Summary Statement. Pedicle screws provide robust fixation and rigid immobilization. There has been no attempt to correlate the anatomic dimensions of thoracic and lumbar pedicles with the accuracy of navigated insertion. This study demonstrates that comparable accuracy using this technique. Introduction. Pedicle screws provide robust mechanical fixation, which makes their use attractive; their use enables fixation of the three spinal columns. There remains concern about the potential both for misplacement; various investigators have studied the accuracy of pedicle screw insertions, comparing different techniques. What is not clear, however, is whether there is any relation between the variables of pedicles’ anatomic dimensions, screw dimensions and accuracy. This study aims to elucidate the relationship between these variables. Patients & Methods. We conducted a retrospective review of consecutive pedicle screws that were inserted in the thoracic and lumbar spine at our institution. Screws were inserted using the navigated method (Stealth Station® TREON™, Medtronic, Louisville, CO). The accuracy of the screw insertion was measured using the classification system developed by Gertzbein and Robbins; pedicle dimensions were measured from post-operative computed tomography scans. The corresponding pre-operative scans were then used to measure the pedicle dimensions at the other levels. The magnitude of a cortical breach in the pedicle was represented by a letter: A (no breach), B (<2mm), C (>2mm, <4mm), D (>4mm, <6mm) and E (>6mm). In addition, measurements were made of the anatomic dimensions of the pedicles. The combination of these two measures allowed for direct correlation to be made between the accuracy of screw insertion, screw dimensions and pedicle anatomy. We then computed the proportion of each pedicle (width) occupied by a screw. Results. A total of 765 screws were reviewed, 493 were in the thoracic spine and 272 in the lumbar spine. Of the screws in the thoracic spine, 472 (96%) were either fully in the pedicle or less than 2mm beyond the cortex (within the A+B classification); when considered separately, 323 (66%) were completely within the pedicle (A) and 149 (30%) were less than 2mm beyond the cortex. A total of 21 (4%) screws were beyond 2mm but within 6mm (C+D). In the lumbar spine, 270 (99%) were either completely within the cortex or less than 2mm exposed (classified as A or B). The nadir of pedicle width was at T4. From L1 to L5, measured pedicle width also rose. This pattern was followed, although it was less profound, when screw diameter was measured in the lumbar spine (and even less so in the thoracic vertebrae). The height of pedicles was noted to progressively increase, peaking at the thoraco-lumbar junction. The mid thoracic region was associated with screws occupying the greatest proportion of pedicle diameter. Discussion/Conclusion. The use of pedicle screws in the thoracic and lumbar spine remains relatively safe. The accuracy of navigated insertion was found to compare well to previous series’. Although there is some association between the anatomical dimensions of pedicles and the dimensions of screws, this doesn't seem to be a strong association. Based on the findings in this series, future studies that relate the long term outcome (e.g. failure or screw loosening) with proportion of pedicle diameter taken up by a screw may be warranted

Aging has been associated with decreases in muscle strength and bone quality. In elderly patients, paravertebral muscle atrophy is accompanied by vertebral osteoporosis. The purpose of this study was to use paravertebral injection of botulinum toxin-A (BTX) to investigate the effects of paravertebral muscle atrophy on lumbar vertebral bone quality. Forty 16-week-old female SD rats were randomly divided into four groups: (1) a control group (CNT); (2) a resection of erector spinae muscles group (RESM); (3) a botulinum toxin-A group (BTX) that was treated with local injection of 5U BTX into the paravertebral muscles bilaterally; and (4) a positive control group (OVX) that underwent bilateral ovariectomy. At 3 months post-surgery the lumbar vertebrae (L3 – L6) were collected. The BMDs of the RESM and BTX groups were significantly lower than that of the CNT group (P < 0.01). Micro-CT scans showed that rats in the three experimental groups had fewer trabeculae and trabecular connections than rats in the CNT group. The bone loss trend of the trabecular networks was most obvious in the OVX rats. Vertebral compression testing revealed that the three experimental groups had significantly lower maximum load, energy absorption, maximum stress, and elastic modulus values than the CNT group (P < 0.01), and these parameters were lowest in the OVX group (P < 0.05). Our results demonstrate that the new paravertebral muscle atrophy model using local BTX injection causes sufficient muscle atrophy and dysfunction to result in local lumbar vertebral bone loss and quality deterioration

