CT image-based biomarkers for opportunistic screening of osteoporotic fractures: a systematic review and meta-analysis.

The use of opportunistic computed tomography (CT) image-based biomarkers may be a low-cost strategy for screening older individuals at high risk for osteoporotic fractures and populations that are not sufficiently targeted. This review aimed to assess the discriminative ability of image-based biomarkers derived from existing clinical routine CT scans for hip, vertebral, and major osteoporotic fracture prediction. A systematic search in PubMed MEDLINE, Embase, Cochrane, and Web of Science was conducted from the earliest indexing date until July 2023. The evaluation of study quality was carried out using a modified Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. The primary outcome of interest was the area under the curve (AUC) and its corresponding 95% confidence intervals (CIs) obtained for four main categories of biomarkers: areal bone mineral density (BMD), image attenuation, volumetric BMD, and finite element (FE)-derived biomarkers. The meta-analyses were performed using random effects models. Sixty-one studies were included in this review, among which 35 were synthesized in a meta-analysis and the remaining articles were qualitatively synthesized. In comparison to the pooled AUC of areal BMD (0.73 [95% CI 0.71-0.75]), the pooled AUC values for predicting osteoporotic fractures for FE-derived parameters (0.77 [95% CI 0.72-0.81]; p < 0.01) and volumetric BMD (0.76 [95% CI 0.71-0.81]; p < 0.01) were significantly higher, but there was no significant difference with the pooled AUC for image attenuation (0.73 [95% CI 0.66-0.79]; p = 0.93). Compared to areal BMD, volumetric BMD and FE-derived parameters may provide a significant improvement in the discrimination of osteoporotic fractures using opportunistic CT assessments.

Refracture and mortality risk in the elderly with osteoporotic fractures: the AGES-Reykjavik study.

There is imminent refracture risk in elderly individuals for up to six years, with a decline thereafter except in women below 75 who face a constant elevated risk. Elderly men with fractures face the highest mortality risk, particularly those with hip and vertebral fractures. Targeted monitoring and treatment strategies are recommended. PURPOSE: Current management and interventions for osteoporotic fractures typically focus on bone mineral density loss, resulting in suboptimal evaluation of fracture risk. The aim of the study is to understand the progression of fractures to refractures and mortality in the elderly using multi-state models to better target those at risk. METHODS: This prospective, observational study analysed data from the AGES-Reykjavik cohort of Icelandic elderly, using multi-state models to analyse the evolution of fractures into refractures and mortality, and to estimate the probability of future events in subjects based on prognostic factors. RESULTS: At baseline, 4778 older individuals aged 65 years and older were included. Elderly men, and elderly women above 80 years of age, had a distinct imminent refracture risk that lasted between 2-6 years, followed by a sharp decline. However, elderly women below 75 continued to maintain a nearly constant refracture risk profile for ten years. Hip (30-63%) and vertebral (24-55%) fractures carried the highest 5-year mortality burden for elderly men and women, regardless of age, and for elderly men over 80, lower leg fractures also posed a significant mortality risk. CONCLUSION: The risk of refracture significantly increases in the first six years following the initial fracture. Elderly women, who experience fractures at a younger age, should be closely monitored to address their long-term elevated refracture risk. Elderly men, especially those with hip and vertebral fractures, face substantial mortality risk and require prioritized monitoring and treatment.

Lower Trapezius and Latissimus Dorsi Transfer relieve Teres Minor Activity into the Physiological Range in Collin D Irreparable Posterosuperior Massive Rotator Cuff Tears: A Biomechanical Analysis.

