Physiologic weight‐bearing increases new vessel formation during distraction osteogenesis: A micro‐tomographic imaging study

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Abstract
During distraction osteogenesis, large volumes of new bone are formed through the slow distraction of fracture callus. The newly formed bone is closely linked to angiogenesis and positively influenced by physiologic loading. In this study, a rat model was used to explore the correlation between these two observations. Unilateral femoral lengthenings were performed in 18 male Sprague-Dawley rats (400-500 g, age<6 months). Half of the animals were allowed to bear weight freely (WB) while the remaining animals were made non-weight-bearing via a through-knee amputation (NWB). After a seven-day latency period, femurs were lengthened 7 mm over 21 days. Animals were sacrificed at 7, 21, 35, and 49 days (0, 4.7, 7, and 7 mm of distraction) at which time lower extremity vessels were perfused with a 60% (w/v) barium sulfate suspension. High-resolution three-dimensional images of the vascular architecture were generated using a fan-beam micro-tomography machine by digitally separating the contrast-filled vessels from surrounding tissue. For two subvolumes, VOI(1), which included vessels in the medullary canal, cortex, and periosteum, and VOI(2), which included only vessels in the canal and cortex, the total tissue volume (TV), the volume of vessels (VV), and vessel diameter (VD) were determined. For the larger subvolume (VOI(1)), VV and vessel density (VV/TV) increased as a function of time (p<0.001) in WB animals. In NWB animals, VV increased significantly with time (p=0.029), while VV/TV did not (p=0.36). Increases in VV and VV/TV were significantly greater in WB animals than in NWB animals (p<0.01 and 0.05, respectively). VD was similar in both groups and did not change with time. Our data suggest that weight bearing stimulates new vessel formation during distraction osteogenesis.