Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m²/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. The present trial failed to show a significant effect of G-CSF in primary end point.

Osteoporosis is a common disease in elderly populations and is a major public health problem worldwide. It is not uncommon for spine surgeons to perform spinal instrumented fusion surgeries for osteoporotic patients. However, in patients with severe osteoporosis, instrumented fusion may result in screw loosening, implant failure or nonunion because of a poor bone quality and decreased pedicle screw stability as well as increased graft subsidence risk. In addition, revision surgeries to correct failed instrumentation are becoming increasingly common in patients with osteoporosis. Therefore, techniques to enhance the fixation of pedicle screws are required in spinal surgeries for osteoporotic patients. To date, various instrumentation methods, such as a supplemental hook, sublaminar taping and sacral alar iliac screws, and modified screwing techniques have been available for reinforcing pedicle screw fixation. In addition, several materials, including polymethylmethacrylate and hydroxyapatite stick/granules, for insertion into prepared screw holes, can be used to enhance screw fixation. Many biomechanical tests support the effectiveness of these augmentation methods. We herein review the current therapeutic strategies for screw fixation and augmentation methods in the surgical treatment of patients with an osteoporotic spine.

To date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis. Human articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature. We identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA. This is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.

Percutaneous pedicle screw (PPS) can provide internal fixation of the thoracolumbar spine through a minimally invasive surgical procedure. PPS fixation has been widely used to treat various spinal diseases. Rigid fixation of PPS is essential for managing osteoporotic spine in order to prevent the risks of screw loosening and implant failure. We recently developed a novel augmentation method using hydroxyapatite (HA) granules for PPS fixation. The aim of this study was to evaluate the strength and stiffness of PPS fixation augmented with HA granules using an osteoporotic bone model. Screws were inserted into uniform synthetic bone (sawbones) with and without augmentation. The uniaxial pullout strength and insertion torque of the screws were evaluated. In addition, each screw underwent cyclic toggling under incrementally increasing physiological loads until 2 mm of screwhead displacement occurred. The maximal pullout strength (N), maximal insertion torque (N·cm), number of toggle cycles and maximal load (N) required to achieve 2-mm screwhead displacement were compared between the screws with and without augmentation. The maximal pullout strength was significantly stronger for screws with augmentation than for those without augmentation (302 ± 19 N vs. 254 ± 17 N, p < 0.05). In addition, the maximal insertion torque was significantly increased in screws with augmentation compared to those without augmentation (48 ± 4 N·cm vs. 26 ± 5 N·cm, p < 0.05). Furthermore, the number of toggle cycles and the maximal load required to reach 2 mm of displacement were significantly greater in screws with augmentation than in those without augmentation (106 ± 9 vs. 52 ± 10 cycles; 152 ± 4 N vs. 124 ± 5 N, p < 0.05). Augmentation using HA granules significantly enhanced the rigidity of PPS fixation in the osteoporotic bone model. The present study suggested that novel augmentation with HA granules may be a useful technique for PPS fixation in patients with osteoporotic spine.