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The Use of Animal Models in Fusionless Scoliosis Investigations

Braun, John T., MD*†; Akyuz, Ephraim, MS‡§; Ogilvie, James W., MD*∥

doi: 10.1097/01.brs.0000175187.61474.9a
Focus Paper
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Study Design. Review article of current knowledge of animal models used in the investigations of fusionless scoliosis surgery.

Objective. To provide a summary of available data on animal studies in the area of fusionless scoliosis surgery.

Summary of Background Data. 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.

Methods. Literature review of animal models used in the investigation of fusionless scoliosis surgery.

Results. 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.

Conclusion. 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.

This review article discusses the use of animal models in fusionless scoliosis surgery investigations. Although fusionless scoliosis surgery has significant theoretical advantages over other current forms of treatment, it remains controversial because of a paucity of data regarding its safety and efficacy. Animal models have provided a unique opportunity to test a variety of fusionless scoliosis implants, to study spinal growth modulation, and to refine implant strategies.

From the Departments of *Orthopaedics, †Neurosurgery, and §Bioengineering, and ‡Orthopaedic Research Laboratory, University of Utah, School of Medicine, Salt Lake City, UT; and ∥Intermountain Shriners Hospital for Children, Salt Lake City, UT.

Acknowledgment date: February 16, 2005. Acceptance date: May 31, 2005.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States. (The bone anchor/ligament tether falls under this category.) The device(s)/drug(s) is/are FDA-approved or approved by corresponding national agency for this indication. (The SMA staple is FDA 510K approved but not for scoliosis or spine surgery.)

Corporate/Industry funds were received to support this work. One or more of the author(s) has/have received benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript: e.g. honoraria, royalties.

Address correspondence and reprint requests to John T. Braun, MD, Department of Orthopaedics, University Orthopaedics Center, 590 Wakara Way, Salt Lake City, UT 84108; E-mail: john.braun@hsc.utah.edu

Idiopathic scoliosis is a complex three-dimensional spinal deformity with limited treatment options.1–5 For growing children with a significant and progressive scoliosis deformity, the options include brace treatment or surgery. Although brace treatment is attractive because it is noninvasive and, therefore, lower risk than surgery, the effectiveness of bracing is modest. While brace treatment does preserve growth, motion, and function of the spine, it offers little or no chance of deformity correction. At best, bracing prevents scoliosis progression. The success of brace treatment can also be hampered by patient compliance issues, and the psychological impact of bracing is not negligible in adolescence.6–14

For growing children that fail brace treatment or have more severe scoliosis, surgery is often considered. Although an instrumented spinal fusion provides better deformity correction than brace treatment, it is more invasive and thus carries more risk.15–22 Fusion procedures, whether anterior, posterior, or both, require extensive surgical dissection to expose the spine and prepare for fusion. Bone graft harvest is also routinely necessary. The instantaneous correction of spinal deformity achieved during an instrumented spinal fusion procedure also carries risk of neurologic injury. And even with safe correction of scoliosis and a solid fusion, the growth, motion, and function of the fused portion of the spine are eliminated, perhaps increasing the risk of adjacent segment degeneration and spinal imbalance problems in the future.

Fusionless scoliosis surgery has received increasing attention over the past several years because of perceived advantages over currently available forms of treatment.23–26 Like bracing, fusionless scoliosis surgery potentially preserves growth, motion, and function of the spine23–25 and, like surgery, fusionless implants applied directly to the spine may offer improved mechanical advantage for correction of spinal deformity. In contrast, however, to a standard instrumented spinal fusion, it is less extensive and perhaps more physiologic. The preservation of spinal motion and function may protect adjacent segments from premature degeneration over time.

There are many synonyms for fusionless scoliosis surgery, including endoscopic vertebral stapling, anterior thoracic stapling, convex scoliosis tethering, mechanical modulation of spinal growth, guided spinal growth, and even internal bracing of spinal deformity.23–25 These anterior fusionless scoliosis surgeries should be considered distinct from other posterior nonfusion surgeries as the latter represent more temporizing measures of managing scoliosis progression rather than a definitive treatment of the deformity. Subcutaneous, or submuscular rod techniques,27 and more recently, the vertical expandable prosthetic titanium rib (VEPTR),28 are often more invasive than fusionless scoliosis surgery, usually require multiple procedures throughout growth (with the ultimate requirement for definitive fusion surgery), and may be associated with a substantial complication rate. In contrast, fusionless scoliosis treatments usually involve a single intervention, through a minimally invasive or endoscopic anterior approach, that offers more permanent control of the spinal deformity.24,29

