Experimental Scoliosis Research Articles

Continuous Hypodynamic Change of Cerebrospinal Fluid Flow as A Potential Factor Working for Experimental Scoliotic Formation

Scoliosis is often associated with syringomyelia (SM). As an important role in SM formation, the influence from abnormal cerebrospinal fluid (CSF) flow is still unclear to scoliosis. The aim of this experimental work is to explore the connection between CSF flow and scoliosis through imaging and histological analysis on the basis of a kaolin-induced scoliotic rabbit model. For imaging observation, in 40 kaolin-induced rabbits by C7 spinal cord injection, through pre- and postoperative MRI and radiography, CSF flow and scoliosis formation were detected at consecutive phases. According to the final formation of scoliosis until postoperative week 12, the kaolin-induced rabbits were divided into 2 groups. Through comparing the 2 groups, the relationship between the changes of CSF flow velocity and scoliosis formation were reviewed and analyzed. For histological observation, another 20 kaolin-induced rabbits were used for consecutive histological observations of spinal cord at postoperative 3-day, 2-week, 4-week and 6-week. After kaolin-induction, abnormal spinal coronal curve was observed from postoperative week 6 in the 37 survived rabbits. At postoperative week 12, scoliosis formation was detected in 73.0% kaolin-induced rabbits and the mean Cobb angle was 27.4°. From the comparison between scoliotic and non-scoliotic groups, the difference of the velocities of CSF flow was more obviously from postoperative week 4 to 12, especially after week 6. In the scoliotic group, the peak velocity of CSF flow was diseased gradually following scoliosis formation after induction. Moreover, the decrease of the peak velocities of CSF flow from preoperation to postoperative 12 weeks (ΔVmax), including up-flow (ΔVUmax) and down-flow (ΔVDmax), were positively correlated to the final scoliotic Cobb angle (P < 0.01). Through histological observation at different phases, the distinctive pathological changes of the spinal cord included early inflammatory reaction, adhesion and blockage in the subarachnoid space and the central canal, perivascular space enlargement, central canal expansion, which suggested the CSF flow being blocked by multiple ways after kaolin-induction. In conclusion, experimental scoliosis can be successfully induced by intraspinal kaolin injection. In this model, continuous hypodynamic change of CSF flow was correlated to the formation of scoliosis, which could be an important factor of scoliotic pathogenesis being explored furtherly.

Novel porcine experimental model of severe progressive thoracic scoliosis with compensatory curves induced by interpedicular bent rigid temporary tethering.

The tether release model will be used to evaluate corrective non-fusion technologies in future investigations. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:174-182, 2018.

Idiopathic scoliosis: Static analysis of the influence of shim use on postural angles

Abstract Introduction: Scoliosis is characterized as a three-dimensional deformity. In this scenario, the use of shims can promote correction of postural imbalances. Objective: To verify the static changes associated with unilateral manipulation of shims in idiopathic scoliosis. Methods: Two experimental groups composed of participants with scoliosis with double and single curves, and a control group of participants without scoliosis. 10 reflective markers were used, filmed for 15 seconds in the static position in three conditions (no shim; low shim of 1 cm, and high shim of 3 cm) on the right and left foot. The following postural angles were calculated: alpha 1, alpha 2, alpha 3, and alpha 4. Results: There were differences in the shim condition between the control group (CG) and experimental scoliosis with “S” (GES) for alpha 2 and 4 and Scoliosis “C” (GEC) for alpha 2. For shims under the right foot, there were differences between the control group and GES for alpha 4 and the GEC for alpha 1, 2 and 4, and between shims for the GES for alpha 3 and 4. Shims under the left foot were responsible for significant differences between the control group and the GES and GEC groups. Conclusion: These static postural changes indicate that scoliosis curves show adaptability and postural reorganization in response to manipulation with shims, and the greatest influence is seen in the lower segments, both in simple and double curves. According to the results it is concluded that residual scoliotic curvatures have flexibility that allows postural adjustment with shims.

