Stimulation of Bone Formation by Recombinant Fibroblast Growth Factor-2 in Callotasis Bone Lengthening of Rabbits

Bone lengthening by callotasis is one of the most useful methods not only for the treatment of short extremities but also for extensive bone defects; however, the procedure takes a long time especially for the consolidation of the distracted callus. In this study, effects of a single local injection of recombinant human fibroblast growth factor-2 (FGF-2 or basic FGF) on callotasis bone lengthening were examined in rabbits. Ten days after the osteotomy at the middle of the tibia and the installment of an external fixator, the osteotomized site was distracted at a rate of 1.4 mm/day for 7 days, resulting in 9.8 mm lengthening. On the final day of distraction, 200 μg of FGF-2 in 150 μl of saline solution or vehicle alone was injected into the center of the distracted callus. Injection of FGF-2 increased bone formation at the distracted callus radiologically and histologically. A significant effect on bone mineral content (BMC) at the callus was observed as early as 2 weeks, and FGF-2 increased the BMC about twofold at 5 weeks after a normal remodeling process. We conclude that the callotasis method in combination with FGF-2 injection at the consolidation step could be clinically beneficial to shorten the bone lengthening period. Received: 6 May 1997 / Accepted: 1 November 1998     

Dual-energy X-ray absorptiometry predicts bone formation in lower limb callotasis lengthening.

The rate of regenerate bone mineral content (BMC) acceleration was studied using dual-energy X-ray absorptiometry (DEXA) in callotasis lengthening of the lower limb. Eleven youngsters (age range 5-17 years) undergoing callotasis lengthening for congenital, post-traumatic or post-infective conditions were studied longitudinally. Patients were initially scanned once a week until completion of the lengthening phase, and at 2-week intervals thereafter until removal of the fixator. They were subsequently followed up at regular intervals on an outpatient basis for up to 2 years after removal of the fixator (average, 14 months). The BMC accretion slopes exhibited by the patients and the rate of new bone formation allowed the identification of three groups. In the fast formation group, the rate of new bone formation was 0.3-0.6% per day. In the moderate formation group the rate of new bone formation is 0.1-0.3% per day, while in the poor formation group the rate of new bone formation is < 0.1% per day. From the analysis of time graphs, a direct correlation emerged between early bone formation and subsequent bone mineral content accretion. Measurement of BMC during callotasis lengthening in the lower limb allows precise monitoring of the process. It may prove useful to prevent complications occurring after removal of the fixator at an unduly early stage, such as plastic deformation and fracture through the regenerate bone. It may be used to predict the bone formation rate in a given patient, and to implement measures to try to influence it.     

Graner's procedure in Kienböck disease: A series of four cases with 25 years of follow-up

Advanced stages of Kienböck's disease are treated by several techniques, one of which is Graner's procedure, nearly abandoned nowadays. The results of long-term follow-up of a series of four cases Graner's procedure are presented. Four patients were reviewed with a follow-up of 25 years. There were two women and two men mean aged 37 years at the time of surgery. Two of them were manual workers. Graner's procedure was the first surgery in three cases and secondary to failure of radius shortening in one case of Stage IIIa. Three patients underwent bone healing and the fourth benefited secondarily from radiocarpal arthrodesis. At maximal follow-up, the mean DASH score was 36.6 and pain assessed by visual analogic scale was 3.25 out of 10; the range of movement was half of the opposite side; the wrist strength was 80.9% of the opposite side. In the three consolidated cases, a spontaneous remodeling of the radiocarpal articular surfaces was noted. Graner's procedure is logical as it aims at creating a new radiocarpal articulation, either by the fusion of the lunate with the capitate (Graner I) or by replacing the lunate with the head of the capitate (Graner II and III). However, this old procedure should no longer be one of the surgical procedures for Kienböck disease due to its drawbacks: necrosis or non-union of the head of the capitate, necessity to perform a wrist fusion in the long-term and side effects of bone graft harvesting.Level of evidenceII. Retrospective study.     

