Vertebral Growth Research Articles

Magnetically controlled growing rods increase 3D true spine length in idiopathic early onset scoliosis patients: results from a multicenter study.

To determine, at 2year follow-up, 3D spine growth for idiopathic early onset scoliosis (iEOS) patients treated with magnetically controlled growing rods (MCGR). From an international EOS registry, patients with iEOS treated with MCGR were identified. Scoliosis, kyphosis, traditional coronal height, and 3D true spine length (3D-TSL) were measured pre-index surgery, post-index, and at 2year follow-up. 135 participants, mean age 8.1years (2.7-15.6) were included. Scoliosis improved from 71° pre-index to 41° post-index (p < 0.001) and remained constant at 2years (43°, p = 0.58). Kyphosis improved from 49° to 36° (p < 0.001); then increased by 2years to 42° (p = 0.002). Traditional T1-S1 height, which reflects both spine growth and changes in deformity, increased from pre-index to post-index (274mm vs. 310mm; p < 0.001), and again at 2years (332mm, p < 0.001). As 3D-TSL reflects growth of the spine, independent of changes in deformity, as expected it did not change perioperatively (335mm vs. 339mm, p = 0.83), but significantly changed by 2years (367mm; p < 0.001). Participants < 5years at surgery increased 22mm (8.2%), 5-10years increased 26mm (7.8%), and > 10 increased 41mm (11.0%). For instrumented levels, mean vertebral growth was 1.3mm/level for < 5years, 1.4mm/level for 5-10years, and 2.2mm/level for > 10years. As kyphosis increased over time, these out of the coronal plane changes justify the use of 3D-TSL for this cohort of patients. For idiopathic EOS patients treated with MCGR, 3D spine length increased by 28mm during the 2year post-operative period.

Cellular and molecular mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas.

Despite the functional importance of the vertebral skeleton, little is known about how individual vertebrae elongate or achieve disproportionate lengths as in the giraffe neck. Rodent tails are an abundantly diverse and more tractable system to understand mechanisms of vertebral growth and proportion. In many rodents, disproportionately long mid-tail vertebrae form a 'crescendo-decrescendo' of lengths in the tail series. In bipedal jerboas, these vertebrae grow exceptionally long such that the adult tail is 1.5x the length of a mouse tail, relative to body length, with four fewer vertebrae. How do vertebrae with the same regional identity elongate differently from their neighbors to establish and diversify adult proportion? Here, we find that vertebral lengths are largely determined by differences in growth cartilage height and the number of cells progressing through endochondral ossification. Hypertrophic chondrocyte size, a major contributor to differential elongation in mammal limb bones, differs only in the longest jerboa mid-tail vertebrae where they are exceptionally large. To uncover candidate molecular mechanisms of disproportionate vertebral growth, we performed intersectional RNA-Seq of mouse and jerboa tail vertebrae with similar and disproportionate elongation rates. Many regulators of posterior axial identity and endochondral elongation are disproportionately differentially expressed in jerboa vertebrae. Among these, the inhibitory natriuretic peptide receptor C (NPR3) appears in multiple studies of rodent and human skeletal proportion suggesting it refines local growth rates broadly in the skeleton and broadly in mammals. Consistent with this hypothesis, NPR3 loss of function mice have abnormal tail and limb proportions. Therefore, in addition to genetic components of the complex process of vertebral evolution, these studies reveal fundamental mechanisms of skeletal growth and proportion.

7598 A Humanized PTH Receptor Mouse Model Of Eiken Syndrome: Delayed Bone Mineralization Caused By A Receptor C-tail Truncation

