Twenty-nine patients (thirty-two femora) had femoral lengthening over an intramedullary nail, with the nail and the external fixator applied concomitantly at the time of the femoral osteotomy. After gradual distraction at a rate of one millimeter per day, the nail was locked and the fixator was removed. The mean age was twenty-six years (range, ten to fifty-three years), and the mean amount of lengthening was 5.8 centimeters (range, two to thirteen centimeters). For comparison, thirty-one patients (thirty-two limbs) who had had standard Ilizarov femoral lengthening were matched with the group that had had lengthening over an intramedullary nail; the matching was performed on the basis of the amount of lengthening, the age of the patient, the etiology of the indication for lengthening, and the level of difficulty of the procedure. Lengthening over an intramedullary nail reduced the average duration of external fixation by almost one-half. The radiographic consolidation index (the number of months needed for radiographic consolidation for each centimeter of lengthening) for the limbs that had had lengthening over an intramedullary nail was reduced significantly (p < 0.001) compared with that for the matched-case group. The range of motion of the knee returned to normal a mean of 2.2 times faster in the group that had had lengthening over an intramedullary nail. There were six refractures of the distraction bone in the matched-case group. In the group that had had lengthening over an intramedullary nail, one nail and one proximal locking screw failed. The over-all rate of complications was 1.4 per cent in the group that had had lengthening over an intramedullary nail compared with 1.9 per cent in the matched-case group. With the numbers of patients available for study, we could not detect a significant difference between the groups with respect to the operative time (p = 0.124); however, the cost of treatment and the estimated blood loss were higher in the group that had had lengthening over an intramedullary nail. On the basis of clinical and radiographic criteria, there were twenty-three excellent, seven good, and two fair results in the group that had had lengthening over an intramedullary nail compared with twenty-six excellent, four good, and two fair results in the matched-case group (p = 0.37). The advantages of lengthening over an intramedullary nail include a decrease in the duration of external fixation, protection against refracture, and earlier rehabilitation.

Femoral Lengthening Over an Intramedullary Nail. A Matched-Case Comparison With Ilizarov Femoral Lengthening

Bone lengthening with osteotomy and gradual distraction was achieved in 57 rats, and the effect of mechanical tension-stress on gene expression of bone morphogenetic proteins (BMPs) was investigated by in situ hybridization and Northern blot analysis using probes of BMP-2, BMP-4, BMP-6, BMP-7, and growth/differentiation factor (GDF)-5. There was a lag phase for 7 days after femoral osteotomy until gradual distraction was carried out for 21 days at a rate of 0.25 mm/12 h using a small external fixator. The signals of the above BMPs mRNA were not detected in the intact rat bone but they were induced after osteotomy except those for BMP-7. By 4 days after osteotomy, BMP-2 and BMP-4 mRNAs were detected in chondrogenic precursor cells in the subperiosteal immature callus. BMP-6 and GDF-5 mRNA were detected in more differentiated cells in chondroid bone. By 7 days after osteotomy, cartilaginous external callus and bony endosteal callus were formed. Meanwhile, the signals of BMP-2 and BMP-4 mRNAs declined to preoperative levels, whereas the signals of BMP-6 and GDF-5 mRNAs were rather elevated. As distraction was started, the callus elongated and eventually separated into proximal and distal segments forming a fibrous interzone in the middle. Expression of BMP-2 and BMP-4 mRNAs was markedly induced at this stage. Their signals were detected widely among chondrogenic and osteogenic cells and their precursor cells sustaining mechanical tension-stress at the fibrous interzone. BMP-6 and GDF-5 mRNAs were detected exclusively in chondrogenic cells at both ends of the fibrous interzone, where endochondral ossification occurred. But neither mRNA was detected in terminally differentiated hypertrophic chondrocytes. As distraction advanced, the cartilage was progressively resorbed from both ends and new bone was formed directly by intramembranous ossification. There was no new cartilage formation in the advanced stage of distraction. The signals of BMP-6 and GDF-5 mRNA declined by this stage, while those of BMP-2 and BMP-4 were maintained at high level for as long as distraction was continued. After completion of distraction, the fibrous interzone fused and the lengthened segment was consolidated. BMP-2, BMP-4, BMP-6, nor GDF-5 was expressed at this stage. The signals of BMP-7 were not detected throughout the experiment. The present results suggest that excellent and uninterrupted bone formation during distraction osteogenesis owes to enhanced expression of BMP-2 and BMP-4 genes by mechanical tension-stress. Abundant gene products of BMP-2 and BMP-4 could induce in situ bone formation by paracrine and autocrine mechanisms.