Previous studies of fusionless scoliosis surgery in an animal model began more than 50 years ago when Nachlas and Borden pilot tested an anterior lumbar staple in a dog model.30 The application of a stainless steel staple to the anterior lumbar spine, spanning multiple vertebral motion segments, was used to create mild scoliosis deformities. However, the curves created were likely “sciatic” scolioses, rather than structural deformities, as the posterior implantation of an anterior lumbar staple probably crimps the exiting nerve roots, causing unilateral pain and paraspinal muscle spasm. Correction of these curves, perhaps by the same mechanism, was described after application of the staple to the opposite side of the lumbar spine. Although no measurements or data were provided on the six animals in this study, multiple radiographs were included. All of these images reveal a rather weak appearing staple spanning two to three lumbar motion segments with multiple examples of staple malposition, dislodgement, and even breakage. Analysis of the information provided in this study does not justify the optimistic conclusions in support of this form of treatment. It was perhaps predictable that subsequent application of this staple by DeForest Smith to the anterior spine of three children with congenital scoliosis met with failure and was abandoned for decades.31

In 1996, Ogilvie, under an IRB approved protocol, treated 6 skeletally immature children with progressive scoliosis using an anterior endoscopic thoracic stapling procedure.29 In 2 children with idiopathic scoliosis curves in the 40° to 50° range, who had failed brace treatment, stapling controlled the deformity and modest correction was observed over the remainder of growth. In 1 of these patients, a 44° right thoracic curve, stapled at Risser 0, corrected to 41° over a 2-year period. At the cessation of spinal growth (Risser 4), the curve remained 41°. An instrumented spinal fusion procedure was avoided in these 2 patients. In the remaining 4 patients with scoliosis curves in the 60° to 80° range and additional diagnoses such as neurofibromatosis and congenital scoliosis, the stapling procedure had little effect on progression and eventually an instrumented spinal fusion was required. Despite some success in controlling the progression of moderate idiopathic scolioses with a more rigid stainless steel implant, Ogilvie expressed dissatisfaction with the long-term fixation of this implant. This prompted the design of a less rigid shape memory alloy staple with the goal of improving staple fixation over time via the “crimping” effect of this device. Further application of fusionless scoliosis treatments in humans was postponed until more extensive analysis of these devices could be accomplished in a laboratory setting. To validate the safety and efficacy of these implants for the treatment of progressive idiopathic scoliosis, it became necessary to develop an animal model that would allow appropriate preclinical testing of these devices.

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Animal Models for Idiopathic Scoliosis

A variety of animal models have been created in an attempt to better understand the unique three-dimensional deformity of idiopathic scoliosis. Some of these models use mechanical methods to alter spine symmetry and create an abnormal curvature. These include resection of bone or soft tissue,32–42 immobilization of the spine using external fixation,43,44 elongation of the ribs,45 damage to the vertebral growth plate by irradiation,46,47 tethering of bone and/or soft tissue on either side of the spine,48–56 electrostimulation of the back muscles,57–60 and even magnet implantation.61 Other models alter the biochemistry or endocrine status of the animal by administering mutagenic agents to pregnant animals,62,63 by inducing rickets64 or lathrysm,65,66 or by pinealectomy.67–70 Additional methods have created scoliosis by inducing neurologic damage either at the cord or root level.71–77 Despite the variety and ingenuity of these approaches, only posterior asymmetric tethering of the thoracic spine in growing animals consistently produces a significant and progressive three-dimensional deformity that approximates idiopathic scoliosis with only minimal violation of the spinal elements along the curve.51,78

Perhaps the most practical mechanical method of consistently creating an experimental scoliosis that approximates an idiopathic deformity was described by Smith and Dickson in 1987.51 Using sublaminar suture as a posterior asymmetric tether in the thoracic spine, these investigators produced progressive, structural, lordoscoliotic curves in a growing rabbit model. Although this experimental scoliosis in a small animal model provides a reasonable framework for the study of complex three-dimensional deformity, size limitations and variations in bone quality often restrict appropriate testing of clinically relevant implants. Larger animal models also have limitations. However, these provide a better approximation of human anatomy and bone quality than smaller animal models.

