment movement increases. In distraction osteogenesis, with slowly increasing gap size, ossication occurs as long as strain rates do not exceed a certain threshold. Theoretical considerations and experimental data suggest a general upper limit of distraction strain in which the formation of a bony bridge is hindered (Fig. 5). To facilitate bony consolidation, a multistep approach of strain application seems to be advisable. CLINICAL CONSIDERATIONS The clinical applicability of distraction osteogenesis is dependent upon device-related and tissue-related factors. Device-related factors affect the mechanical integrity of the distractor and the stability of bone xation (Mc Tavish et al., 2000). The number, length, and diameter of xation pins, the rigidity of the distractor xation, and the material properties of the device affect the clinical result of the distraction procedure (Brunner et al., 1994). Additionally, the orientation of the distraction device and the resulting distraction vector relative to the anatomical axis of the distracted bone segments (as well as in the case of jaws the occlusal plane and the joint position) are important considerations (Cope et al., 1999). The signicance of device orientation has been established in clinical settings and renements have been made to optimize the treatment outcome. Tissue-related parameters affecting the quality of the distraction tissue generated include the geometric shape, the crosssectional area, the density of the distracted bone segments, the length of the distraction gap, and the tension of the soft tissue envelope (Hollis et al., 1992). In cranio-maxillofacial and alveolar distraction osteogenesis it is important to consider dental aspects in the planning of distraction osteogenesis. These aspects include predistraction orthodontics, osteotomy design and location, selection of the distraction device, orientation of the distraction vector, use of distraction splints, postdistraction orthodontics, and functional loading of the generated bone (Skerry et al., 1989; Smolka et al., 2001). As elongation of the mandible leads to force transmission to the temporomandibular joints, structural alterations in the anatomy of the joints as well as the overlying soft tissue might also be expected. Distraction procedures should take these joint effects into account (KruseLosler et al., 2001). . The correction of complex malformations should be based not only on plain radiographs but also on computed tomographical (CT) data. Computerassisted planning tools allow the virtual determination of the osteotomy lines as well as the simulation of distraction progress (Meyer et al., 2002). A stereolithography model may be used as an additional tool. The planning of the distraction procedure in maxillo-mandibular movements should be based

on the established principles of orthognathic surgery. Model operations with gliding splints and end point markers in the splint should be used to monitor the distraction process in order to gain optimal occlusion.

CLINICAL OUTCOME Distraction osteogenesis was performed in 39 craniofacial cases by a multistep approach in our department (Table 1). In all of these, a multiple step distraction protocol was executed by a standardized application of 10 cycles of 20,000 mstrain per day. For the application of 20,000 mstrain the initial osteotomy gap was measured. The initial distraction length (2% of the gap length) was calculated according to the distractor parameters. Subsequent distractions were then performed in 2% increments of distractor axis rotation, i.e. in a strain dependant manner, independently of the applied forces. All but one multistep distractions were clinically successful. In one case, elongation of the maxillary segment failed due to an incomplete osteotomy. No signs of instability of the segments were observed in any patient. No premature ossication of the callus was present. Segment displacements were stable during the follow-up periods (6 month4 years) in all cases as revealed by radiographic and clinical investigations (lateral and a.p. radiographs, dental casts, clinical measurements). Two representative cases illustrate the treatment approach. Case #1: Distraction was planned in an 18-year-old patient with severe deciency of the midface, Angles class III skeletal relationship and open bite anteriorly (Fig. 6). Preoperative planning included a predistraction orthodontic treatment, plain radiography and computed tomography. Based on the computed tomography, a stereolithographic model was constructed. The distraction vector was dened by a virtual computer operation as well as by a plaster and stereolithography model operation. A multiple distraction protocol was applied to advance the midface following a Le-Fort III osteotomy (Fig. 7). A gliding splint was used to control and monitor the midface movement. Elastics were applied for 3 weeks following the distraction procedure to stabilize the maxillo-

Table 1 Number of patients and extent of bone elongation, achieved by the various types of craniofacial treatment Treatment Mandibular advancement Mandibular widening Maxillary advancement Maxillary widening Midfacial advancement Total (mean) Number of patients 8 1 6 15 9 39 Bone elongation (mm) 1021 11 512 48 59 8.7

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Fig. 6 Planning and execution of midface advancement. (a) 18-year-old patient with severe deciency of the midface prior to treatment. (b) Lateral radiograph demonstrates class III relation with an open bite. (c) Computed tomography and (d) stereolithographic model.