BACKGROUND: Tendon transfers are established techniques to regain external rotation mobility in patients suffering from an irreparable, posterosuperior massive rotator cuff tear (MRCT). Posterosuperior MRCT with intact teres minor (Type D MRCT) can lead to excessive teres minor loading to maintain external rotation. We hypothesize that tendon transfers are effective in relieving teres minor loading in Type D MRCTs. Our aim was to biomechanically assess muscle synergism with latissimus dorsi (LD-Transfer) and lower trapezius (LT-Transfer) tendon transfer during external rotation at different abduction heights. METHODS: Using musculoskeletal modeling, we analyzed and compared the moment arm, muscle torque and muscle activity between a healthy and Type D MRCT pathological model with and without the LD- or LT-Transfer at infraspinatus and teres minor insertion sites. Output measures were analyzed during external rotation at different abduction angles and 10 to 50N resistance against external rotation. We assessed its impact on teres minor loading in a Type D MRCT. Morphological variations were parameterized using the critical shoulder angle and the acromiohumeral distance to address variations among patients. RESULTS: Both transfer types reduced teres minor torque and activity significantly, reaching physiological state at 40N external resistance (p<0.001), with insertion to infraspinatus site being more effective than teres minor site (p<0.001). External rotation moment arms of LD-Transfer were larger than LT-Transfer at 90° abduction (25.1±0.8mm vs. 21.2±0.6mm, p<0.001) and vice versa at 0° abduction (17.4±0.5mm vs. 24.0±0.2mm, p<0.001). While the healthy infraspinatus was the main external rotator in all abduction angles (50-70% torque), a Type D MRCT resulted in a 70-90% increase of teres minor torque and an up to sevenfold increase in its activity leading to excessive loadings beyond 10N resistance against external rotation. Varying the critical shoulder angle and the acromiohumeral distance led to minor variations in muscle moment arm and muscle activity. CONCLUSION: We identified biomechanical efficacy of both tendon transfers in Type D MRCT regarding teres minor load relieve and superior performance of the transfers at the infraspinatus insertion site.

A Novel Fiber-Reinforced Poroviscoelastic Bovine Intervertebral Disc Finite Element Model for Organ Culture Experiment Simulations.

Intervertebral disc (IVD) degeneration and methods for repair and regeneration have commonly been studied in organ cultures with animal IVDs under compressive loading. With the recent establishment of a novel multi-axial organ culture system, accurate predictions of the global and local mechanical response of the IVD are needed for control system development and to aid in experiment planning. This study aimed to establish a finite element model of bovine IVD capable of predicting IVD behavior at physiological and detrimental load levels. A finite element model was created based on the dimensions and shape of a typical bovine IVD used in the organ culture. The nucleus pulposus (NP) was modeled as a neo-Hookean poroelastic material and the annulus fibrosus (AF) as a fiber-reinforced poroviscoelastic material. The AF consisted of 10 lamella layers and the material properties were distributed in the radial direction. The model outcome was compared to a bovine IVD in a compressive stress-relaxation experiment. A parametric study was conducted to investigate the effect of different material parameters on the overall IVD response. The model was able to capture the equilibrium response and the relaxation response at physiological and higher strain levels. Permeability and elastic stiffness of the AF fiber network affected the overall response most prominently. The established model can be used to evaluate the response of the bovine IVD at strain levels typical for organ culture experiments, to define relevant boundaries for such studies, and to aid in the development and use of new multi-axial organ culture systems.

Association between sagittal alignment and loads at the adjacent segment in the fused spine: a combined clinical and musculoskeletal modeling study of 205 patients with adult spinal deformity.

PURPOSE: Sagittal malalignment is a risk factor for mechanical complications after surgery for adult spinal deformity (ASD). Spinal loads, modulated by sagittal alignment, may explain this relationship. The aims of this study were to investigate the relationships between: (1) postoperative changes in loads at the proximal segment and realignment, and (2) absolute postoperative loads and postoperative alignment measures. METHODS: A previously validated musculoskeletal model of the whole spine was applied to study a clinical sample of 205 patients with ASD. Based on clinical and radiographic data, pre-and postoperative patient-specific alignments were simulated to predict loads at the proximal segment adjacent to the spinal fusion. RESULTS: Weak-to-moderate associations were found between pre-to-postop changes in lumbar lordosis, LL (r = - 0.23, r = - 0.43; p < 0.001), global tilt, GT (r = 0.26, r = 0.38; p < 0.001) and the Global Alignment and Proportion score, GAP (r = 0.26, r = 0.37; p < 0.001), and changes in compressive and shear forces at the proximal segment. GAP score parameters, thoracic kyphosis measurements and the slope of upper instrumented vertebra were associated with changes in shear. In patients with T10-pelvis fusion, moderate-to-strong associations were found between postoperative sagittal alignment measures and compressive and shear loads, with GT showing the strongest correlations (r = 0.75, r = 0.73, p < 0.001). CONCLUSIONS: Spinal loads were estimated for patient-specific full spinal alignment profiles in a large cohort of patients with ASD pre-and postoperatively. Loads on the proximal segments were greater in association with sagittal malalignment and malorientation of proximal vertebra. Future work should explore whether they provide a causative mechanism explaining the associated risk of proximal junction complications.

