**8. Differential diagnosis**

radiographs and presence of the cleft sign on MRI. Finally, in Stage III included the severe collapse of the vertebral body with dynamic mobility and rupture of the posterior cortical, as well as IVC with retropulsion of bone fragments and compression of the spinal cord. At this

Also were reported three stages related to the pathogenesis of progression to delayed vertebral collapse. Stage 1 showed presence of intravertebral cleft, Stage 2 showed IVC plus intravertebral instability, and Stage 3 showed complete vertebral collapse [104]. We can summarize that the main application of these classification proposals has not only been to describe the evolution of osteoporotic CF, but also to evaluate the clinical efficacy and to determine the

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

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

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

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,

stage, the patients presented back pain, deformity and neurological deficit [103].

follow-up of different surgical procedures.

were termed "multiple microscopic fractures" [107].

of cracks and microhemorrhages that lead to ON.

of the fracture [110].

**7. Histopathology**

28 Osteonecrosis

The imaging characteristics described in vertebral ON such as sclerosis and calcification on computed tomography (CT) scan, hypointense images on T1 or hyperintense on T2, and nonreinforcement with Gadolinium (Gd) of the ischemic zone on MRI represent edema and necrosis. These changes could be confounded with other bone lesions such as the bone cyst, bone infarct, bone island, hemangioma, osteoblastoma, and osteoblastic metastatic tumor [113]. The literature reports cases of nontypical vertebral ON, on MRI, do not show low-intensity signal on T1 or double line sign on T2. In these cases, it has been suggested that the difference in the imaging findings could be due to the processes of ON and repair. Also, the vertebral bodies in these patients did not present collapse and the cortical intact was observed [113].

## **9. Treatment**

As mentioned, the main symptom of delayed post-traumatic vertebral collapse is chronic back pain. This is usually localized, persistent, with a tendency to progression and irradiation to the peripheral nerve roots. Among conservative management protocols for back pain, the combination of exercise therapy and nonsteroidal anti-inflammatory drugs has been used with partially satisfactory results [114]. In addition to the medical aspects, psychosocial factors have been related to the pathophysiology of pain and response to treatment [115, 116]. Among this, anxiety, depression, notably distress and somatization have been associated, so strategies related to supportive psychotherapy, cognitive-behavioral methods and psychiatric medical treatments have been proposed in some cases [115, 117].

In some cases, teriparatide, an osteoanabolic agent frequently used in the treatment of osteoporosis, has been effective in promoting the reparative bone process and reducing pain [23, 118].

In the absence of neurological compromise and under the assumption of nonaffectation of the posterior cortical vertebral body has been suggested the conservative management of pain by analgesic drugs and bed rest [7]. It is now known that the incidence of vertebral compression following the conservative management of osteoporotic vertebral fractures reaches 14.8% at 1 month and 21.8% at 6 months [119]. However, when conservative management fails, minimally invasive procedures such as vertebroplasty or kyphoplasty are suggested to stabilize the fracture site, align the vertebral segment and consequently alleviate pain [23]. The first reports in the literature on the treatment of KD emphasize conservative management, whereas the latest information has demonstrated that patients can be treated successfully with surgery. The choice of surgical treatment has depended to a large extent upon three factors, the severity of the back pain, the degree of kyphotic deformity, and the neurologic deficit [5, 7]. The main objective of the surgery lies in the decompression of the neural elements and sagittal alignment, consequently, earlier ambulation is promoted [120].

Techniques such as percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) with polymethyl methacrylate (PMMA) have been used in patients with osteoporotic CF with and without IVC [10, 121–127]. It was reported on both types of surgical procedures to relieve pain and restore collapsed vertebral body immediately after surgery. However, they reported aggravation of vertebral collapse and kyphotic deformity within 2 years after surgery in those patients with IVC. This also conditioned an increase in back pain, suggesting that this progression was due to intravertebral instability [121]. Therefore, both PVP and PKP have been considered as noneffective procedures in chronic spinal compression or acute vertebral compression with posterior cortical rupture, suggesting surgical stabilization via fusion [128]. The response to a foreign body that can occur with the use of PMMA with extensive fibrosis that could induce micromotion and secondary instability should also be mentioned [129, 130]. In addition, the mass of PMMA could spontaneously migrate to extra vertebral sites such as the disc space or the anterior vertebral space [8, 131–133].

Likewise, the distribution pattern and proportion of bone cement required in PVP could be predicted according to the area of ischemic necrosis on MRI [134]. Also, taking into account the proportion of necrosis on MRI recently raised that this variable could allow selecting the type of surgical procedure vertebroplasty, kyphoplasty, or surgery. Those cases with IVC, as well as those that required a surgical procedure were those that presented a higher percentage of necrosis [119].

Another reported proposal was the management of the posttraumatic osteoporotic vertebral ON with balloon kyphoplasty. It was suggested that restoration of the vertebral body and correction of kyphotic deformation could be achieved in relation to the sufficient volume of cement used. In addition, cement injection was performed in middle to later stages of solidification in patients with a defect of the anterior wall of the vertebral body or supported by X-ray fluoroscopy and balloon expansion in posterior defects to avoid leakage of the same [127].

The anterior decompression via corporectomy and fusion with intervertebral tricortical graft [135, 136] or ceramic glass spacers [137], posterior decompression with pedicle subtraction osteotomy [138–140] or the combination of both approaches [139] have been proposed in several studies. In the previous decompression, the fusion can be achieved with a spacer and a plate with a screw and in the posterior approach by means of the placement of transpedicular screws and hooks [141]. Spinal fusion, however, has been associated with procedural complications and long surgical time.

Subsequently, the technique of posterior one-segmental fixation combined with vertebroplasty and posterior-shortening osteotomy showed satisfactory results regarding correction of deformity, pain relief and functional improvement in patients with KD [142]. However, due to short segment fixation failures [143], the use of long segments to reestablish sagittal alignment was proposed. In the cases, it was reported to remove the upper end plate of the affected vertebral body and the superior intervertebral disc during the transpedicular subtraction and disc osteotomy combined with long-segment fixation, which favored bone fusion [144]. The placement of cages and long-segment fixation in pedicle subtraction osteotomy and disc resection has been useful in thoracolumbar post-traumatic kyphosis [145].