The Development of a Representative Porcine Early-Onset Scoliosis Model With a Standalone Posterior Spinal Tether

Study DesignIn vivo analysis in a porcine model. ObjectivesTo develop a porcine experimental scoliosis model representative of early-onset scoliosis (EOS) with the use of a radiopaque ultra-high molecular weight polyethylene (UHMWPE) posterior spinal tether. Summary of Background DataLarge animal experimental scoliosis models with substantial growth potential are needed to test new fusionless scoliosis correction techniques. Previously described scoliosis models involve rib procedures, which violate the thoracic cage and affect subsequent corrective procedures. Models omitting these rib procedures have experienced difficulties in producing persistent three-dimensional structural deformities representative of EOS. MethodsScoliosis was induced in 14 immature pigs using an asymmetric posterior radiopaque UHMWPE spinal tether fixated to an offset device at lumbar and thoracic levels. Radiographs were taken at 2-week intervals, and frontal and sagittal Cobb angles were measured. A tether release was performed at the 10-week follow-up, and the animals were observed for another 10 weeks. ResultsFour animals had complications (infections and/or screw breakout) and were excluded from the study. Eight animals developed progressive curves with a mean frontal Cobb angle of 62°. A thoracic lordosis (34°) and a thoracolumbar kyphosis (22°) formed. CT analysis, acquired prior to tether release, showed a mean vertebral rotation of 37° at the apex with a mean vertebral wedge angle of 10°. After tether release, the frontal Cobb angles decreased to 46° at the 20-week follow-up. Sagittal curvature was not substantially affected after tether release. ConclusionsWe describe a large animal scoliosis model, which exhibits a substantial deformity in three planes without the use of rib procedures additional to a posterior spinal tether. The created deformities showed persistence after tether release. With the management of infection and enhancement of instrumentation stability, the creation of a valid model for testing new devices in fusionless scoliosis surgery seems feasible. Level of EvidenceLevel V.

A novel self-growing rod technique for early onset scoliosis: an experimental study based on a porcine scoliosis model

To evaluate the efficacy of a growth-guidance growing rod in an established porcine scoliosis model via the Cobb angle correction and the continued spinal growth. Immature pigs (age: 6 weeks old, weight: 6-8 kg) were instrumented and tethered using a three separate incisions fashion.After considerable scoliosis was induced, the pigs were randomly assigned to an experiment group (EG) and a sham group (SG). In EG, the growing rod was implanted and the pigs were euthanized 8 weeks postoperatively; while in SG, the whole instrumentations were only removed and the pigs were followed up over a 8-week period.Dorsoventral (DV) X-ray radiographs were taken prior to and immediately after the growing rod implanting surgery, and at 4-week intervals to assess the Cobb angle orrection and instrumentation positioning.The continued spinal growth and the rod sliding were also assessed from the radiographs. Of the 16 pigs, one pig encountered infection during the inducement of the experimental scoliosis and thus was excluded from analysis.Of the remaining 15 pigs, all animals developed progressive, structural scoliosis.The 15 pigs were randomized into EG(n=10) and SG(n=5). Two pigs in EG encountered infection and were also excluded from analysis.Of the remaining 8 pigs in EG, no neurologic complications, implant failure or infection were observed.In EG, the Cobb angle of the scoliosis before the growing rod implanted was (52.1 ±14.1)° and it decreased to (25.4±15.2)° postoperatively.After 8 weeks, the Cobb angle was (20.2±11.4)°.In SG, the Cobb angle of the scoliosis after 8-week tethering period was (55.2±15.7)° and it decreased to (53.6±15.8)° after removal of the tethering.The curvature remained stable (51.2°) during the subsequent 8 weeks.During the 8-16th week, the spinal height increased 14.2 cm and radiographic analysis of the growing rod sliding revealed an average distraction of 39.8 mm in EG; while in SG, the increased spinal height was 14.9 cm.The difference of the increased spinal height between EG and SG was not significant (P=0.821). The novel growing rod system can provide substantial correction of deformity, and additionally, allow for continually spinal growth without significant growing disturbance.

A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.