Summary Statement. Using abdominal CT scans to evaluate bone mineral density following acute fractures of the thoracic and lumbar spine demonstrates significant levels of osteoporosis in older patients; this approach may help save on time and resources, and reduce unnecessary radiation exposure. Introduction. While a reduction in bone mineral density (BMD) is associated with aging, relatively few patients have formal dual-energy X-ray absorptiometry (DXA) to quantify the magnitude of bone loss, as they age. This loss of bone may predispose to fractures. Recent data, which correlates mean Hounsfield units (HU) in an area of the L1 vertebra with BMD, now makes it possible to screen for osteoporosis using incidental abdominal Computed Tomography (CT) scans to measure bone density. This innovation has the potential to reduce both cost and radiation exposure, and also make it easier to identify patients who may be at risk. The aims of this study were to evaluate the utility of this approach in patients with acute thoracic and lumbar spine fractures and to evaluate the impact of aging on BMD, using CT screening. Patients & Methods. Following institutional review board approval, we performed a retrospective study of patients who presented to a level I trauma center with acute fractures of the thoracic and lumbar spine between 2010 and 2013; patients also had to have had an abdominal (or L1) CT scan either during the admission or in the 6 months before or after their injury. Using a picture archiving and communication (PACS) system, we generated regions of interest (ROI) of similar size in the body of L1 (excluding the cortex) and computed mean values for HU. Values derived were compared against threshold values which differentiate between osteoporosis and osteopenia - for specificity of 90%, a threshold of 110 was set; for balanced sensitivity and specificity, a threshold of <135 HU was set and for 90% sensitivity a threshold of <160 HU was set. A student's t test was used to compare the age stratified mean HU (younger than 65yrs; 65yrs and older), while Fisher's exact test was used to perform aged stratified comparisons between the proportions of patients above and below the thresholds outlined (in each of the three threshold groups). Results. A total of 124 patients were evaluated, with 74 having thoracic and 50 having lumbar fractures. Among those with thoracic fractures, there were 33patients in the younger cohort, who also had a mean BMD of 196.51HU and 41 in the older cohort, who had mean BMD of 105.90HU (p<0.001). In patients with lumbar fractures, 27 patients were in the younger cohort, with mean BMD of 192.26HU and 23 patients in the older cohort with mean BMD of 114.31HU (p<0.001). At the threshold of 110 HU, set for specificity, the magnitude of difference between the age stratified cohorts was greater in the thoracic spine (p<0.001 vs. p=0.003). At the other thresholds: 135HU (balanced for sensitivity and specificity) and 160 HU (90% sensitivity), age of 65 years or older was significantly associated with reduction in CT derived measure of BMD (p<0.001 in all cases). Discussion. This study demonstrates the relative frequency of osteoporosis in acute fractures of the thoracic and lumbar spine, and how this changes with age; it is also the first study to do this using opportunistic CT scans. There seems to be a strong association between a reduction in bone mineral density and advanced age, in patients presenting with acute fractures of the spine. This approach may save on the extra cost and additional radiation exposure that may be associated with DXA scanning; in addition, it may help provide clinicians and patients with an approach to monitor developing problems with BMD before it becomes clinically apparent, especially in younger patients