Abstract Disclosure: J. Höppner: None. P. Hanna: None. M.N. Wein: None. H. Jueppner: None. T.J. Gardella: None. R. Civitelli: None. I.A. Portales-Castillo: None. Abstract The parathyroid hormone receptor-1 (PTH1R) plays a key role in bone development and acts in the growth plates in response to PTHrP ligand. Eiken syndrome is characterized by a delay in bone mineralization and is caused by homozygous PTH1R mutations. One such mutation, R485X, truncates the receptor's C-tail and removes serine phosphorylation sites involved in βarrestin binding. In HEK293 cells, R485X-hPTH1R exhibits deficient interaction with βarrestin and increased cAMP signaling both basally and in response to PTHrP (Portales-Castillo et al., Comms. Biology 2023). To understand how the R485X mutation causes delayed bone mineralization, we generated humanized R485X-hPTH1R knock-in mice. Homozygous hPTH1RR485X/R485X mice closely recapitulate the delayed bone mineralization seen in Eiken patients, as skeletal whole mount preparations from neonatal mutant mice showed reduced Alizarin red staining compared to WT controls, and metatarsal explants from the mutant mice showed a pronounced absence of mineralized bone. Tails of hPTH1RR485X/R485X mice were ∼50% shorter than those of WT littermates, and H&amp;E-stained sections revealed only proliferative chondrocytes in the growth plates of mutant mice. This delay in growth plate chondrocyte maturation in hPTH1RR485X/R485X mice resolved with age, although older long bones and tails remained smaller in size than WT controls (Höppner et al. Presented at ASBMR 2023).Based on our in vitro findings and initial mouse characterization, we reasoned that the phenotype of Eiken mice may be explained by increased PTHrP/PTH1R signaling in growth plate chondrocyte. The class IIa histone deacetylase HDAC4 suppresses chondrocyte maturation downstream of PTH1R signaling. Therefore, we generated compound mutant mice bearing both Hdac4 deletion and the mutant R485X PTH1R allele. Indeed, Hdac4 deletion largely rescued the mineralization defect apparent in metatarsals of P1 hPTH1RR485X/R485X mice. We then assessed the contribution of endogenous PTHrP to the Eiken-like phenotype by generating hPTH1RR485X/R485X/PTHrPflox/+/Col2-Cre(tg) mice. Remarkably, these mice exhibit approximately the same tail lengths as hPTH1R-WT littermate controls, indicating that reduced PTHrP production can rescue the effects of homozygosity for R485X-PTH1R. In line, vertebral growth plates of the rescued mice exhibited normal zones of chondrocytes, including hypertrophic cells. The overall results support a disease mechanism for Eiken syndrome by which excess cAMP signaling by PTH1R-R485X, as induced in part by endogenous PTHrP, results in delayed chondrocyte differentiation and bone mineralization. Further studies employing βarr1/2-KO mice may help shed light on the specific roles of βarrestins in growth plate development by PTH1R in Eiken syndrome. Presentation: 6/3/2024

Assessment of age-dependent sexual dimorphism in paediatric vertebral size and density using a statistical shape and statistical appearance modelling approach

This work focuses on the growth patterns of the human fourth lumbar vertebra (L4) in a paediatric population, with specific attention to sexual dimorphism. The study aims to understand morphological and density changes in the vertebrae through age-dependent statistical shape and statistical appearance models, which can describe full three-dimensional anatomy. Results show that the main growth patterns are associated with isotropic volumetric vertebral growth, a decrease in the relative size of the vertebral foramen, and an increase in the length of the transverse processes. Moreover, significant sexual dimorphism was demonstrated during puberty. We observe significant age and sex interaction in the anterior vertebral body height (P = 0.005), where females exhibited an earlier increase in rates of vertebral height evolution. Moreover, we also observe an increase in cross-sectional area (CSA) with age (P = 0.020), where the CSA is smaller in females than in males (significant sex effect P = 0.042). Finally, although no significant increase in trabecular bone density with age is observed (P = 0.363), a trend in the statistical appearance model suggests an increase in density with age.

Three-dimensional fiber patterning in the annulus fibrosus can be derived from vertebral endplate topography.

The annulus fibrosus (AF) of the Intervertebral disc (IVD) is composed of concentric lamellae of helically wound collagen fibers. Understanding the spatial variation of collagen fiber orientations in these lamellae, and the resulting material anisotropy, is crucial to predicting the mechanical behavior of the complete IVD. This study builds on a prior model predicated on path-independent displacement of fiber endpoints during vertebral body growth to predict a complete, three-dimensional annulus fibrosus fiber network from a small number of subject-independent input parameters and vertebral endplate topographies obtained from clinical imaging. To evaluate the model, it was first fit to mid-plane fiber orientations obtained using polarized light microscopy in a population of bovine caudal discs for which computed tomography images vertebral endplates were also available. Additionally, the model was used to predict the trajectories based on human lumbar disc geometries and results were compared to previously reported data. Finally, the model was employed to investigate potential disc-related variations in fiber angle distributions. The model was able to accurately predict experimentally measured fiber distributions in both bovine and human discs using only endplate topography and three input parameters. Critically, the model recapitulated previously observed asymmetry between the inclinations of right- and left-handed fibers in the posterolateral aspect of the human AF. Level to level variation of disc height and aspect ratio in the human lumbar spine was predicted to affect absolute values of fiber inclination, but not this asymmetry. Taken together these results suggest that patient-specific distributions of AF fiber orientation may be readily incorporated into computational models of the spine using only disc geometry and a small number of subject-independent parameters.

