In posterior fixation for deformity correction and spinal fusion, there is increasing discussion around auxiliary rods secured to the pedicle screws, sharing the loads, and reducing stresses in the primary rods. Dual-rod, multiaxial screws (DRMAS) provide two rod mounting points on a single screw shaft to allow unique constructs and load-sharing at specific vertebrae. These implants provide surgical flexibility to add auxiliary rods across a pedicle subtraction osteotomy (PSO) or over multiple vertebral levels where higher bending loads are anticipated in primary rods. Other options include fixed-angle devices as multiple rod connectors (MRC) and variable-angle dominoes (VAD) with a single-axis rotation in the connection. The objective in this simulation study was to assess rod bending in adult spinal instrumentation across an osteotomy using constructs with DRMAS, MRC, or VAD multi-rod connections.

The study was performed using computer biomechanical models of two adult patients having undergone posterior instrumented spinal fusion for deformity. The models were patient-specific, incorporating the biomechanics of the spine, have been calibrated to assess deformity correction and intra- and postoperative loads across the instrumented spine. One traditional bilateral-rod construct was used as a control for six multi-rod configurations. Spinal fixation scenarios from T10 through S1 with the PSO at L4 were simulated on each patient-specific model. The multi-rod configurations were bilateral and unilateral DRMAS at L2 through S1 (B-DRMAS and U-DRMAS), bilateral DRMAS at L3 and L5 (Hybrid), bilateral MRC over L3-L5, bilateral and unilateral VAD over L3-L5 (B-VAD and U-VAD). Postoperative gravity plus 8-Nm flexion and extension loads were simulated and bending moments in the rods were computed and compared.

In the simulated control for each case (#1 & #2), average rod bending moments (of the right and left rods) at the PSO level were 6.7Nm & 5.5Nm, respectively, in upright position, 8.8Nm & 7.3Nm in 8-Nm flexion, and 4.6Nm & 3.7Nm in 8-Nm extension. When the primary rods of the multi-rod constructs were normalized to this control, the bending moments in the primary rods of Case #1 & #2 were respectively 57% & 58% (B-DRMAS), 54% & 62% (B-VAD), 60% & 61% (MRC), 72% & 69% (Hybrid), 81% & 70% (U-DRMAS), and 81% & 73% (U-VAD). Overall, the reduction in primary rod bending moments ranged from 19–46% for standing loads. Under simulated 8-Nm functional moments, the primary rod moments were reduced by 18–46% in flexion and 17–48% in extension. More rods and stiffer connections produced the largest reductions for the primary rods, but auxiliary rods had bending moments that varied from 49% lower to 13% higher than the primary ones.

Additional rods through DRMAS, MRC, and VAD connections noticeably reduced the bending loads in the primary rods compared with a standard bilateral-rod construct. Yet, bending loads in the auxiliary rods were higher or lower than those in the primary rods depending on the 3D spinal deformity and stiffness of the auxiliary rod connections. Additional studies and patient-specific analyses are needed to optimize instrumentation parameters that may improve load-sharing in these constructs.

Introduction: Over the last three years, we have demonstrated the complex role of melatonin, a hormone produces mainly in the brain, in the development of scoliosis and in particular by reporting for the first time that cells from AIS patients cannot respond to melatonin, which contrasted with similar cells isolated from healthy subjects. We have determined that this phenomenon is caused by chemical modifications affecting the activity of Gi proteins, a group of small proteins normally associated with both melatonin receptors. Interestingly, previous studies showed that melatonin deficiency could also induce a scoliosis suggesting that the asymmetrical growth of the spine in humans and in melatonin deficient animals could be caused by a common downstream effector regulated by melatonin. This study was then designed to determine and characterise the early biochemical, cellular and molecular changes underlying the formation of spinal deformities in growing pinealectomized chicken and in bipedal C57Bl/6 mice, a naturally melatonin deficient strain of mice.