Introduction. DXA areal-bone-mineral-density (aBMD) is used clinically as a surrogate for true volumetric-BMD to assess bone fragility. Trabecular-Bone-Score (TBS) provides an assessment of bone quality based on the DXA-derived two-dimensional images. Calculated from bone area (BA), aBMD may under- or overestimate true BMD in individuals with relatively low and high BA respectively. This study investigated relationships between BA at the lumbar-spine (L1–L4) and measurements of BMD and TBS. Method. Lumbar spine scans were performed (GE Lunar Prodigy) on 114 women (mean 53 yrs). The study population was divided by L1–L4 BA using the 20th and 80th centiles, and BMD v TBS correlations calculated for the subgroups. BMD and TBS, converted to Z-scores, were correlated with BA. Results. For the whole group, r = 0.23 for BMD v BA, whereas r = −0.12 for TBS v. BA: the correlation between BMD and TBS was r=0.38. Correlations between BMD and TBS for BA subgroups were r = 0.23, r=0.44 and r=0.59 for the >20th, 20th −80th and >80th centile groups respectively. Conclusion. Low correlation between BMD and TBS for the entire group indicates that TBS reflects some bone quality properties unrelated to BMD. The correlation of BMD with BA suggests that it incorrectly estimates true BMD at BA extremes. Correlation for BMD v TBS in the lowest area-subgroup was substantially lower than for the middle and highest area subgroups suggesting that TBS may afford valuable complementary information on bone fragility at the lowest extreme of BA where distortions in BMD measurement potentially occur

Summary Statement. Spinal flexibility in bending and axial torque has been shown to exhibit very modest changes with advancing disc degeneration. This study is the first to address the possible relationship in pure anterior shear and no clear relationship was observed. Introduction. Disc degeneration (DD) is a risk factor for low back pain. Stable or unstable spine segments may be treated with an isolated decompression or instrumented stabilization, respectively. The effect of DD on spinal flexibility has been addressed by several groups in bending but not in shear; a highly relevant load direction in the lumbar spine is anterior shear. The objective of our study was to determine the effect of DD on anterior translation and specimen stiffness under shear loading in an in vitro model of degenerative spondylolisthesis. Methods. Magnetic resonance images were obtained for human cadaveric lumbar FSUs (N=30). Disc degeneration was assessed with the Pfirrmann five-point grading scale. Three surgeons independently graded the discs and the grade common to at least two of the surgeons was assigned to that specimen. Each specimen was then tested in three sequential states: intact, facet destabilization, and disc destabilization, with the latter two states representing the clinical scenario of degenerative lumbar spondylolisthesis. The specimens were loaded with a constant 300 N axial compressive force, representing body weight, combined with a cyclic anterior shear force (5–250 N). Vertebral translation was tracked with an optoelectronic motion capture system. Kruskal-Wallis ANOVA and multiple comparison Dunn's tests were performed to determine the effect of DD on anterior translation and specimen stiffness. Results. There was only one specimen with disc grade V, and it was grouped with specimens with disc grade IV for the statistical analyses. DD had no effect on anterior translation or specimen stiffness for the intact and disc destabilization conditions. In the facet destabilization condition, specimens with disc grade II translated more than those with disc grades IV and V (p=0.03). Stiffness increased with DD in the facet destabilization condition (ANOVA p=0.04; Dunn's test was not significant). However, we re-analyzed the data with each surgeon's disc grades and found no significant differences in any of the specimen conditions for all three surgeons. Discussion. In the original data analysis, the translation results showed a trend to reduced anterior translation in shear with advancing degeneration only in the facet destabilization condition. These results suggest that shear stiffness of an intact specimen is not affected by overall degeneration, except in the case where the facets are not competent to resist load. In the subsequent data analyses, no significant effects were found. These findings indicate the sensitivity of the analyses to the assignment of disc grade. There are numerous disc grading scales reported in the literature and it is not clear which scale best defines disc degeneration. We are continuing to assess our methods to determine the most appropriate method of defining disc degeneration by disc grade

