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Evaluation of the mechanical environment during distraction osteogenesis.

Physical forces have been hypothesized to direct the process of bone regeneration during distraction osteogenesis. However, despite significant clinical experience, relatively little is known about how the mechanics of distraction influence bone formation. This study investigated net fixator forces and strains in the distraction callus during bilateral lengthening of tibiae in New Zealand White rabbits. Distractions yielded a classic viscoelastic response with a sharp increase in fixator force, followed immediately by significant relaxation. Tension acting on mesenchymal gap tissue caused by distraction was estimated to reach more than 30 N by the time full lengthening was achieved. Average maximum cyclic strains within the distraction zone during ambulation were estimated to be 14% to 15% and supported by the results of fluoroscopic imaging. Paradigms for fracture healing have hypothesized that such strains are incompatible with new bone formation. The documented clinical success of distraction osteogenesis at stimulating large volumes of new bone suggests that other mechanisms that warrant additional investigation may be at work during distraction.

Animals↗

Osteogenesis by recombinant human bone morphogenetic protein-2 at skeletal sites.

Osteogenesis was evaluated in the mandibular bone by combinations of various dosages of recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite (four groups: Group I, 2 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Group II, 10 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Group III, 50 micrograms recombinant human bone morphogenetic protein-2, atelopeptide Type I collagen, and porous hydroxyapatite; Control Group, only atelopeptide Type I collagen and porous hydroxyapatite). The prepared materials were implanted in the mandibular bone hole (7 mm in diameter, 2 mm deep). Three weeks later, the alkaline phosphatase activity in the implanted region was determined, and the histologic features of the excised tissue were examined. There were significant differences in histologic and biochemical findings among the four groups. In the recombinant human bone morphogenetic protein-2 implanted groups, osteogenesis increased with the dosage of recombinant human bone morphogenetic protein-2, as assessed by alkaline phosphatase activity and histologic findings. The results suggest that atelopeptide Type I collagen is an effective carrier for recombinant human bone morphogenetic protein-2 and that porous hydroxyapatite would be advantageous for clinical application as a material to maintain its original form after implantation.

Alkaline Phosphatase↗

Distraction osteogenesis for nonunion after high tibial osteotomy.

The purpose of this study was to determine whether distraction osteogenesis can be used to treat hypertrophic nonunion associated with angular deformity and shortening after Coventry style high tibial osteotomy. Five consecutive patients were retrospectively reviewed. In all patients the alignment had collapsed into excessive varus or valgus and leg length discrepancy was present. The leg length discrepancy, malalignment, and nonunion were treated simultaneously with distraction. Union was achieved by the time of fixator removal, which averaged 4.4 months. The Hospital for Special Surgery knee score significantly improved from 42 to 89. The mechanical axis deviation significantly improved by 5 cm. The coronal plane deformity significantly improved by 13 degrees, and leg length discrepancy improved significantly from 2.3 to 0.5 cm. Metaphyseal bone stock increased by 43%, and the Insall-Salvati ratio increased from 1.1 to 1.2 and remained within normal limits. All patients were satisfied with the procedure, and none have had or need a total knee replacement at an average followup of 4 years. Distraction osteogenesis of nonunion after high tibial osteotomy is a minimally invasive and successful procedure. It leads to bony union with correction of deformity and leg length discrepancy and prevents the need for total knee replacement at intermediate-term followup. The increase in metaphyseal bone stock may make total knee replacement technically easier.

Adult↗

Ultrasound can predict regenerate stiffness in distraction osteogenesis.

Assessing the regenerate strength in distraction osteogenesis is crucial for clinical treatment. Several methods have been used to achieve this, including plain radiography, digital radiography, quantitative computed tomography, dual energy xray absorptiometry, and ultrasound. The aim of the current study was to investigate the use of ultrasound in monitoring regenerate formation and to correlate this to biomechanical testing results. An osteotomy was done on the tibia of 30 Yucatan micropigs and an Ilizarov-type half-ring external fixator was mounted. After a 5-day latency period, the tibias were distracted for 10 days and then left to consolidate for 10 days. Seven ultrasound examinations were done during Day 15 through Day 25. After sacrifice, the bone mineral density was measured using quantitative computed tomography. Maximum load and torsional stiffness were measured and correlated with ultrasound measurements and bone mineral density. The ultrasound penetration depth and the bone mineral density correlated closely with torsional stiffness. Ultrasound can be a noninvasive predictor of bone regenerate strength in the early phase of distraction osteogenesis, which may reduce the need for radiographs.

Animals↗

Histomorphometry of distraction osteogenesis during experimental tibial lengthening.