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An Immature Goat Model for Idiopathic Scoliosis

The mechanics of scoliosis creation in larger animal models has been more challenging than in smaller animals; thus, successful methods have typically required violation of the spinal elements along the curve. Karaharju, using an immature porcine model, achieved progressive, structural, lordoscoliotic curves using a combination of convex resection of ribs and concave tethering of ribs to the spinous processes.54 However, the removal of multiple rib heads on the convexity of the spinal deformity disrupted not only the costovertebral and costotransverse joints but likely disrupted the disc anulus as well. And exposure of the posterior spine, to allow tethering of the ribs to the spinous processes, likely violated the lamina and facets on the concavity of the scoliosis and may have encouraged bony fusion in these areas. Although these curves approximated idiopathic scoliosis radiographically, extensive violation of the spinal elements throughout the maximal curvature was required, thus making this model suboptimal for the subsequent study of fusionless scoliosis treatments.

The original scoliosis model developed by our group sought to create an experimental deformity in a larger animal that not only approximated idiopathic scoliosis but resulted in minimal violation of the spinal elements along the curve (Figure 1).78 Using a rigid posterior asymmetric tether, in combination with convex rib resection and concave rib tethering, progressive, three-dimensional deformities were created in an immature goat that clinically, radiographically, biochemically, and histologically resembled idiopathic scoliosis. All deformities were similar with right thoracic curves spanning T6–T13 in the majority of animals. Other than the left hemilaminotomy dissections at T4–T5 and L1–L2, and submuscular tunneling of the rod, the essential spinal elements along the maximal curvature were maintained in a pristine state. Further, the rib procedures, performed several centimeters from the midline, did not disturb the spinal elements. This unique model offered an ideal opportunity to study growth modulation and fusionless scoliosis treatments in the setting of a progressive deformity.

Figure 1

Figure 1

Of the 40 goats that underwent rigid posterior asymmetric tethering in our original study, 27 of 33 (82% of surviving animals, 68% of all study animals) developed progressive, structural, idiopathic-type curves convex to the right in the thoracic spine. Seven of 40 goats (18%) died in the early postoperative period, and 6 of 33 goats (18%) failed to develop progressive curves. The average initial scoliosis in the 27 progressors measured 42° (range, 33°–50°) after rigid posterior asymmetric tethering and increased to 60° (range, 44°–73°) over the 6- to 15-week tethering period (P < 0.001). In the sagittal plane, the initial thoracic kyphosis decreased from 10.8° (range, 4.0°–23.0°) on average to 2.8° (range, −10.0°–18.0°) after posterior asymmetric tethering and further progressed to −1.0° (range, −16.0°–15.0°) lordosis over 6 to 15 weeks (P < 0.05).

Despite the close approximation of idiopathic scoliosis in our original animal model, several limitations were noted. The rigidity of the posterior asymmetric tether created curves substantially stiffer than those usually seen in a typical adolescent idiopathic scoliosis. Even with removal of the posterior asymmetric tether, minimal motion was demonstrated in the region of scoliosis using a push-prone maneuver. This environment was felt to be less than optimal for the study of spinal growth modulation and fusionless scoliosis treatments. Additionally, removal of the tether resulted in somewhat unpredictable behavior in curve progression (unless the tethering was maintained for 10–12 weeks or more). Unfortunately, the predictability of progression, associated with longer periods of tethering, consumed the more rapid phase of goat growth leaving less growth available for modulation using various fusionless treatments.

Our subsequent experimental scoliosis model sought to address the limitations of the original model by replacing the rigid hook/rod construct with a more flexible ligament tether (Figure 2).79 Our goal was to create three-dimensional deformities, similar to those produced in our original model, in a shorter tethering period with less rigid curves. Further, it was thought that the flexible tether could be maintained during subsequent fusionless scoliosis studies in all animals without creating excessively stiff curves. With the necessity for tether removal eliminated, it was hoped that more consistent progression would be observed in the fusionless scoliosis treatment phases.

Figure 2

Figure 2

Of the 24 goats that underwent flexible posterior asymmetric tethering in our subsequent study, 20 of 22 (91% of surviving animals, 83% of all study animals) developed progressive, structural, idiopathic-type, lordoscoliotic curves convex to the right in the thoracic spine. Two goats (8%) died in the early postoperative period and two goats (8%) failed to develop progressive curves. The average initial scoliosis in the 20 progressors measured 55.4° (range, 37°–75°) after posterior asymmetric tethering and increased to 74.4° (range, 42°–93°) over the 8-week tethering period (P < 0.001). In the sagittal plane, the initial thoracic lordosis after posterior asymmetric tethering progressed from −18.9° (range, −13°–−27°) to −40.7° (range, −28°–−56°) over 8 weeks (P < 0.001).

