Viral Behavior of Paracrystalline Inclusions in Osteoclasts of Paget's Disease of Bone

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Abstract
Fresh tissues from six patients with Paget's disease of bone were examined ultrastructurally to investigate whether the characteristic paracrystalline inclusions in pagetic osteoclasts revealed viral behavior. These inclusions appeared as microfil-amentous aggregates in both nuclei and cytoplasm of the osteoclasts in all six cases. The filamentous elements of the inclusions with a diameter of 11-15 nm showed tubular structures with a central electron-lucent zone measuring 5-7 nm in diameter. Viral budding-like structures containing these inclusions were found at the peripheral cytoplasm or cell processes in the ruffled border of some pagetic osteoclasts in two cases. The inclusions in the budding-like structures were often arrayed in a parallel fashion on the cytoplasmic side of the cell membranes of extruded cytoplasm or cell processes. Virion-like particles were also found in the extracellular spaces of the ruffled border. Marked nuclear degeneration was often seen in pagetic osteoclasts of three cases, although other nuclei in the same osteoclasts appeared normal. The degenerated nuclei showed nuclear ring formation where destroyed nuclear membranes were seen and disappearance of nuclear matrices was noted. Since the modifications were always associated with the accumulation of abundant inclusions, they were probably caused by the inclusions. These findings suggested that the inclusions showed viral behavior in pagetic osteoclasts, and that the nuclear modifications were caused by virus infection.