OBJECTIVES: The aim of the current study was to analyze distraction osteogenesis histomorphometrically to investigate the amount of enchondral ossification adjacent to intramembranous ossification. STUDY DESIGN: Species-specific, longitudinal time study. METHODS Lengthening of 25% of the right tibia was performed in 24 beagle dogs by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day with a distraction rate of 0.5 mm twice a day. Twelve dogs were killed at the end of the distraction phase of 25 days (group A) and the remaining 12 dogs after an additional consolidation period of 25 days (group B). The tibia was removed from the distracted right leg and from the left control side of each animal, and longitudinal sections were cut and stained with Pentachrome. In all tibiae, an area of 0.5 x 2.4 cm within the endosteal bone was evaluated histomorphometrically with a Merz grid, and the results were compared between distraction and control side as well as between the dogs of group A and group B. RESULTS: On the distraction side, the typical signs of an increased de novo bone formation with a significant increase of osteoblasts and osteoid in group A, as well as an additional significant increase of bone volume and trabecular thickness in group B, were found. In all distraction cases, islands of cartilage formation, which underwent enchondral ossification, were found, besides membranous ossification. The ratio between membranous and enchondral ossification was found to be five to one. CONCLUSION: Bone formation during distraction osteogenesis results from both membranous and enchondral ossification.

Animals↗

Heterotopic neo-osteogenesis from vascularized periosteum and bone grafts.

BACKGROUND: Periosteum is an osteogenic, flexible tissue. This study investigated the osteogenic potential of vascularized periosteal flaps in heterotopic conditions and compared it to the neo-osteogenesis from vascularized periosteal flaps combined with bone grafts with different properties (autologous and xenograft). METHODS: Vascularized periosteal flaps from the hindlimbs of 48 rabbits formed cylindrical pouches that were buried in muscles. The pouches were filled with autologous bone grafts (P/A group, n = 16), xenograft (P/X group, n = 16), or left empty (P/E group, n = 16). Specimens were harvested between 1 and 4 months and underwent radiographic, histologic, and histomorphometric evaluation. RESULTS: The total surface area was larger in the groups combined with bone grafts. Osseous apposition did not differ significantly in the P/A and P/X groups (p > 0.05). The central cavity contained hematopoietic cells (P/A), xenograft (P/X), or was absent (P/E). CONCLUSION: Vascularized periosteal flaps presented strong osteogenic capacity in heterotopic conditions. Combination with bone grafts resulted in larger specimens. The quality of neo-osteogenesis was not influenced by the different properties of combined bone grafts.

Animals↗

Induced osteogenesis for repair and construction in the craniofacial region.

Solid and powdered forms of undemineralized and demineralized bone grafts were implanted in rat cranial defects. Demineralized calvarial discs healed the defects as well as did the fresh discs, as judged by histology and 45Ca incorporation. Gross and histologic evaluations demonstrated predictable endochondrial osteogenesis by demineralized bone powder (DBP). Undemineralized grafts, in contrast, showed poor and unpredictable bony healing. Construction of facial bones was achieved by implantation of demineralized bone powder within the soft tissues. The phenomenon of induced osteogenesis by demineralized implants was not species specific. These studies of osseous transformation provide insight into the mechanism of, and possible answers to, the problems of osseous transplantation.

Animals↗

Multidimensional distraction osteogenesis: the canine zygoma.

The principle of distraction osteogenesis, well-established in the enchondral bones of the axial skeleton, has recently been applied to the membranous bones (mandible, cranium) of the craniofacial skeleton in the experimental animal and in the human. In the craniofacial skeleton, however, the technique has been used only to lengthen bone in a direction along its major axis, i.e., unidimensional distraction. A canine model is presented to demonstrate the feasibility of distracting membranous bone away from its dominant axis, i.e., multidimensional distraction. Four mongrel dogs, 5 months of age, were the subjects of this study. Two osteotomies were made in the zygomatic arch, and the bone-lengthening device was fixed to the zygoma. After 7 days of external fixation, the osteotomized segment was lengthened 1 mm/day away from the long axis of the bone for 15 days. External fixation was then maintained for a minimum of 4 weeks, after which the dogs were sacrificed. Craniofacial CT with three-dimensional reconstruction documented multidimensional bone lengthening, and histologic analysis of the specimen confirmed the presence of new cortical bone in the expanded areas. Refinement in technique and miniaturization and internalization of the bone-lengthening device may allow for more precise changes in the amount and direction of lengthening, thus making distraction osteogenesis more widely applicable for use in the human craniofacial skeleton.

Animals↗

Distraction osteogenesis in the hand.

