Aims: This experiment study was undertaken to evaluate the differences, in bone response to various grafts.

Methods: Ninety, 3.5 months New Zeland white rabbits, weighing 4kg, were divided randomly in 6 groups of 15 animals. Under anesthesia, a 4.5mm hole was drilled in the 2 posteriors femoral condyles of each rabbit, in totaling 180 condyles. Holes were filled with various grafts as follow: Group I-autograft, Group II-xenograft (Lubboc®), Group III-allograft DBM (Grafton®), Group IV-substitute calcium sulfate (Osteoset®), Group V-substitute calcium phosphate hydroxyapatite (Ceraform®), Group VI- was used control. After the implantation, the animals were sacrificed at 1, 3 and 6 months intervals tissue samples from the implanted areas were processed for histological evaluation.

Results: Group I: At 1 month, autologous grafts were lined with activated osteoblasts and osteoclasts. Lamellar bone and cartilage were evident. Neoangiogenesis was prominent. At 3, 6 months defects were filled with mature bone. Group II: Lubboc® displayed moderate (1 month) to intense (3 months) remodeling activity and pronounced neoangiogenesis. At 3 months, endochondral osteogenesis and lamellar bone production were more prominent. At 6 months graft material was significantly restricted and lamellar had considerably replaced woven bone. Group III: Grafton® putty was present at 1, 3 months. There were few osteoblasts and numerous multinuclaeated cells rimming implant surfaces. Endochondral ossification foci, new bone formation and neovascularisation were observed (1, 3 months). At 6 months DBM fibers were absent. Lamellar and woven bone was evident. Group IV: At 1 month new bone (mostly woven) was present, lined with activated osteoblast and few osteoclasts. Endochondral ossification and angiogenesis were evident. At 3, 6 months bone remodeling was augmented, and Osteoset® graft was diminished. Complete closure of defects was observed, at 6 months. Group V: Ceraform® exhibited almost the same properties as Osteoset®. However, endochondral osteopoiesis and bone remodeling were less intense. Additionally, after 6 months, Ceraform® was still evident. Group VI: The defect areas were clearly observed at 1, 3 months.

Conclusion: Autografts are the most effective graft materials. Although Lubboc® is not totally resorbed, it seems to induce lamellar bone synthesis stronger than Grafton®. Bone substitutes are inferior to allografts.

Aims: To evaluate the effectiveness of external fixation exchange by intramedullary nailing during consolidation phase following callus distraction phase. Methods: In 12 skeletally mature female sheep, equally divided in two groups (group A and group B), we performed tibial shaft osteotomy and 2cm gradual callus distraction using Ilizarov external fixator in a 0,5mm/12h rate. In group A, Ilizarov fixator was removed immediately after lengthening completion, and static unreamed intramedullary nail was inserted. In group B, Ilizarov device remained during consolidation phase. Formatted callus was studied, with radiographs, ultrasonograms, and triplex. All animals were sacrificed 70 days after osteotomy and bone specimens, were evaluated by DEXA and histopathologic examination. Results: In group A, all animals successfully tolerated intramedullary nailing and limb alignment was attained. All but one formatted mature callus and had started the remodeling phase retaining callus length, before being sacrificed. One animal had delayed callus maturation and 0,5cm loss of callus length, because of failed insertion of distal locking screw in the nail. In group B, all formatted mature callus too, but 2 had serious axis disorder, 3 persistent superficial pin-track infections and 1 deep infection in the same time. Conclusions: Replacement of Ilizarov device by static unreamed intramedullary nail during callus consolidation phase decreases the total duration of external fixation, limits joint stiffness, pin-track infections and axial deformities, and provides protection against refracture. Our results suggest that there is no considerable difference between callus maturation in the two groups.

Aim: Osteosarcomas represent the most common primary malignant bone tumors. However, their pathogenesis is unclear. In vitro and in vivo studies have demonstrated the participation of the JNK–c-Jun signal transduction cascade and oncoproteins c-Jun and c-Fos in osteoblast proliferation and differentiation. JNKs activate c-Jun, which forms the AP-1 transcription factor as a homo/heterodimeric complex. Alpha-NAC is an osteo-blast-specific AP-1 coactivator that potentiates c-Jun/c-Jun, but not c-Jun/c-Fos transcriptional activity. We addressed the possibility that upregulation of the JNK–c-Jun pathway, as well as expression/activation of c-Fos and á-NAC, are implicated in osteosarcoma pathogenesis.

Materials and method: We assessed immunohistochemically the protein levels of the two major JNK isoforms (JNK1,2), their phosphorylated/activated species, p-JNK, their substrate, c-Jun, its phosphorylated/activated form, pc-Jun, its partner, c-Fos, and á-NAC, in 71 human osteo-sarcomas (56 high and 15 low grade).

Results: Positive immunostaining for JNK1, JNK2, p-JNK, c-Jun, pc-Jun, c-Fos and á-NAC was observed in 86%, 93%, 94%, 99%, 97%, 99% and 97.5% of the samples, respectively, but not in normal bone. Cellular levels of all proteins were significantly correlated to each other (p< 0.001). Moreover, significantly higher expression levels of all proteins were detected in high-grade osteosarcomas, compared to low-grade ones (p< 0.001).

Discussion: Our findings provide novel evidence that the JNK–AP-1 pathway is involved in osteoblast malignant transformation and osteosarcoma development and progression. Furthermore, the expression profile of α-NAC suggests that the active AP-1 population in human osteosarcomas is most likely comprised of c-Jun/c-Jun homodimers. Evaluation of c-Jun expression and JNK-dependent activation may facilitate an improved prediction of tumors’ clinical behaviour and potentially be exploited in designing patient-tailored treatment regimens.