Micro-CT data of early physiological cancellous bone formation in the lumbar spine of female C57BL/6 mice.

Micro-CT provides critical data for musculoskeletal research, yielding three-dimensional datasets containing distributions of mineral density. Using high-resolution scans, we quantified changes in the fine architecture of bone in the spine of young mice. This data is made available as a reference to physiological cancellous bone growth. The scans (n = 19) depict the extensive structural changes typical for female C57BL/6 mice pups, aged 1-, 3-, 7-, 10- and 14-days post-partum, as they attain the mature geometry. We reveal the micro-morphology down to individual trabeculae in the spine that follow phases of mineral-tissue rearrangement in the growing lumbar vertebra on a micrometer length scale. Phantom data is provided to facilitate mineral density calibration. Conventional histomorphometry matched with our micro-CT data on selected samples confirms the validity and accuracy of our 3D scans. The data may thus serve as a reference for modeling normal bone growth and can be used to benchmark other experiments assessing the effects of biomaterials, tissue growth, healing, and regeneration.

Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity.

In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding 'queen' status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also upregulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.

Some social animals are highly cooperative creatures that live in tight-knit colonies. Bees and ants are perhaps the most well-known examples of social insects, while Damaraland mole-rats and naked mole-rats, two rodent species found in southern and eastern Africa, are among the most cooperative mammal species. In these colony-forming animals, only one or a few females reproduce and these fertile females are frequently referred to as "queens". When an animal becomes a queen, her body shape can change dramatically to support the demands of high fertility and frequent reproduction. The molecular basis of such changes has been well-described in social insects. However, they are poorly understood in mammals. To address this knowledge gap, Johnston et al. studied how transitioning to queen status affects bone growth and structural integrity in Damaraland mole-rats, as well as body shape and size. The experiments compared non-breeding female mole-rats with other adult females recently paired with a male to become the sole breeder of a new colony. Johnston et al. also used bone-derived cells grown in the laboratory to assess underlying gene regulatory changes in new queen mole-rats. Johnston et al. showed that transitioning to the role of queen leads to a cascade of skeletal changes accompanied by shifts in the regulation of genetic pathways linked to bone growth. Queen mole-rats show accelerated growth in the spinal column of their lower back. These bones are called lumbar vertebrae and this likely allows them to have larger litters. However, queen mole-rats also lose bone growth potential in their leg bones and develop thinner thigh bones, which may increase the risk of bone fracture. Therefore, unlike highly social insects, mole-rats do not seem to have escaped the physical costs of intensive reproduction. This work adds to our understanding of the genes and physical traits that have evolved to support cooperative behaviour in social animals, including differences between insects and mammals. It also shows, with a striking example, how an animal's genome responds to social cues to produce a diverse range of traits that reflect their designated social role.

Physiological variation of the vertebral bone marrow water T2 relaxation time.

The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = -0.429/-0.210 female/male) and for water T2 versus PDFF (r = -0.580/-0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.

Anterior Vertebral Body Growth-Modulation Tethering in Idiopathic Scoliosis: Surgical Technique.

The management of idiopathic scoliosis in the skeletally immature patient can be challenging. Posterior spinal fusion and instrumentation is indicated for severe scoliosis deformities. However, the skeletally immature patient undergoing posterior fusion and instrumentation is at risk for developing crankshaft deformities. Moreover, bracing treatment remains an option for patients who are skeletally immature, and although it was found to be effective, it does not completely preclude deformity progression. Recently, fusionless treatment options, such as anterior vertebral body growth modulation, have been developed to treat these patients while avoiding the complications of posterior rigid fusion. Good results have been shown in recent literature with proper indications and planning in the skeletally immature patient.