Distraction osteogenesis was used to correct congenital hand deformities in 12 digits. The patients' ages at the time of distraction ranged between 2.5 and 7 years. A total of nine patients underwent lengthening of 12 bones. The average period of distraction was 31.1 +/- 17.6 days. The average length of distraction was 23.6 +/- 7.3 mm. Seventeen percent of the patients after lengthening had an angular deformity that required remodeling of the regenerate. No infections were noted. Distraction osteogenesis provides a useful tool for reliable and predictable correction of osseous defects with vascular bone in patients with congenital anomalies of the hand.

Acrocephalosyndactylia↗

Successful distraction osteogenesis across a growing cranial suture without an osteotomy.

The application of distraction osteogenesis to the membranous bones of the craniofacial skeleton and its effects on cranial volume and overall skull shape have not been fully studied. This pilot study was designed to compare distraction of a cranial suture in the rabbit model with distraction across an osteotomy and to evaluate the response of the suture both grossly and histologically. Additionally, the need for a period of rigid fixation after distraction was evaluated. Calibrated distraction of either the coronal suture or an osteotomy in the midsection of the parietal bone using an internal distractor (Synthes Maxillofacial, Paoli, Pa.) was studied in juvenile and adult New Zealand White rabbits. Skull growth and distraction were followed by serial cephalograms, and bone biopsies of the distracted sites were obtained after death for histologic evaluation. Craniometric analysis of the skulls was also performed. There was significantly greater mean marker separation in the juvenile suture distraction group (6.6 +/- 0.2 mm; n = 3) than in the control group (2.2 +/- 0.2 mm; p < 0.01). Marker separation was also significantly greater across the parietal osteotomy (6.4 +/- 0.1 mm) than in the sham group (no marker separation). Craniometric data demonstrated the ability of the juvenile skull to distribute the change at the coronal suture throughout the skull to maintain symmetry and minimize disproportion. No distraction was obtained across the adult suture. In the juvenile suture distraction group without a period of stable fixation, a relapse of 17 +/- 6 percent was noted after 1 week, an additional 2.3 +/- 0.5 percent after the second week, and no further change in the third postdistraction week (n = 2; p < 0.01). These results show that in this animal model, distraction osteogenesis can be achieved across a growing cranial suture without an osteotomy or suturectomy and that the degree of distraction and new bone formation is comparable to that across an osteotomy. This suggests that cranial expansion can be obtained in a growing animal without using a more invasive cranial osteotomy. Additionally, the first week after distraction seems to be the most critical time period to maintain stable fixation.

Animals↗

Manipulation of callus after linear distraction: a "lifeboat" or an alternative to multivectorial distraction osteogenesis of the mandible?

Despite impressive results, distraction osteogenesis of the mandible is still compromised by difficulties with vector control. Because of the action of the masticatory muscles, the gonion angle has the tendency to open, resulting in an open bite. We report two patients, aged 10 and 12 years, who developed a severe open bite during mandibular distraction. As a salvage procedure, manual shaping of the soft regenerate was done immediately after distraction. Uneventful bony consolidation was observed, which resulted in anatomically shaped gonion angles. The fact that a regenerate created by distraction osteogenesis can be molded to virtually any shape offers interesting perspectives for the correction of complex mandibular deformities.

Bony Callus↗

Distraction osteogenesis: a new surgical technique for use with the multiplanar mandibular distractor.

If distraction osteogenesis is to reach its full potential and achieve the level of accuracy that is possible with orthognathic surgery, its outcomes need to be as predictable. To this end, the authors developed a planning process for distraction osteogenesis similar to that used in orthognathic surgery. However, the success of the planning process depends on the authors' ability to execute the plan at the time of surgery. As a result, the authors needed to develop a surgical technique that would enable them to precisely install the distractor as indicated in the presurgical plan. The surgical technique presented in this article was developed for this purpose. The authors used this technique in seven patients (four boys and three girls; age range, 4 to 10 years). Four patients presented with unilateral deformities, and three patients presented with bilateral deformities. The follow-up period in this group of patients ranged from 12 to 33 months. The purpose of the technique is to replicate the position of the distractor on the mandible as determined by the presurgical plan. To this purpose, a custom drill guide and a surgical template have been developed. Both of these are used following the principles of triangulation to establish the pin position and orientation of the distractor. In the authors' hands, the use of this surgical technique has resulted in outcomes close to those predicted by the planning process.

Child↗

Remodeling of the temporomandibular joint following mandibular distraction osteogenesis in the transverse dimension.