Although this subsequent experimental scoliosis model created progressive three-dimensional deformities with greater consistency, and in a shorter period of time, the curves were more severe in magnitude and progressed more rapidly than in our original scoliosis model. Additionally, the sagittal plane deformity was much greater, and the progression more malignant, than that seen in our previous study. And, much like the curves produced in our original model, the deformities were quite stiff. Overall, the original model probably represents a better three-dimensional approximation of idiopathic scoliosis but is less efficient in the testing of fusionless scoliosis treatments. The subsequent experimental scoliosis, created using a flexible posterior asymmetric tether, is more efficient in generating curves but a more severe deformity results than is typical of idiopathic scoliosis. Seen in the best light, this more severe model represents an extremely challenging testing environment for fusionless implants.

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Implant Strategies for Fusionless Scoliosis Treatment

A variety of implants have been investigated for the fusionless treatment of scoliosis, ranging from more rigid to more flexible anterior vertebral tethers.23–26,29–31 Stainless steel staples29–31 and staples augmented with a screw/plate construct26 represent the more rigid end of the spectrum. Shape memory alloy (NiTiNOL) staples (Figure 3)23,24 are somewhat less rigid but not as flexible as those implants at the other end of the spectrum, including screw/cable25 or bone anchor/ligament (Figure 4)80 constructs.

Figure 3

Figure 3

Figure 4

Figure 4

Newton et al25 studied the effects of more flexible anterior tethering on spine growth in an immature bovine model. With a cable/screw construct spanning a single motion segment in a well-aligned thoracic spine, a mean scoliosis of 11.6° ± 4.8° and kyphosis of 5.1° ± 5.8° were created over a 12-week period. Sixty percent of the angulation, however, was due to disc wedging. Wall et al26 studied the effects of a more rigid anterior tether on spine growth in an immature porcine model. With the addition of hemiepiphysiodesis to multilevel staples augmented with a screw/plate construct, mean scolioses of 22.4° ± 2.8° were created over an 8-week tethering period in previously well-aligned thoracic spines. A comparison of the effectiveness of these implants in treating scoliosis is somewhat difficult because they have been tested in different environments. The results of implant testing across a single motion segment, in a well-aligned spine, and/or for a short duration may not translate well when compared with the results of implant testing across multiple segments or in a progressive scoliosis deformity over an extended period of time.

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Fusionless Implant Testing in an Experimental Goat Scoliosis Model

The goal of our original fusionless scoliosis implant testing was to evaluate, in as rigorous a fashion as possible, the safety and efficacy of a shape memory alloy staple in treating moderately severe versus more malignant progressive scolioses.23 Twenty-seven goats with progressive, structural, lordoscoliotic curves, created using a rigid posterior asymmetric tether, were randomized into one of four treatment groups. In the eight goats that underwent anterior thoracic stapling using one staple per level over the four levels of maximal curvature (designated as moderately severe scoliosis after removal of the rigid posterior asymmetric tether), scoliosis corrected on average from 57° (range, 44°–64°) to 43° (range, 30°–58°) over the 7- to 13-week treatment period (P = 0.001) (Figure 5). The control for this group consisted of six goats that underwent removal of the posterior tether alone and demonstrated correction of scoliosis from 67° (range, 61°–73°) to 60° (range, 45°–77°) over the same period (NSD). In the six goats that underwent anterior thoracic stapling over four levels of maximal curvature (designated as more malignant scoliosis with maintenance of the rigid posterior asymmetric tether), the scoliosis progression was halted with modest correction on average from 65° (range, 59°–73°) to 63° (range, 60°–65°) over the 6- to 14-week treatment period (NSD). The control for this group consisted of seven goats that maintained the posterior tether alone and demonstrated relentless progression of scoliosis from 55° (range, 49°–67°) to 67° (range, 55°–79°) over the same period (P = 0.005).