Continued vertebral body growth in patients with juvenile idiopathic scoliosis following vertebral body stapling.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To quantitatively measure the rate of growth of vertebral bodies in juvenile idiopathic scoliosis (JIS) treated with vertebral body stapling (VBS). VBS has been suggested to be a safe and effective method for modulating the growth of the young scoliotic spine, but few long-term studies have examined its efficacy. METHODS: Seven patients with JIS 11 years of age or younger underwent VBS with a minimum 6-year follow-up. Vertebral body height on the unstapled and stapled aspects of the curve was measured from initial and final postoperative radiographs and converted into rate of growth per year. Known staple dimensions were used to standardize the measurements between radiographs. Interstaple distance was measured to demonstrate continued growth of the spine. Adjacent vertebral bodies without instrumentation served as an internal control of growth. Each vertebral body (n = 35) was analyzed as an individual experimental unit. RESULTS: The average rate of growth was 0.86 mm/year (standard deviation [SD] 0.44, 95% confidence interval [CI] 0.71-1.0) per vertebral body on the stapled side and 0.83 mm/year (SD 0.46, 95% CI 0.67-0.98) per vertebral body on the unstapled side of the vertebral body. The adjacent vertebral body segments grew at a rate of 0.91 mm/year (SD 0.42, 95% CI 0.66-1.15) on the stapled side and 0.99 mm/year (SD 0.66, 95% CI 0.61-1.37) on the unstapled side, p < 0.01. The distance between staples increased significantly from 3.0 mm (SD 2.0, 95% CI 2.3-3.6) to 8.4 mm (SD 2.4, 95% CI 7.7-9.3). CONCLUSIONS: Vertebral body growth in the presence of VBS occurred at a similar rate on the stapled and unstapled sides of the curve. The high standard deviation of instrumented segment growth further supports the conclusion that VBS is not a reliable method of growth modulation in the young scoliotic spine. LEVEL OF EVIDENCE: IV.

The IMpact of Vertical HIV infection on child and Adolescent SKeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study.

INTRODUCTION: The scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a range of morbidities due to chronic HIV infection and its treatment. Impaired linear growth (stunting) is a common manifestation, affecting up to 50% of children. However, the effect of HIV on bone and muscle development during adolescent growth is not well characterised. Given the close link between pubertal timing and musculoskeletal development, any impairments in adolescence are likely to impact on future adult musculoskeletal health. We hypothesise that bone and muscle mass accrual in CWH is reduced, putting them at risk of reduced bone mineral density (BMD) and muscle function and increasing fracture risk. This study aims to determine the impact of HIV on BMD and muscle function in peripubertal children on ART in Zimbabwe. METHODS AND ANALYSIS: Children with (n=300) and without HIV (n=300), aged 8-16 years, established on ART, will be recruited into a frequency-matched prospective cohort study and compared. Musculoskeletal assessments including dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, grip strength and standing long jump will be conducted at baseline and after 1 year. Linear regression will be used to estimate mean size-adjusted bone density and Z-scores by HIV status (ie, total-body less-head bone mineral content for lean mass adjusted for height and lumbar spine bone mineral apparent density. The prevalence of low size-adjusted BMD (ie, Z-scores <-2) will also be determined. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Medical Research Council of Zimbabwe and the London School of Hygiene and Tropical Medicine Ethics Committee. Baseline and longitudinal analyses will be published in peer-reviewed journals and disseminated to research communities.

Growth pattern of lumbar bone mineral content and trunk muscles in adolescent male soccer players.