Transverse mandibular distraction osteogenesis involves moving the osteotomized segments of the mandible in either a varus or valgus direction. This maneuver allows for widening of the bigonial distance or for a lateral shift of an asymmetric mandibular midline. During this process, a significant amount of torque is placed on the mandibular condyles, because they act as the pivot point for the mandibular translation. Although standard linear distraction osteogenesis induces transient, reversible changes in the temporomandibular joint, it is not known what effect the varus and valgus stresses of transverse distraction have on the temporomandibular joint. We therefore designed a study to document the temporomandibular joint changes following various degrees of transverse distraction. Bilateral transverse mandibular distraction was performed on 10 adult, female mongrel dogs using an external, multiplanar mandibular distraction device. The distraction protocol was as follows: (1) complete osteotomy at the angle of the mandible, (2) 5-day latency period, (3) distraction rate of 1 mm/day, (4) rhythm of one turn per day, (5) linear activation 16 to 30 mm bilaterally, and (6) 8-week consolidation period. A variety of varus and valgus distraction vectors were applied to the mandible only after 10 mm of initial linear distraction had been achieved. Posteroanterior and lateral cephalograms were performed throughout the entire process. Pre-distraction and post-consolidation computed tomographic scans were also performed. Changes in mandibular conformation, axis of rotation, temporomandibular joint structure, and glenoid fossa changes were directly assessed by evaluating the postmortem craniofacial skeleton. The findings were compared with those of normal, age-matched mongrel dog skulls. Significant remodeling changes were observed in the temporomandibular joints of all animals involved in the study. The mandibular condyles demonstrated varying degrees of flattening and erosion at all contact points with the craniofacial skeleton. In some cases, the condyle became part of the distraction regenerate process and was hypertrophied in all dimensions. The condyles were frequently displaced out of the glenoid fossa, particularly on the side in the direction of varus distraction. When the latter occurred, a new fossa was created on the undersurface of the zygomatic arch. Varying degrees of mandibular rotation in the sagittal plane were also observed, which led to abnormal torquing of the condyles in the coronal plane, depending on whether the axis of rotation occurred primarily around the condyle or around the distraction regenerate zone.In conclusion, transverse mandibular distraction is an effective means of producing a varus or valgus shift in the gonion relative to the midsagittal plane. However, unlike linear or angular mandibular distraction, transverse distraction has a multitude of nontransient effects on the temporomandibular joint. Therefore it must be emphasized that in clinical practice, transverse distraction should be used cautiously. One must also be aware that such a maneuver in distraction can have negative effects on the temporomandibular joint.

Animals↗

Effects of mandibular distraction osteogenesis on the inferior alveolar nerve: an experimental study in monkeys.

A series of experimental studies were performed in monkeys to study the effect of mandibular distraction osteogenesis on the inferior alveolar nerve at different times before and after distraction. A mandible osteotomy was performed and distraction was carried out unilaterally in 10 young rhesus monkeys and bilaterally in six. The intact nerves on the contralateral side of the 10 monkeys were used for the control. Care was taken to avoid destroying the integrity of the inferior alveolar nerve during the surgical procedure. After a 5-day latency period, the distraction device was activated at a rate of 0.5 mm twice each day for 15 days. Sensory nerve action potential testing was applied before and 1 day after the operation, at completion of distraction, and at 2, 4, 6, 9, and 12 weeks of fixation. Necropsy was performed at the completion of distraction and 2, 4, 6, and 12 weeks of fixation. The mental nerves were taken, sectioned, and stained with lead citrate and uranyl acetate, and examined with a transmission electron microscope. The inferior alveolar nerves in the distraction gap were obtained, and paraffin slides were made and stained with hematoxylin and eosin, Luxol fast blue, and Bodian methods. The authors found that immediately after the mandible osteotomy, most nerves showed signs of slight acute injury; the latency was increased by 5.553 percent, and the amplitude was decreased to 1808 microV. This might be caused by the surgical procedure or by compressions produced by swelling tissues around the nerves. When distraction was completed, the latency was prolonged for an average of 22.18 percent, and the amplitude average had attenuated to 28.54 percent (804 microV) of the preoperative value on the distracted side. Most nerve fibers exhibited signs of degeneration, such as myelin disruption, swelling of cell organs greatly increased in axoplasm, axon tearing, and myelin fragments engulfed by macrophages. These were nerve reactions to the tensions produced by mandible lengthening. As time elapsed, the nerve's action potential recovered gradually because of its repairing ability, the latency shortened, amplitude increased, Schwann cells proliferated and formed new myelin sheaths, and the tearing axons reconnected. After 12 weeks of consolidation, there was still a latency of 12.384 percent prolongation because of the prolonged conduction distance, and the average amplitude was restored to 2786 microV, the approximate preoperative value. The nerve seemed to be repaired completely; its myelin thickness, axon diameter, and ultrastructure were all similar to those of the control. It was concluded that mandibular distraction osteogenesis can produce some degree of harmful effects on the function and structure of inferior alveolar nerves, but it is reversible and relatively slight. Along with the regeneration of the nerve's myelin and axon, the nerve function can gradually rehabilitate to a normal level.

