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PubMed2005

Transient disturbance in physeal morphology is associated with long-term effects of nitrogen-containing bisphosphonates in growing rabbits.

UNLABELLED: Bisphosphonates have clinical benefit in children with severe osteogenesis imperfecta or osteoporosis and potential benefit in children with Perthes disease or undergoing distraction osteogenesis. However, there is concern about the effects of bisphosphonates on the physis and bone length. In 44 growing rabbits, zoledronic acid caused a transient disruption of physeal morphology, retention of cartilaginous matrix in trabeculae and cortical bone of the metaphysis, and a minor decrement in tibial bone length at maturity. INTRODUCTION: Data from growing animal models suggest that bisphosphonates cause retention of longitudinal cartilaginous septa at the chondro-osseous junction, extension of trabeculae to the metaphyseal-diaphyseal junction, and varying dose-dependent effects on longitudinal growth. However, there is a lack of data regarding effects of intermittent use of nitrogen-containing bisphosphonates on the physis and on tibial length in models reaching maturity. MATERIALS AND METHODS: Contralateral tibias of juvenile rabbits were examined after right tibial distraction osteogenesis from two previous studies. Animals were randomized to receive 0.1 mg/kg zoledronic acid (ZA) IV at 8 weeks of age (ZA*1) or 8 and 10 weeks of age (ZA*2) or saline. Body mass was analyzed from 5 to 44 weeks of age; tibial length and proximal physeal-metaphyseal histology and histomorphometry were analyzed at 8-52 weeks of age. RESULTS: Tibial length was 3% less at 14 weeks of age in the ZA*2-treated versus saline group (p<0.05) in both studies, and this difference persisted at maturity in the long-term study group (26 weeks of age, p<0.05). Total body mass gain from 5 to 26 weeks of age was 14% less in ZA*2-treated than saline animals (p<0.05). Rate of weight gain from 8 to 10 weeks of age was 76% less in ZA*2 compared with saline animals (p<0.05). Radiographs showed radiodense lines in the metaphyses of ZA-treated bones, corresponding to the number of doses. Histologically, lines resulting from the first dose of ZA contained longitudinal cartilaginous matrix cores surrounded by bone, whereas those from the second dose contained spherical cores of matrix caused by transient disruption of physeal morphology after the first dose of ZA. Resorption of these lines at later times was radiographically and histologically evident, but remnants of cartilaginous matrix remained in the cortical bone of ZA-treated animals. CONCLUSIONS: ZA treatment within the final 13.5% of the rabbit tibial growth period caused a transient disruption in physeal morphology and resorption associated with retention of cartilaginous matrix and coinciding with a persistent 3% decrement in tibial length. Disruption of physeal morphology and potential loss of bone length should be considered when administering nitrogen-containing bisphosphonates to children before closure of the major physes.

Animals↗
PubMed2004

Parathyroid hormone--possible future drug for orthopedic surgery.

Parathyroid hormone naturally secreted by the parathyroid glands is a potent anabolic agent for bone. Parathyroid hormone is primarily thought of as a catabolic protein involved in the physiologic release of calcium from bone. Whereas during recent years, a number of animal studies and clinical trials have demonstrated that intermittent parathyroid hormone administration induces anabolic effects on both cancellous and cortical bone, enhances bone mass and increases mechanical strength of the bones. Most of the studies, both animal and human, have addressed the treatment of osteoporosis and parathyroid hormone represents an important new advance in the therapy of osteoporosis. Few studies have investigated the effect of intermittent parathyroid hormone treatment in the field of orthopedics on fracture healing and fixation of orthopedic implants. The results of those studies indicated an enhancement of fracture healing, faster bone repair and better fixation of the implant. Recently there were few animal studies started to investigate the effects of parathyroid hormone treatment on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening. Distraction osteogenesis is a technique for bone lengthening that is widely used clinically and experimentally. Newly forming bone during distraction osteogenesis is expected to be an appropriate pattern for parathyroid hormone anabolic effect. Preclinical studies as well as clinical trials suggest that parathyroid hormone might be useful as a stimulator of bone formation whereas a lot of questions regarding parathyroid hormone therapy remain unanswered and require further experimental studies and investigations.