Growth modulation response in vertebral body tethering depends primarily on magnitude of concave vertebral body growth

PurposeThere is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT.MethodsA multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years.ResultsFifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p < 0.001), 3D spine length growth (r = 0.36, p = 0.008), and decreased convex disc height (r = − 0.42, p = 0.002). High modulators (patients experiencing GM > 10°) experienced an additional 1.6 mm (229% increase) of mean concave vertebra growth during study period compared to the Poor Modulators (GM < − 10°) group, (2.3 vs. 0.7 mm, p = 0.039), while convex vertebra height growth was similar (1.3 vs. 1.4 mm, p = 0.91).ConclusionWhen successful, VBT enables asymmetric vertebra body growth, leading to continued postoperative coronal angulation correction (GM). A strong GM response is correlated with concave vertebral body height growth and overall instrumented spine growth. A poor GM response is associated with an increase in convex disc height (suspected tether rupture). Future studies will investigate the patient and technique-specific factors that influence increased growth remodeling.

Pediatric Solid-State 3D Models of Lumbar Vertebrae and Spine.

Introduction While various 3D vertebral models have been utilized in numerous studies, there is a notable gap in the representation of pediatric lumbar vertebrae and spine. This study aimed to describe the changing shapes of lumbar vertebrae and spine with age and to develop precise 3D models. Materials and methods Solid-state 3D models of pediatric lumbar vertebrae and spine were created using SOLIDWORKS® Simulation softwarefor five age groups:newborns, infants (ages 0-1), toddlers (ages 1-3), middle childhood (ages 4-7), and preadolescents (ages 8-12). Models were composed of components with varying biomechanical characteristics. Results Created 3D models replicate variations in the dimensions and configurations of vertebrae, taking into account osteometric analyses conducted on actual vertebral specimens. These models also include elements made of cartilage, representing various phases of vertebral growth during ontogeny. Additionally, through 3D parametric design, we developed comprehensive lumbar spine models, incorporating both the vertebrae and intervertebral disks. Conclusion Created pediatric solid-state vertebral 3D models can be utilized in developing virtual or augmented reality applications and for medical research. Users can interact with models, allowing virtual exploration and manipulation, enhancing learning experiences and facilitating a better understanding of spatial relationships. These solid-state 3D models allow finite element analysis and can be used for further research to calculate internal relative deformations and stress distribution under different conditions.

Differential vertebral body growth is maintained after vertebral body tethering surgery for idiopathic scoliosis: 4-year follow-up on 888 peri-apical vertebrae and 592 intervertebral discs.

To radiographically evaluate if vertebral body tethering (VBT) can maintain differential peri-apical vertebral growth at medium-term follow-up of 4years. A prospective, international, multicenter database was queried to identify idiopathic scoliosis patients treated with thoracic VBT. Concave vs. convex vertebral body height, vertebral wedging, and disc wedging of the 3 peri-apical vertebrae were measured by two independent observers at 5 timepoints (pre-operative to 4-year follow-up). 65 skeletally immature patients (60 female, mean 12.8years old, 21 with open triradiate cartilages) met inclusion criteria. Mean pre-operative maximum scoliosis of 50 ± 8° decreased significantly post-operatively to 27 ± 9° (p < 0.001), which remained stable at 4-year follow-up 30 ± 17° (p = 0.38 vs. post-operative). Mean instrumented scoliosis was 21 ± 14° at 4-year follow-up, which was significantly different than 4-year maximum scoliosis (p < 0.001). Mean pre-operative kyphosis of 30 ± 12° did not significantly change post-operatively (p = 1.0) and remained stable at 4-year follow-up (35 ± 18°; p = 0.05). Mean individual convex vertebral height increased from 17.7 ± 1.9mm to 19.8 ± 1.5mm (p < 0.001), while mean individual concave height increased from 14.8 ± 1.9mm to 17.6 ± 1.6mm (p < 0.001). Summing the peri-apical heights, the difference in height from pre-operative to 4-year follow-up was greater on the concave (8.3 ± 4.7mm) than on the convex side (6.2 ± 4.7mm) (p < 0.001). Mean individual vertebral wedging decreased from 6 ± 2° at pre-operative to 4 ± 2° at 4-year follow-up (p < 0.001). Mean total vertebral and disc wedging started at 29 ± 7° pre-operatively, decreased to 16 ± 6° at post-operative (p < 0.001), then further decreased to 14 ± 8° at 4-year follow-up (p < 0.001). Patients with open triradiate cartilages at the time of surgery had a larger height change over the 4years compared to those with closed triradiate cartilages (p < 0.001). Patients with idiopathic scoliosis treated with VBT demonstrated differential vertebral growth which was maintained at minimum 4-year follow-up. This effect was more pronounced in patients whose triradiate cartilages were open at the time of surgery. III.