Summary. Nucleotomy almost doubles the transmitted forces on the facet joints in human lumbar spine, regardless of the amount of removed nucleus pulposus. Introduction. Low back pain involves the lumbar facet joints in 15% to 45% of the cases. The surgical intervention, nucleotomy, might also lead to painful facets with a high risk; however, its mechanism is yet to be fully understood. The aim of this study is to reveal how a small amount of nucleus removal can change the force transmission on the facets. 1.1.1.1 Methods. Nine human lumbar motion segments with a median age of 48 years (interquartile range: 8.3) were tested quasi-statically (0.2 Hz) in extension and flexion (+/−5°) under constant compression loading (700 N). Specimens were tested in vitro by a servo-hydraulic test rig (MTS, USA) equipped with an additional superstructure enabling independent actuation of axial compression, extension-flexion and anterior-posterior shear on the top of the specimen. Forces and moments were measured beneath the specimen. The test method is based on recording intact and nucleotomy performed (range of removed nucleus 0.888–1.708 g) kinematics, which were applied in sequence, at different reduction stages of the same specimen. In the last steps, the facets were the only force transmitting structures, therefore, the load cell beneath the specimen revealed the force transmission on the facets. 1.1.2 Results. The average proportion of force transmitted through the facets increased significantly due to nucleotomy for both an intact capsular ligament (caps. lig.) (p=0.008) from 8.6% (5.2) to 15.8% (6.2), and without a caps. lig. from 8.4% (2.3) to 10.3% (4.9, p = 0.008). Amount of removed nucleus did not show statistically significant correlation to the force increase on facets due to nucleotomy (p>0.19). Forces on the facets were the highest in extension: fully intact 10.7% (6.6), nucleotomy with caps. lig. 19.0% (9.6), intact without caps. lig. 9.37% (3.42), and nucleotomy without caps. lig. 12.6% (6.5). Discussion. Results show, that even a small amount of nucleus removal increase the transmitted forces on facet joints, independent of the amount of removed nucleus. Therefore, a surgeon's decision on the amount of nucleus to remove might perhaps be based on aspects other than facet loading - for example, the avoidance of reherniation. Since facet loading is highest in extension, patients after nucleotomy should perhaps limit this motion as far as possible

Summary

Lumbar spinal specimens exhibited high fatigue strength. The cycles to failure are not only dependent on the maximum peak load, but also on the load offset or the amplitude, respectably.

Designs of medical devices are tested for their mechanical behaviour, ability to transfer the load that is normally bore by the healthy tissue, and prove of the resistance to fatigue. The virtual testing in silico is widely accepted technique based on three sets of input data – geometry is normally obtained from CT or MRI scan as well as the tissue density that is translated into mechanical properties of the tissue. The virtual behaviour of the system is controlled by set of constrains accordingly while the third set of data consist of the load that system normally transfers through the load-bearing tissue. The magnitude and character of the load is highly dependent on the physical activity, external loads, physical condition of the subject and its specific factors such as gender, health condition, etc. Most of the published simulations use estimated simplified loads, which barely simulate the real behaviour of the system. The evaluation of the spinal load published some years back estimated a normal (N) and shear force (S) accompanied by the flexing moment (M). Due to lack of experimental possibility we used these data to test the biomechanical response of the lumbar segment with isotropic material models of all tissues.

Then we investigated the possibility to evaluate muscular forces and their recruitment. It is a complex task and even today it is not possible to measure directly in vivo all muscular forces contributing to the movement. The musculo-skeletal system is a statically indeterminate system. The forces can be solved by means of computational modelling based on the measured trajectories of the body motion and additional optimization functions combined with static equations. The trajectories were recorded by the fast camera system in our motion laboratory and consequently exported into an open simulation software that uses a generic skeleton with around two hundreds muscle fascicles. The skeleton was scaled to correspond to our subject's anthropometric data and further scaling to mock-up the generic vertebrae was performed to eliminate discrepancies between the generic and subject's bones. Once these adjustments were done a kinematics and inverse dynamics modules were engage with selected objective function controlling the muscular recruitment that the max. relative muscular force is as small as possible. The 84 muscular forces acting on the segment were exported to a text file in APDL language and uploaded in the Finite Element (FE) database.

The results of FE analysis were compared to the results obtained earlier using N,S,M load [1]. The comparison between the two models shows that the results of segment's total displacement was reduced by 36 percent compared to initial results. The stress and stress intensity increased six times. The identical model with orthotropic material showed reduced displacement by 80 percent and the stress and stress intensity was reduced by 60 percent compared to initial results.