Fig. 7 Same patient as in Fig. 6 before (a) and directly at the end (b) of the distraction. (c,d) Occlusion after removal of the gliding splint.

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Fig. 8 Dental aspect of a 24-year-old patient with (a) transverse mandibular deciency, (b) median osteotomy performed (c) postoperative radiograph. (d) Intraoperative and (e) radiographic examination of the regenerated bone 3 weeks after distraction (prior to removal of the device). (f) Mandibular arch after orthodontic treatment.

mandibular relationship. Two weeks later orthodontic treatment was resumed to rene dental occlusion. Case #2: Mandibular widening is demonstrated in a 24-year-old patient with crowding of the front teeth due to a transverse deciency of the mandible (Fig. 8). A median osteotomy (initial gap size: 2 mm) was performed under general anaesthesia and a distractor (Modus, Switzerland) was placed transversely across the osteotomy line on the labial aspect of the symphysis. After a latent period of 4 days, distraction was performed by application of 20,000 microstrains 10 times a day. The daily increment was calculated individually based on the initial gap of 2 mm. Distraction was performed for 14 days until the preoperatively planned positions were reached. The distraction was monitored continuously by clinical and instrumental examinations. Sonographic images in combination with radiographs revealed normal mineral formation during the distraction period. At all times the gap tissue displayed a homogenous structure. When bony consolidation was complete 3 weeks later, mature bone formation was observed in the gap tissue with a spontaneous movement of teeth into the newly formed bone. This was completed using postsurgical orthodontic treatment for 9 months. The patient was re-examined 1 year after distractor removal and the mandibular widening was found to be radiographically stable. The patient was preoperatively informed that the aesthetic impairment of the broadened chin can be corrected surgically. However, the patient refused to undergo such a genioplasty because she considered the nal facial appearance as acceptable.

CONCLUSION Taking biomechanical aspects of bone regeneration into consideration allows a better understanding of how distraction osteogenesis operates in craniomaxillofacial surgery.