Are the Spinal Changes in the Course of Scoliogeny Primary but Secondary?

In this opinion article, there is an analysis and discussion regarding the effects of growth on the spinal and rib cage deformities, the role of the rib cage in scoliogeny, the lateral spinal profile in adolescent idiopathic scoliosis (AIS), the genetics and epigenetics of AIS, and the interesting and novel field investigating the sleep impact at nighttime on AIS in relation to the sequence of the scoliogenetic changes in scoliotics. The expressed opinions are mainly based on the published peer-reviewed research of the author and his team of co-authors. Based on the analysis noted above, it can be postulated that the vertebral growth changes in the spine during initial idiopathic scoliosis (IS) development are not primary-intrinsic but secondary changes. The primary cause starting the deformity is not located within the vertebral bodies. Instead, the deformations seen in the vertebral bodies are the secondary effects of asymmetrical loads exerted upon them, due to muscular loads, growth, and gravity.

Abstract 3339: TTFields for the management of spinal metastases in in vitro and in vivo models

Abstract Spine metastases often affect cancer patients, leading to significant morbidity and mortality. Their prevalence has increased over time due to the progressive improvements in cancer management which led to a longer survival of these individuals. Radiation therapy is the mainstay treatment for local control of these lesions, with surgery reserved for selected cases (e.g., spinal instability, neurological deficits secondary to neural compression requiring urgent decompression, separation surgery). Chemotherapy addresses the diffusely metastatic spread. However, when spinal metastases progress despite using all the appropriate available treatment, there follows a progressive decline in function and further treatment options are limited, highlighting the need for development of novel therapies. Tumor treating fields (TTFields) has demonstrated to impair tumor cell replication and are influenced by surrounding tissue, such as bone (presents non-conductive properties). Our goal was to investigate the effects of TTFields in in vitro and in vivo spinal metastasis models. We hypothesize that the deposition of TTFields is increased in bone, and this would ultimately result in vertebral metastasis growth suppression. A computational model using a simulated spine resection cavity with metallic hardware was used to investigate the TTFields intensity in various tissues. For in vitro studies, luciferase tagged KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized human bone graft. These were treated with TTFields and cell viability was quantified. In vivo assays were performed using a previous validated murine orthotopic tumor model. The effects of TTFields in these animals were monitored with imaging (bioluminescence and MRI) and clinical findings (progressive neurological deficits milestones that corresponds to the degree of spinal cord compression). At the end of the study, tissue was collected for histologic analysis. Sham stimulation was used for control groups. Computational simulation demonstrated an elevated TTFields intensity in the tumor-bone interface of the resected vertebral body. In all experimental models, TTFields significantly suppressed tumor cell growth. In vivo models, this effect on cell proliferation prevented tumor growth into the spinal canal, delaying, or even preventing, neurological deficits. TTFields inhibited tumor growth in three-dimensional cultures and orthotopic murine models of spinal metastases, preventing functional loss. The bony environment surrounding the tumor demonstrated to enhance the intensity of electric fields on a computational simulation, which stands as an advantage with the use of TTFields for vertebral tumors. These results provide solid evidence supporting future clinical trials investigating the effects of this novel and promising technology for the treatment of spine metastases. Citation Format: Romulo Augusto Andrade de Almeida, Daniel Ledbetter, Xizi Wu, Ariel Naveh, Chirag Patel, Queena Gonzalez, Thomas H. Beckham, Robert Y. North, Laurence Rhines, Christopher A. Alvarez-Breckenridge, Claudio E. Tatsui. TTFields for the management of spinal metastases in in vitro and in vivo models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3339.

A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc.

Interactions between notochord and sclerotome are required for normal embryonic spine patterning, but whether the postnatal derivatives of these tissues also require interactions for postnatal intervertebral disc (IVD) growth and maintenance is less established. We report here the comparative analysis of four conditional knockout mice deficient for TonEBP, a transcription factor known to allow cells to adapt to changes in extracellular osmotic pressure, in specific compartments of the IVD. We show that TonEBP deletion in nucleus pulposus (NP) cells does not affect their survival or aggrecan expression, but promoted cell proliferation in the NP and in adjacent vertebral growth plates (GPs). In cartilage end plates/GPs, TonEBP deletion induced cell death, but also structural alterations in the adjacent NP cells and vertebral bodies. Embryonic or postnatal TonEBP loss generated similar IVD changes. In addition to demonstrating the requirement of TonEBP in the different compartments of the IVD, this comparative analysis uncovers the in vivo interdependency of the different IVD compartments during the growth of the postnatal IVD-vertebral units.

Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms

Intervertebral disc degeneration is closely related to abnormal phenotypic changes in disc cells. However, the mechanism by which disc cell phenotypes are maintained remains poorly understood. Here, Hedgehog-responsive cells were found to be specifically localized in the inner annulus fibrosus and cartilaginous endplate of postnatal discs, likely activated by Indian Hedgehog. Global inhibition of Hedgehog signaling using a pharmacological inhibitor or Agc1-CreERT2-mediated deletion of Smo in disc cells of juvenile mice led to spontaneous degenerative changes in annulus fibrosus and cartilaginous endplate accompanied by aberrant disc cell differentiation in adult mice. In contrast, Krt19-CreER-mediated deletion of Smo specifically in nucleus pulposus cells led to healthy discs and normal disc cell phenotypes. Similarly, age-related degeneration of nucleus pulposus was accelerated by genetic inactivation of Hedgehog signaling in all disc cells, but not in nucleus pulposus cells. Furthermore, inactivation of Gli2 in disc cells resulted in partial loss of the vertebral growth plate but otherwise healthy discs, whereas deletion of Gli3 in disc cells largely corrected disc defects caused by Smo ablation in mice. Taken together, our findings not only revealed for the first time a direct role of Hedgehog-Gli3 signaling in maintaining homeostasis and cell phenotypes of annuls fibrosus and cartilaginous endplate, but also identified disc-intrinsic Hedgehog signaling as a novel non-cell-autonomous mechanism to regulate nucleus pulposus cell phenotype and protect mice from age-dependent nucleus pulposus degeneration. Thus, targeting Hedgehog signaling may represent a potential therapeutic strategy for the prevention and treatment of intervertebral disc degeneration.

Massive bone destruction in a human proximal femur from ancient Nubia.

Massive bone destruction in a human right proximal femur is described and differentially discussed in this case study. The individual was an older adult female buried at the ancient Nubian site of Tombos (modern-day Sudan) dating to the early Napatan/Third Intermediate Period (c. 1069-750 BCE). The right femur displayed a pathologic fracture with extensive lytic destruction and resorption of the entire femoral neck, most of the femoral head, and trochanters. Macroscopic and radiographic analyses revealed cortical thinning of the proximal diaphysis with new bone formation enclosing the medullary cavity. The lesion is eccentrically located involving the anterior aspect of the neck. Numerous vascular channels are apparent in the underlying bone. Sclerotic bone marks the limit of the lesion, and osseous lucency is visible in the radiograph. The individual displayed no other lytic lesions; vertebral osteophytic growth, compression fractures, and Schmorl's nodes were observed along with dental disease typical for older individuals. A traumatic etiology is eliminated due to the extensive osteolysis. Vascular, congenital, and developmental conditions are also not consistent with the observed changes. Expansive osteolytic lesions may have been caused by a cyst. Neoplastic tumors resulting in lytic lesions with a high risk of pathologic fracture are also consistent. There have been few reports of such extensive lytic lesions of the proximal femur in the paleopathological and clinical literature; this case adds an example of this underreported condition.

A vertebra of a small species of Pachycetus from the North Sea and its inner structure and vascularity compared with other basilosaurid vertebrae from the same site.

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of Pachycetus (Morphotype 1b), a not-elongated vertebra of a large 'dorudontid' basilosaurid (Morphotype 2) and 'shortened' vertebrae of a new, unnamed taxon (Morphotype 3). This article deals with a still undescribed, smaller vertebra, NMR-16642, from this site. Our first aim was to date it by dinoflagellate cysts in adhering sediments. Yielding an age of about 38 Ma, it is one of the very few remains of basilosaurids from Europe, of which the age could be assessed with reasonable certainty. The vertebra, Morphotype 1a, is assigned to a small species of Pachycetus. High-quality CT scans are used to differentiate between NMR-16642, Morphotype 1a, and the large species of Pachycetus, Morphotype 1b. Another aim of this paper is to investigate the inner structure and vascularity of the study vertebra and that of the other morphotypes (1b, 2, 3) from this area by using high-quality CT scans. Notwithstanding differences in size, shape and compactness, the vertebral inner structure with a multi-layered cortex of periosteal bone, surrounding two cones of endosteal bone appears to be basically similar in all morphotypes. Apparently, this inner structure reflects the ontogenetic vertebral growth. An attempt to reconstruct the vascularity of the vertebrae reveals a remarkable pattern of interconnected vascular systems. From the dorsal and, if present, ventral foramina, vascular canals are running to a central vascular node. From this node a system of vascular canals goes to the epiphyseal ends, giving rise to separate systems for cortex and cones. It is the first time that the vascularity of vertebrae of archaeocetes is investigated.