Stiffness measurements to assess healing in bone transport: a preliminary report

Little is known about the pattern of healing in patients undergoing bone transport for limb reconstruction. We evaluated the possibility of using bone stiffness for assessing healing in 8 consecutive patients treated with the Orthofix limb reconstruction system for non–union or bone loss. Six procedures were successful in achieving restoration of leg length and healing at both the docking site and the callotasis segment. Two procedures were unsuccessful, resulting in below–knee amputation. Of the six successful procedures, five were followed with bending stiffness measurements, while one patient was temporarily lost to follow–up. In all cases, the docking site took longer to heal than the callotasis segment. Patterns of healing of the callotasis segment were similar to that found in limb lengthening, and the docking site healed with a rate similar to that found in severe tibial fractures. The stiffness value proved to be a clinically useful, objective measure of healing in bone transport. A level of 15 Newton metres/degree (nm/d) allowed safe fixator removal in these cases.     

The behaviour of the periosteum during callotasis

Periosteal behaviour during callotasis has been studied in animals but not in humans. Markers were inserted into the periosteum of seven patients who underwent callotasis. All of them had tibial callotasis, five patients had bone transport procedure and two had leg lengthening due to congenital disorder. They were followed up radiologically at regular intervals and during the distraction the movement of the periosteal markers was recorded. This enabled observation of the way the periosteum elongates during the procedure and also the calculation of periosteal strain at different stages at the points where the periosteum is fixed to bone. The study indicated that in most cases the periosteum acts as an elastic sleeve surrounding the newly formed tissue during lengthening. The site of attachment between sleeve and cortex became established early during lengthening, and hardly changed position at later stages. There was a wide spread of attachment sites and periosteal strains. Attachment sites were not related to pin or wire entry points, and strains were not predictive of callus shape or healing time.     

Bone mineralization at the callotasis site after completion of lengthening.

We studied the course of bone mineralization of regenerate bone after callotasis lengthening. Twenty-three patients (eight boys) (mean age at operation 11.5 years, range 4-17 years; leg length discrepancy [LLD] at surgery ranging from 4 to 13 cm) underwent dual-energy X-ray absorptiometry (DEXA) scanning weekly during the distraction phase, at 2 week intervals until removal of the fixator, and at the time of their out-patient visits thereafter, for a mean of 794 +/- 420 days after removal of the apparatus. At removal of the fixator, the bone mineral content (BMC) of the regenerate was nearly 70% of the normal contralateral limb. With time, this value gradually increased, and tended to reach normal values, with no significant difference between femur and tibia. With time, the BMC of the regenerate tends to return to the value of the normal contralateral limb. Probably, once the limb length discrepancy has been equalized, the mechanical stimuli imparted through weight-bearing to the lengthened limb are of the same magnitude bilaterally. In this instance, then, the newly formed bone, responding to these physical stimuli, would normalize its mineral content, confirming that bone remodeling continues well after lengthening is terminated. Mineralization of the regenerate after completion of the lengthening process reaches values significantly greater than at removal of the fixator, with an increase of >50% of the prelengthening values, regardless of the underlying pathology. The final value of this increased BMC is not significantly different than in the normal contralateral unoperated limb. At least part of the increase in bone mineralization following callotasis lengthening is due to the normal process of growth and development.     

Bone lengthening osteogenesis,a combination of intramembranous and endochondral ossification: an experimental study in sheep

We evaluated the morphological features of the newly formed tissue in an experimental model of tibial callotasis lengthening on 24 lambs, aged from 2 to 3 months at the time of operation. A unilateral external fixator prototype Monotube Triax^® (Stryker Howmedica Osteonics, New Jersey) was applied to the left tibia. A percutaneous osteotomy was performed in a minimally traumatic manner using a chisel. Lengthening was started 7 days after surgery and was continued to 30 mm. The 24 animals were randomly divided into three groups of 8 animals each: in Group 1, lengthening took place at a rate of 1 mm/day for 30 days; in Group 2, at a rate of 2 mm/day for 15 days; in Group 3, at a rate of 3 mm/day for 10 days. In each group, 4 animals were killed 2 weeks after end of lengthening, and the other 4 animals at 4 weeks after end of lengthening. To assess bony formation in the distraction area, radiographs were taken every 2 weeks from the day of surgery. To study the process of vascularization, we used Spalteholz’s technique. After killing, the tibia of each animal was harvested, and sections were stained with hematoxylin and eosin, Masson’s trichrome, and Safranin-O. Immunohistochemistry was performed, using specific antibodies to detect collagens I and II, S100 protein, and fibronectin. A combination of intramembranous and endochondral ossification occurred together at the site of distraction. Our study provides a detailed structural characterization of the newly formed tissue in an experimental model of tibial lengthening in sheep and may be useful for further investigations on callotasis.     