We performed a biomechanical study on human cadaver spines to determine the effect of three different interbody cage designs, with and without posterior instrumentation, on the three-dimensional flexibility of the spine. Six lumbar functional spinal units for each cage type were subjected to multidirectional flexibility testing in four different configurations: intact, with interbody cages from a posterior approach, with additional posterior instrumentation, and with cross-bracing. The tests involved the application of flexion and extension, bilateral axial rotation and bilateral lateral bending pure moments. The relative movements between the vertebrae were recorded by an optoelectronic camera system. We found no significant difference in the stabilising potential of the three cage designs. The cages used alone significantly decreased the intervertebral movement in flexion and lateral bending, but no stabilisation was achieved in either extension or axial rotation. For all types of cage, the greatest stabilisation in flexion and extension and lateral bending was achieved by the addition of posterior transpedicular instrumentation. The addition of cross-bracing to the posterior instrumentation had a stabilising effect on axial rotation. The bone density of the adjacent vertebral bodies was a significant factor for stabilisation in flexion and extension and in lateral bending

Pedicle screw fixation is an effective and reliable method for achieving stabilization in lumbar degenerative disease. The procedure carries a risk of violating the spinal and neural canal which can lead to nerve injury. This audit examines the accuracy of screw placement using intra-operative image guidance.

Retrospective audit of patients undergoing lumbar pedicle screw fixation using image guidance systems over an 18-month period. Case records were reviewed to identify complications related to screw placement and post-operative CT scans reviewed to study the accuracy of screw position.

Of the 98 pedicle screws placed in 25 patients, pedicle violation occurred in 4 screw placements (4.1%). Medial or inferior breach of the pedicle cortex was seen in 2 screws (2%). Nerve root injury as a consequence of this violation was seen in one patient resulting in irreversible partial nerve root dysfunction. Mean set up time for the guidance system was 42 minutes. The mean operative time was 192 minutes.

Violation of either the medial or inferior pedicle cortex during placement of fixation screws is a rare, but potentially serious complication bearing lasting consequences. Image-guided placement can be helpful and possibly improve accuracy; particularly in patients with distorted spinal anatomy.

Osteoporosis is a common disorder characterized by low bone mass and reduced bone quality that affects the bone strength negatively and leads to increased risk of fracture. Bone mineral density (BMD) has been the standard instrument for the diagnosis of osteoporosis and the determination of fracture risk. Despite the approximation of the bone mass, BMD does not provide information about the bone structure. Trabecular bone score (TBS), which provides an indirect evaluation of skeletal microarchitecture, is calculated from dual X-ray absorptiometry and a simple and noninvasive method that may contribute to the prediction of osteoporotic fractures in addition to the measure of bone density. The goal of this study was to determine the mean TBS values in healthy postmenopausal women and the overall association between TBS and demographic features, bone mineral density of the lumbar spine and femoral neck and bone mineral density to body mass index ratio (BMD/BMI) of the lumbar spine. Fifty-three postmenopausal healthy women participated. The bone mineral density of the lumbar spine and femoral neck were measured dual X-ray absorptiometry. Anteroposterior lumbar spine acquisitions were used to calculate TBS for L1-L4. Age, height, weight, BMI and the ratio of BMD to BMI, which was considered to be a simple tool for assessing fracture risk in especially obese individuals, were calculated. The relationship between TBS and other variables was examined using Spearman's rank correlation coefficients. Mean BMD of the lumbar spine and the femoral neck were 0.945 ± 0.133 and 0.785 ± 0.112 g/cm2, respectively (Table 1). Mean TBS was 1.354 ± 0.107. There was a significant positive moderate correlation between TBS and total lumbar BMD/BMI ratio (r=0.595, pTBS values of postmenopausal women were negatively correlated with age and BMI and positively with bone mineral density and BMD/BMI ratio. The ratio between lumbar BMD and BMI presented a stronger correlation with TBS than that of BMD with TBS. Because of the better correlation, the BMD/BMI ratio may be used as a simple tool for the assessment of the risk of fractures. Further investigation may be needed to evaluate the factors influencing exercise intervention on TBS on this population of patients