Mechanism of osteoporosis in adolescent idiopathic scoliosis: experimental scoliosis in pinealectomized chickens

To clarify the mechanism of osteoporosis in adolescent idiopathic scoliosis (AIS), we investigated radiological and histological changes in the cervical vertebrae of a chicken thoracic scoliosis model. Forty newly hatched broiler chicks were randomly divided into four equal groups: sham-operated chickens serving as control (CON), pinealectomized chickens (PNX), sham-operated (CON + MLT) and pinealectomized chickens (PNX + MLT) that received intraperitoneal administration of melatonin. Pinealectomy was performed at the age of 3 days, and the chickens were killed at 2 months of age. Postmortem X-rays were examined for the presence of scoliosis, and micro-computed tomography (micro-CT) images were taken to evaluate the microstructure of the cervical vertebrae. Histological specimens of the scanned cervical vertebra were prepared, and a midsagittal section was stained with hematoxylin and eosin and tartrate-resistant acid phosphatase to evaluate the numbers of osteoblasts and osteoclasts, respectively. Scoliosis developed at the thoracic spine in all chickens of the PNX and in two of the PNX + MLT group. Micro-CT data revealed that chickens in the PNX group had a greater degree of generalized osteoporosis compared with the other birds. The number of osteoblasts was significantly decreased in the PNX group, while no significant difference was observed among chickens in the numbers of osteoclasts. Our results suggest that melatonin deficiency reduces osteoblast proliferation and leads to the development of scoliosis and osteoporosis. The restoration of melatonin prevented the development of scoliosis and osteoporosis, indicating that melatonin levels may be crucial to the development of deformity and osteoporosis in AIS.

Influence of growth modulation on the effective permeability of the vertebral end plate. A porcine experimental scoliosis model

Background Abnormal mechanical loading occurs in scoliosis as compared to normal spines. Intervertebral disc degeneration has been correlated with alteration of bone density in adjacent vertebral bodies. How vertebral end plate remodels in scoliosis and the consequences on disc homeostasis are not well understood. Permeability is a relevant physical measure to quantify mass transport in porous media. We hypothesized that effective permeability of the vertebral end plate was modified by growth modulation in a scoliosis animal model. Methods Flexible asymmetric posterior instrumentation was undertaken on six healthy four-week-old pigs. Two sets of left pedicle screws were inserted and connected with a stainless steel cable. After two months, the apical intervertebral unit and three units located cranially and caudally, were harvested. One central and two lateral specimens were investigated using a previously validated method for measuring permeability. Findings A three-dimensional deformity was obtained in all six animals with an average of 42° right thoracic curve, 44° lordosis and 21° rotation. Permeability was significantly greater in the center of the end plates than in the periphery and it was decreased by − 45% towards the apex of the deformity. Fluid flow direction did not play a significant role. No significant difference was found between the convex side and the concave side. Interpretation The end plate is a crucial zone for diffusive and convective transport and we showed in a scoliosis animal model that a growth modulation may decrease its effective permeability. The proposed methodology and associated results could help to understand degenerative changes in human spine.

Muscle study in experimental scoliosis in rabbits with costotransversectomy: evidence of ischemic process

Scoliosis involves the central nervous system diseases, ligaments, articulations and skeletal muscles, but there is no consensus on its pathogeny and progression of muscle abnormalities. In this study, we investigate the morphologic changes in the muscle of rabbit submitted to experimental scoliosis, with special emphasis on abnormalities related to blood supply. We studied 26 rabbits subjected to costotransversectomy by pulling out six transverse processes at thoracic level and six rabbits were used as controls. All the animals operated upon developed scoliosis showing an average angle of 29.1 degrees on the 60th day, with its apices located at T4 and T12 when they were subjected to paraspinal muscle biopsy on both sides. The muscle biopsies were subjected to histological stains and histochemical reactions, as well as to a morphometric study. On the concave side, the changes were not statistically significant regarding the control group. On the convex side conjunctive tissue proliferation, infiltration by adipose tissue, central nucleus excess, inflammatory reaction, segmental fibrosis, type 1 fiber hypertrophy, type 2 fiber hypertrophy and atrophic angular dark fibers in the unspecific esterase were statistically significant. The segmental fibrosis reached a circumscribed muscle segment, compatible with an ischemic phenomenon. The histological diagnoses on the concave side of the animals had unspecific alterations (atrophy and hypertrophy) in 13, myopathy in 3, denervation in 3 and normal in 7. The convex side diagnoses were myopathy in 14, denervation in 8, mixed in 3 and normal in 1. The procedure determined morphologic changes on the convex side indicating possible denervation or myopathy of ischemic origin.