INTRODUCTION: Previous studies have reported that the peak in lean body mass (LBM) precedes the peak in bone mineral content (BMC). However, it is unknown whether the trunk region growth is similar. MATERIALS AND METHODS: We investigated the difference between pubertal peak age in the increase of LBM in the trunk (trunk LBM) and pubertal peak age in the increase of BMC in the lumbar spine (lumbar BMC) in a longitudinal study of 201 Japanese male adolescent soccer players. The age of peak height velocity (PHV) and the developmental age were calculated. The participants were followed over a 2-year period, with height and dual-energy X-ray absorptiometry scans taken every 6 months. RESULTS: The trunk LBM (ρ = 0.732, p < 0.0001) and the lumbar BMC (ρ = 0.621, p < 0.0001) significantly correlated with the developmental age. The increase of trunk LBM and lumbar BMC was significantly different according to the developmental stages (Kruskal-Wallis test; p < 0.0001 and p < 0.001, respectively). We used a cubic spline to estimate the developmental age, when the increase reached its peak: the peak age of the increase in trunk LBM was estimated to be - 0.08 years (approximately - 1 month) prior to PHV age, whereas the peak age of the increase in lumbar BMC was estimated to be 0.42 years (approximately 5 months) after the PHV age. CONCLUSIONS: The maximal increase in trunk LBM occurs just before PHV age and approximately 6 months before the maximal increase in lumbar BMC during the pubertal growth spurt in the Japanese adolescent male soccer players.

Lumbar spinal cord neurons putatively involved in ejaculation are sexually dimorphic in early postnatal mice.

A crucial role in ejaculation is thought to be played by a population of lumbar spino-thalamic neurons (LSt), which express galanin and other neuropeptides. In rats, these neurons are activated with ejaculation and their lesion selectively abolishes ejaculation but not other mating behaviors. Consistently with their role, in adult rats and humans, LSt neurons are sexually dimorphic, being more numerous in males. Here we examined whether sexual dimorphism arises early in development, using a transgenic mouse line in which the expression of fluorescent protein is driven by the galanin promoter. We focused on postnatal day 4, shortly after a transient perinatal androgen surge in males that could play an organizational role in LSt development. We found a population of brightly fluorescent neurons organized in bilateral columns dorsolateral to the central canal in segments L1-L5, the expected location of the LSt group. Their number was close to that of adult preparations and significantly greater in male than in female siblings (+19%; CI95% : +13% to +27%; p < .01). This was not due to a generalized higher galanin expression in the male since fluorescent L4 DRG neurons, innervating the hindlimbs and lower back, were not significantly dimorphic (-4%; CI95% : -10% to +8%; p = .92). Unexpectedly, we found in cervical segments a population of fluorescent neurons having a location relative to the central canal similar to the LSt. Thus, the LSt group is sexually dimorphic soon after birth. However, it is possible that only a subset of its neurons participate in the control of ejaculation.

BK ablation attenuates osteoblast bone formation via integrin pathway.

Impaired bone formation is one of the major causes of low bone mass and skeletal fragility that occurs in osteoporosis. However, the mechanisms underlying the defects in bone formation are not well understood. Here, we report that big conductance calcium-activated potassium channels (BKs) are required for bone formation and osteoblast function both in vivo and in vitro. By 15 weeks of age, BK knockout (BKO) mice exhibited a decline in bone mineral density and trabecular bone volume of the tibiae and lumbar vertebrae, which were associated with impaired bone formation and osteoblast activity. Mechanistically, BK ablation in bone and bone marrow mesenchymal stem cells (BMSCs) of BKO mice inhibited integrin signaling. Furthermore, the binding of α subunit of BK with integrin ß1 protein in osteoblasts was confirmed, and FAK-ERK1/2 signaling was proved to be involved by genetic modification of KCNMA1 (which encodes the α subunit of BK) in ROS17/2.8 osteoblast cells. These findings indicated that BK regulates bone formation by promoting osteoblast differentiation via integrin pathway, which provided novel insight into ion transporter crosstalk with the extracellular matrix in osteoblast regulation and revealed a new potential strategy for intervention in correcting bone formation defects.

Differential growth patterns of the abdominal aorta and vertebrae during childhood.