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration. A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China. The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%). we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation

Intra-Discal Vacuum Phenomenon (IDVP) represents an intradiscal nitrogen gas accumulation where a cavity opens in a supine position, lowering intra-discal pressure and generating a bubble. IDVP has been observed in up to 20% of elderly patients and reported in almost 50% of chronic LBP patients. With a highly accurate detection on CT, its significance lacks clarity and consideration within normative data. IDVP occurs with patterns of lumbar and/or lumbopelvic morphology and associated diagnoses. Over-60s population based sample of 2020 unrelated CT abdomen scans without acute spinal presentations, with sagittal reconstructions, inclusive of T12 to femoral heads, were analyzed for IDVP and pelvic incidence (PI). Subjects with diagnostic morphological associations of the lumbar spine, including previous fracture, autofusion, transitional vertebra and listhesis, were selected out and analyzed separately. Subjects were then equally grouped into low, medium and high PI. Prevalence of lumbar spine IDVP is 41.3%. 125 cases were excluded. 1603 subjects yielded 663 IDVP. This was increased in severity towards the lumbosacral junction (L1L2 9.4%, L2L3 10.9%, L3L4 13.7%, L4L5 19.9%, L5S1 28.5%) and those with low PI, while distribution was more even with high PI. 292 had positive diagnostic associations, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to lumbosacral transitional vertebra (p<0.05). This study has identified normative values for prevalence and severity of IDVP in a normal aging population. Morphological patterns that influence the pattern of IVDP such as pelvic incidence and diagnostic associations provide novel insights to the function of the aging spine

The pelvic girdle and spine vertebral column work as a long chain influenced by pelvic tilt. Spinal deformities or other musculoskeletal conditions may cause patients to compensate with excessive pelvic tilt, producing alterations in the degree of lumbar lordosis and subsequently causing pain. The objective of this study is to assess the effect of open and closed chain anterior or posterior pelvic tilt on lumbar spine kinematics using an in vitro cadaveric spine model. Three human cadaveric spines with intact pelvis were suspended with the skull fixed in a metal frame. Optotrak 3D motion system tracked real-time coordinates of pin markers on the lumbar spine. A force-torque digital gage applied consistent force to standardize the acetabular or sacral axis’ anterior and posterior pelvic tilt during simulated open and closed chain movements, respectively. In closed chain PPT, significant differences in relative intervertebral compression existed between L1/L2 [-2.54 mm] and L5/S1 [-11.84 mm], and between L3/L4 [-2.78 mm] and L5/S1 [-11.84 mm] [p <.05]. In closed chain APT, significant differences in relative intervertebral decompression existed between spinal levels L1/L2 [2.87mm] and L5/S1[24.48 mm] and between L3/L4 [2.94 mm] and L5/S1 [24.48 mm] [p <.05]. In open chain APT, significant differences in relative intervertebral decompression existed between spinal levels L4/L5 [1.53mm] and L5/S1 [25.14 mm] and between L2/L3 [1.68 mm] and L5/S1 [25.14 mm] [p<.05 for both]. Displacement during closed chain PPT was significantly greater than during open chain PPT, whereas APT showed no significant differences. In PPT, open chain pelvic tilts did not produce as much lumbar intervertebral displacement compared to closed chain. In contrast, APT saw no significant differences between open and closed chain. Additionally, results illustrate the increase in lumbar lordosis during APT and the loss of lordosis during PPT