Unilateral pedicle screws asymmetric tethering: an innovative method to create idiopathic deformity

ObjectiveTo evaluate the feasibility of the method that unilateral pedicle screws asymmetric tethering in concave side in combination with convex rib resection for creating idiopathic deformity.Summary of background dataVarious methods are performed to create idiopathic deformity. Among these methods, posterior asmmetric tethering of the spine shows satisfying result, but some drawbacks related to the current posterior asymmetric tether were still evident.Materials and methodsUnilateral pedicle screws asymmetric tethering was performed to 14 female goats (age: 5–8 week-old, weight: 6–8 kg) in concave side in combination with convex rib resection. Dorsoventral and lateral plain radiographs were taken of each thoracic spine in the frontal and sagittal planes right after the surgery and later every 4 weeks.ResultsAll animals ambulated freely after surgery. For technical reasons, 2 goats were excluded (one animal died for anesthetic during the surgery, and one animal was lost for instrumental fail due to postoperative infection). Radiography showed that 11 goats exhibited scoliosis with convex toward to the right side, and as the curve increased with time, only 1 goat showed nonprogressive. The initial scoliosis generated in the progressors after the procedures measured 29.0° on average (range 23.0°–38.5°) and increased to 43.0° on average (range 36.0°–58.0°) over 8 to 10 weeks. The average progression of 14.0° was measured. The curvature immediately after tethering surgery (the initial Cobb angle) did have a highly significant correlation with the final curvature (p < 0.001). The progressive goats showed an idiopathic-like deformity not only by radiography, but in general appearance.ConclusionUnilateral pedicle screws asymmetric tethering is a practical method to create experimental scoliosis, especially for those who would like to study the correction of this deformity.

Relative Versus Absolute Modulation of Growth in the Fusionless Treatment of Experimental Scoliosis

Absolute and relative growth modulation of apical spinal segments were measured during creation and correction of an experimental scoliosis in a goat model. To differentiate relative and absolute changes in growth on the concavity and convexity of an experimental scoliosis treated with anterior vertebral stapling. The creation and correction of vertebral wedge deformities have been previously described in a rat tail model using external fixation as well as in a goat model using anterior vertebral body stapling. Progressive, structural, scoliotic curves convex to the right in the thoracic spine were created in 14 Spanish Cross-X female goats using a posterior asymmetric tether. After 7-13 weeks, all tethers were removed, and goats were randomized into stapled (n = 8) and untreated (n = 6) groups. Stapled goats underwent anterior vertebral stapling with 4 shape memory alloy staples (Medtronic Sofamor Danek, Memphis, TN) along the convexity of the maximal curvature. All goats were observed for an additional 7-13 weeks. There were 12 additional goats matched for age, sex, and weight used as growth controls throughout the study. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity, and changes in relative and absolute growth at the apical spinal segment T9-10 (2 adjacent vertebrae and the intervening disc). All tethered goats had progressive, structural, scoliotic curves of significant magnitude during the tethering period (average 61.4 degrees, range 49 degrees to 73 degrees) (P = 0.001). There was 1 goat from each group eliminated from the study because its apical spinal segment did not match the T9-10 level used to establish normal growth in controls. During the treatment period, stapled goats had a correction of -6.9 degrees (P = 0.03), whereas untreated goats had little change (-1.4 degrees). Apical spinal segment wedging progressed in all tethered goats, from 11.1 degrees to 22.4 degrees, during the tethering period (P = 0.001). During the treatment period, wedging corrected -2.2 degrees (range 22.5 degrees to 20.3 degrees) in the stapled goats but progressed +3.5 degrees (range 22.3 degrees to 25.8 degrees) in the untreated goats (P < 0.05). Apical spinal segment growth in all tethered goats was decreased on the concavity by 78% and increased on the convexity by 33% when compared to growth controls (P < 0.001). During the treatment period, growth on the concavity of the apical spinal segment of the stapled goats was decreased by 10% but increased in the untreated goats by 37% when compared to growth controls. On the convexity, apical spinal segment growth at T9-10 was decreased in the stapled goats by 18% and increased in the untreated goats by 29% when compared to growth controls (P < 0.04). Data in this study show the ability to modulate relative and absolute growth, according to the Hueter-Volkmann law, at the apical spinal segment of a progressive experimental scoliosis. However, anterior vertebral stapling, although able to control progressive wedging and scoliosis at the apical spinal segment, was not able to reverse fully the Hueter-Volkmann effect.