The adult vertebral level of the splanchnic branches of the abdominal aorta relies on a complex series of fusion and regression steps during embryological development, such that variation is common. Little is known however regarding the anatomy of the abdominal aorta in children. This study aimed to investigate the spatial relationship between the abdominal aorta and the vertebral column during childhood development to inform clinical management of pediatric patients. Retrospective multislice computed tomography abdominopelvic angiograms of children aged neonate to 19 years (n = 232) were used to examine vertebral levels of the celiac trunk (CoT), superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and aortic bifurcation (AB) using multiplanar formatting views in OsiriX. The abdominal aorta length, AB angle, and displacement of the aorta from the midline were quantified with the effect of age and sex analyzed using multinomial logistic regression and general linear models. The most frequent origins of CoT, SMA, IMA, and AB were T12, L1, L3, and L4, respectively, with significant variation in vertebral level for each vessel. SMA level was significantly more proximal with age, and CoT and AB demonstrated marked sex differences in vertebral level. As the age of the child increased, AB angle decreased, aortic displacement increased, and the length of the abdominal aorta increased at a slower velocity to the vertebral column (P < 0.001). Our study highlights the variation of the location and geometry of the abdominal aorta in children; this knowledge will positively impact pediatric surgical approaches and endovascular procedures. Clin. Anat. 32:783-793, 2019. © 2019 Wiley Periodicals, Inc.

Normal trabecular vertebral bone is formed via rapid transformation of mineralized spicules: A high-resolution 3D ex-vivo murine study.

At birth, mouse vertebrae have a reticular fine spongy morphology, yet in the adult animal they exhibit elaborate trabecular architectures. Here, we characterize the physiological microstructural transformations in growing young female mice of the widely used C57BL/6 strain. Extensive architectural changes lead to the establishment of mature cancellous bone in the spine. Vertebrae were mapped in 3D by high resolution microcomputed tomography (µCT), backed by conventional histology. Three different phases are observed in the natural bony biomaterial: In a prenatal templating phase, early vertebrae are composed of foamy, loosely-packed mineralized spicules. During a consolidation phase in the first 7 days after birth, bone material condenses into struts and forms primitive trabeculae accompanied by a significant (>50%) reduction in bone volume/tissue volume ratio (BV/TV). After day 7, the trabeculae expand, reorient and increase in mineral density. Swift growth ensues such that by day 14 the young lumbar spine exhibits all morphological features observed in the mature animal. The greatly varied micro-morphologies of normal trabecular bone observed in 3D within a short timespan are typical for rodent and presumably for other mammalian forming spines. This suggests that fully structured cancellous bone emerges through rapid post-natal restructuring of a foamy mineralized scaffold. STATEMENT OF SIGNIFICANCE: Cancellous bone develops in stages that are not well documented. Using a mouse model, we provide an observer-independent quantification of normal bone formation in the spine. We find that within 14 days, the cancellous bone transforms in 3 phases from a scaffold of spicules into well organized, fully mineralized trabeculae in a functional spine. Detailed knowledge of the physiological restructuring of mineralized material may help to better understand bone formation and may serve as a blueprint for studies of pharmaceuticals effects, tissue healing and regeneration.

Integrating Growth Variability of the Ilium, Fifth Lumbar Vertebra, and Clavicle with Multivariate Adaptive Regression Splines Models for Subadult Age Estimation.

Subadult age estimation should rely on sampling and statistical protocols capturing development variability for more accurate age estimates. In this perspective, measurements were taken on the fifth lumbar vertebrae and/or clavicles of 534 French males and females aged 0-19 years and the ilia of 244 males and females aged 0-12 years. These variables were fitted in nonparametric multivariate adaptive regression splines (MARS) models with 95% prediction intervals (PIs) of age. The models were tested on two independent samples from Marseille and the Luis Lopes reference collection from Lisbon. Models using ilium width and module, maximum clavicle length, and lateral vertebral body heights were more than 92% accurate. Precision was lower for postpubertal individuals. Integrating punctual nonlinearities of the relationship between age and the variables and dynamic prediction intervals incorporated the normal increase in interindividual growth variability (heteroscedasticity of variance) with age for more biologically accurate predictions.

