Extradiscal bone formation after intradiscal injection of rhBMP-7. Radiography, computed tomography (CT), macroscopy, and histology of intervertebral discs (IVDs) injected with 2.5 μg (A), 25 μg (B), and 250 μg (C, D) rhBMP-7. A. Unremarkable findings after injecting 2.5 μg rhBMP-7 into the IVD. The histological image shows a typical example of an early degenerated NP, consisting of clusters of chondrocyte-like cells. B. On the left lateral site of the vertebral column extradiscal new bone formation is shown on the radiograph and CT image (white arrow) next to the IVD injected with 25 μg rhBMP-7. Histology was consistent with early degenerative changes in the IVD as shown in A. C. Extradiscal new bone formation ventrally of the vertebral column and sclerosis of the ventral vertebral cortex is shown on radiography (white arrow), CT, macroscopy, and histology (**) after injecting 250 μg rhBMP-7 into the IVD. D. Rupturing of the dorsal AF and protrusion of NP material into the spinal canal (black arrow) on CT, macroscopy and histology image of an IVD injected with 250 μg rhBMP-7. Irregularity of the endplates and focal sclerosis in the subchondral bone (white arrowheads) was seen on macroscopy and confirmed on histology (not shown in this image). AF = annulus fibrosus, EP = endplate, F = facet joint, I = ilium, L = lumbar vertebra, NP = nucleus pulposus, S = sacral vertebra, SC = spinal cord, Tr = transverse process.