Animals↗
PubMed2004

[Injectable carrier system for growth factor application in minimally invasive stimulation of bone healing].

The characterization and cloning of growth factors for bone healing provide an enormous potential for minimally invasive treatment procedures for bone defects or fractures. However, the clinical application of injection vehicles for these growth factors must be made user-friendlier. In this study, two different injection vehicles were tested for their practicability and efficacy to enhance callus maturation during distraction osteogenesis. Calcium phosphate carriers showed a rather low user-friendliness and were less efficient in the animal model of distraction osteogenesis in sheep. Collagen carriers provided both a higher practicability for injection procedures and a higher efficacy.

Animals↗
PubMed2002

[Distraction and tissue regeneration].

Distraction osteogenesis has become a popular method of bone regeneration since 1980's in Japan. Bone is a regenerative tissue and its distraction enhances bone regeneration and remodelling. We review the relationship between distraction osteogenesis and tissue regeneration.

English Abstract↗
PubMed1996

Recorticalization after bifocal internal bone transport in the double-plated sheep femur.

Distraction osteogenesis and bone remodelling after the end of bone transport were investigated in one femur each of six adult male sheep. A newly designed internal distraction device was used. A custom-made osteosynthesis plate was fixed on the lateral side of the femur, and two transporting plates driven by a transcutaneously inserted screwdriver moved two bone cylinders simultaneously over a 40 mm defect. An additional plate was applied ventrally to stabilize the device. Bone transport was begun 2 weeks postoperatively at 1 mm/day at each transporting plate until they came into contact. New bone formation within the distraction gaps was evaluated by computed tomography scans and was quantified at 4 and 6 months by dual energy x-ray absorptiometry as well as histomorphometry on polyfluorochrome-labelled undecalcified ground sections and microradiographs. At 4 months, all distraction gaps were bridged by abundant newly formed bone trabeculae, which were reduced and condensed to cortex-like layers of new bone at 6 months. Less new bone was always found under the lateral device than in the unplated medical and dorsal segments, but the amount of new bone under the ventral plate was comparable with that in the unplated regions. The results of this pilot study show that distraction osteogenesis can be achieved with an internal device such as this one and that recorticalization and restoration of a medullary canal occur despite the relatively rigid internal stabilization by the plates.

Animals↗
PubMed2001

Orthodontic spring guidance of bilateral mandibular distraction in rabbits.

Although distraction osteogenesis can lengthen congenitally small mandibles, the distraction procedure can be difficult to control. To study the efficacy and safety of orthodontic spring guidance on bilateral mandibular distraction, an 8-mm anterior open bite was experimentally produced and corrected during bilateral mandibular distraction in rabbits. Orthodontic springs were attached to the anterior maxilla and mandible to redirect an ongoing distraction procedure. Sixteen rabbits underwent mandibular distraction: 6 rabbits received heavy springs (8 oz), 6 rabbits received light force springs (2 oz), and 4 rabbits served as control animals with anterior open bites without spring guidance. Nickel-titanium springs were applied during the last week of osseous distraction and the first week of consolidation. Distractors were left in place throughout a 2-month consolidation period. None of the animals developed fibrous union as a result of spring guidance. The 8-mm open bite did not close in the control group or in the light spring group after 2 weeks of spring wear or during the consolidation period. Heavy springs completely closed the experimental open bites within 2 weeks (P <.01, analysis of variance). Bite corrections did not change during the consolidation period. This study indicated that the addition of an orthodontic spring to a mandibular distraction procedure did not impair bone healing. With the distraction device in place, heavy spring forces redirected an ongoing mandibular distraction procedure and corrected an open bite, distraction side effect. Direct measurements, radiographic measurements, and tissue histologic factors described changes in segment position and shape of the distraction site.

Analysis of Variance↗
PubMed1999

A comparison of gradual distraction techniques for modification of the midface in growing sheep.