Predicted final spinal height in patients with adolescent idiopathic scoliosis can be achieved by surgery regardless of maturity status.

AIMS: The aim of this study was to investigate the impact of maturity status at the time of surgery on final spinal height in patients with an adolescent idiopathic scoliosis (AIS) using the spine-pelvic index (SPI). The SPI is a self-control ratio that is independent of age and maturity status. PATIENTS AND METHODS: The study recruited 152 female patients with a Lenke 1 AIS. The additional inclusion criteria were a thoracic Cobb angle between 45° and 70°, Risser 0 to 1 or 3 to 4 at the time of surgery, and follow-up until 18 years of age or Risser stage 5. The patients were stratified into four groups: Risser 0 to 1 and selective fusion surgery (Group 1), Risser 0 to 1 and non-selective fusion (Group 2), Risser 3 to 4 and selective fusion surgery (Group 3), and Risser 3 to 4 and non-selective fusion (Group 4). The height of spine at follow-up (HOSf) and height of pelvis at follow-up (HOPf) were measured and the predicted HOS (pHOS) was calculated as 2.22 (SPI) × HOPf. One-way analysis of variance (ANOVA) was performed for statistical analysis. RESULTS: Of the 152 patients, there were 32 patients in Group 1, 27 patients in Group 2, 48 patients in Group 3, and 45 patients in Group 4. Significantly greater HOSf was observed in Group 3 compared with Group 1 (p = 0.03) and in Group 4 compared with Group 2 (p = 0.02), with similar HOPf (p = 0.75 and p = 0.83, respectively), suggesting that patients who undergo surgery at Risser grade of 0 to 1 have a shorter spinal height at follow-up than those who have surgery at Risser 4 to 5. HOSf was similar to pHOS in both Group 1 and Group 2 (p = 0.62 and p = 0.45, respectively), indicating that undergoing surgery at Risser 0 to 1 does not necessarily affect final spinal height. CONCLUSION: This study shows that fusion surgery at Risser 0 may result in growth restriction unlike fusion surgery at Risser 3 to 4. Despite such growth restriction, AIS patients could reach their predicted or 'normal' spinal height after surgery regardless of baseline maturity status due to the longer baseline spinal length in AIS patients and the remaining growth potential at the non-fusion levels. Cite this article: Bone Joint J 2018;100-B:1372-6.

[Growth Guidance System in Treatment of Early Onset Scoliosis]. / Systémy usmernovaného rustu v lécbe raných detských skolióz.

PURPOSE OF THE STUDY The Growth Guidance System (GGS) represent a relatively new alternative to the traditional growing systems used for the treatment of early onset scoliosis. Ranking among the main aims of this surgical treatment is a three-dimensional correction of the deformity, maintenance of spinal growth and postponement of the necessity of final treatment by spondylodesis. MATERIAL AND METHODS Our study retrospectively evaluates the results of surgical correction in a group of 35 patients treated by GGS technique. The group consisted of patients with idiopathic, neuromuscular and syndromic spine deformity with the average age of 8 years and 2 months at the time of the surgery. The time of the follow-up is 3 years and 5 months on average. We evaluated the correction of the curve itself, the growth of the spine measured in the thoracic and lumbar part separately, and the growth of the trunk as a whole in the mentioned range on X-ray pictures. RESULTS The average correction of the scoliotic curve was 67%, from 75 preoperative degrees to 20 postoperative degrees. After the first operation 11% elongation of the trunk (from 321 mm to 356 mm) was reached, the thoracic spine was elongated by 10% (from 196 to 217 mm) and the lumbar spine was elongated by 11% (from 125 to 139 mm). The elongation of the trunk by 16% (from 322 to 375 mm) was observed in the cohort of patients with two years postoperative follow-up (21 patients). The total protraction of the trunk by 21% (from 318 to 386 mm) was reached in patients treated by definitive fusion (7 patients). DISCUSSION There is a very low number of studies analysing the long-term clinical results with the use of GGS. The first pilot results indicate that it is a technique allowing to achieve at least comparable results in correction of frontal plane compared with the distraction type of instrumentations. A negative aspect of this method is the abrasion of metal followed by metallosis. The new types of fixation screws enable more effective sliding of rods, maintenance of continuity of body grow by the shifting of rods as well as lower abrasion of the instrumentation. CONCLUSIONS The main advantage of GGS is the limited continuous growth of the spine, partial three-dimensional correction of the deformity, minimisation of inevitable reoperations under general anaesthesia and the possibility to quit a brace. Key words: growth guided system, early onset scoliosis, distraction, spinal growth, spondylodesis.