FUSIONLESS ALL PEDICLE SCREWS POSTERIOR DEFORMITY CORRECTION IN AIS IMMATURE PATIENTS PERMITS RESTORATION OF THE NORMAL VERTEBRAL MORPHOLOGY AND REMOVAL OF THE INSTRUMENTATION ONCE BONE MATURITY IS REACHED

The aim of this study was to report the restauration of the normal vertebral morphology and the absence of curve progression after removal the instrumentation in AIS patients that underwent posterior correction of the deformity by common all screws construct whitout fusion. A series of 36 AIS immature patients (Risser 3 or less) were include in the study. Instrumentation was removed once the maturity stage was complete (Risser 5). Curve correction was assessed at pre and postoperative, before instrumentation removal, just post removal, and more than two years after instrumentation removal. Epiphyseal vertebral growth modulation was assessed by a coronal wedging ratio (WR) at the apical level of the main curve (MC). The mean preoperative coronal Cobb was corrected from 53.7°±7.5 to 5.5º±7.5º (89.7%) at the immediate postop. After implants removal (31.0±5.8 months) the MC was 13.1º. T5–T12 kyphosis showed a significant improvement from 19.0º before curve correction to 27.1º after implants removal (p&lt;0.05). Before surgery, WR was 0.71±0.06, and after removal WR was 0.98±0.08 (p&lt;0.001). At the end of follow-up, the mean sagittal range of motion (ROM) of the T12-S1 segment was 51.2±21.0º. SRS-22 scores improved from 3.31±0.25 preoperatively to 3.68±0.25 at final assessment (p&lt;0.001). In conclusion, fusionless posterior approach using a common all pedicle screws construct correct satisfactory scoliotic main curves and permits removal of the instrumentation once the bone maturity is reached. The final correction was highly satisfactory and an acceptable ROM of the previously lower instrumented segments was observed.

Lateral bone ridge expansion and internal tissue replacement for vertebral body growth in Pacific bluefin tuna Thunnus orientalis.

Vertebral growth is an essential developmental process to support the expansion of the vertebrate body. In teleosts, the lateral side of the vertebral bodies develops to form different structures among species in the late stages of vertebral growth, although lateral structures are not apparent in the early stages. Lateral structures are one of the structural features that determine the diversity of teleost vertebrae. However, explanations for the formation of lateral structures are conflicting because few reports have investigated the growth of teleost vertebral bodies. To clarify the growth process, we analyzed the morphological changes in the vertebral body of Pacific bluefin tuna Thunnus orientalis at different developmental stages using micro-computed tomography(CT) scans. The micro-CT scans showed that the vertebral centrum formed a plate-like ridge on the lateral side along the cranial-caudal direction and extended laterally with increasing thickness. Simultaneously, the proximal region of the lateral ridges became porous as the vertebrae grew to form bone marrow cavities. Furthermore, we used histological observations to describe the relationship between these morphological changes and osteoblast and osteoclast activities. Osteoblasts accumulated on the distal edges of the lateral ridges, whereas osteoclasts were distributed in the bone marrow cavities. These observations suggest that bone resorption occurs proximally to form bone marrow cavities in addition to bone synthesis at the edges of the lateral ridges. The bone marrow cavities were occupied by blood vessels, extracellular matrix, and adipocytes, and the internal tissue composition changed to increase the area of adipose tissue. Because the ratio of bone volume decreases in large vertebrae, bone formation and resorption are regulated to separate the external cortical and internal trabecular bones to support the vertebrae. This study is the first to report the formation of lateral structures and can be applied to similar lateral structures in the vertebrae of other teleost species.