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576

Abstract. OBJECTIVES. Bone health deterioration is a major public health issue. General guidelines for the limitation of bone loss prescribe a healthy lifestyle and a minimum level of physical activity. However, there is no specific recommendation regarding targeted activities that can effectively maintain lumbar spine bone health. To provide a better understanding of such influencing activities, a new predictive modelling framework was developed to study bone remodelling under various loading conditions. METHODS. The approach is based on a full-body subject-specific musculoskeletal model [1] combined with structural finite element models of the lumbar vertebrae. Using activities recorded with the subject, musculoskeletal simulations provide physiological loading conditions to the finite element models which simulate bone remodelling using a strain-driven optimisation algorithm [2]. With a combination of daily living activities representative of a healthy lifestyle including locomotion activities (walking, stair ascent and descent, sitting down and standing up) and spine-focused activities involving twisting and reaching, this modelling framework generates a healthy bone architecture in the lumbar vertebrae. The influence of spine-focused tasks was studied by adapting healthy vertebrae to an altered loading scenario where only locomotion activities were performed. RESULTS. The spine-focused activities were responsible for 57% of the overall bone mechanical stimulus of the five lumbar vertebrae. Cortical bone maintenance was more influenced by these activities in the superior vertebrae than in the inferior ones, with a stimulus degradation of 74% in L1 against 24% in L5 when adapted to the altered loading scenario. Trabecular bone stimulus degradation varied between 53% and 68%. CONCLUSION. The study suggests that locomotion activities are insufficient to maintain lumbar spine bone health. When appropriate, larger spine movements should be recommended as part of the minimum daily physical activities. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

Lumbar diseases have become a major problem affecting human health worldwide. Conservative treatment of lumbar diseases is difficult to achieve ideal results, and surgical treatment of trauma, complications, it is imperative to develop a new treatment method. This study aims to explore the regulatory mechanism of cartilage endplate ossification caused by abnormal stress, and design intervention targets for this mechanism, so as to provide theoretical reference for the prevention and treatment of lumbar degeneration. In vivo, we constructed spinal instability model in mice. In vitro, we used a mechanical tensile machine to simulate the abnormal stress conditions of the endplate cartilage cells. Through the high-throughput sequencing, we found the enrichment of Hippo signaling pathway. As YAP is a key protein in the Hippo signaling pathway, we then created cartilaginous YAP elimination mice (Col2::YAPfl/fl). The lumbar spine model was constructed again in these mice for H&E, SOFG and immunofluorescence staining. In vitro lentivirus was used to knock out YAP, immunofluorescence staining, WB and qPCR were performed. Finally, we conducted therapeutic experiments by using YAP agonist and AAV5 carrying YAP plasmids. We collected 8w samples from C57/BL6 mice after modeling. We found ossification of the endplate in mice similar to human disc degeneration. High-throughput sequencing of stretched cells demonstrated high enrichment of the Hippo signaling pathway. By immunofluorescence staining, it was confirmed that Col-II decreased and Col-X gradually increased in the endplate cartilage of mice. This was also confirmed at 7 days after an in vitro stretch of 5% and 12%. Meanwhile, we found that cartilaginous YAP elimination mice developed very severe endplate degeneration. However, the endplate was well protected by intraperitoneal injection of YAP agonist or AAV5-YAP endplate injection, and the results in vitro were consistent with that. In the process of cartilaginous ossification, abnormal stress regulates Col10a1 to promote cartilage endplate ossification through Hippo signaling pathway mediated YAP, and we expect to find potential drug targets for treatment through this mechanism