Changes in human intervertebral disc biochemical composition and bony end plates between middle and old age.

OBJECTIVE: This study evaluates molecular, nutritional and biochemical alterations in human intervertebral discs between middle and old age. METHODS: Twenty-eight human lumbar intervertebral discs from donors were evaluated and separated into two groups: Middle-aged (35-50 years old, relatively non-degenerate discs of Pfirrmann grades 1-3, n = 15) and Old-aged (≥80 years old, all degenerate Pfirrmann grade 4 or 5, n = 13). Parameters which might be expected to to be related to nutrient supply and so the health of disc cells (eg the porosity of the vertebral endplate, cell viability and cell density) and to disc extracellular composition (ie quantification of glycosaminoglycan disaccharides and hyaluronic acid molecular weight) and collagen organization, were analyzed. Three regions of the intervertebral disc (anterior annulus fibrosus, nucleus pulposus, and posterior annulus fibrosus) were examined. RESULTS: The old-aged group showed a decrease in content of sulphated and non-sulphated glycosaminoglycans relative to middle-aged and there were also alterations in the proportion of GAG disaccharides and a decrease of collagen fiber size. Hyaluronic acid molecular weight was around 200 kDa in all regions and ages studied. The anterior annulus differed from the posterior annulus particularly in relation to cell density and GAG content. Additionally, there were changes in the bony endplate, with fewer openings observed in the caudal than cranial endplates of all discs in both groups. CONCLUSIONS: Results show the cranial vertebral endplate is the main vascular source for the intervertebral discs. Hylauronic acid molecular weight is the same through the intervertebral disc after age of 50 years.

Contribution of Lateral Decubitus Positioning and Cable Tensioning on Immediate Correction in Anterior Vertebral Body Growth Modulation.

STUDY DESIGN: Computational simulation of lateral decubitus and anterior vertebral body growth modulation (AVBGM). OBJECTIVES: To biomechanically evaluate lateral decubitus and cable tensioning contributions on intra- and postoperative correction. SUMMARY OF BACKGROUND DATA: AVBGM is a compression-based fusionless procedure to treat progressive pediatric scoliosis. During surgery, the patient is positioned in lateral decubitus, which reduces spinal curves. The deformity is further corrected with the application of compression by cable tensioning. Predicting postoperative correction following AVBGM installation remains difficult. METHODS: Twenty pediatric scoliotic patients instrumented with AVBGM were recruited. Three-dimensional (3D) reconstructions obtained from calibrated biplanar radiographs were used to generate a personalized finite element model. Intraoperative lateral decubitus position and installation of AVBGM were simulated to evaluate the intraoperative positioning and cable tensioning (100 / 150 / 200 N) relative contribution on intra- and postoperative correction. RESULTS: Average Cobb angles prior to surgery were 56° ± 10° (thoracic) and 38° ± 8° (lumbar). Simulated presenting growth plate's stresses were of 0.86 MPa (concave side) and 0.02 MPa (convex side). The simulated lateral decubitus reduced Cobb angles on average by 30% (thoracic) and 18% (lumbar). Cable tensioning supplementary contribution on intraoperative spinal correction was of 15%, 18%, and 24% (thoracic) for 100, 150, and 200 N, respectively. Simulated Cobb angles for the postoperative standing position were 39°, 37°, and 33° (thoracic) and 30°, 29°, and 28° (lumbar), respectively, whereas growth plate's stresses were of 0.54, 0.53, and 0.51 MPa (concave side) and 0.36, 0.53, and 0.68 MPa (convex side) for the three tensions. CONCLUSION: The majority of curve correction was achieved by lateral decubitus positioning. The main role of the cable was to apply supplemental periapical correction and secure the intraoperative positioning correction. Increases in cable tensioning furthermore rebalanced initially asymmetric compressive stresses. This study could help improve the design of AVBGM by understanding the contributions of the surgical procedure components to the overall correction achieved. LEVEL OF EVIDENCE: Level III.