Experimental scoliosis in melatonin‐deficient C57BL/6J mice without pinealectomy

The etiology of idiopathic scoliosis is unknown. Scoliosis with many characteristics closely resembling those seen in idiopathic scoliosis has been produced in young chickens and bipedal rats after pinealectomy. In this study, we induced experimental scoliosis in C57BL/6J mice without pinealectomy and melatonin treatment suppressed the development of scoliosis. A total of 100 mice were divided into four groups: 20 quadrupedal mice served as controls; 30 mice underwent resection of two forelegs and tail at 3 wk of age (bipedal mice); the remaining 20 quadrupedal and 30 bipedal mice received intraperitoneal melatonin (8 mg/kg BW) at 19:00 hr daily. Before killing, blood samples were collected in the middle of dark cycle and melatonin levels were measured by radioimmunoassay. Spine X-ray and helical 3D-CT were examined after killing at 5 months of age. The bipedal mice without a tail were able to walk with standing posture, whereas the quadrupedal mice did not walk with standing posture. In C57BL/6J mice, the serum melatonin was reduced to nearly zero; however, the normal level was restored in both bipedal and quadrupedal mice after the injection of melatonin. Scoliosis with rib humps developed in 29 of 30 bipedal and in five quadrupedal mice. None of mice with melatonin treatment developed scoliosis. The results suggest that melatonin deficiency in bipedal mice appears to play crucial role for development of scoliosis. Also the restoration of melatonin levels prevents the development of scoliosis.

Creation of an Experimental Idiopathic-Type Scoliosis in an Immature Goat Model Using a Flexible Posterior Asymmetric Tether

Longitudinal follow-up of animals after a surgically initiated scoliosis. To create a progressive, structural, idiopathic-type, lordoscoliotic curve convex to the right in the thoracic spine of the immature goat using a flexible posterior asymmetric tether with minimal disruption of the spinal elements along the curve. Our previous work created an experimental scoliosis model using a rigid posterior asymmetric tether to study the safety and efficacy of fusionless scoliosis treatments. Posterior asymmetric tethers, whether rigid or flexible, represent the most reliable method of creating an experimental deformity that approximates idiopathic scoliosis. Although our initial rigid model was unique in creating progressive structural scolioses without violation of the essential spinal elements along the curve, there were a number of shortcomings associated with the model. These included substantially stiff curves and unpredictability of curve progression. Scoliosis was created in 24 Spanish Cross X female goats (age, 6-8 weeks; weight, 8-12 kg) using a braided synthetic ligament as a left posterior asymmetric tether from T5 to L1. Convex rib resection and concave rib tethering from ribs 8 to 13 were performed without disruption of the spinal elements before tensioning of the posterior tether. All goats were followed over an 8-week period with serial radiographs to document progression of the deformity. At the end of 8 weeks, the 20 goats with progressive curves were randomized into treatment groups for a separate study. However, 6 of these 20 remained untreated in the subsequent study and, therefore, were followed for an additional 12 to 16 weeks. There were two deaths in the early postoperative period due to pulmonary complications. Of the remaining 22 goats, 20 (91%) developed progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine. Initial scoliosis after tethering measured 55.4 degrees on average (range, 37 degrees-75 degrees) and progressed to 74.4 degrees on average (range, 42 degrees-93 degrees) over 8 weeks. The average progression of 19.0 degrees (range, 5 degrees-33 degrees) was statistically significant (P < 0.001). The average initial lordosis after tethering measured -18.9 degrees (range, -13 degrees to -27 degrees) and progressed to -40.7 degrees on average (range, -28 degrees to -56 degrees) over 8 weeks. The average progression in lordosis of -21.8 degrees (range, -5 degrees to -43 degrees) was significant (P < 0.001). This study demonstrated the effectiveness of a flexible posterior asymmetric tether in creating idiopathic-type deformities in a shorter tethering period than previously described. With substantial remaining spinal growth after the 8-week tethering period and preservation of the essential spinal elements in an undisturbed state, this model is suitable for the study of scoliosis progression and various fusionless scoliosis treatment methods.