Figure 5

Figure 5

The results of this original study demonstrate the safety and efficacy of an anterior thoracic staple in correcting moderately severe scoliosis and halting the progression of a more malignant scoliosis without fusion in an experimental model. Although some scoliosis correction was noted in all of the moderately severe groups, treated and untreated, a trend toward greater correction was observed in the stapled versus control animals. In contrast, the more malignant scoliosis groups demonstrated a significant difference in progression between stapled animals and their controls. Stapled goats did not progress in this more malignant scoliosis group, whereas all untreated goats progressed relentlessly. In all study animals, stapling along the convexity of the scoliosis provided substantial control of deformity progression when compared with no treatment.

Although no staple broke or completely dislodged during the treatment period in this study, 27% (15 of 56) of staples demonstrated some evidence of loosening with 5% (3 of 56) no longer thought to be in a functional position. Although the shape memory alloy staple is more flexible than a stainless steel staple, it remains a relatively rigid implant spanning a motion segment and, thus, with preserved motion, is likely to loosen or break over time. Implant failure might likely be reduced by the elimination of motion across the disc space, either with ankylosis or fusion. However, with the purpose of preserving spinal motion using fusionless devices, this outcome is not desired.

The goal of our subsequent fusionless scoliosis implant testing was to evaluate the differences between first- and second-generation devices.80,81 As a first-generation device, the shape memory alloy staple demonstrated safety and efficacy as a fusionless scoliosis implant but offered two areas for potential improvement. These included the mechanism of attachment to bone and the overall rigidity of the implant. A hollow, threaded bone anchor with a ligament loop tether was designed to potentially address the shortcomings of the staple. In a head-to-head fashion, the effectiveness of these first- and second-generation devices in controlling scoliosis deformity in three dimensions was compared with additional sophisticated analyses of implant integrity.

In our subsequent fusionless scoliosis implant testing, 20 goats with progressive, structural, lordoscoliotic curves, created using a flexible posterior asymmetric tether, were randomized into one of three treatment groups. In the six goats that were left untreated, scoliosis progressed from 79.5° (range, 69°–89°) on average to 96.8° (range, 89°–108°) over the 12- to 16-week treatment period. In the seven goats that underwent anterior thoracic stapling (Figure 6) using one staple per level over the six levels of maximal deformity, scoliosis progressed from 77.3° (range, 59°–93°) to 94.3° (range, 78°–110°) over the same period. In contrast, the seven goats with the bone anchor/ligament tether construct, implanted over the six levels of maximal deformity (Figure 7), demonstrated no scoliosis progression and actually a modest scoliosis correction from 73.0° (range, 63°–84°) to 69.9° (range, 55°–82°) over the treatment period.

Figure 6

Figure 6

Figure 7

Figure 7

Using plain radiographs and computed tomography scans to further evaluate these 20 animals a three-dimensional deformity score (D) was created using scoliosis (S), lordosis (L) and axial rotation (R) measurements, where S + L + R = D. Both the untreated and stapled groups demonstrated progression in overall deformity from D = 148.3 (79.5(S) + 40.3(L) + 28.5(R)) to 185.8 (96.9(S) + 61.0(L) + 28.0(R)) and D = 149.6 (77.3(S) + 37.3(L) + 35.0(R)) to 182.7 (94.3(S) + 49.0(L) + 39.4(R)), respectively. The bone anchor/ligament tether group demonstrated an initial reduction in overall deformity score from D = 139.5 (73.0(S) + 44.4(L) + 22.1(R)) to 120.6 (62.0(S) + 37.1(L) + 21.4(R)) immediately following implantation, but this effect was lost over time (153.9(D) = 69.9(S) + 58.9(L) + 25.2(R)). The overall three-dimensional progression of deformity differed in these three groups not only quantitatively but qualitatively. Whereas the untreated group progressed in the coronal and sagittal planes, it did not progress in the axial plane. The stapled group progressed primarily in the coronal and axial planes and the bone anchor group progressed in the sagittal plane. The anterolateral vertebral body placement of the staple may have allowed slightly better control of sagittal plane deformity in this group. The direct lateral vertebral body placement of the bone anchors likely allowed better control of the coronal deformity at the expense of sagittal plane control.