In Vitro Biomechanics of the Cervical Spine: A Systematic Review.

In vitro testing has been conducted to provide a comprehensive understanding of the biomechanics of the cervical spine. This has allowed a characterization of the stability of the spine as influenced by the intrinsic properties of its tissue constituents and the severity of degeneration or injury. This also enables the preclinical estimation of spinal implant functionality and the success of operative procedures. The purpose of this review paper was to compile methodologies and results from various studies addressing spinal kinematics in pre- and postoperative conditions so that they could be compared. The reviewed literature was evaluated to provide suggestions for a better approach for future studies, to reduce the uncertainties and facilitate comparisons among various results. The overview is presented in a way to inform various disciplines, such as experimental testing, design development, and clinical treatment. The biomechanical characteristics of the cervical spine, mainly the segmental range of motion (ROM), intradiscal pressure (IDP), and facet joint load (FJL), have been assessed by testing functional spinal units (FSUs). The relative effects of pathologies including disc degeneration, muscle dysfunction, and ligamentous transection have been studied by imposing on the specimen complex load scenarios imitating physiological conditions. The biomechanical response is strongly influenced by specimen type, test condition, and the different types of implants utilized in the different experimental groups.

Silicon Nitride as a Biomedical Material: An Overview.

Silicon nitride possesses a variety of excellent properties that can be specifically designed and manufactured for different medical applications. On the one hand, silicon nitride is known to have good mechanical properties, such as high strength and fracture toughness. On the other hand, the uniqueness of the osteogenic/antibacterial dualism of silicon nitride makes it a favorable bioceramic for implants. The surface of silicon nitride can simultaneously inhibit the proliferation of bacteria while supporting the physiological activities of eukaryotic cells and promoting the healing of bone tissue. There are hardly any biomaterials that possess all these properties concurrently. Although silicon nitride has been intensively studied as a biomedical material for years, there is a paucity of comprehensive data on its properties and medical applications. To provide a comprehensive understanding of this potential cornerstone material of the medical field, this review presents scientific and technical data on silicon nitride, including its mechanical properties, osteogenic behavior, and antibacterial capabilities. In addition, this paper highlights the current and potential medical use of silicon nitride and explains the bottlenecks that need to be addressed, as well as possible solutions.

Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc-1α expression: Follow-up to an in vitro magnetic mitohormetic study.

Exercise modulates metabolism and the gut microbiome. Brief exposure to low mT-range pulsing electromagnetic fields (PEMFs) was previously shown to accentuate in vitro myogenesis and mitochondriogenesis by activating a calcium-mitochondrial axis upstream of PGC-1α transcriptional upregulation, recapitulating a genetic response implicated in exercise-induced metabolic adaptations. We compared the effects of analogous PEMF exposure (1.5 mT, 10 min/week), with and without exercise, on systemic metabolism and gut microbiome in four groups of mice: (a) no intervention; (b) PEMF treatment; (c) exercise; (d) exercise and PEMF treatment. The combination of PEMFs and exercise for 6 weeks enhanced running performance and upregulated muscular and adipose Pgc-1α transcript levels, whereas exercise alone was incapable of elevating Pgc-1α levels. The gut microbiome Firmicutes/Bacteroidetes ratio decreased with exercise and PEMF exposure, alone or in combination, which has been associated in published studies with an increase in lean body mass. After 2 months, brief PEMF treatment alone increased Pgc-1α and mitohormetic gene expression and after >4 months PEMF treatment alone enhanced oxidative muscle expression, fatty acid oxidation, and reduced insulin levels. Hence, short-term PEMF treatment was sufficient to instigate PGC-1α-associated transcriptional cascades governing systemic mitohormetic adaptations, whereas longer-term PEMF treatment was capable of inducing related metabolic adaptations independently of exercise.