Mechanical Modulation of Vertebral Growth in the Fusionless Treatment of Progressive Scoliosis in an Experimental Model

Wedging of apical spinal segments was measured during creation and correction of an experimental scoliosis in a goat model. To create and correct apical vertebral wedge deformities in a progressive experimental scoliosis model by purely mechanical means. The creation and correction of vertebral wedge deformities has been previously described in a rat tail model using external fixation. Experimental scoliosis was created in 14 goats using a posterior asymmetric tether with convex rib resection and concave rib tethering. After a period of up to 13 weeks, all tethers were removed and goats were randomized into treated (n = 8) and untreated (n = 6) groups. Treated goats underwent anterior thoracic stapling with four shape memory alloy staples along the convexity of the maximal curvature. Goats were followed for an additional 7 to 13 weeks during treatment. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity as well as to measure the wedging of the apical spinal segment (two adjacent vertebrae and the intervening disc). During the tethering period, all goats achieved a progressive, structural, lordoscoliotic curve of significant magnitude (mean: 61 degrees, range: 49 to 73 degrees). Wedging of the apical spinal segment measured 11.1 degrees at the beginning and 22.4 degrees at the end of the tethering period. The increase in apical spinal segment wedging of +11.3 degrees (10.7 degrees vertebral/0.6-degree disc) was significant (P = 0.001). During the treatment period, the scoliosis in the stapled goats measured 56.8 degrees at the beginning and 43.4 degrees at the end for an average correction of -13.4 degrees (range: 0 to-22 degrees) (P = 0.001), whereas the untreated goats measured 67.0 degrees at the beginning and 59.8 degrees at the end for an average correction of -7.2 degrees (range: +7 to -21 degrees) (P = 0.19). Additionally, wedging of the apical spinal segment in the stapled goats measured 22.5 degrees at the beginning and 20.3 degrees at the end for an average correction of -2.2 degrees (-0.6 degrees vertebral/-1.6-degree disc); wedging of the apical vertebral segment in the untreated goats measured 22.3 degrees at the beginning and 25.8 degrees at the end of the treatment period for an average progression of +3.5 degrees (3.5 degrees vertebral/0.0-degree disc). The difference in apical spinal segment correction versus progression in the stapled (-2.2 degrees) versus control (+3.5 degrees) goats was significant (P < 0.05). This study demonstrates the ability to create wedge deformities at the apex of an experimental scoliosis in a large animal model and to control the progression of these deformities using anterior thoracic staples.

Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels

In addition to the induction of scoliosis in chickens by pinealectomy (PINX), we previously demonstrated that removal of the pineal gland also produces scoliosis in bipedal rats, which can be inhibited by melatonin treatment. Using C57BL/6J mice with genetically low circulating melatonin levels, the main objective of the present study was to investigate whether bipedal ambulation in C57BL/6J mice has the same effects on spinal deformity as those seen in pinealectomized bipedal rats. The present study consisted of two phases. The aim of the first experiment was to determine whether the C57BL/6J mouse strain actually exhibits depressed plasma concentrations and/or pineal contents of melatonin during both the light and the dark phase of the light:dark cycle. The aims of the second experiment were to evaluate; (i) whether bipedal ambulation alone in the C57BL/6J mouse induces scoliosis, and (ii) whether PINX with bipedal ambulation in another mouse strain, i.e. C3H/HeJ, which normally exhibits diurnal fluctuations in melatonin synthesis and secretion, has effects similar to those of bipedal ambulation alone in C57BL/6J mice. C3H/HeJ mice, serving as controls, showed significant increases in both plasma concentrations and pineal contents of melatonin during the dark phase when compared with the light phase. In contrast, there were no differences in either circulating levels or pineal contents of melatonin between the light and dark phases in C57BL/6J mice. Moreover, plasma melatonin levels were below the detection limit of the assay in both phases and pineal melatonin was < 10% of that in C3H/HeJ mice. Bipedal ambulation for 40 wk in C57BL/6J mice induced scoliosis at a rate of 64.3%, and two of nine scoliotic mice showed two sites of spinal deformity. This type of ambulation in C3H/HeJ mice resulted in scoliosis at a lower rate (25%), and affected animals had only a single scoliotic site. However, PINX combined with bipedal ambulation in C3H/HeJ mice produced scoliosis at a rate (70%) similar to that seen in C57BL/6J mice, and some double deformations were induced. These results confirm our previous observations in rats, and also support our hypothesis that melatonin as well as the bipedal ambulation appear to play a critical pathogenic role in scoliosis in experimental mammals.

