SummaryWe assessed the safety and feasibility of a unified conservative treatment protocol for osteoporotic vertebral fractures in the elderly patients with a 24-week follow-up. Our results showed that initial hospitalization with rigorous bed rest followed by a rehabilitation program using a Jewett brace was safe and feasible in managing patients.PurposeThe purpose of this study was to prove the safety and feasibility of a unified conservative treatment protocol, which included initial hospitalization with rigorous bed rest followed by a rehabilitation program with Jewett brace for osteoporotic vertebral fractures (OVFs) in the elderly patients with a 24-week follow-up.MethodsBetween April 2012 and Mach 2015, one hundred fifty-four patients met the eligibility for this study. Radiological findings at the 3-week, 6~8-week, 24-week assessment were evaluated. Among these, 11 patients underwent early surgery within the first 2 weeks after admission and 19 patients lost follow-up. Therefore, 124 patients were assessed at the final follow-up visit.ResultsThe average vertebral instability in all the present series was 4.9 ± 4.8° at 3-week, 2.9 ± 3.5° at 6~8-week, and 1.8 ± 3.0° at 24-week follow-up visit. Delayed union was observed in 16 patients on the 24-week follow-up visit. Therefore, the present conservative treatment protocol resulted in bony union in 98 out of 124 patients (79.0%, per protocol set analysis) and 98 out of 154 patients including drop-out (63.6%, intention-to-treat analysis). There was no severe adverse event related to initial bed rest. The vertebral instability at 3-week assessment was significantly higher in the delayed union group when compared with that in the union group. Univariate analyses followed by multivariate logistic regression analysis revealed that T2-weighted image of confined high intensity on MRI and having more than 5° of vertebral instability on dynamic X-ray at 3-week assessment are the independent risk factors for delayed union of conservative treatment in the present series.ConclusionsOur results showed that initial hospitalization with rigorous bed rest followed by a rehabilitation program using a Jewett brace was safe and feasible. Therefore, the present conservative treatment protocol can be one of the acceptable treatment options in managing OVF patients.

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. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

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IntroductionGranulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial.Methods and analysisThe objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients).Ethics and disseminationThe study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper.Trial registration numberUMIN000018752.