A Biomimetic Macroporous Hybrid Scaffold with Sustained Drug Delivery for Enhanced Bone Regeneration.

Bone regeneration is a highly complex physiological process regulated by several factors. In particular, bone-mimicking extracellular matrix and available osteogenic growth factors such as bone morphogenetic protein (BMP) have been regarded as key contributors for bone regeneration. In this study, we developed a biomimetic hybrid scaffold (CEGH) with sustained release of BMP-2 that would result in enhanced bone formation. This hybrid scaffold, composed of BMP-2-loaded cryoelectrospun poly(ε-caprolactone) (PCL) (CE) surrounded by a macroporous gelatin/heparin cryogel (GH), is designed to overcome the drawbacks of the relatively weak mechanical properties of cryogels and poor biocompatibility and hydrophobicity of electrospun PCL. The GH component of the hybrid scaffold provides a hydrophilic surface to improve the biological response of the cells, while the CE component increases the mechanical strength of the scaffold to provide enhanced mechanical support for the defect area and a stable environment for osteogenic differentiation. After analyzing characteristics of the hybrid scaffold such as hydrophilicity, pore difference, mechanical properties, and surface charge, we confirmed that the hybrid scaffold shows enhanced cell proliferation rate and apatite formation in simulated body fluid. Then, we evaluated drug release kinetics of CEGH and confirmed the sustained release of BMP-2. Finally, the enhanced osteogenic differentiation of CEGH with sustained release of BMP-2 was confirmed by Alizarin Red S staining and real-time PCR analysis.

Variable fixation promotes callus formation: an experimental study on transverse tibial osteotomies stabilized with locking plates.

BACKGROUND: A new locking screw technology, named variable fixation, has been developed aiming at promoting bone callus formation providing initial rigid fixation followed by progressive fracture gap dynamisation. In this study, we compared bone callus formation in osteotomies stabilized with standard locking fixation against that of osteotomies stabilized with variable fixation in an established tibia ovine model. METHODS: A 3 mm tibial transverse osteotomy gap was stabilized in three groups of six female sheep each with a locking plate and either 1) standard fixation in both segments (group LS) or 2) variable fixation in the proximal and standard fixation in the distal bone segment (group VFLS3) or 3) variable fixation in both segments (group VFLS6). The implantation site and fracture healing were compared between groups by means of radiologic, micro tomographic, biomechanical, and histological investigations. RESULTS: Compared to LS callus, VFLS3 callus was 40% larger and about 3% denser, while VFLS6 callus was 93% larger and its density about 7.2% lower. VFLS3 showed 65% and VFLS6 163% larger amount of callus at the cis-cortex. There wasn't a significant difference in the amount of callus at the cis and trans-cortex in groups featuring variable fixation only. Investigated biomechanical variables were not significantly different among groups and histology showed comparable good healing in all groups. Tissues adjacent to the implants did not show any alteration of the normal structure in all groups. CONCLUSIONS: Variable fixation promoted the formation of a larger amount of bone callus, equally distributed at the cis and trans cortices. The histological and biomechanical properties of the variable fixation callus were equivalent to those of the standard fixation callus. The magnitude of variable fixation had a biological effect on the formation of bone callus. At the implantation site, the usage of variable fixation did not raise additional concerns with respect to standard fixation. The formation of a larger amount of mature callus suggests that fractures treated with variable fixation might have a higher probability to bridge the fracture gap. The conditions where its usage can be most beneficial for patients needs to be clinically defined.

Medial unicompartmental knee arthroplasty in ACL-deficient knees is a viable treatment option: in vivo kinematic evaluation using a moving fluoroscope.