Action Potentials↗

Osteogenesis imperfecta and associated hearing loss in five kindreds.

We examined audiometric data of 30 medically confirmed cases of osteogenesis imperfecta, evaluating pure tone threshold and impedance data to determine the prevalence, type, and degree of hearing loss in five kindreds. Nineteen of the 30 individuals evaluated had normal hearing bilaterally, while 11 had hearing losses of various types and degrees. The results of pure tone testing, tympanometry, and acoustic reflex measurements suggest no clearly established pattern of hearing loss in this population. However, the presence of air-bone gaps and absent acoustic reflexes during the first and second decades support the findings of others, indicating that conductive hearing loss is most prevalent in younger individuals with osteogenesis imperfecta.

Acoustic Impedance Tests↗

Osteogenesis imperfecta with arthrogryposis multiplex congenita (Bruck syndrome)--evidence for possible autosomal recessive inheritance.

We report a son and a daughter of a first cousin Pakistani marriage who both have osteogenesis imperfecta and the son in addition has arthrogryposis multiplex congenita. Bruck [(1897): Dtsch Med Wochenschr 23: 152-155] first reported the case of a boy who had multiple fractures and joint ankylosis, subsequently only one sibship with three affected cases and seven sporadic cases have been reported to our knowledge. On the basis of consanguinity this suggests that the association of osteogenesis imperfecta and arthrogryposis multiplex congenita is inherited in this family as an autosomal recessive condition with variable expression.

Arthrogryposis↗

Ethanol-induced inhibition of bone formation in a rat model of distraction osteogenesis: a role for the tumor necrosis factor signaling axis.

BACKGROUND: Chronic ethanol exposure inhibits the rapid bone formation demonstrated during limb lengthening by distraction osteogenesis (DO). This inhibition is attenuated by simultaneous administration of antagonists to the cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. The individual effects on inhibition of osteogenesis by these cytokines were tested. We hypothesized that administration of individual antagonists to these cytokines [IL-1 receptor antagonist (IL-1ra) or polyethylene glycol-conjugated soluble TNF receptor type 1 (sTNFR1)] would enhance DO and that the individual administration of each cytokine [recombinant rat (rr) IL-1 or recombinant rat (rr) TNF] would inhibit DO. METHODS: Rats were either infused with a liquid diet with or without ethanol (antagonist studies) or given rat chow (recombinant studies) and underwent tibial fractures stabilized with external fixators for DO. The bioactive substances were administered by systemic (antagonist studies) or local (recombinant) diffusion. RESULTS: A comparison of histologic sections from these distracted tibias demonstrated a protective effect on bone formation by sTNFR1 (p<0.05), unexpectedly, an IL-1ra-related decrease in bone formation (p<0.02), significant decreases in bone formation with rrTNF compared with the vehicle controls (p<0.02), and no significant changes in bone formation with rrIL-1. The cellular responses (fibroblastic and inflammatory cells) were unique for each recombinant cytokine administered. CONCLUSIONS: These results suggest that the osteoinhibitory effects of chronic ethanol exposure are mediated in part by the TNF signaling axis.

Alcoholism↗

Distraction osteogenesis for knee arthrodesis in infected tumor prostheses.

Three patients had distraction osteogenesis as a salvage method for infected endoprostheses. At the first operation, the infected prosthesis was removed and stabilization was achieved with an external fixator to preserve limb length. An additional external fixator was applied later for distraction osteogenesis after ensuring that there was no infection. Osteotomy was done at two sites on the femur, or tibia and femur, respectively, as a second operation. A third surgery was done at the docking site at the edge of the transported bone fragments. Curettage, refreshing, and soft tissue release were done to enhance bone union. The healing index was 18.3 days/cm in Patient 1, 17.7 days/cm in Patient 2, and 33.0 days/cm in Patient 3. All patients walk without a cane. It has been shown that patients can obtain a long-lasting and weight-bearable leg with our method, because their viable bone establishes biomechanical stability. Loss of knee function, a longer treatment period, and pin site treatment are the weaknesses of our method. Our method is indicated for patients in whom systemic disease can be controlled well and who have longer life expectancy.

Adolescent↗