Postoperative Cox inhibitors and late prosthetic loosening—suspicion increases!

Background and purpose In clinical practice, achieved lengthening of a callotasis zone should be maintained after the external fixator has been removed. The common understanding has been that the regenerated bone may subside. To investigate this, we used high-resolution radiostereometric analysis (RSA) with accurate measurement of the lengthening zone.

Patients and methods We assessed the longitudinal subsidence of a callotasis zone after removal of the external fixator in distraction osteogenesis in 16 patients who underwent 17 segmental lengthening operations on the tibia (n = 9) or femur (n = 8). Median lengthening was 32 (6–80) mm. RSA was performed at the end of the consolidation period before the external fixation device was removed, and this was later repeated at a median time of 11 (4–32) weeks after frame removal.

Results A minimal median longitudinal change of 0.01 (–0.28 to 0.60) mm across the lengthening zone occurred in uncomplicated cases.

Interpretation Our results indicate that no subsidence of clinical interest occurs after external frame removal.     

Management of congenital pseudarthrosis of the tibia by excision of the pseudarthrosis, onlay grafting, and intramedullary nailing

Fourteen skeletally immature children with congenital pseudarthrosis of the tibia were treated by excision of the pseudarthrosis, double onlay autogenous cortical bone grafting, and intramedullary nailing. Union was achieved in 12 patients, and no refractures occurred at the site of the original pseudarthrosis. In three patients, a fresh pseudarthrosis developed at a different site; these united after repeat onlay grafting. Five skeletally mature patients were treated by excision of the pseudarthrosis, compression at the site, and limb lengthening by callotasis. Union was achieved in three. Gain in tibial length ranged from 6 to 13 cm, with no significant complications during lengthening. The authors conclude that union can be achieved and refractures prevented in a significant proportion of skeletally immature children with congenital pseudarthrosis of the tibia by excision of the pseudarthrosis, dual onlay bone grafting, and intramedullary nailing. Any residual shortening of the limb can be treated at skeletal maturity.     

Metatarsal lengthening in congenital brachymetatarsia: one-stage lengthening versus lengthening by callotasis.

We retrospectively reviewed and compared the outcomes of 15 one-stage metatarsal lengthenings with intercalary bone graftings in 10 patients with those of nine metatarsal lengthenings by callotasis in five patients younger than 15 years. In the one-stage lengthening group, the diaphyseal osteotomy site was gradually distracted intraoperatively for 20-30 min to relax the surrounding soft tissues. In the callotasis group, lengthening was achieved with mini-Orthofix M-100. There was little difference in the outcomes between the two groups in terms of length gain, percentage increase, and complications. However, the period to achieve bony consolidation was longer in the callotasis group (2.7 months/cm) than in the one-stage lengthening group (1.5 months/cm). No case of neurovascular impairment was found in both groups.     

Efficiency of low-intensity pulsed ultrasound on distraction osteogenesis in case of delayed callotasis -- clinical results

AIM: Low-intensity pulsed ultrasound has been proven to accelerate fracture healing both clinically and experimentally. In this study the influence of low-intensity pulsed ultrasound during distraction-osteogenesis in case of delayed callotasis was investigated. METHOD: 20 patients could be included in this study. 16 patients initially were treated because of fractures of the lower leg, 2 because of fractures of the femur with resulting shortening of the afflicted limb. One patient suffered from chronic osteitis at the thigh and one from chronic osteitis at the upper arm without previous trauma. Because of delayed callotasis an adjunctive ultrasound treatment device was transcutaneously applied (frequency 1.5 MHz, signal burst width 200 microseconds, signal repetition frequency 1.0 kHz, intensity 30 mW/cm (2)) with the transducer placed at the distraction zone for 20 minutes daily. In all cases in-home treatment was performed. Evaluation was done by radiographic and sonographic controls of the distraction zone during examination of all patients at the outpatients' department every 3-4 weeks. RESULTS: Progress of callotasis was achieved in 15 out of 20 patients. Patients who were smokers during ultrasound therapy showed lower healing rates than those who never smoked. 2 patients suffering from osteitis of the tibia and missing callotasis had to be amputated. 3 other patients needed additional operative treatment including cancellous bone grafts because of missing new bone formation. Negative effects of low-intensity pulsed ultrasound during therapy could not be detected. CONCLUSION: We conclude that ultrasound treatment can accelerate bone maturation and formation in distraction osteogenesis, sometimes even in states of poor callotasis. It may provide a method of great promise in cases where delayed bone formation during distraction osteogenesis occurs.     

