Effects of Bone Cross-Link Bridging on Fracture Mechanism and Surgical Outcomes in Elderly Patients with Spine Fractures

Study Design This study adopted a cross-sectional study design. Purpose This study was designed to investigate the effects of bone cross-link bridging on fracture mechanism and surgical outcomes in vertebral fractures using the maximum number of vertebral bodies with bony bridges between adjacent vertebrae without interruption (maxVB). Overview of Literature The complex interplay of bone density and bone bridging in the elderly can complicate vertebral fractures, necessitating a better understanding of fracture mechanics. Methods We examined 242 patients (age >60 years) who underwent surgery for thoracic to lumbar spine fractures from 2010 to 2020. Subsequently, the maxVB was classified into three groups: maxVB (0), maxVB (2–8), and maxVB (9–18), and parameters, including fracture morphology (new Association of Osteosynthesis classification), fracture level, and neurological deficits were compared. In a sub-analysis, 146 patients with thoracolumbar spine fractures were classified into the three aforementioned groups based on the maxVB and compared to determine the optimal operative technique and evaluate surgical outcomes. Results Regarding the fracture morphology, the maxVB (0) group had more A3 and A4 fractures, whereas the maxVB (2–8) group had less A4 and more B1 and B2 fractures. The maxVB (9–18) group exhibited an increased frequency of B3 and C fractures. Regarding the fracture level, the maxVB (0) group tended to have more fractures in the thoracolumbar transition region. Furthermore, the maxVB (2–8) group had a higher fracture frequency in the lumbar spine area, whereas the maxVB (9–18) group had a higher fracture frequency in the thoracic spine area than the maxVB (0) group. The maxVB (9–18) group had fewer preoperative neurological deficits but a higher reoperation rate and postoperative mortality than the other groups. Conclusions The maxVB was identified as a factor influencing fracture level, fracture type, and preoperative neurological deficits. Thus, understanding the maxVB could help elucidate fracture mechanics and assist in perioperative patient management

MRI characterization of paranodal junction failure and related spinal cord changes in mice.

The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the paranodal junctions of the spinal cord in cerebroside sulfotransferase knock-out (CST-KO) mice. Here, we showed that high-resolution MRI and DTI characteristics can reflect paranodal junction failure in CST-KO mice. We found significantly lower T1 times and significantly higher T2 times in the spinal cord MRIs of CST-KO mice as compared to wild-type (WT) mice. Spinal cord DTI showed significantly lower axial diffusivity and significantly higher radial diffusivity in CST-KO mice as compared to WT mice. In contrast, the histological differences in the paranodal junctions of WT and CST-KO mice were so subtle that electron microscopy or immunohistological analyses were necessary to detect them. We also measured gait disturbance in the CST-KO mice, and determined the conduction latency by electrophysiology. These findings demonstrate the potential of using MRI and DTI to evaluate white matter disorders that involve paranodal junction failure

Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity.

Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic

Diffusion tensor imaging in the spinal cords of WT and CST-KO mice.

<p>(A) FA map and ROI analysis of the FA values. The FA value of the CST-KO mice was significantly lower than that of WT mice. (B) Axial and radial diffusivity (AD and RD) maps and ROI analyses of the diffusivities. The AD of CST-KO mice was significantly lower than that of WT mice, whereas the RD was significantly higher. (A, B) Values shown are means ± s.d. (<i>ex vivo</i>: n = 7), with statistical significance determined by the unpaired t-test. ***: p<0.001, **: p<0.01, *: p<0.05.</p

Functional and electrophysiological analyses of WT and CST-KO mice.

<p>(A) Forelimb step width of WT and CST-KO mice, obtained by gait analysis. The CST-KO forelimb steps were significantly wider than those of WT mice. (B) Hindlimb step width of each group, obtained by gait analysis. The CST-KO hindlimb steps were significantly wider than those of WT mice. (C) Time on the rotating rod in each group. CST-KO mice stayed on the rod for a significantly shorter time than WT mice. (D) Representative profiles of motor-evoked potentials (MEPs) from each mouse. (E) Quantitative analysis of MEP latency. The MEP latency was significantly longer in CST-KO mice than in WT mice. (A, B, C, E) Values show the means ± s.d. (n = 4), and significant differences were determined by the Mann-Whitney test. *: p<0.05.</p

Magnetic resonance images of the spinal cords of WT and CST-KO mice.

<p>(A) T1 measurement. The T1 time in the major white matter tracts within the ventral regions was significantly lower in CST-KO mice than in WT mice (circled in panel C), both <i>ex</i> and <i>in vivo</i>. (B) T2 measurement. The T2 time was significantly higher in CST-KO mice than in WT mice, both <i>ex</i> and <i>in vivo</i>. (C) Representative axial images of <i>ex vivo</i> and <i>in vivo</i> T2WI in WT and CST-KO mice. (D) Representative sagittal images of <i>in vivo</i> T2WI in WT and CST-KO mice. Scale bars: 5 mm. (A, B) Values shown are means ± s.d. (<i>ex vivo</i>: n = 6, <i>in vivo</i>: n = 6), with statistical significance determined by the unpaired t-test. *: p<0.05.</p

Histological analyses of the spinal cords of WT and CST-KO mice.

<p>(A) Representative images of HE-stained axial spinal cord sections. (B) Quantitative analysis of the spinal cord areas of the HE-stained axial sections revealed no significant difference between WT and CST-KO mice. (C) Representative images of LFB-stained axial spinal cord sections. (D) Quantitative analysis of the ventral spinal cord areas measured in the LFB-stained axial sections revealed no significant difference between WT and CST-KO mice. (E) Representative EC-stained images of axially sectioned spinal cords. (F) Quantitative analysis of the ventral spinal cord areas measured in the EC-stained axial sections revealed no significant difference between WT and CST-KO mice. Scale bars: 500 µm in (A), (C), and (E). (B, D, F) Values show the means ± s.d. (n = 4), and significant differences were determined by the Mann-Whitney test.</p

Grafted hiPSC-NS/PCs spare descending motor axons but do not induce abnormal innervations of pain-related CGRP positive afferents after SCI.

<p>(<b>A-1</b>) Representative images of RT97-positive neurofilament staining in the ventral region of the spinal cord at the lesion epicenter at 12 weeks post-engraftment. (<b>A-2</b>) Quantification of RT97-positive areas at the lesion epicenter. The overall RT97-postive area was larger in the transplantation group than in the control group. Data represent the mean ± SEM (n = 5 per group, *p<0.05, **p<0.01). (<b>B-1</b>) Representative images of CaMK-IIα-positive descending motor axons in the dorsal corticospinal tract (CST) area of the lesion epicenter. (<b>B-2</b>) Quantification of CaMK-IIα-positive areas at the lesion epicenter. The overall CaMK-IIα-positive area was increased in the transplantation group compared with that in the control group at 1 week post SCI. Data represent the mean ± SEM (n = 4 for each group, *p<0.05). (<b>C-1</b>) Representative images of CGRP-positive fibers in the dorsal horn 6 mm rostral and caudal to the lesion epicenter. (<b>C-2</b>) Quantitative analysis of the CGRP-positive areas in the dorsal horn 6 mm rostral and caudal to the lesion epicenter. There were no significant differences in the size of the CGRP-positive areas in the dorsal horn between the transplantation and control groups. Data represent the mean ± the SEM (n = 3 per group.)</p