PURPOSE: Unicompartmental knee arthroplasty (UKA), resulting in similar kinematics to native knees, is functionally superior to total knee arthroplasty (TKA). However, ACL deficiency is generally considered to be a contraindication. The main purpose of this study was to investigate if UKA in ACL-deficient knees would result in similar kinematics to conventional UKA with an intact ACL. METHODS: Ten conventional UKA patients were compared to eight ACL-deficient patients with a reduced tibial slope to compensate for instability, resulting from the deficient ACL. Knee kinematics was evaluated with a moving fluoroscope, tracking the knee joint during daily activities. In a standing position (baseline), posterior shift of the femur was observed for ACL-deficient UKA patients, compared to conventional UKA patients. RESULTS: A significant posterior femoral shift in the ACL-deficient group was observed during the first 25% (near extension) of deep knee bend, while there was no difference in kinematic waveforms for all other activities. No significant range of motion differences across different activities between the two UKA groups were detected, except for an increase of medial AP translation in the ACL-deficient group, during deep knee bend and stair descent. CONCLUSION: Despite the posterior femoral shift due to ACL deficiency, both UKA groups showed similar kinematic waveforms, indicating that posterior tibial slope reduction can partially compensate for ACL function. This supported our hypothesis that fixed bearing UKA can be a viable treatment option for selected ACL-deficient patients, allowing patient-specific kinematics. While anteroposterior laxity can be compensated, rotational stability was a prerequisite for this approach. LEVEL OF EVIDENCE: III.

Videofluoroscopic Evaluation of the Influence of a Gradually Reducing Femoral Radius on Joint Kinematics During Daily Activities in Total Knee Arthroplasty.

BACKGROUND: Paradoxical anterior translation in midflexion is reduced in total knee arthroplasties (TKAs) with a gradually reducing femoral radius, when compared to a 2-radii design. This reduction has been shown in finite element model simulations, in vitro tests, intraoperatively, and recently also in vivo during a lunge and unloaded flexion-extension. However, TKA kinematics are task dependent and this reduction has not been tested for gait activities. METHODS: Thirty good outcome subjects (≥1 year postoperatively) with a unilateral cruciate-retaining TKA with a gradually reducing (n = 15) or dual (n = 15) femoral radius design were assessed during 5 complete cycles of level walking, stair descent (0.18-m steps), deep knee bend, and sitting down onto and standing up from a chair, using a moving fluoroscope (25 Hz, 1 ms shutter time). Kinematic data were extracted by 2D/3D image registration. RESULTS: Tibiofemoral ranges of motion for flexion-extension, abduction-adduction, internal-external rotation, and anteroposterior (AP) translation were similar for both groups, whereas the pattern of AP translation-flexion-coupling differed. The subjects with the dual-radii design showed a sudden change in direction of AP translation around 30° of flexion, which was not present in the subjects with the gradually reducing femoral radius design. CONCLUSION: Through the unique ability of moving fluoroscopy, the present study confirmed that the gradually reducing femoral radii eliminated the paradoxical sudden anterior translation at 30° present in the dual-radii design in vivo during daily activities, including gait and stair descent.

Current Preclinical Testing of New Hip Arthroplasty Technologies Does Not Reflect Real-World Loadings: Capturing Patient-Specific and Activity-Related Variation in Hip Contact Forces.

