4.

The results of this study revealed significant relationships between plain radiograph and MR images of acute phase OVFs and the incidence of nonunion. As these risk factors are defined more clearly and further validated, they may become essential assessment tools for determining subsequent OVF treatments. Patients with one or more of the earlier-described risk factors for nonunion should be observed carefully and provided with more intensive treatments.

Noggin is a major extracellular antagonist to bone morphogenetic proteins (BMPs) which binds to BMPs and blocks binding of them to BMP-specific receptors and negatively regulates BMP-induced osteoblastic differentiation. In this study, we investigated the effect of noggin silencing by transfection of small interfering RNA (siRNA) on BMP-induced osteoblastic differentiation in vitro and ectopic bone formation in vivo induced by recombinant human BMP-2 (rhBMP-2). Noggin mRNA expression was up-regulated in response to rhBMP-2 in C2C12 cells, a myoblastic cell line, in dose- and time-dependent fashion as determined by real-time RT-PCR assay. Silencing of noggin expression by transfection of noggin siRNA suppressed BMP-stimulated noggin expression, resulting in acceleration of BMP-induced osteoblastic differentiation. For in vivo noggin silencing, siRNA was injected locally into back muscles and transfected into local cells by electroporation, where rhBMP-2-retaining (5 microg) collagen disks had been surgically placed. The implants were harvested at 2 weeks after surgery from experimental and control group mice and analyzed by radiological and histological methods. As a result, bone mineral content of ossicles ectopically induced by rhBMP-2 was significantly increased by silencing of noggin. Our findings suggest that silencing of noggin enhances the osteoblastic differentiation of BMP-responding cells in vitro and new bone formation induced by rhBMP-2 in vivo by eliminating negative regulation of the effects of BMP. RNA interference might be useful for intensifying the effects of BMP in promoting new bone (callus) formation in repair of damaged bone.

2.

No abstract

The purpose of this study was to examine factors affecting the severity of neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture (OVF). Reports of insufficient union following OVF have recently increased. Patients with this lesion have various degrees of neurological deficits and back pain. However, the factors contributing to the severity of these are still unknown. A total of 45 patients with insufficient union following OVF were included in this study. Insufficient union was diagnosed based on the findings of vertebral cleft on plain radiography or CT, as well as fluid collection indicating high-intensity change on T2-weighted MRI. Multivariate logistic regression analysis was performed to determine the factors contributing to the severity of neurological deficits and back pain in the patients. Age, sex, level of fracture, duration after onset of symptoms, degree of local kyphosis, degree of angular instability, ratio of occupation by bony fragments, presence or absence of protrusion of flavum, and presence or absence of ossification of the anterior longitudinal ligament (OALL) in the adjacent level were used as explanatory variables, while severity of neurological deficits and back pain were response variables. On multivariate analysis, factors significantly affecting the severity of neurological deficits were angular instability of more than 15°[adjusted odds ratio (OR), 9.24 (95% confidence interval, CI 1.49-57.2); P \ 0.05] and ratio of occupation by bony fragments in the spinal canal of more than 42% [adjusted OR 9.23 (95%CI 1.15-74.1); P \ 0.05]. The factor significantly affecting the severity of back pain was angular instability of more than 15°[ adjusted OR 14.9 (95%CI 2.11-105); P \ 0.01]. On the other hand, presence of OALL in the adjacent level reduced degree of back pain [adjusted OR 0.14 (95%CI 0.03-0.76); P \ 0.05]. In this study, pronounced angular instability and marked posterior protrusion of bony fragments in the canal were factors affecting neurological deficits. In addition, marked angular instability was a factor affecting back pain. These findings are useful in determining treatment options for patients with insufficient union following OVF.

This study demonstrated the radiological factors predicting delayed union after an OVF. T2 high-signal changes showed the strongest association with delayed union. Consecutive MRIs were particularly useful as a differential tool to predict delayed union following OVFs.

MRI signal changes were associated with the compression degree and angular motion of fractured vertebrae. This classification showed sufficient reliability in categorizing MRI findings of OVFs.