Three-Dimensional Analysis of 2 Fusionless Scoliosis Treatments: A Flexible Ligament Tether Versus a Rigid-Shape Memory Alloy Staple

Experimental scoliosis was created and subsequently corrected in goats. The 3-dimensional (3-D) effects of the treatments were analyzed. To analyze the 3-D effect of 2 different fusionless scoliosis treatment techniques on an experimental idiopathic-type scoliosis using plain radiographs and computerized tomography. Scoliosis is a complex 3-D spinal deformity with limited treatment options. By preserving growth, motion, and function of the spine, fusionless scoliosis surgery provides theoretical advantages over current forms of treatment. Scoliosis was created in 24 Spanish cross-X female goats using a flexible, left posterior asymmetric tether from the T5 to L1 laminae, with convex rib resection and concave rib tethering from T8 to T13. After 8 weeks of posterior tethering, goats were randomized into 3 treatment groups: group 1, no treatment; group 2, anterior-shape memory alloy staple; and group 3, anterior ligament tether with bone anchor. The 6 levels of maximal curvature were instrumented in groups 2 and 3. All goats were observed for an additional 12-16 weeks. Serial radiographs and computerized tomography were used to document progression/correction of coronal, sagittal, and transverse plane deformities throughout the study. There were 20 goats that had progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine over the 8-week tethering period. An overall deformity score equaling the sum of the scoliosis, lordosis, and axial rotation measurements was calculated for each goat at 3 times. The data in this study show the ability of a ligament tether attached to a bone anchor to correct scoliosis modestly in the coronal plane, but not in the sagittal or transverse plane. In addition, although a significant decrease in the deformity score was shown initially in this group (P < 0.001), the effect was lost over time. The final deformity in the bone anchor/ligament tether group wassignificantly less than either the stapled or untreated groups (P < 0.03). Further study is warranted to provide a better understanding of the 3-D effects of fusionless scoliosis treatments.

Unilateral Enucleation Affects the Laterality but Not the Incidence of Scoliosis in Pinealectomized Chicken

Randomized prospective study using an experimental scoliosis model in a pinealectomized chicken. To investigate the effect of the side of visual impairment on the incidence and laterality of the curves on a pinealectomized chicken model. Visual impairment has been shown to increase the incidence of idiopathic-like scoliosis in human subjects when compared to the incidence of the general population. However, an association between the laterality of the visual impairment and incidence or laterality of scoliosis has not been established. A total of 60 newly hatched white leghorn chicks was divided equally into 3 study groups of no visual impairment (n = 20) (group 1), left-sided blindness by enucleation (n = 20) (group 2), and right-sided blindness (n = 20) (group 3). Pinealectomies and enucleations were performed on the second day after hatching. Anteroposterior radiographs were obtained at the 5th and 10th weeks, and the incidence, side, and magnitude of the resulting scoliotic curves were recorded. The pinealectomy model yielded a general scoliosis incidence of 60%. The occurrence of scoliosis was not different among the groups (65%, 55%, 60%, respectively, P = 0.812). The incidences at the 5th and 10th weeks were both 40%, as a result of the death of 6 chickens between the 5th and 10th weeks, as well as the appearance or disappearance of curves during this time, again not different among the groups. However, the laterality of the curves was significantly different (P = 0.045). The visually impaired groups tended to have left thoracic curves as frequently as the right thoracic curves (7 right and 4 left in group 2, and 7 right and 6 left in group 3), whereas in group 1, the thoracic curves were predominantly right sided (12 right and 1 left). The average magnitude of the curves was 30.47 degrees +/- 19.32 degrees , not significantly different among the groups (27.6 degrees +/- 16.7 degrees , 23.7 degrees +/- 21.5 degrees , 39.8 degrees +/- 17.7 degrees , respectively, P = 0.109). Unilateral visual impairment does not have a significant effect on the overall incidence and magnitude of scoliosis in the pinealectomized chicken. It does affect the laterality of the curves though, visually impaired subjects having a significantly higher likelihood of left thoracic curves, regardless of the side of blindness. It may be worthwhile to see if such an association is present in human beings as well.