BACKGROUND: Total hip arthroplasty (THA) implants are routinely tested for their tribological performance through regulatory preclinical wear testing (eg, ISO-14242). The standardized loading conditions defined in these tests consist of simplified waveforms, which do not specifically represent in vivo loads in different groups of patients. The aim of this study is to investigate, through musculoskeletal modeling, patient-specific and activity-related variation in hip contact forces (HCFs) in a large cohort of THA patients during common activities of daily living (ADLs). METHODS: A total of 132 THA patients participated in a motion-capture analysis while performing different ADLs, including walk, fast walk, stair ascent, and descent (locomotor); sit to stand, stand to sit, squat, and lunge (nonlocomotor). HCFs were then calculated using the AnyBody Modeling System and qualitatively compared across all activities. The influence of gender on HCFs was analyzed through statistical parametric mapping analysis. RESULTS: Systematic differences were found in HCF magnitudes and individual components in both locomotor and nonlocomotor ADLs. The qualitative analysis of the ADLs revealed a large range and a large variability in forces experienced at the hip during different activities. Significant differences in the 3-dimensional loading patterns were observed between males and females across most activities. CONCLUSION: THA patients present a large variability in the forces experienced at the hip joint during their daily life. The interpatient variation might partially explain the heterogeneity observed in implant survival rates. A more extensive preclinical implant testing standard under clinically relevant loading conditions has been advocated to better predict and avoid clinical wear problems.

The effect of muscle ageing and sarcopenia on spinal segmental loads.

PURPOSE: The interrelations between age-related muscle deterioration (sarcopenia) and vertebral fractures have been suggested based on clinical observations, but the biomechanical relationships have not been explored. The study aim was to investigate the effects of muscle ageing and sarcopenia on muscle recruitment patterns and spinal loads, using musculoskeletal multi-body modelling. METHODS: A generic AnyBody model of the thoracolumbar spine, including > 600 fascicles representing trunk musculature, was used. Several stages of normal ageing and sarcopenia were modelled by reduced strength of erector spinae and multifidus muscles (ageing from 3rd to 6th life decade: ≥ 60% of normal strength; sarcopenia: mild 60%, moderate 48%, severe 36%, very severe 24%), reflecting the reported decrease in cross-sectional area and increased fat infiltration. All other model parameters were kept unchanged. Full-range flexion was simulated using inverse dynamics with muscle optimization to predict spinal loads and muscle recruitment patterns. RESULTS: The muscle changes due to normal ageing (≥ 60% strength) had a minor effect on predicted loads and provoked only slightly elevated muscle activities. Severe (36%) and very severe (24%) stages of sarcopenia, however, were associated with substantial increases in compression (by up to 36% or 318N) at the levels of the upper thoracic spine (T1T2-T5T6) and shear loading (by up to 75% or 176N) along the whole spine (T1T2-L4L5). The muscle activities increased for almost all muscles, up to 100% of their available strength. CONCLUSIONS: The study highlights the distinct and detrimental consequences of sarcopenia, in contrast to normal ageing, on spinal loading and required muscular effort. These slides can be retrieved under Electronic Supplementary Material.

The influence of spinal fusion length on proximal junction biomechanics: a parametric computational study.

PURPOSE: Proximal junctional kyphosis and failure are frequent complications in adult spinal deformity surgery with long fusion constructs. The aim of this study was to assess the biomechanics of the proximal segment for fusions of various lengths. METHODS: A previously established musculoskeletal model of thoracolumbar spine was used to simulate full-range flexion task for fusions (modeled by introduction of rigid constraints) with lower instrumented vertebrae at L5 or S1 and upper instrumented vertebrae (UIV) at any level above, up to T2. Inverse dynamics simulations with force-dependent kinematics were performed for gradually increasing spinal flexion in order to predict global and segmental range of flexion, maximum passive moment, segmental compression and shear forces, which were compared to the uninstrumented case. RESULTS: For long fusions, with the UIV at T11 or higher, the model predicted an increase in segmental flexion (by 33-860%, or 1.6°-4.7°) and passive moment (by 39-1370%, or 13-31 Nm) at the proximal junction-generally increasing with fusion length. While the maximum shear force was 57-239% (135-283 N) higher for the proximal junction at the upper thorax (UIV at T6 or above), the compression forces were reduced by up to 44% (375 N). CONCLUSIONS: The length of the instrumentation has an important effect on the proximal segment biomechanics. Despite the limitations of the current model, musculoskeletal modeling appears to be a promising and versatile method to support planning of spinal instrumentation surgeries in the future. These slides can be retrieved under Electronic Supplementary Material.

Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of proinflammatory cytokine and TRP channel expression.