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Mechanical Tension-Stress Induces Expression of Bone Morphogenetic Protein (BMP)-2 and BMP-4, but Not BMP-6, BMP-7, and GDF-5 mRNA, During Distraction Osteogenesis

The current concepts of fracture healing are mainly based on two variables: blood supply and stability. The effect of electricity on delayed union has not been explained. Possible individual differences in the primary osteogenetic activity and the effect of soft-tissue injuries are seldom considered. In recent years, interesting data have revealed how biomechanical forces and electric currents can be translated to biochemical mediators such as prostaglandins (PGE2), morphogens, and growth factors. It is likely that the fracture ends emit osteogenic signal substances (such as bone morphogenetic protein) to the exudate in addition to those mediators (interleukin-1, growth factors) which are released from the blood clot as in wound healing. Movement of the fragments increases the fracture exudate with its migrating cells and sprouting vessels, resulting in exuberant callus. Cartilage is formed in the well-vascularized granulation tissue due to its ability to repel vessels. Rigid fixation minimizes granulation tissue and external callus. Rigid plates may also retard effusion of morphogens and growth factors from bone ends. Reaming of the intramedullary canal and nailing may cause additional bone damage, which may increase the osteogenetic activity. Weight bearing stimulates growth factors and PGE2. The molecular activity of the fracture exudate is the most decisive factor for bone healing. This activity can be impeded by diastasis, infections, and soft-tissue crushing injuries that cause extensive activation of macrophages and activate mediators, disturbing the osteogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Current concepts of fracture healing.

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, 'transchondroid bone formation'. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis.

Three modes of ossification during distraction osteogenesis in the rat

We report the results of distraction osteogenesis (callotasis) for the reconstruction of extensive defects after the excision of skeletal tumours in the limbs. Bone transport was performed in ten patients (five osteosarcomas and five giant-cell tumours), shortening-distraction in three (two osteosarcomas and one Ewing's sarcoma), and distraction osteogenesis combined with an intramedullary nail to reduce the time of external fixation in six (three osteosarcomas, two chondrosarcomas, and one malignant fibrous histiocytoma). The mean length of the defects after excision of the lesion was 8.4 cm. The mean external fixation index was 39.5 days/cm for the group treated by bone transport, 34.1 days/cm for the shortening-distraction group, and 24.0 days/cm for the group treated by distraction and an intramedullary nail. Functional evaluation gave excellent results in 12 patients, good in five and fair in two. There were ten complications in 19 patients, all of which were successfully treated. We also classified reconstruction using distraction osteogenesis into five types based on the location of the defects after resection of the tumour: type 1, diaphyseal; type 2, metaphyseal; type 3, epiphyseal; type 4, subarticular reconstruction; and type 5, arthrodesis. Our results suggest that reconstruction using distraction osteogenesis provides bone which will develop sufficient biomechanical strength and durability. It is beneficial in patients with an expectation of long-term survival and in growing children.

Limb salvage using distraction osteogenesis: a classification of the technique

Callotasis is a new technique of limb lengthening involving slow distraction of the callus formed in response to a proximal submetaphyseal corticotomy. Using a dynamic axial fixator with telescoping capabilities, distraction begins after 2 weeks. When the required length is attained, the fixator is held in the rigid mode until radiographic evidence of callus is observed. The locking screw is then released, and dynamic axial loading is instituted to promote corticalization. One hundred bony segments have been lengthened; 50 patients had limb length inequality, and 23 had achondroplasia. The mean lengthening achieved was 22% (maximum, 58%). There were 14 complications (14%).

Renzi-Brivio L

Papers

Limb lengthening by callus distraction (callotasis).