Expression profiles of MicroRNAs from multiple lumbar spine in sheep.

The formation of the spine is a critical stage of mammalian development. The increase of the number of individual axons affects its performance, especially in meat production. To understand the role of miRNAs in sheep vertebrae development, the purpose of this article is to screen candidate microRNAs (miRNAs) associated with sheep spine development. MicroRNAs (miRNAs) are a rich family of small regulatory RNAs that negatively regulate gene expression at the post-transcriptional level. In this study, we used high-throughput sequencing techniques to analyze the microRNAs (miRNAs) expression profiles of L6 (6 lumbar vertebrae) and L7 (7 lumbar vertebrae) in sheep. A total number of 223 miRNAs were detected in the two libraries, and a total of 150 and 148 conserved miRNAs were obtained in L6 and L7, respectively. A total of 5 miRNAs expression differences in L6 compared to L7 (P < 0.05). Of the five obviously differently expressed miRNAs, four miRNAs were down-regulated in the L6 of sheep, and one was up-regulated. In order to further explore the functions of these miRNAs, we predicted the target genes of these differently expressed miRNAs, and obtained 1298 target genes. At the same time, NDRG2 gene, targeted by novel miR-391, which possible plays an important role in the development of the spine. Linkage-integration analysis method was used to construct the interaction network of spinal-associated miRNA and its hypothesized target. In summary, this study provides valuable resources for the transcriptome of multiple vertebral traits in sheep.

Sagittal plane parameters in growing rod patients following final fusion.

Almost half of growing rod (GR) patients that undergo final fusion (FF) have an extension of instrumented levels. The purpose of this study was to review sagittal plane radiographic parameters of patients with distal extension of instrumented levels at FF to those whose levels remained the same. Radiographs were assessed preoperatively, after GR insertion/first lengthening, following GR treatment before FFs, and after FF. Measurements included sagittal balance, lumbar lordosis, thoracic kyphosis, and distal junction angle (DJA). Twenty-one patients were included. There was no change in sagittal balance. There was a significant decrease in lordosis and kyphosis following initial GR implantation. Kyphosis and lordosis increased during the GR period, but remained unchanged at time of FF. DJA increased 8° on average. Seven patients had distal extension of instrumented levels at time of FF (average 2 levels, range: 1-4). Indication for distal extension was sagittal plane decompensation in four cases. When comparing patients who had distal extension at the time of FF to those whose levels remained the same, there was no difference in the change in sagittal balance, lordosis, or kyphosis. Final DJA was significantly smaller in those patients with distal extension. Most GR patients that undergo FF demonstrate acceptable correction of sagittal plane radiographic parameters. A small cohort of patients requires distal extension at FF due to sagittal plane decompensation. LEVEL OF EVIDENCE: Level IV, Therapeutic.

Growth Patterns of the Neurocentral Synchondrosis (NCS) in Immature Cadaveric Vertebra.