Dose-Effect of Proton and Photon Craniospinal Irradiation on Vertebral Growth in Pediatric Patients with Medulloblastoma

Craniospinal irradiation (CSI) directly damages vertebral growth plates causing skeletal dysplasia leading to reduced height in pediatric long-term survivors. The objective of this study is to quantify the adjusted effect of CSI on standing and sitting height by radiation dose and modality in children. Two hundred sixty-five patients (M/F 169/96) were treated at a single institution on a clinical and molecular risk-directed trial for medulloblastoma (NCT01878617) using proton or photon therapy. Three CSI dose regimens were evaluated: 15 Gy (n = 31), 23.4 Gy (n = 103), ≥36 Gy (n = 131). Vertebral body dose was limited to 18-20 CGE for 23.4 Gy or 36 Gy proton therapy. All patients received post-CSI protocol-specified chemotherapy. Non-parametric tests were applied for baseline patient comparison. Changes in growth over time were calculated using random coefficients models using patient-specific intercepts and slopes. Dose-effects were modeled for ages 5, 10, and 18 years. Age at CSI and race were similar between the three dose levels. Females most often received 23.4 Gy and males ≥36 Gy (p = 0.001). Higher CSI doses were associated with photon therapy (p<0.001). Median follow-up was 3 years (range 0.1-7.1). Annual growth rate was significantly different between 15 Gy (3.66 cm/year) and the higher dose levels of 23.4 Gy (2.81 cm/year, p = 0.0389) and ≥36 Gy (2.46 cm/year, p = 0.0032). Lower annual growth rate in females (vs. males, p = 0.0331) was observed in models for those aged 5 (-0.17 cm/year), 10 (-0.35 cm/year), and 18 years (-0.62 cm/year). In multivariate analysis, modelled annual growth rate was dose-dependent at ages 5 and 10 years. The differences were, respectively, 1.68 cm/year between 15 and 23.4 Gy (p = 0.0005) and 0.98 cm/year between 23.4 and ≥36 Gy (p = 0.0002), and 1.13 cm/year between 15 and 23.4 Gy (p = 0.0002) and 0.68 cm/year between 23.4 and ≥36 Gy (p = 0.0003). Radiation modality did not impact standing height over time significantly. Annual sitting height growth was 2.34, 1.67 and 1.1 cm/year for the three dose levels (p<0.0001-0.001). In the multivariate model, a 5-year-old receiving 15 or 23.4 Gy had similar annual sitting height growth, but not when 23.4 Gy was compared to ≥36 Gy (0.83 cm/year, p<0.0001). In a separate model for a patient aged 10 years, there was a difference comparing all CSI regimens (0.81 cm/year, p<0.0001, 15 vs 23.4 Gy; 0.54 cm/year, p = 0.0002, 23.4 vs ≥36 Gy). Sitting height growth was affected by CSI dose at age 18 years, with a difference of 2.2 cm/year between 15 vs 23.4 Gy (p = 0.0013), and no difference between 23.4 and ≥36 Gy. Annual growth rates show a dose-response relationship, independent of treatment modality. A dose-response in sitting height growth rate is seen at any age, while the annual standing height growth rate was only affected by CSI dose in 5- and 10-year-olds. While all CSI doses had a significant impact on the annual standing height, sitting height growth rates approximated normal values for those treated with a low CSI dose.

Pre-operative parameters influencing vertebral body tethering outcomes: patient's characteristics play an important role in determining the outcomes at a minimum of 2 years post-op.

The aim of this study is to determine preoperative predictors of good radiographic outcomes in VBT patients at a minimum 2-year follow-up. From a single-center dataset, we reviewed patients who underwent VBT from January 2014 to November 2018. Data analysis included age, gender, Risser grade and biometric data. Radiographically, maximum Cobb angle, C-DAR and apical vertebral and disc wedging were measured preop and at a minimum 2-year follow-up. Patients were divided into two cohorts following two different outcome measures: (1) vertebral growth modulation, those patients that growth modulated or corrected ≥ 5° and those who did not; and (2) Maximum Cobb angle at 2years, < and ≥ 40°. Student T and Chi2 tests were used for comparison and a multiple linear correlation test was implemented between statistically significant variables. 79 patients were recruited. 26 patients (33%) did growth modulate their spine at 2-year follow-up. These patients were significantly younger, and more skeletally immature with less height (147cm vs 155cm;p < 0.0001), weight (38kg vs. 45kg;p = 0.0009) and BMI (17 vs 18.8;p = 0.0229) as those who did not. Multiple linear regression model with these variables resulted in a moderate correlation (r2 = 0.234). 67 patients (85%) finished at a 2-year follow-up with a maximum Cobb angle < 40°. These patients were also younger and skeletally immature. We found significant differences in outcome 2 regarding the average preoperative maximum Cobb angle (48.5° ± 9.5 vs. 59.1° ± 10), average C-DAR (7 ± 1.5 vs. 8.5 ± 2.1), average apical vertebral wedging (6.5° vs. 8.3°), average vertebral/disc wedging ratio (1.5 vs. 2.4) and the average immediate postoperative Cobb angle (25° vs. 38°). These variables predicted a 36% of the variation in final Cobb angle measurement at a 2-year follow-up (r2 = 0.362). Curve severity determined by a preoperative C-DAR, preoperative Cobb angles and immediate postoperative Cobb angle are significantly related to curves < 40° at a minimum 2-year follow-up, while the potential to growth modulate the spine is more dependent on skeletal maturity, lower body weight and lower BMI. These patients' characteristics should be considered preoperatively.