Perhaps the improved control of deformity in multiple planes demonstrated by the bone anchor/ligament tether group was due to the integrity of these implants over the course of this study. Using plain radiographs, 43% (18 of 42) of staples demonstrate loosening (with two staples completely dislodged), whereas only 4% (2 of 49) of anchors demonstrated slight drift without radiolucency. Additional sophisticated analysis of implant integrity was carried out using three histologic indexes as well as implant pullout testing. Gross histologic evaluation of coronal sections, through the center of the implant and vertebral body, revealed a consistent halo of fibrous soft tissue around the staple tines and well-fixed bone anchors at all sites. This observation was consistent with the quantitative indexes of integrity obtained from backscattered electron imaging. Osseointegration values, representing the percentage of the implant osseointegrated with the host bone, were 40.1% ± 17.5% for the staples and 76.4% ± 6.8% for the anchors (P < 0.001). The bone proximity index, representing the average distance between the implant and host bone, measured 702 ± 138 μm for the staples and 215 ± 69 μm for the bone anchors. Additional fixation of the bone anchor was achieved through 11.0% ± 3.8% of bony ingrowth within the hollow chamber. Standard implant pullout testing was performed at two time points (time zero and 12–16 weeks postimplantation). The time zero pullout strength of the staple was 101.4 ± 23.0 N, which decreased to 86.0 ± 48.6 N following 12 to 16 weeks in vivo. In contrast, the pullout strength of the bone anchor significantly increased from 495.4 ± 171.3 N to 639.8 ± 213.4 N during the same time frame (P = 0.004).

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Study of Vertebral Growth Modulation

Although the etiology of idiopathic scoliosis is unknown, it is thought that mechanical factors play an important role in the progression of this deformity during growth.82–90 More specifically, the progression of vertebral wedge deformities is thought the be governed by the Hueter-Volkmann Law.91–96 Under this Law, growth plates subjected to increased compressive forces will demonstrate reduced growth, while those subjected to increased distractive forces will demonstrate accelerated growth. The vicious cycle established by this growth differential is thought to contribute to the progression of scoliosis deformity.97

Using a rat-tail model Stokes et al92 demonstrated that mechanical modulation of vertebral growth could be predicted by the Hueter-Volkmann Law. With the application of an external fixator to rat-tail vertebral segments symmetric compressive axial loads reduced growth to 68% of controls, whereas symmetric tensile axial loads augmented growth to 114% of controls. Subsequent studies of asymmetric loads applied to vertebral segments in a rat-tail not only resulted in differential growth but also allowed for the creation and correction of vertebral wedge deformities.94,95

Although Stokes et al92 laid the groundwork for additional studies of mechanical modulation of growth in the vertebrae, the rat-tail model did not provide adequate approximation of the anatomy and function of the spine. The rat-tail model is ideal for an isolated study of growth modulation in a single vertebra. However, the methods and fixators used in this model are not directly applicable to scoliosis. To better understand the mechanics of growth modulation in scoliosis, a true spinal deformity in a larger animal model, approximating the size of a juvenile human, was thought to be most appropriate.

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Study of Spinal Growth Modulation in an Experimental Goat Scoliosis Model

The goal of our initial spinal growth modulation study was twofold.98 First, to create vertebral wedge deformities at the apex of a progressive experimental scoliosis in the thoracic spine of an immature goat using a rigid posterior asymmetric tether. Second, to correct these same vertebral wedge deformities using convex vertebral body stapling after removal of the posterior asymmetric tether. Measurements of both the maximal curvature and the apical spinal segment (two adjacent vertebrae at the apex of the maximal curvature and the intervening disc) were made using the Cobb method.99

In this study, 14 goats with progressive, structural, lordoscoliotic curves, that progressed from 40.9° (range, 34°–50°) to 61.1° (range, 49°–73°) on average over a 7- to 13-week tethering period, also developed apical spinal segment wedging that progressed from 11.1° (range, 7°–16°) to 22.4° (range, 19°–33°) over the same period (P = 0.001). During the 7- to 13-week treatment period, wedging of the apical spinal segment in the stapled goats (n = 8) measured 22.5° on average (range, 19°–29°) at the start and 20.3° (range, 14°–30°) at the end for an average correction of −2.2° (Figure 8). Wedging of the apical spinal segment in the untreated goats (n = 6) measured 22.3° on average (range, 19°–33°) at the start and 25.8° (range, 20°–36°) at the end of the treatment period for an average progression of 3.5°. Although the correction in the stapled group of −2.2° was small, it was significant when compared with the 3.5° of progression in the untreated group (P < 0.05).