Rib Length in Experimental Scoliosis Induced by Pinealectomy in Chickens

This study was designed to investigate the difference of rib length of idiopathic scoliosis using experimentally induced scoliosis by pinealectomy in chickens. To find whether the difference of rib length may play a role for the development of scoliosis in pinealectomized chickens. In experimental and clinical studies, asymmetric growth of the rib has been considered to be one of factors for the development of idiopathic scoliosis. Pinealectomy in chickens consistently produces scoliosis with lordosis, vertebral rotations, and rib humps, which have anatomic characteristics similar to those of human idiopathic scoliosis. A total of 30 chickens were divided into two groups: pinealectomy in 15 chickens and sham operation in 15 chickens served as control. The surgeries were performed on the second day after hatching. The chickens in both groups were killed at 3 months of age. The spines were examined radiologically for the presence of a scoliotic curve. Also, the ribs at each level were measured and compared between left and right sides. All pinealectomized chickens that developed scoliosis showed rib humps. In contrast, none of chickens in a sham operation developed scoliosis. In both groups, there were no significant asymmetries in the rib length. Our results indicated that rib length was not related to the experimental scoliosis examined in this study. Further study is encouraged to investigate if the asymmetric rib length plays a role in causing or promoting other types of scoliosis, especially in primate or human idiopathic scoliosis.

The Use of Animal Models in Fusionless Scoliosis Investigations

Review article of current knowledge of animal models used in the investigations of fusionless scoliosis surgery. To provide a summary of available data on animal studies in the area of fusionless scoliosis surgery. Fusionless scoliosis surgery is an emerging treatment for patients with idiopathic scoliosis as it offers theoretical advantages over current forms of treatment. These advantages include correction of spinal deformity while preserving growth, motion, and function of the spine. Literature review of animal models used in the investigation of fusionless scoliosis surgery. At present, the theoretical advantages of fusionless scoliosis surgery in the treatment of idiopathic scoliosis are unproven clinically. However, investigations using animal models have demonstrated promise for this new form of treatment. These studies have demonstrated the safety and efficacy of a variety of fusionless scoliosis implants in treating experimental scoliosis and in modulating spinal growth. Fusionless scoliosis surgery offers theoretical advantages over brace treatment and surgery. Like bracing, fusionless treatments preserve growth, motion, and function of the spine. Like surgery, these treatments offer substantial correction of deformity. However, minimally invasive fusionless scoliosis surgery is less extensive than fusion surgery and may avoid adjacent segment degeneration and other complications related to fusion. Additional investigations are required to identify optimal implant strategies, to evaluate the effects of these implants of the spine and surrounding structures, and to define the appropriate patient population for these interventions.

The Efficacy and Integrity of Shape Memory Alloy Staples and Bone Anchors with Ligament Tethers in the Fusionless Treatment of Experimental Scoliosis

Scoliosis is a complex three-dimensional deformity with limited treatment options. Current treatments present potential problems that may be addressed with use of fusionless techniques for the correction of scoliosis. However, there are few data comparing the efficacy of different fusionless implant strategies in controlling scoliosis or on the integrity of rigid compared with flexible devices in an in vivo setting over time. The objective of this study was to compare the efficacy and integrity of rigid and flexible anterior thoracic tethers used to treat experimental scoliosis. Experimental scoliosis was created in twenty-four Spanish Cross-X female goats and was subsequently treated with either anterior shape memory alloy staples or anterior ligament tethers attached to bone anchors. Serial radiographs were analyzed to determine the efficacy of the implants in controlling scoliosis progression as well as the integrity of the implants at study completion. After the goats were killed, the implants were analyzed with use of three quantitative indices of implant integrity and implant pullout testing. Over the treatment period, scoliosis progressed from 77.3 degrees to 94.3 degrees in the goats treated with staples and was corrected from 73.4 degrees to 69.9 degrees in the goats treated with bone anchors, with loosening of eighteen of forty-two staples (two of the eighteen dislodged) and evidence of drift in two of forty-nine anchors. Histologic sections revealed a consistent halo of fibrous tissue around the staple tines but well-fixed bone anchors at all sites. Pullout testing demonstrated that bone anchors had greater strength than staples initially and at the study completion, with an increase in bone anchor fixation over the course of the study. In this scoliosis model, the flexible ligament tethers attached to bone anchors demonstrated greater efficacy and integrity than the more rigid shape memory alloy staples.