Quantifying Muscle Size Asymmetry in Adolescent Idiopathic Scoliosis Using Three-dimensional Magnetic Resonance Imaging.

This is a case-control study of prospectively collected data. To quantify paraspinal muscle size asymmetry in adolescent idiopathic scoliosis (AIS) and determine if this asymmetry is (i) greater than observed in adolescent controls with symmetrical spines; and (ii) positively associated with skeletal maturity using Risser grade, scoliosis severity using the Cobb angle, and chronological age in years. AIS is a three-dimensional deformity of the spine which occurs in 2.5% to 3.7% of the Australian population. There is some evidence of asymmetry in paraspinal muscle activation and morphology in AIS. Asymmetric paraspinal muscle forces may facilitate asymmetric vertebral growth during adolescence. An asymmetry index [Ln(concave/convex volume)] of deep and superficial paraspinal muscle volumes, at the level of the major curve apex (Thoracic 8-9 th vertebral level) and lower-end vertebrae ( LEV , Thoracic 10-12 th vertebral level), was determined from three-dimensional Magnetic Resonance Imaging of 25 adolescents with AIS (all right thoracic curves), and 22 healthy controls (convex=left); all female, 10 to 16 years. Asymmetry index of deep paraspinal muscle volumes was greater in AIS (0.16±0.20) than healthy spine controls (-0.06±0.13) at the level of the apex ( P <0.01, linear mixed-effects analysis) but not LEV ( P >0.05). Asymmetry index was positively correlated with Risser grade ( r =0.50, P <0.05) and scoliosis Cobb angle ( r =0.45, P <0.05), but not age ( r =0.34, P >0.05). There was no difference in the asymmetry index of superficial paraspinal muscle volumes between AIS and controls ( P >0.05). The asymmetry of deep apical paraspinal muscle volume in AIS at the scoliosis apex is greater than that observed at equivalent vertebral levels in controls and may play a role in the pathogenesis of AIS.

Хирургическое лечение аневризмальных костных кист поясничного отдела позвоночника: описание клинического случая

Introduction Pediatric and adolescent patients with aneurysmal bone cyst of the spine are normally treated by orthopaedic, neuro surgeons and oncologists. There is no consensus on the strategy and volume of preoperative and surgical treatment of the condition. There is a higher risk of pathological fracture and secondary neurological complications, tumor recurrence if open surgery is not performed in time. A second surgical intervention can hardly be avoided in such cases. The objective was to report the result of surgical treatment of a patient with aneurysmal bone cyst of the spine. Material and methods Outcome of a patient with an aneurysmal bone cyst of the L3 vertebra is presented. The technique of using therapeutic punctures as a preoperative preparation to be followed by an open surgical treatment is described. Absence of complaints and tumor recurrence, stability of the metal construct and bone fusion were the evaluation criteria. Results The patient was followed for 17 months after open surgery and CT scans showed no recurrence and demonstrated bone fusion at a long term. Discussion Many aspects of the course of the disease are to be considered in the treatment of children and adolescents with aneurysmal bone cyst of the spine. In our opinion, the step in the treatment of aneurysmal bone cyst of the spine should be considered Puncture for therapeutic and diagnostic purposes is to be performed to reduce pathological process is reduced, and the procedure to be followed by surgical intervention to remove the tumor. The strategy of surgical treatment would rely on impaired supporting columns of the spine, the degree of neural structure compression and a secondary spinal deformity. The need and extent of metal fixation is to be evaluated, potential vertebral growth identified, expediency of bone grafting after tumor removal, radical excision of the pathological focus to be considered. Conclusion The clinical case showed an effective combination of surgical techniques in the treatment of an aneurysmal bone cyst of the spine. Preoperative therapeutic puncture of the cyst allowed for reduction of the pathological process (decreasing pressure inside the cyst, thickening the cortical layer of the cyst and delimiting the tumor from the surrounding tissues), decreased volume of surgical intervention and blood loss due to a decreased activity of the pathological process compared to cases of untimely performed open surgery. Metal fixation in combination with bone auto- and allograft was practical for bone fusion.