Figure 8

Figure 8

Although this initial spinal growth modulation study demonstrated a relative modulation of vertebral growth, using angular measurements across the apical spinal segment, our subsequent study of growth modulation sought to evaluate absolute growth as well. The goal of our subsequent spinal growth modulation study100 was to establish the role of the Hueter-Volkmann Law in governing absolute changes in growth on the concavity and convexity of the apical spinal segment. This study also sought to establish the role of a fusionless scoliosis treatment (shape memory alloy stapling) in reversing the Hueter-Volkmann effect. Using the same 14 goats from the initial study, additional measurements of convex and concave apical spinal segment heights were compared with 12 growth control goats matched for age, sex, and weight.

During the creation of scoliosis using a rigid posterior asymmetric tether (7- to 13-week tethering period), apical spinal segment growth in all tethered goats was decreased on the concavity by 78.0% (0.75 mm vs. 3.38 mm) and increased on the convexity by 33.3% (4.92 mm vs. 3.68 mm) when compared with growth controls (P < 0.001). During the 7- to 13-week treatment period, apical spinal segment growth was decreased on the concavity and convexity of stapled goats by 10.0% (3.71 mm vs. 4.11 mm) and 18.0% (4.14 mm vs. 5.03 mm), respectively, when compared with growth controls. Although the absolute and relative modulation of vertebral growth during the tethering period was governed by the Hueter-Volkmann Law, demonstrating decreased concave and increased convex growth, anterior vertebral body stapling was unable to fully reverse this effect during the treatment period. Rather than stimulating the lagging concave growth, and inhibiting the exuberant convex growth, stapling diminished growth both on the concavity and convexity.

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Discussion

Although many models for scoliosis exist, few achieve a three-dimensional deformity in a larger animal that approximates idiopathic scoliosis without violating the essential spinal elements along the maximal curvature. The scoliosis models used in our investigations use both rigid and flexible posterior asymmetric tethers, with convex rib resection and concave rib tethering, to achieve progressive, structural, lordoscoliotic curves in an immature goat. These methods consistently create right thoracic curves that span similar spinal segments creating uniformity among animals subsequently randomized to treated and untreated study groups. Additionally, a goat model was chosen as continued growth throughout the tethering and treatment periods could be reasonably predicted from previous investigations.101,102 This provided an ideal opportunity to compare the effectiveness of different fusionless scoliosis treatments in three dimensions, to analyze the integrity of implants over time and to evaluate the differential growth on the concavity and convexity of curves during progression of scoliosis and with subsequent fusionless scoliosis treatments.

As with all animal models, however, caution should be exerted when analogies to humans are made. First, the etiology of idiopathic scoliosis is unknown; therefore, true modeling of this disease is impossible. Second, forces acting on the spine of a quadruped are significantly different than those in a bipedal human. And third, the pyramidal shape of the goat thorax contrasts with the more cubical shape of the human thorax increasing the overall rigidity of the goat thoracic spine. Yet, given these limitations, the immature goat represents a reasonable approximation of a juvenile human with respect to general spinal anatomy, size of spinal osseous structures, contours in the sagittal and coronal planes, and growth potentials of the vertebrae. Additionally, the progression of vertebral wedge deformities, an essential factor in the progression of idiopathic scoliosis, is well simulated in our models according to the Hueter-Volkmann Law.

At present, motion preservation treatments, such as fusionless scoliosis surgery, are attractive because of the perceived theoretical advantages over current forms of treatment. However, little is understood about the biomechanics of fusionless scoliosis implants and their effect on the deformed spine and surrounding tissues. And with multiple proposed implant types and strategies on the horizon the optimal application of these devices may be difficult to establish. Rigorous testing of these novel implants and validation of various treatment strategies should proceed in a testing environment that allows for head-to-head comparison of devices, optimization of implant design, and identification of the most appropriate patient population for these interventions.

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Key Points

  • Fusionless scoliosis surgery is an emerging treatment for patients with idiopathic scoliosis as it offers theoretical advantages over current forms of treatment.
  • Animal model studies have demonstrated the safety and efficacy of a variety of fusionless scoliosis implants in treating experimental scoliosis and in modulating spinal growth.
  • 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.
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References

1.Bridwell K. Adolescent idiopathic scoliosis: Surgical treatment. In: Weinstein S, ed. The Pediatric Spine: Principles and Practice. New York: Raven Press, 1994:511–55.
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Keywords:

scoliosis; animal models; fusionless correction; growth modulation

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