The value of ultrasonography in monitoring limb lengthening]

The authors attempted to assess the value of ultrasound for monitoring of the new bone formation at the site of distraction in patients undergoing limb lengthening after Bastiani. Twenty patients were assessed; 12 cases of femur lengthening and 8 cases of tibia lengthening. It was found, that ultrasound allowed to detect the new bone formation visible as hyperechogenic foci as soon as 4 to 14 days postoperatively, while regular radiology showed this only 4 to 8 weeks after operation. Detection of the new bone formation at the site of lengthening permits, in authors opinion, to choose an optimal onset of distraction and its pace according to the speed of bone formation. Regular ultrasound monitoring prevents premature bone union or disintegration of the newly generated bone in case of to slow or to fast distraction respectively. In two cases sonography early demonstrated cystic changes at the location of distraction. It also permits detection of an axial displacement of the fragments of bone in every case.     

Techniques for small-bone lengthening in congenital anomalies of the hand and foot.

The purpose of this study is to analyse three different lengthening techniques used in 31 small bones for congenital malformations of the hand and foot: 15 metacarpals, 12 metatarsals, 1 foot stump and 3 spaces between a previously transplanted phalanx end of the carpus or the metacarpal. Progressive lengthening with an external fixator device was performed in 23 cases: the callus distraction (callotasis) technique was used in 15 cases, whereas in the other 8 cases the speed of lengthening was faster and the defect bridged with a bone graft as a second stage. In another eight cases, a one-stage lengthening was performed. In the callotasis group, the total length gained ranged from 9 mm to 30 mm and the percentage of lengthening obtained (compared with the initial bone length) averaged 53.4%; in the fast lengthening group, the length gained ranged from 8 mm to 15 mm, and the average percentage of lengthening was 53.1%; and in the one-stage group, the length gained ranged from 7 mm to 15 mm, and the average percentage of lengthening was 43%. The overall complication rate was 22.5%.     

Deformation across the zone of callotasis during loading. radiostereometric analysis in a patient with achondroplasia.

The present study demonstrates that high-resolution radiostereometric analysis (RSA) can be used to assess global longitudinal compressive deformation across the callotasis zone during loading. In an achondroplastic patient operated with bifocal lengthening of the tibia by use of the Ilizarov external fixator, the axial compressive intersegmental strain in the proximal lengthening zone under a load of 71% of body weight was 7.7 mm. The proximal lengthening zone was 51.0 mm, and accordingly the overall linear strain across the callotasis was 15.1%. This large strain value found in distraction osteogenesis 6 weeks after end of distraction is not consistent with classical theory of the magnitude of micromotion needed for adequate stimulation of bone formation in fracture healing. The increased axial displacement did not stimulate bone healing and delayed union was observed. This one single observation does not allow for any conclusions to be drawn about the relationship of strain to fracture healing, but further and refined use of the RSA method will certainly improve our understanding of the role of axial strains in distraction osteogenesis.     

The effect of tibial diaphyseal lengthening on the longitudinal growth of the tibia

Limb lengthening by tibial callotasis is usually performed in the metaphysis but may cause growth inhibition. Is diaphyseal lengthening more advantageous? Sixteen immature rabbits underwent 30% diaphyseal lengthening by tibial callotasis. The tibial length was measured on radiographs at the end of the distraction period and after an additional 5 weeks. The proximal and distal growth plates were assessed histomorphometrically. Osteotomy stimulated tibial elongation; however, combined with diaphyseal lengthening the stimulation was suppressed resulting in longitudinal growth that matched the control side. In longer lengthenings of limbs diaphyseal callotasis may be more advantageous than metaphyseal by not inhibiting longitudinal growth.     