STUDY DESIGN: Gross anatomic study of osteological specimens. OBJECTIVES: To evaluate the age of closure for the neurocentral synchondrosis (NCS) in all 3 regions of the spine in children aged 1 to 18 years old. SUMMARY OF BACKGROUND DATA: The ossification of the human vertebra begins from a vertebral body ossification center and a pair of neural ossification centers located within the centrum called the NCS. These bipolar cartilaginous centers of growth contribute to the growth of the vertebral body, spinal canal, and posterior elements of the spine. The closure of the synchondroses is dependent upon location of the vertebra and previous studies range from 2 to 16 years of age. Although animal and cadaveric studies have been performed regarding NCS growth and early instrumentation's effect on its development, the effects of NCS growth disturbances are still not completely understood. METHODS: The vertebrae of 32 children (1 to 18 y old) from the Hamann-Todd Osteological collection were analyzed (no 2 or 9 y old specimens available). Vertebrae studied ranged from C1 to L5. A total of 768 vertebral specimens were photographed on a background grid to allow for measurement calibration. Measurements of the right and left NCS, pedicle width at the NCS, and spinal canal area were taken using Scandium image-analysis software (Olympus Soft Imaging Solutions, Germany). The percentage of the growth plate still open was found by dividing the NCS by the pedicle width and multiplying by 100. Data were analyzed with JMP 11 software (SAS Institute Inc., Cary, NC). RESULTS: The NCS was 100% open in all 3 regions of the spine in the 1- to 3-year age group. The cervical NCS closed first with completion around 5 years of age. The lumbar NCS was nearly fully closed by age 11. Only the thoracic region remained open through age 17 years. The left and right NCS closed simultaneously as there was no statistical difference between them. In all regions of the spine, the NCS appeared to close sooner in males than in females. Spinal canal area increased with age up to 12 years old in the cervical and thoracic spine but did not significantly change after age 3 in the lumbar spine. CONCLUSIONS: In conclusion, closure of the NCS differed among the cervical, thoracic, and lumbar spine regions. The NCS reached closure in males before females even though females mature faster and reach skeletal maturity sooner than males. However, it is not determined whether the continued open NCS in females to a later age may be a factor in their increased rate of scoliosis.

3D correction over 2years with anterior vertebral body growth modulation: A finite element analysis of screw positioning, cable tensioning and postoperative functional activities.

BACKGROUND: Anterior vertebral body growth modulation is a fusionless instrumentation to correct scoliosis using growth modulation. The objective was to biomechanically assess effects of cable tensioning, screw positioning and post-operative position on tridimensional correction. METHODS: The design of experiments included two variables: cable tensioning (150/200N) and screw positioning (lateral/anterior/triangulated), computationally tested on 10 scoliotic cases using a personalized finite element model to simulate spinal instrumentation, and 2years growth modulation with the device. Dependent variables were: computed Cobb angles, kyphosis, lordosis, axial rotation and stresses exerted on growth plates. Supine functional post-operative position was simulated in addition to the reference standing position to evaluate corresponding growth plate's stresses. FINDINGS: Simulated cable tensioning and screw positioning had a significant impact on immediate and after 2years Cobb angle (between 5°-11°, p<0.01). Anterior screw positioning significantly increased kyphosis after 2years (6°-8°, p=0.02). Triangulated screw positioning did not significantly impact axial rotation but significantly reduced kyphosis (8°-10°, p=0.001). Growth plates' stresses were increased by 23% on the curve's convex side with cable tensioning, while screw positioning rather affected anterior/posterior distributions. Supine position significantly affected stress distributions on the apical vertebra compared to standing position (respectively 72% of compressive stresses on convex side vs 55%). INTERPRETATION: This comparative numerical study showed the biomechanical possibility to adjust the fusionless instrumentation parameters to improve correction in frontal and sagittal planes, but not in the transverse plane. The convex side stresses increase in the supine position may suggest that growth modulation could be accentuated during nighttime.