The authors carried out experiments to advance the midface in growing sheep using a distraction force across the zygomaticomaxillary sutures. They wished to assess the possibility of performing distraction osteogenesis across intact sutures as well as distraction after Le Fort osteotomies. Their results demonstrate that the technique of gradual distraction after osteotomy is successful in the growing animal. Bilateral distraction across intact sutures did not advance the midface or change the dental relationship. Unilateral distraction was successful in angulating the midface away from the distracting force in the intact growing animal. Alternating unilateral distraction or "waltzing" was surprisingly effective in advancing the midface in one of the animals studied and may become applicable in some craniofacial deformities. In all intact animals there was some expansion of the zygomaticomaxillary suture as well as a substantial migration of the distraction devices through the bone.

Animals↗
PubMed1999

Intraoral mandibular distraction: indications, technique and long-term results.

This report describes the experience of the Trousseau Hospital, Paris, France, with distraction osteogenesis of the mandible using an intraoral distraction device. From 1993 to 1998, 26 paediatric patients with mandibular hypoplasia underwent distraction of the mandible using the Leibinger Intraoral Distractor. The majority of the patients had hemifacial microsomia. Distraction was performed at a rate of 1 mm a day following complete osteotomy of the mandible. A mean of 15 mm of distraction was obtained. In conjunction with combined orthodontic management, satisfactory morphologic results were achieved in the majority of patients with good facial symmetry, adequate occlusal relationships and balanced maxillary mandibular relationships. Radiographic evaluation revealed that substantial new bone formation and remodelling was induced by the intraoral distraction along the entire hemimandible on the distracted side and that this contributed significantly to the aesthetically pleasing clinical results.

Adolescent↗
PubMed1999

Mandibular lengthening using preprogrammed intraoral tooth-borne distraction devices.

PURPOSE: This report describes the application of an intraoral device for treatment of malocclusions characterized by mandibular deficiency and the surgical technique for its placement. PATIENTS AND METHODS: In an office setting, 5 retrognathic patients underwent mandibular lengthening via distraction osteogenesis with an intraoral tooth-borne distraction device. Under local anesthesia and sedation, mandibular corticotomies, mobilization, and placement of the distractors were performed. Preoperative, intradistraction, and postoperative dental casts, photographs, and cephalometric radiographs were used to analyze the results. RESULTS: In 3 of the 5 cases, distraction occurred along the planned vector. The remaining 2 cases showed opening rotations of the mandibular anterior segment along with the advancement. CONCLUSIONS: This study documents that the mandible and the dental arch can be lengthened successfully using this technique.

Adolescent↗
PubMed2001

Mechanobiology of initial pseudarthrosis formation with oblique fractures.

Mechanical stresses play an important role in regulating tissue differentiation in a variety of contexts during skeletal development and regeneration. It has been shown that some intermittent loading at a fracture site can accelerate secondary fracture healing. However, it has not been shown how the stress and strain histories resulting from mechanical loading of a fracture might, in some cases, inhibit normal fracture healing and induce pseudarthrosis formation. In this study, finite element analysis is used to calculate hydrostatic stress and maximum principal tensile strain patterns in regenerating tissue around the site of an oblique fracture. Using a mechanobiologic view on tissue differentiation, we compared calculated stress and strain patterns within the fracture callus to the histomorphology of a typical oblique pseudarthrosis. Tissue differentiation predictions were consistent with the characteristic histomorphology of oblique pseudarthrosis: in the interfragmentary gap. tensile strains led to "cleavage" of the callus; at the ends of both fracture fragments, hydrostatic pressure and tensile strain caused fibrocartilage formation, and, at discrete locations of the periosteum at the oblique fracture ends, mild hydrostatic tension caused bone formation. We also found that discrete regions of high hydrostatic pressure correlated with locations of periosteal bone resorption. When previous findings with distraction osteogenesis are considered with these observations, it appears that low levels of hydrostatic pressure may be conducive to periosteal cartilage formation but high hydrostatic pressure may induce periosteal bone resorption during bone healing. We concluded that tissue differentiation in pseudarthrosis formation is consistent with concepts previously presented for understanding fracture healing, distraction osteogenesis, and joint formation.

Biomechanical Phenomena↗
PubMed1995

Use of the Ilizarov technique for treatment of non-union of the tibia associated with infection.

