Gait in patients with symptomatic osteoporotic vertebral compression fractures over 6 months of recovery

BACKGROUND: One factor related to disability in people with spinal deformity is decreased postural control and increased risk of falling. However, little is known about the effect of osteoporotic vertebral compression fractures (OVCFs) and their recovery on gait and stability. Walking characteristics of older adults with and without vertebral fractures have not yet been compared. AIMS: The purpose of the current study was to examine the spatiotemporal gait parameters and their variability in patients with an OVCF and healthy participants during treadmill walking at baseline and after 6 months of recovery. METHODS: Twelve female patients suffering a symptomatic OVCF were compared to 11 matched controls. Gait analysis was performed with a dual-belt instrumented treadmill with a 180° projection screen providing a virtual environment (computer-assisted rehabilitation environment). Results of patients with an OVCF and healthy participants were compared. Furthermore, spatiotemporal gait parameters were assessed over 6 months following the fracture. RESULTS: Patients suffering from an OVCF appeared to walk with significantly shorter, faster and wider strides compared to their healthy counterparts. Although stride time and length improved over time, the majority of the parameters analysed remained unchanged after 6 months of conservative treatment. DISCUSSION: Since patients do not fully recover to their previous level of mobility after 6 months of conservative treatment for OVCF, it appears of high clinical importance to add balance and gait training to the treatment algorithm of OVCFs. CONCLUSIONS: Patients suffering from an OVCF walk with shorter, faster and wider strides compared to their healthy counterparts adopt a less stable body configuration in the anterior direction, potentially increasing their risk of forward falls if perturbed. Although stride time and stride length improve over time even reaching healthy levels again, patients significantly deviate from normal gait patterns (e.g. in stability and step width) after 6 months of conservative treatment

Activation of NF-κB/p65 Facilitates Early Chondrogenic Differentiation during Endochondral Ossification

BACKGROUND: NF-κB/p65 has been reported to be involved in regulation of chondrogenic differentiation. However, its function in relation to key chondrogenic factor Sox9 and onset of chondrogenesis during endochondral ossification is poorly understood. We hypothesized that the early onset of chondrogenic differentiation is initiated by transient NF-κB/p65 signaling. METHODOLOGY/PRINCIPAL FINDINGS: The role of NF-κB/p65 in early chondrogenesis was investigated in different in vitro, ex vivo and in vivo endochondral models: ATDC5 cells, hBMSCs, chicken periosteal explants and growth plates of 6 weeks old mice. NF-κB/p65 activation was manipulated using pharmacological inhibitors, RNAi and activating agents. Gene expression and protein expression analysis, and (immuno)histochemical stainings were employed to determine the role of NF-κB/p65 in the chondrogenic phase of endochondral development. Our data show that chondrogenic differentiation is facilitated by early transient activation of NF-κB/p65. NF-κB/p65-mediated signaling determines early expression of Sox9 and facilitates the subsequent chondrogenic differentiation programming by signaling through key chondrogenic pathways. CONCLUSIONS/SIGNIFICANCE: The presented data demonstrate that NF-κB/p65 signaling, as well as its intensity and timing, represents one of the transcriptional regulatory mechanisms of the chondrogenic developmental program of chondroprogenitor cells during endochondral ossification. Importantly, these results provide novel possibilities to improve the success of cartilage and bone regenerative techniques

Local bone metabolism during the consolidation process of spinal interbody fusion

INTRODUCTION: Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. 18F sodium fluoride (18F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations. This study aimed to quantify the changes in local bone metabolism during consolidation of LIF. MATERIALS AND METHODS: Six skeletally mature sheep underwent LIF surgery. 18F-NaF PET/CT scanning was performed 6 and 12 weeks postoperatively to quantify the bone volume and metabolism in the operated segment. Bone metabolism was expressed as a function of bone volume. RESULTS: Early in the fusion process, bone metabolism was increased at the endplates of the operated vertebrae. In a next phase, bone metabolism increased in the center of the interbody region, peaked, and declined to an equilibrium state. During the entire postoperative time period of 12 weeks, bone metabolism in the interbody region was higher than that of a reference site in the spinal column. CONCLUSION: Following LIF surgery, there is a rapid increase in bone metabolism at the vertebral endplates that develops towards the center of the interbody region. Knowing the local bone metabolism during uncompromised consolidation of spinal interbody fusion might enable identification of impaired bone formation early after LIF surgery using 18F-NaF PET/CT scanning

Predictability of the spontaneous lumbar curve correction after selective thoracic fusion in idiopathic scoliosis

