BsmI, ApaI and TaqI Polymorphisms in the Vitamin D Receptor Gene (VDR) and Association with Lumbar Spine Pathologies: An Italian Case-Control Study.

Three adjacent single nucleotide polymorphisms of the vitamin D receptor gene (VDR) BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) are commonly studied in several pathologies. We aimed to evaluate the distribution of VDR BsmI, ApaI, and TaqI allele, genotype, and haplotype frequencies in an Italian cohort of 266 patients with lumbar spine disorders assessed by Magnetic Resonance Imaging and 252 asymptomatic controls. The exposure to putative risk factors was evaluated by a questionnaire. Polymorphisms were detected by PCR-RFLP and TaqMan\uae SNP Genotyping Assay. The results were statistically adjusted for the identified conventional risk factors. The three SNPs were in linkage disequilibrium. For all cases BbAaTT was a 3-fold risk factor OR = 3.38), whereas bbAATT (OR = 0.22), and bbaaTT (OR = 0.47) genotypes were found to be protective. Specifically, for patients affected by disc herniation only (n = 88) and all lumbar pathologies excluding stenosis and/or spondylolistesis (n = 215) B allele, Bb, Aa, and BbAaTT genotypes were risky, whereas b allele, bb, aa, and bbaaTT genotypes were protective. In patients affected by osteochondrosis with or without disc hernation (n = 50), T allele, Aa, and bbAaTT genotypes were risky, whereas t allele, AA, tt genotypes were protective. In patients affected by stenosis and/or spondylolistesis (n = 51) no significant associations were found. This is the first study showing an association of the three genetic VDR variants BsmI, ApaI, and TaqI and lumbar spine pathologies. Our study contributes to delineate genetic risk factors for specific subgroups of patients with lumbar spine pathologies highlighting the importance of haplotype analysis, and of detailed clinical evaluation of the patients for identification of genetic biomarkers

Biomechanics of the lumbar spine after dynamic stabilization

Target of the study was to predict the biomechanics of the instrumented and adjacent levels due to the insertion of the DIAM spinal stabilization system (Medtronic Ltd). For this purpose, a 3-dimensional finite element model of the intact L3/ S1 segment was developed and subjected to different loading conditions (flexion, extension, lateral bending, axial rotation). The model was then instrumented at the L4/L5 level and the same loading conditions were reapplied. Within the assumptions of our model, the simulation results suggested that the implant caused a reduction in range of motion of the instrumented level by 17% in flexion and by 43% in extension, whereas at the adjacent levels, no significant changes were predicted. Numerical results in terms of intradiscal pressure, relative to the intact condition, predicted that the intervertebral disc at the instrumented level was unloaded by 27% in flexion, by 51% in extension, and by 6% in axial rotation, while no variations in pressure were caused by the device in lateral bending. At the adjacent levels, a change of relative intradiscal pressure was predicted in extension, both at the L3/L4 level, which resulted unloaded by 26% and at the L5/S1 level, unloaded by 8%. Furthermore, a reduction in terms of principal compressive stress in the annulus fibrosus of the L4/L5 instrumented level was predicted, as compared with the intact condition. These numerical predictions have to be regarded as a theoretical representation of the behavior of the spine, because any finite element model represents only a simplification of the real Structure

Planning the Surgical Correction of Spinal Deformities: Toward the Identification of the Biomechanical Principles by Means of Numerical Simulation

The set of surgical devices and techniques to perform spine deformity correction has widened dramatically. Nevertheless, the rate of complications due to mechanical failure remains rather high. Indeed, basic research about the principles of deformity correction and the optimal surgical strategies (i.e. the choice of the fusion length, the most appropriate instrumentation, the degree of tolerable correction) did not progress as much as the techniques. In this work, a software approach for the biomechanical simulation of the correction of patient-specific spinal deformities aimed to the identification of its biomechanical principles is presented. The method is based on three dimensional reconstructions of the spinal anatomy obtained from biplanar radiographic images. A user-friendly graphical interface allows for the planning of the deformity correction and to simulate the instrumentation. Robust meshing of the instrumented spine is provided by using consolidated computational geometry and meshing libraries. Based on finite element simulation, the program predicts the loads acting in the instrumentation as well as in the biological tissues. A simple test case (reduction of a low grade spondylolisthesis at L3-L4) was simulated as a proof-of-concept. Despite the limitations of this approach, the preliminary outcome is promising and encourages a wide effort towards its refinement

The strain distribution in the lumbar anterior longitudinal ligament is affected by the loading condition and bony features: An in vitro full-field analysis

The role of the ligaments is fundamental in determining the spine biomechanics in physiological and pathological conditions. The anterior longitudinal ligament (ALL) is fundamental in constraining motions especially in the sagittal plane. The ALL also confines the intervertebral discs, preventing herniation. The specific contribution of the ALL has indirectly been investigated in the past as a part of whole spine segments where the structural flexibility was measured. The mechanical properties of isolated ALL have been measured as well. The strain distribution in the ALL has never been measured under pseudo-physiological conditions, as part of multi-vertebra spine segments. This would help elucidate the biomechanical function of the ALL. The aim of this study was to investigate in depth the biomechanical function of the ALL in front of the lumbar vertebrae and of the intervertebral disc. Five lumbar cadaveric spine specimens were subjected to different loading scenarios (flexion-extension, lateral bending, axial torsion) using a state-of-the-art spine tester. The full-field strain distribution on the anterior surface was measured using digital image correlation (DIC) adapted and validated for application to spine segments. The measured strain maps were highly inhomogeneous: the ALL was generally more strained in front of the discs than in front of the vertebrae, with some locally higher strains both imputable to ligament fibers and related to local bony defects. The strain distributions were significantly different among the loading configurations, but also between opposite directions of loading (flexion vs. extension, right vs. left lateral bending, clockwise vs. counterclockwise torsion). This study allowed for the first time to assess the biomechanical behaviour of the anterior longitudinal ligament for the different loading of the spine. We were able to identify both the average trends, and the local effects related to osteophytes, a key feature indicative of spine degeneration