Non-union of the tibia associated with infection was treated with radical resection of the necrotic bone and distraction osteogenesis in twenty-eight patients who were eighteen to seventy-four years old. Non-union, infection, shortening, deformity, and osteoporosis were all addressed simultaneously. All patients had either one-segment or two-segment lengthening of bone with a technique of bone transport in which a bone fragment is moved toward the site of non-union, leaving a defect that is bridged by distraction osteogenesis. The size of the bone defect that was bridged averaged six centimeters (range, two to thirteen centimeters). The infection was eradicated in all patients before the fixator was removed. The mean duration of treatment was ten months. The mean time to union, calculated from the day that the intercalary segment came into contact with the target segment, was six months. The mean duration of follow-up was thirty-nine months. The deformity and the inequality of the lengths of the legs were corrected successfully--to less than 7 degrees and to less than 2.5 centimeters, respectively--in fourteen of the twenty-eight patients. In these fourteen patients, the bone result--determined according to the criteria of union, healing of the infection, status of the deformity, and amount of residual shortening--was considered excellent. Of the fourteen remaining patients, eight had a good bone result; one, a fair result; and five, a poor result. The functional result was excellent in seven patients, good in eleven, fair in four, and poor in five. One patient had an amputation. Three patients (11 per cent) had a problem with union that was treated with augmentation with a bone graft. One patient, who had sustained a refracture, had an amputation. Twenty-five patients (89 per cent) had a total of seventy-one minor or major complications, a rate of 2.5 complications per patient.

Adolescent↗
PubMed1997

Limb lengthening in Turner syndrome.

We report the results and complications of eight consecutive patients who underwent bilateral tibial lengthenings for dwarfism associated with Turner syndrome. Lengthening was performed via distraction osteogenesis with monolateral external fixation. Tibias were lengthened an average distance of 9.2 centimeters or 33 percent of the original tibial length. The average total treatment time was 268 days. The overall complication rate was 169 percent for each tibia lengthened and each segment required an average of 1.7 additional procedures. Seven cases (44 percent) required Achilles tendon lengthening and nine cases (56 percent) developed angulation before or after fixator removal; six of these segments required corrective osteotomy for axial malalignment. Two cases (12.5 percent) developed distraction site nonunion and required plating and bone grafting. From this series we conclude that tibial lengthening via distraction osteogenesis can be used to treat disproportionate short stature in patients with Turner syndrome. However, the benefit of a cosmetic increase in height may not compensate for the high complication rate. Efforts to determine the psychosocial and functional benefits of limb lengthening in patients with short stature is necessary to determine the true cost-benefit ratio of this procedure.

Adolescent↗
PubMed2002

A case report: reconstruction of a damaged knee following treatment of giant cell tumor of the proximal tibia with cryosurgery and cementation.

OBJECTIVE: Reconstruction of a knee damaged by cement packed to cure a giant-cell tumor is sometimes difficult. We reconstructed such a knee by removal of the cement, autologous bone transplantation and distraction osteogenesis using the Ilizarov apparatus. In this paper the results 29 months after the salvage surgery are given. PATIENT AND METHODS: We saw a 31-year-old woman's knee joint that showed osteoarthritic change after curettage, cryosurgery and cementation performed 4 years previously for a giant-cell tumor of the proximal tibia. We reconstructed the knee joint. This procedure included cement removal, alignment correction by tibial osteotomy, subchondral bone reconstruction by autologous bone transplantation, and filling the defect after removing the bone cement by elongating the diaphysis using the Ilizarov apparatus. RESULTS: Distraction was terminated 4 months later when 54 mm of elongation was performed. All devices were removed 12 months after the surgery. Seventeen months after the removal of the apparatus, the range of motion of the right knee was 0 degrees extension and 110 degrees flexion, and the patient was able to walk without pain. CONCLUSIONS: Although the treatment period is long and there may be some complications of Ilizarov lengthening and distraction osteogenesis, this procedure has numerous benefits. Bony defects can be soundly reconstructed and, at the same time, the alignment of the knee can be corrected. Also it is not necessary to reconstruct the ligaments because the insertions are intact. If osteoarthritis progresses, a surface type total knee replacement can be performed, not constrained type prosthesis, which would be used if the bony structure had not been reconstructed. This procedure may be one of the candidates for reconstructing such knee joints destroyed by bone cement.