Methods: For this study, 145 newly hatched chickens (Mountain Hubbard) were purchased at a local hatchery and divided into three distinct groups. First group, pinealectomized (n=100), underwent complete removal of the pineal gland. The second group, sham (n=20), underwent superficial cranial incision without the ablation of the pineal gland. The third group, control (n=25), the chickens did not undergo any surgical procedure. All surgeries were performed by the same surgeon between day three and five after hatching. At days 14, 21 and 28 chicken underwent radiographic examination with a DEXA bone densitometer (PIXImus II, Lunar Corp., Madison, WI). Each digital image was evaluated for the presence of scoliosis and the degree of curvature was measured. Cobb angle threshold value of 10° and higher was retained as a significant scoliotic condition. Blood samples (1 to 2 ml) were taken from a peripheral wing vein of each chicken (from 6 am to 9 am) at the age of 14, 21 and 28 days. Sera were collected by centrifugation and immediately stored at −80°C until assayed. Serum melatonin concentrations were determined using an ELISA method (IBL, Hamburg, Germany). At day 28, chicken were euthanised and tissues were collected to extract mRNA for expression analysis or proteins for subsequent detection. C57Bl/6 mice (n=50) were purchased from Charles-Rivers and bipedal mice were generated by removing the forelimbs and tail after weaning (three weeks old) according to a protocol approved by our institutional animal health care committee. Sera of AIS patients and matched healthy controls were also analysed to determine the levels of circulating P factor using an ELISA assay.

Results: Our results demonstrated a more dynamic variation of circulating melatonin level only in pinealectomised chicken developing a scoliosis, which allowed us to separate scoliotic chicken in two distinct groups. In the first group, the animals showed a biphasic response with a strong decrease of melatonin level between days 14 to 21, followed by a rapid recovery to almost reach the normal values at day 28. In the second group, pinealectomised chickens showed a linear decrease of circulating melatonin over the three-week period while, non-scoliotic pinealectomised chicken showed non-significant variations in melatonin concentration with values close to those obtained with the shams. At the molecular level, expression analysis demonstrated higher expression of a gene encoding a protein that has been termed P factor only in paraspinal muscles of pinealectomized chicken developing a scoliosis. Accumulation of P factor was also confirmed at the protein level by Western blot analysis. Bipedal C57Bl/6 mice, which are naturally melatonin deficient, developed also scoliotic deformities in a proportion of 45% over a two-month period. Interestingly, we observed that genetically modified mice devoid of P factor (n=60) or one of its receptor (n=40) in the same genomic background (C57Bl/6) cannot develop a scoliosis in the same conditions. Moreover, P factor circulating levels in scoliotic patients showed a 2–4 fold increase when compared to healthy matched individuals.

Conclusions: These results showed for the first time a more dynamic variation in circulating melatonin levels among pinealectomised chicken, which was unsuspected by previous studies. Interestingly, a transient decrease of circulating melatonin level was sufficient to induce scoliotic deformities during the first two weeks even if melatonin concentration was subsequently recovered a week later. This may explain why melatonin injection in pinealectomised chicken is not always efficient in preventing scoliosis. Taken together, these observations further suggest that a melatonin decrease below a certain threshold during a specific postnatal window may be sufficient to trigger a scoliosis and reconcile the data concerning AIS patients showing in most of the studies no significant variation when analysed at late stages. The study of early molecular changes in animal models also led us to identify a novel factor, which appears essential to initiate scoliosis through a specific signalling action. The clinical relevance of the P factor in AIS and related spinal syndromes is further strengthened by the detection of high levels of P factor only in scoliotic patients and could pave the way for the development of innovative diagnosis tools as well as the first pharmacological treatments to prevent scoliosis deformities in children.

Research project supported by La Fondation Yves Cotrel de l’Institut de France

Background: The neurocentral junction often has been identified as a potential cause of adolescent idiopathic scoliosis (AIS). Disparate growth at this site has been thought to lead to pedicle asymmetry, which then causes vertebral rotation in the transverse plane and ultimately, the development of scoliotic curves.