The use of lumbar fusion procedures in the USA and Europe has rapidly increased over the last decade and a large number of these procedures involve the use of bone grafts. Despite of technical progress of spinal surgery and operative materials the risk of vertebral fusion failure occurs in 5 – 35 % of cases. Autografting has been considered the gold standard for bone graft procedures. However, the harvesting from the iliac crest can be associated with short and long-term morbidity in up to 22 % of cases. Main goal of this experimental study was to compare newly developed hybrid biodegradable nanocomposit porous implant (HBNPI) against bone craft from iliac crest as a new and better alternative for lumbar interbody fusion. 24 male pigs 4 months old weighting around 40 Kg were included in our study. These pigs were divided into two study groups depending on fusion method. Group A – 12 pigs underwent lateral lumbal interbody fusion (L2/3) with implantation of iliac crest bonegraft. Group B - 12 pigs underwent lateral lumbal interbody fusion (L2/3) with newly developed HBNPI. Each group were divided into two subgroups from these 6 spines were harvested 8 weeks (subgroup A1, B1) and 6 spines 16 weeks (group A2, B2) after surgery. After sacrifice, the lumbar spines were taking out and micro-CT, biomechanical testing and histomorphological analysis in all groups were performed to evaluate a quality of intervertebral fusion. As controls (group N), 6 cadaveric intact lumbar spines underwent biomechanical, micro-CT and histological testing. All 24 animals recovered from general anesthesia without unusual events. The operations lasted between 50–90 minutes (mean 70) in Group A and between 35–72 minutes (mean 43) in Group B. All of the pigs from group A could stand up and were mobile within 20 hours (range 7–20). When bone graft harvesting was not necessary (group B) this time was shortened, ranging from 1 – 1,5 hour. All pigs from Group A were limping on the first postoperative day. No limping animal was observed in group B. Total body weight of the pigs increased from 37 kg (range 36–40) at the start to 85 (range 80–89) at sacrifice. Biomechanics evaluation shows that extension flexural stiffness values are statistically significantly different between A2 (16 weeks post-implant) and A1 (8 weeks post-implant). Group A2 achieves higher values than Group A1, which is attributed to the adhesion of the implant to the surrounding vertebrae. Similarly, this also applies to groups B2 and B1. The flexural stiffness at group B2 extension is statistically significantly higher than the A2 group and also than the native N group. Biomechanical evaluation supports findings on micro-CT and histological specimens, where both adjacent vertebrae are completely fused in groups B2, unlike in group A2, where there is no or incomplete fusion. Newly developed HBNPI represents new possibility how to do intervertebral fusion, and simultaneous become chance how to improve and accelerate bone healing process against standard procedures

Pelvic bone defect in patients with severe congenital dysplasia of the hip (CDH) lead to abnormalities in lumbar spine and lower limb alignment that can determine total hip arthroplasty (THA) patients' outcome. These variables may be different in uni- or bilateral CDH. We compared the clinical outcome and the spinopelvic and lower limb radiological changes over time in patients undergoing THA due to uni- or bilateral CHD at a minimum follow-up of five years. Sixty-four patients (77 hips) undergoing THA due to severe CDH between 2006 and 2015 were analyzed: Group 1 consisted of 51 patients with unilateral CDH, and group 2, 113 patients (26 hips) with bilateral CDH. There were 32 females in group 1 and 18 in group 2 (p=0.6). The mean age was 41.6 years in group 1 and 53.6 in group 2 (p<0.001). We compared the hip, spine and knee clinical outcomes. The radiological analysis included the postoperative hip reconstruction, and the evolution of the coronal and sagittal spinopelvic parameters assessing the pelvic obliquity (PO) and the sacro-femoro-pubic (SFP) angles, and the knee mechanical axis evaluating the tibio-femoral angle (TFA). At latest follow-up, the mean Harris Hip Score was 88.6 in group 1 and 90.7 in group 2 (p=0.025). Postoperative leg length discrepancy of more than 5 mm was more frequent in group 1 (p=0.028). Postoperative lumbar back pain was reported in 23.4% of the cases and knee pain in 20.8%, however, there were no differences between groups. One supracondylar femoral osteotomy and one total knee arthroplasty were required. The radiological reconstruction of the hip was similar in both groups. The PO angle improved more in group 1 (p=0.01) from the preoperative to 6-weeks postoperative and was constant at 5 years. The SFP angle improved in both groups but there were no differences between groups (p=0.5). 30 patients in group 1 showed a TFA less than 10º and 17 in group 2 (p=0.7). Although the clinical outcome was better in terms of hip function in patients with bilateral CDH than those with unilateral CDH, the improvement in low back and knee pain was similar. Patients with unilateral dysplasia showed a better correction of the PO after THA. All spinopelvic and knee alignment parameters were corrected and maintained over time in most cases five years after THA