Adult↗
PubMed2003

Distinct anabolic response of osteoblast to low-intensity pulsed ultrasound.

Low-intensity pulsed ultrasound, a form of mechanical energy transmitted as high-frequency acoustical pressure waves, provides noninvasive therapeutic treatment for accelerating fracture repair and distraction osteogenesis. Relatively young osteoblasts respond to ultrasound by transiently upregulating message levels of immediate-early genes as well as that of osteocalcin and insulin-like growth factor I (IGF-I). Osteocytes derived from newborn rat tibia and calvaria responded to a lesser extent only in c-fos and cyclooxygenase-2 (COX-2) messages. Compared with the stretched osteocytes, which use stretch-activated and parathyroid hormone (PTH)-potentiated Ca2+ influx as an entry route to the protein kinase A (PKA) signal transduction pathways, there was no evidence of Ca2+ internalization by any of the cells tested on exposure to the ultrasound. On the other hand, inhibitors of p38 mitogen-activated protein kinase (MAPK) and upstream phosphoinositide 3-kinase (PI3K) blocked COX-2 and osteocalcin upregulation by the ultrasound-exposed ST2, murine bone marrow-derived cells. This is distinct from the aforementioned osteocytic response to low-frequency stretching and implies the involvement of integrins. Our findings suggested that accelerated fracture repair and distraction osteogenesis by the low-intensity pulsed ultrasound depend, at least in part, on the stimulation of osteoblastic cells at relatively early stages of osteogenic lineage. Bone is under control of multiple regulatory mechanisms so that diverse physical forces can be reflected to the microenvironment of each cell, in turn, to the entire bone.

Animals↗
PubMed1999

Unilateral coronal synostosis treated by internal forehead distraction.

A 1-year-old infant with left hemicoronal synostosis was treated by distraction osteogenesis of the craniofacial skeleton using an internal distraction device. Surgery was performed through a coronal incision. The frontal bone and upper half of both orbits were first osteotomized en bloc after minimal epidural dissection of the supraorbital area and no epidural dissection around the coronal osteotomy site. The lateral one fourth of the frontal bone, including the right lateral half of the orbit, was left intact. The internal distraction device was fixed in the left temporal area. A 0.5-mm per day rate of distraction was performed up to an elongation of 17 mm after a 5-day latency period. The distraction device was removed after a consolidation period of 2 months. The results obtained were satisfactory, with symmetry of the forehead, orbit, and nose achieved without complications. The merits of this procedure are no extradural dead space after the operation (which prevents infection), shortened operative time, reduced blood loss, filling in the bone gap created by advancement with new bone, acceptable cosmesis by the parents during distraction, and no fixation device left after the second operation.

Craniosynostoses↗
PubMed2006

The revised "reconstructive ladder" and its applications for high-energy injuries to the extremities.

In this report, we tried to evaluate the merits of the classic "reconstructive ladder" and other reconstructive tools, such as acute shortening followed by distraction osteogenesis and a vacuum-assisted closure device, for the treatment of high-energy injuries. Thirty-seven patients suffering from high-velocity injuries to the extremities caused by war weapons and blast terror attacks were treated at our institution. The fractures were initially stabilized by the Association for the Study of Internal Fixation (AO/ASIF) unilateral tubular external fixator, which was changed 2-3 days later to a circular Ilizarov frame for 19 patients. Temporary acute shortening was performed for 5 patients. Skin grafts were performed for 21 patients, local or regional flaps for 14 patients, and free flaps for 6. Vacuum-assisted closure was selected for 8 patients. The wounds were successfully closed in all the patients. Two patients with upper-limb injuries had nonunion. Motor nerve injuries recovered in 7/10 patients. Due to hypergranulating tissue, 2 patients treated with vacuum-assisted closure (VAC) had to stop treatment early. Their wounds were closed with skin graft or local flap. The classic reconstructive ladder, starting from direct closure and ending with a free flap, should be extended for limb traumas and include acute shortening with or without angulation, followed by distraction osteogenesis and the VAC system on the same step as the free flap.

Adult↗