PURPOSE: To investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine by a gene array and subsequent qPCR and to investigate the mechanistic involvement of transient receptor potential channels TRPC6 and TRPV4. METHODS: The gene expression of inflammatory cytokines and TRP channels was measured in human disc samples obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and analyzed for differences with regard to spinal level, IVD degeneration grade, Modic grade, age, sex, disc region and surgical extent. RESULTS: Aside from genes with known implication in DDD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) and IVD degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15), nucleus and annulus (IL-6, TNF-α, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or between cytokines and TRP channels, exist in the disc. CONCLUSION: This study supports the relevance of IL-6 and IL-8 in disc diseases, but furthermore points toward a possible pathological role of IL-15 and type I interferons, as well as a mechanistic role of TRPC6. With limited differences in the inflammatory profile of cervical and lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the treatment of disc pathologies may be applicable independent of the spinal region.

TRPC6 in simulated microgravity of intervertebral disc cells.

PURPOSE: Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. METHODS: Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5 days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. RESULTS: Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3 days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. CONCLUSIONS: Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies. These slides can be retrieved under Electronic Supplementary Material.

Determining 3D Kinematics of the Hip Using Video Fluoroscopy: Guidelines for Balancing Radiation Dose and Registration Accuracy.

BACKGROUND: Video fluoroscopy is a technique currently used to retrieve the in vivo three-dimensional kinematics of human joints during activities of daily living. Minimization of the radiation dose absorbed by the subject during the measurement is a priority and has not been thoroughly addressed so far. This issue is critical for the motion analysis of the hip joint, because of the proximity of the gonads. The aims of this study were to determine the x-ray voltage and the irradiation angle that minimize the effective dose and to achieve the best compromise between delivered dose and accuracy in motion retrieval. METHODS: Effective dose for a fluoroscopic study of the hip was estimated by means of Monte Carlo simulations and dosimetry measurements. Accuracy in pose retrieval for the different viewing angles was evaluated by registration of simulated radiographs of a hip prosthesis during a prescribed virtual motion. RESULTS: Absorbed dose can be minimized to about one-sixth of the maximum estimated values by irradiating at the optimal angle of 45° from the posterior side and by operating at 80 kV. At this angle, accuracy in retrieval of internal-external rotation is poorer compared with the other viewing angles. CONCLUSION: The irradiation angle that minimizes the delivered dose does not necessarily correspond to the optimal angle for the accuracy in pose retrieval, for all rotations. For some applications, single-plane fluoroscopy may be a valid lower dose alternative to the dual-plane methods, despite their better accuracy.

An Inflammatory Nucleus Pulposus Tissue Culture Model to Test Molecular Regenerative Therapies: Validation with Epigallocatechin 3-Gallate.

Organ cultures are practical tools to investigate regenerative strategies for the intervertebral disc. However, most existing organ culture systems induce severe tissue degradation with only limited representation of the in vivo processes. The objective of this study was to develop a space- and cost-efficient tissue culture model, which represents degenerative processes of the nucleus pulposus (NP). Intact bovine NPs were cultured in a previously developed system using Dyneema jackets. Degenerative changes in the NP tissue were induced either by the direct injection of chondroitinase ABC (1-20 U/mL) or by the diffusion of interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) (both 100 ng/mL) from the culture media. Extracellular matrix composition (collagens, proteoglycans, water, and DNA) and the expression of inflammatory and catabolic genes were analyzed. The anti-inflammatory and anti-catabolic compound epigallocatechin 3-gallate (EGCG, 10 µM) was employed to assess the relevance of the degenerative NP model. Although a single injection of chondroitinase ABC reduced the proteoglycan content in the NPs, it did not activate cellular responses. On the other hand, IL-1ß and TNF-α significantly increased the mRNA expression of inflammatory mediators IL-6, IL-8, inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinases (MMP1, MMP3, and MMP13). The cytokine-induced gene expression in the NPs was ameliorated with EGCG. This study provides a proof of concept that inflammatory NP cultures, with appropriate containment, can be useful for the discovery and evaluation of molecular therapeutic strategies against early degenerative disc disease.