The management of brachymetatarsia

We treated 35 brachymetatarsal rays of 18 feet in 12 patients by one-stage lengthening with interpositional bone grafts or by gradual lengthening with callotasis combined with shortening of the adjacent metatarsals and phalanges. Definition of the two parabolas which connect the metatarsal heads and the tips of the toes, and recognition of three patterns of metatarsal length, were helpful guides in treatment. In total, 36 excisions of the phalanges and/or the metatarsals were undertaken. The mean shortening was 8 mm. The radiological results were satisfactory. The mean values were as follows: one-stage lengthening, length gain, 1.3 cm; healing index, 1.3 months/cm; percentage increase, 30%; gradual lengthening, length gain, 2.0 cm; healing index, 2.0 months/cm; percentage increase, 50%. Associated shortening of an adjacent bone can avoid the disadvantages of one-stage lengthening which may not achieve target length and can result in neurovascular complications. Reduction of the target length enables the surgeon to carry out one-stage instead of gradual lengthening. It also shortens the length of treatment in the group undergoing callotasis and improves cosmesis.     

The humerus is the best place for bone lengthening

The aim of this study was to examine the effectiveness of lengthening the humerus in children and young adults. Between 1984 and 2005, the Orthopaedic Department of Semmelweis University elongated 11 humeri (ten patients) for reasons of congenital hypoplasia (four cases), osteomyelitis (three cases), epiphyseolysis, growth plate closure after irradiation and obstetrical paralysis (one case each). The study cohort consisted of five females and five males, with an average age at the time of surgery of 17.8 years (range: 12-31 years). In every case, the lengthening was performed with a unilateral Wagner fixator. The lengthening protocol was 1 mm distraction daily (callotasis) after a 7-day latency period. The fixator was removed after total bone healing. Plate fixation or bone transplantation was not used. The average rate of lengthening was 6.2 cm (4.5-10.5 cm), and the achieved lengthening was 27% (range: 16-44%). The average healing index was 32 day/cm. One patient who suffered from temporary radial paresis, and temporary flexion contracture of the elbow was regarded as a complication following placement of the fixator. Based on our results, humeral shortening can effectively be treated with the unilateral Wagner fixator. The main difference between the original Wagner method and our approach is that we were able to leave the fixator in the humerus until total bony reconstruction so there was no need for plate fixation or bone transplantation.     

A trial of ultrasonographic use for evaluating leg lengthening]

Modified de Bastiani method of callotasis with Wagner apparatus was used as a lengthening procedure of 4 femurs and 1 tibia. The ultrasonography was applied to measure the degree of distraction, to determine the eventual axial deviation of the bone ends and to follow up the callus formation in the gap. The obtained results were compared with radiography.     

Tibial lengthening over an intramedullary nail

Background Long-term application of an external fixator to treat leg-length discrepancy and short stature often causes complications, such as pin-tract infection or loss of range of motion at the knee or ankle (or both). Prolonged fixator use also interferes with the activities of daily living. To minimize such problems, we have combined intramedullary nailing with external fixation. Using this technique, the external fixator can be removed more quickly after completing the lengthening. Methods We combined intramedullary nailing with lengthening in 13 tibias (8 patients) and then compared these cases with 17 standard tibial lengthenings (16 patients) using an external fixator alone. In both groups we excluded patients who had a history of previous bone infection, open fracture, immature bone, soft tissue compromise, antineoplastic chemotherapy, or bone deformity of a severity that required gradual deformity correction. We also excluded cases with lengthening of less than 3 cm. Results The mean external fixation index differed significantly between the two groups, but the consolidation index did not. Mean operating time for lengthening combined with intramedullary nail placement was approximately 60 min longer than for standard lengthening without nail placement; intraoperative blood loss was not greater in the nailing group. Complications related to the external fixator were far fewer in the combined intramedullary nailing and lengthening group compared with the control group, and callus formation was satisfactory for both groups. Conclusions A combination of intramedullary nailing and external fixation produces callus formation as good as that obtained by the standard Ilizarov method of lengthening. Furthermore, this combined procedure decreases the external fixation time and is associated with fewer complications.     

Diaphyseal bone lengthening in children using Wagner device: long-term results

In a series of 32 patients, the tibia was lengthened nine times and the femur 26 times. The lengthening was 4.1 cm in the tibia and 4.9 cm in the femur. The callotasis principle and atraumatic handling of the periosteum were considered important. The leg inequality was corrected appropriately, except in cases where the leg-length inequality was greater than 12 cm as a result of a progressive congenital deformity. Late femoral fractures occurred in six patients, but no tibial fractures were seen. One hip dislocation was seen after femoral lengthening, one talus deformation developed after the tibial lengthening, and one peroneal nerve entrapment was released operatively. One infection caused delayed bone union. Average follow-up time was 5.0 years.