Objectives:

To develop a model that incorporates pedicle growth and growth modulation into an existing finite element model of the thoracic and lumbar spine already integrating vertebral growth and growth modulation

Methods: The model was personalised to the geometry of a non-pathological subject and used as the reference spinal configuration. Left/right asymmetry of pedicle geometry (i.e. initial length) and left/right asymmetry of the pedicle growth rate alone or in combination with other AIS potential pathogenesis (anterior, lateral, or rotational displacement of apical vertebra) were simulated over a period of 24 months. The Cobb angle and local scoliotic descriptors (wedging angle, axial rotation) were assessed at each monthly growth cycle.

Results: Simulations with asymmetrical pedicle geometry did not produce significant scoliosis, vertebral rotation or wedging. Simulations with asymmetry of pedicle growth rate did not cause scoliosis independently and did not amplify the scoliotic deformity caused by other initial deformations tested by Villemure (2004).

Discussion and Conclusion: The results of this biomechanical model do not support the hypothesis that asymmetrical neurocentral junction growth is a cause of AIS. This concurs with recent animal experiments in which neurocentral junction growth was unilaterally restricted and no scoliosis, vertebral wedging or rotation was noted. With regards to addressing the aetiology of scoliotic curve development, biomechanical modelling represents a powerful tool to investigate cause and affect relationships since AIS patients typically present to the scoliosis clinic well after curves have manifested.

Contact person and Presenter: Carl-Éric Aubin, Ph.D., Canada Research Chair “CAD Innovations in Orthopedic Engineering”, Department of Mechanical Engineering, Ecole Polytechnique, Montreal, Canada, Tel: (514) 340-4711, ext. 4437; Fax: (514) 340-5867; E-mail: carl-eric.aubin@polymtl.ca

Introduction: Experimental pinealectomy in chickens shortly after hatch produces scoliosis with morphological characteristics similar to that of human idiopathic scoliosis (Coillard et al., 1996). The objective of this study was to develop a finite element model (FEM) incorporating vertebral growth to analyse how bone growth modulation by mechanical loading affects development of scoliosis in chicken.

Materials and Methods: We have adapted the experimental set-up of Bagnall et al. (1999) to study spine growth of pinealectomised chickens. Three groups were followed for a period of six weeks:

wild-type (controls) (n=25);

The experimental data was used to adapt a FEM previously developed to simulate the scoliosis deformation process in human (Villemure et al. 2002). The FEM consists of 7 thoracic vertebrae and the first lumbar, the intervertebral discs and the zygapophyseal joints. The geometry was measured on specimens using a calliper. The material properties of human spines were used as initial approximation. The growth process included a baseline growth (0.130 mm/day) and a growth modulation behaviour proportional to the stress and to a sensitivity factor. It was implemented through an iterative process (from the 14th to the 28th day). Asymmetric loads (2–14 Nmm) were applied to represent different paravertebral muscle abnormalities influenced by the induced melatonin defect.

Results: Within the pinealectomised group, 55% of the animals (n = 42) developed a scoliosis. In the FEM model, by varying the value of the applied moment, different scoliosis configurations were simulated. The resulting Cobb angle varied between 6° and 37°, while the maximal vertebral wedging appeared at T4 or T5 (range between 5° to 28°). A descriptive comparison of the simulation results with the experimental deformation patterns (n = 41; mean Cobb angle: 26°) was made as a preliminary validation. In 2 typical cases, the scoliotic shapes were quite similar to that seen in the scoliotic chickens.

Discussion and Conclusion: The basic mechanisms by which the metabolism of the growing spine is affected by mechanical factors remain not well known, and especially the role of tissue remodelling and growth adaptation in scoliosis. The agreement between the experimental study and preliminary simulation results shows the feasibility of the model to simulate the scoliotic deformation process in pinealectomised chickens. When completely developed and validated this modelling approach could help investigating the pathomechanisms involved in the scoliotic deformation process. Especially, computer simulations could be used to complement bio-molecular and mechanobiological studies concerning the neuroendocrinal hypothesis implicating melatonin signalling dysfunction, which could trigger a complex cascade of molecules and mechanoreceptors leading to an accumulation of specific factors in specialised tissues (Moreau et al. 2004), directly or indirectly implicated in proprioception, and which can be implicated in the pathomechanisms of scoliotic deformities.