The effect of alternating tensile and compressive force on new bone formation during distraction osteogenesis on a rabbit mandible

Abstract

Mandibular distraction osteogenesis (DO) has become an important technique to lengthen the hypoplastic mandible and to reconstruct osseous defects after ablative surgery. The hallmark of successful DO is the creation of new bone within the distraction gap. Several authors have described alternating compressing and lengthening protocols (i.e., “pumping the regenerate”) to augment regenerate bone formation. The purpose of this experiment was to analyze the influence of an alternating distraction/compression protocol over the conventional distraction protocol on new bone formation. Twenty-two skeletally mature female White New Zealand rabbits underwent bilateral mandibular osteotomy with placement of a custom-made distractor device. In each subject both distraction protocols were performed to a length of 6mm for 15 days. Each left and right hemimandible served as control and experimental side, respectively. After a latency period of 5 days, the conventional protocol was initiated in the control side at a rate of 0.20mm twice daily. In the experimental side the distraction/compression protocol was done with an overdistraction of 0.6mm for the first 12 hours with a subsequent compression of 0.2mm for the rest of the day setting up the same 6mm distracted state as the control side. After completing a consolidation period of 4- (CW4 subgroup, N = 20) and 8-weeks (CW8 subgroup, N = 20), data was obtain through plain radiography, micro-computed tomography, histomorphometry and immunohistochemistry to investigate the effect of the compressive loading on a distracted regenerate. Results are summarized as follows:1.Histology and histomorphometry demonstrated a progressive increase in osteoid volume (OV/BV), with a concomitant decrease in the amount of fibrous tissue (Fb.V/TV). Among subgroups, the experimental DO regenerate showed statistically significant differences (p < 0.05) in connectivity density (CD-2D), BV.N/TV and osteoblast-covered bone surface (Ob.S/BS) by the early consolidation period as well as in BV/TV-2D and Fb.V/TV by the end of late consolidation period. Osteoclast covered bone surface (Oc.S/BS) progressively decreased in all groups.2.The micro-CT microstructure of the regenerate demonstrated statistical significant differences (p < 0.05) in percent bone volume (BV/TV-3D), structural model index (SMI), trabecular bone pattern factor (Tb.Pf), and degree of anisotropy (DA) between DO protocol groups. Bone-surface to bone-volume ratio (BS/BV) and connectivity density (CD-3D) showed statistical significance (p < 0.05) between consolidation groups. Experimental DO regenerate expressed a continuous increase in trabecular number (Tb.N) and trabecular thickness (Tb.Th) while the control DO regenerate showed an increase in trabecular space (Tb.Sp) and SMI by the end of the experiment. 3.The expression pattern of osteocalcin, more intense in EDO-8-week group, and BMP-4, highly expressed for both osteoblasts and chondrocytes in EDO-4-week group, may suggest their origin from a shared population of undifferentiated mesenchymal precursor cells. On the basis of the findings observed in this study of DO rabbit mandibular model suggests that applying a daily distraction/compression protocol may stimulate osteoblast differentiation, synthesis of bone-specific extracellular proteins and accelerate matrix mineralization, especially in the early stage of the consolidation period, where most active period of bone formation occurs. At the microstructural level the increase in bone volume, trabecular thickness, distribution and organization per unit area demostranted the improvement of the mechanical properties of the regenerate and its adaptation to loading forces.