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Biomechanical and clinical implications of distraction osteogenesis in craniofacial surgery 149 Meyer U, Meyer T, Schlegel W, Scholz H, Joos U: Tissue differentiation and cytokine synthesis during strain-related bone formation in distraction osteogenesis. Br J Oral Maxillofac Surg 39: 2229, 2001a Meyer U, Meyer T, Vosshans J, Joos U: Decreased expression of osteocalcin and osteonectin in relation to high strains and decreased mineralization in mandibular distraction osteogenesis. J Cranio-Maxillofac Surg 27: 222227, 1999a . Meyer U, Meyer T, Wiesmann HP, Kruse-Losler B, Vollmer D, Stratmann U, Joos U: Mechanical tension in distraction osteogenesis regulates chondrocytic differentiation. Int J Oral Maxillofac Surg 30: 522530, 2001b Meyer T, Meyer U, Wiesmann HP, Stratmann U, Joos U: Identication of apoptotic cell death in distraction osteogenesis. Cell Biol Int 23: 439446, 1999b Meyer U, Meyer T, Wiesmann HP, Stratmann U, . Maas H, Joos U: The effect of magnitude and Kruse-LoB, frequency of interfragmentary strain on the response to distraction osteogenesis. J Oral Maxillofac Surg 37: 13311341, 1999c Meyer U, Stamm T, Meier N, Joos U: First experience with a public domain computer-aided surgical system. Br J Oral Maxillofac Surg 40: 96104, 2002 Meyer U, Terodde M, Joos U, Wiesmann HP: Mechanische Stimulation von Osteoblasten in der Zellkultur. Mund Kiefer Gesichtschir 5: 166172, 2001c Meyer U, Vollmer D, Homann C, Schuon R, Benthaus S, Vegh A, Felszegi E, Joos U: Experimentelle und Finite-ElementeAnalyse der Biomechanik des Unterkiefers unter Belastung. Mund Kiefer Gesichtschir 4: 1420, 2000 . sche J, Meyer U, Wiesmann HP, Meyer T, Schulze-Osthoff D, Ja . Joos U: Microstructural investigations of strainKruse-LoB, related collagen mineralization. Br J Oral Maxillofac Surg 39: 381389, 2001d Mikuni-Takagaki Y: Mechanical responses and signal transduction pathways in stretched osteocytes. J Bone Miner Metab 17: 5760, 1999 Mosley JR, March BM, Lynch J, Lanyon LE: Strain magnitude related changes in whole bone architecture in growing rats. Bone 20: 191198, 1997 Neidlinger-Wilke C, Stalla I, Claes L, Brand R, Hoellen I, Rubenacker S, Arand M, Kinzl L: Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta-release in response to cyclic strain. J Biomech 28: 14111418, 1995 Robinson RC, ONeal PJ, Robinson GH: Mandibular distraction force: laboratory data and clinical correlation. J Oral Maxillofac Surg 59: 539545, 2001 Rowe NM, Mehrara BJ, Luchs JS, Dudziak ME, Steinbrech DS, Illei PB, Fernandez GJ, Gittes GK, Longaker MT: Angiogenesis during mandibular distraction osteogenesis. Ann Plast Surg 42: 470475, 1999 Sawaki Y, Ohkubo H, Yamamoto H, Ueda M: Mandibular lengthening by intraoral distraction using osseointegrated implants. Int J Oral Maxillofac Implants 11: 186193, 1996 Skerry TM, Bitensky L, Chayen J, Lanyon LE: Early strain-related changes in enzyme activity in osteocytes following bone loading in vivo. J Bone Miner Res 4: 783788, 1989 Smolka K, Meyer U, Joos U, Kleinheinz J: Mandibular distraction osteogenesis: Strain-related bone remodeling for complex anomalies in orthognathic surgery. In: Diner PA, Vasquez MP (Eds.), International Congress on Craniofacial and Facial Bone Distraction Processes, Paris, France, Monduzzi Editore, Bologna, Italy, 2001; 201209 Stewart KJ, Lvoff GO, White SA, Bonar SF, Walsh WR, Smart RC, Poole MD: Mandibular distraction osteogenesis: a comparison of distraction rates in the rabbit model. J CranioMaxillofac Surg 26: 4349, 1998 Takahashi HE (Ed.). Spinal Disorders in Growth and Aging. Tokyo: Springer, 1995 Takei T, Mills I, Arai K, Sumpio BE: Molecular basis for tissue expansion: clinical implications for the surgeon. Plast Reconstr Surg 102: 247258, 1998 Tanaka Y, Nakayamada S, Fujimoto H, Okada Y, Umehara H, Kataoka T, Minami Y: H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts. J Biol Chem 277: 2144621452, 2002 Turner CH, Chandran A, Pidaparti RMV: The anisotropy of osteonal bone and its ultrastructural implications. Bone 17: 8589, 1995 Vollmer D, Meyer U, Joos U, Vegh A, Piffko J: Experimental and nite element study of a human mandible. J Cranio-Maxillofac Surg 28: 9196, 2000 Voo K, Kumaresan S, Pintar FA, Yoganandan N, Sances Jr A: Finite-element models of the human head. Med Biol Eng Comput 34: 375381, 1996 Watson-Jones R: Fractures and Joint Injuries, 3 edition. Baltimore: Williams & Wilkins, 1943 Ulrich Meyer MD, DMD, PhD Department of Cranio-Maxillofacial Surgery University of Munster . Waldeyerstr 30 Munster . D-48149 Germany Tel: +49 251 83 47 201 Fax: +49 251 83 47 203 E-mail: ulmeyer@uni-muenster.de Paper received 22 September 2002 Accepted 23 September 2003