High Levels of Circulating Type II Collagen Degradation Marker (CTx-II) Are Associated with Specific VDR Polymorphisms in Patients with Adult Vertebral Osteochondrosis

Both vitamin D and collagen have roles in osteocartilaginous homeostasis. We evaluated the association between the circulating 25-hydroxyvitamin D (25(OH)D) type I and II collagen degradation products (CTx-I, and CTx-II), and four vitamin D receptor gene (VDR) polymorphisms, in Italian males affected by low back pain (LBP) due to herniation/discopathy and/or vertebral osteochondrosis. FokI, BsmI, ApaI, and TaqI VDR-polymorphisms were detected through PCR-restriction fragment length polymorphism (RFLP), and circulating 25(OH)D, CTx-I and CTx-II were measured by immunoassays in 79 patients (of which 26 had osteochondrosis) and 79 age-, sex- and body mass index (BMI)-matched healthy controls. Among all 158 subjects, carriers of FF and Ff genotypes showed lower 25(OH)D than ff, which suggested a higher depletion of vitamin D in F allele carriers. Higher CTx-I concentrations were observed in TT versus Tt among controls, and Tt versus tt among LBP cases, which suggested a higher bone-cartilaginous catabolism in subjects bearing the T allele. Higher CTx-II concentrations were observed in patients with osteochondrosis bearing FF, bb, TT, or Aa genotypes in comparison with hernia/discopathy patients and healthy controls. Vertebral osteochondrosis shows peculiar genotypic and biochemical features related to vitamin D and the osteocartilaginous metabolism. Vitamin D has roles in the pathophysiology of osteochondrosis

A comparative analysis of a disposable and a reusable pedicle screw instrument kit for lumbar arthrodesis: integrating HTA and MCDA

Objective: Lumbar arthrodesis is a common surgical technique that consists of the fixation of one or more motion segments with pedicle screws and rods. However, spinal surgery using these techniques is expensive and has a significant impact on the budgets of hospitals and Healthcare Systems. While reusable and disposable instruments for laparoscopic interventions have been studied in literature, no specific information exists regarding instrument kits for lumbar arthrodesis. The aim of the present study was to perform a complete health technology assessment comparing a disposable instrument kit for lumbar arthrodesis (innovative device) with the standard reusable instrument. Methods: A prospective and observational study was implemented, by means of investigation of administrative records of patients undergoing a lumbar arthrodesis surgical procedure. The evaluation was conducted in 2013, over a 12- month time horizon, considering all the procedures carried out using the two technologies. A complete health technology assessment and a multi-criteria decision analysis approach were implemented in order to compare the two alternative technologies. Economic impact (with the implementation of an activity based costing approach), social, ethical, organisational, and technology-related aspects were taken into account. Results: Although the cost analysis produced similar results in the comparison of the two technologies (total cost equal to € 4,279.1 and € 4,242.6 for reusable instrument kit and the disposable one respectively), a significant difference between the two instrument kits was noted, in particular concerning the organisational impact and the patient safety. Conclusions: The replacement of a reusable instrument kit for lumbar arthrodesis, with a disposable one, could improve the management of this kind of devices in hospital settings

Intervertebral disc and endplate cell characterisation highlights annulus fibrosus cells as the most promising for tissue-specific disc degeneration therapy

Degenerative processes of the intervertebral disc (IVD) and cartilaginous endplate lead to chronic spine pathologies. Several studies speculated on the intrinsic regenerative capacity of degenerated IVD related to the presence of local mesenchymal progenitors. However, a complete characterisation of the resident IVD cell populations, particularly that isolated from the endplate, is lacking. The purpose of the present study was to characterise the gene expression profiles of human nucleus pulposus (NPCs), annulus fibrosus (AFCs) and endplate (EPCs) cells, setting the basis for future studies aimed at identifying the most promising cells for regenerative purposes. Cells isolated from NP, AF and EP were analysed after in vitro expansion for their stemness ability, immunophenotype and gene profiles by large-scale microarray analysis. The three cell populations shared a similar clonogenic, adipogenic and osteogenic potential, as well as an immunophenotype with a pattern resembling that of mesenchymal stem cells. NPCs maintained the greatest chondrogenic potential and shared with EPCs the loss of proliferation capability during expansion. The largest number of selectively highly expressed stemness, chondrogenic/tissue-specific and surface genes was found in AFCs, thus representing the most promising source of tissue-specific expanded cells for the treatment of IVD degeneration

Age-related impairment of declarative memory: linking memorization of temporal associations to GluN2B redistribution in dorsal CA1

GluN2B subunits of NMDA receptors have been proposed as a target for treating age‐related memory decline. They are indeed considered as crucial for hippocampal synaptic plasticity and hippocampus‐dependent memory formation, which are both altered in aging. Because a synaptic enrichment in GluN2B is associated with hippocampal LTP in vitro, a similar mechanism is expected to occur during memory formation. We show instead that a reduction of GluN2B synaptic localization induced by a single‐session learning in dorsal CA1 apical dendrites is predictive of efficient memorization of a temporal association. Furthermore, synaptic accumulation of GluN2B, rather than insufficient synaptic localization of these subunits, is causally involved in the age‐related impairment of memory. These challenging data identify extra‐synaptic redistribution of GluN2B‐containing NMDAR induced by learning as a molecular signature of memory formation and indicate that modulating GluN2B synaptic localization might represent a useful therapeutic strategy in cognitive aging