**7. Histopathology**

There are few reports in the literature describing the histopathological features of vertebral ON. The first autopsy material related to KD was presented in 1926 [105]. It was described the destruction of spongy bone tissue and the consequent collapse of the vertebral body. Later was reported the pathological examination of the wedge-shaped collapsed L2 vertebral body, atrophic changes in bone trabeculae and multiple hemorrhagic areas [106]. These findings were termed "multiple microscopic fractures" [107].

Afterward, four concentric zones in AVN were proposed. These were a central area of cell death, followed by ischemia, congestion, and a peripheral zone of normal tissue. Early, inflammatory cells, serosanguinolent fluid, without bacterial colonies have been described. Thus, both the ischemic and the congestive zone undergo repair changes being replaced by fibrous tissue or new bone [108, 109]. Likewise, an anatomopathological study of vertebral pseudarthrosis reported a whitish, smooth, fibrocartilage-like lining with scarce chondrocytes, and flattened fibroblasts. As well, the regions after the cleft presented granulation tissue and poor bone formation. The biochemical characteristics of the fluid contained in the cleft showed a similar composition to the blood plasma, except for the lower proportion of total proteins [36].

ON reported in histopathological analysis on biopsy material demonstrated consistent data of new bone formation, bone marrow fibrosis, and bone repair [7, 17, 18, 20, 22]. However, different advances have been proposed from the original approaches, "rarefying osteitis" of inflammatory origin, multiple trauma of bone and ligamentous structures with the formation of cracks and microhemorrhages that lead to ON.

Some studies have suggested the correlation of the sign of the fluid on MRI and the histopathological data of vertebral ON demonstrated by the presence of small necrotic bone fragments between a fibrous stroma. In this regard, it was showed the presence of ON, edema, and fibrosis associated with the sign of fluid and this was significantly related to the severity of the fracture [110].

It has been considered that in the early stages vertebral ON presents edema and exudate, whereas in the late stages air could be contained in the spaces formed by the sclerotic bone [39, 111]. Hence, possibly the changes were described from the intravertebral fluid to gas on MRI [100]. In addition to this proposal, it was reported that the sign of the fluid could be identified on MRI between 1 and 5 months, while the IVC could be noticed between 2 and 10 months after the fracture of the vertebra [112]. Subsequently, regenerative changes in more than 80% of cases occur, which are characterized by bone resorption, the formation of new bone and fibrosis. The still unstable collapse of the vertebra, the involvement of the spinal canal and neurological manifestations can be associated with these changes. However, some cases have been described with absence of unexplained regenerative histological changes [112].

Moreover, in those cases of vertebral body ON without vertebral collapse, empty lacunae, fatty necrosis with vacuolar degeneration and cell debris were described, suggesting necrosis of the bone marrow [113].