In this study we tried to achieve a better understanding of the biodynamic mechanism of balance in the scoliotic spine. Therefore we focused on the pre- and postoperative spine of patients with idiopathic scoliosis with a primary thoracic curve and a secondary lumbar curve. Several studies showed that the lumbar curve spontaneously corrects and improves after selective thoracic fusion. We try to understand and describe this spontaneous compensatory lumbar curve correction after selective thoracic correction and fusion. We performed a retrospective examination of pre- and postoperative radiographs of the spine of 38 patients with idiopathic scoliosis King type II and III. Frontal Cobb angles of the thoracic and lumbar curves were assessed on pre- and postoperative antero-posterior and side bending radiographs. We determined the postoperative corrections of the thoracic and lumbar curves. Relative (%) corrections and correlations of the postoperative corrections were calculated. The group was divided in three subgroups, depending on lumbar curve modifier, according to Lenkes classification system. The calculations were done for the whole group as for each subgroup. As expected, significant correlations were present between the relative correction of the main thoracic and the lumbar curve (mean R = 0.590; P = 0.001). The relation between relative thoracic and lumbar correction decreased with the lumbar modifier type. This study shows a highly significant correlation between the relative corrections of the main thoracic curve and the lumbar curve after selective thoracic fusion in idiopathic scoliosis. This correlation depends on lumbar curve modifier type. This new classification system seems to be of great predictable value for the spontaneous correction of the lumbar curve. Depending on the curve-type, a different technique for predicting the outcome should be used. The lumbar curve correction does not occur throughout the whole lumbar curve. Most correction is achieved in the upper part of the curve. The distal lumbar curve seems to be more rigid and less important in the spontaneous curve correction

Non-genetic expression of adolescent idiopathic scoliosis: a case report and review of the literature

Treating children with idiopathic scoliosis can amaze someone at the many different ways in which the deformity can present. Most authors state that genetics stipulates the course of adolescent idiopathic scoliosis. This is mainly based on the high concordance in monozygotic twins. However, there is indication that environmental factors have influences on adolescent idiopathic scoliosis. This is the first report in which a monozygotic twin pair is described concordant for idiopathic scoliosis but with different apical levels, magnitudes and age at detection of scoliosis which stresses the importance of environmental factors

Adaptation of the protein translational apparatus during ATDC5 chondrogenic differentiation.

IntroductionRibosome biogenesis is integrated with many cellular processes including proliferation, differentiation and oncogenic events. Chondrogenic proliferation and differentiation require a high cellular translational capacity to facilitate cartilaginous extracellular matrix production. We here investigated the expression dynamics of factors involved in ribosome biogenesis during in vitro chondrogenic differentiation and determined whether protein translation capacity adapts to different phases of chondrogenic differentiation.MaterialsSnoRNA expression during ATDC5 differentiation was analyzed by RNA sequencing of samples acquired from day 0 (progenitor stage), 7 (chondrogenic stage) and day 14 (hypertrophic stage). RT-qPCR was used to determine expression of fibrillarin, dyskerin, UBF-1, Sox9, Col2a1, Runx2, Col10a1 mRNAs and 18S, 5.8S and 28S rRNAs. Protein expression of fibrillarin, dyskerin and UBF-1 was determined by immunoblotting. Ribosomal RNA content per cell was determined by calculating rRNA RT-qPCR signals relative to DNA content (SYBR Green assay). Total protein translational activity was evaluated with a puromycilation assay and polysome profiling.ResultsAs a result of initiation of chondrogenic differentiation (Δt0-t7), 21 snoRNAs were differentially expressed (DE). Hypertrophic differentiation caused DE of 23 snoRNAs (Δt7-t14) and 43 when t0 was compared to t14. DE snoRNAs, amongst others, target nucleotide modifications in the 28S rRNA peptidyl transferase center and the 18S rRNA decoding center. UBF-1, fibrillarin and dyskerin expression increased as function of differentiation and displayed highest fold induction at day 5-6 in differentiation. Ribosomal RNA content per cell was significantly increased at day 7, but not at day 14 in differentiation. Similar dynamics in translational capacity and monosomal ribosome fraction were observed during differentiation.ConclusionThe expression of a great number of ribosome biogenesis factors is altered during chondrogenic differentiation of ATDC5 cells, which is accompanied by significant changes in cellular translational activity. This elucidation of ribosome biogenesis dynamics in chondrogenic differentiation models enables the further understanding of the role of ribosome biogenesis and activity during chondrocyte cell commitment and their roles in human skeletal development diseases