Annette Kettler

Are animal models useful for studying human disc disorders / degeneration?

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material.

Are sheep spines a valid biomechanical model for human spines

Study Design. Range of motion, neutral zone, and stiffness parameters of the complete cervical, thoracic, and lumbar sheep spine were determined in flexion and extension, axial left/right rotation, and right/left lateral bending. Objectives. To determine quantitative biomechanical properties of the sheep spine and compare them with those from the human spine. Summary of Background Data. Sheep spines often serve as a model for experimental in vivo and in vitro studies in spine research, but few quantitative biomechanical data from sheep spines for comparison with human specimens are available. Methods. Complete spines were sectioned into single‐joint segments and tested in a spine tester under pure moments in the three main anatomic planes. Results. The craniocaudal variation in range of motion in all load directions was qualitatively similar between sheep spines and values reported in the literature for human specimens. Conclusions. Based on the biomechanical similarities of sheep and human spines demonstrated in this study, it appears that the use of the sheep spine, which already includes evaluation of surgical techniques and bone healing processes, might be extended to spinal implants.

Anatomy of the sheep spine and its comparison to the human spine

The sheep spine is often used as a model for the human spine, although the degree to which these spines are anatomically comparable has yet to be categorically established. The purpose of this study was to investigate the characteristic anatomical dimensions of the sheep spine and to compare these with existing human data.

Review of existing grading systems for cervical or lumbar disc and facet joint degeneration

The aim of this literature review was to present and to evaluate all grading systems for cervical and lumbar disc and facet joint degeneration, which are accessible from the MEDLINE database. A MEDLINE search was conducted to select all articles presenting own grading systems for cervical or lumbar disc or facet joint degeneration. To give an overview, these grading systems were listed systematically depending on the spinal region they refer to and the methodology used for grading. All systems were checked for reliability tests and those recommended for use having an interobserver Kappa or Intraclass Correlation Coefficient >0.60 if disc degeneration was graded and >0.40 if facet joint degeneration was graded. MEDLINE search revealed 42 different grading systems. Thirty of these were used to grade lumbar spine degeneration, ten were used to grade cervical spine degeneration and two were used to grade both. Thus, the grading systems for the lumbar spine represented the vast majority of all 42 grading systems. Interobserver reliability tests were found for 12 grading systems. Based on their Kappa or Intraclass Correlation Coefficients nine of these could be recommended for use and three could not. All other systems could neither be recommended nor not be recommended since reliability tests were missing. These systems should therefore first be tested before use. The design of the grading systems varied considerably. Five grading systems were beginning with the lowest degree of degeneration, 37, however, with the normal, not degenerated state. A 5-grade scale was used in six systems, a 4-grade scale in 24, a 3-grade scale in eight and a 2-grade scale in three systems. In 15 cases the normal, not degenerated state was assigned to “grade 0”, in another 15 cases, however, this state was assigned to “grade 1”. This wide variety in the design of the grading systems makes comparisons difficult and may easily lead to confusion. We would therefore recommend to define certain standards. Our suggestion would be to use a scale of three to five grades, to begin the scale with the not degenerated state and to assign this state to “grade 0”.

Biomechanical effect of different lumbar interspinous implants on flexibility and intradiscal pressure

Interspinous implants are used to treat lumbar spinal stenosis or facet joint arthritis. The aims of implanting interspinous devices are to unload the facet joints, restore foraminal height and provide stability especially in extension but still allow motion. The aim of this in vitro study was to compare four different interspinous implants––Colfex, Wallis, Diam and X-Stop––in terms of their three-dimensional flexibility and the intradiscal pressure. Twenty-four human lumbar spine specimens were divided into four equal groups and tested with pure moments in flexion/extension, lateral bending and axial rotation: (1) intact, (2) defect, (3) after implantation. Range of motion and the intradiscal pressure were determined.In each implant-group the defect caused an increase in range of motion by about 8% in lateral bending to 18% in axial rotation. Implantation had similar effects with all four implants. In extension, Coflex, Wallis, Diam, and X-Stop all overcompensated the instability caused by the defect and allowed about 50% of the range of motion of the intact state. In contrast, in flexion, lateral bending and axial rotation the values of the range of motion stayed about the values of the defect state. Similarly the intradiscal pressure after implantation was similar to that of the intact specimens in flexion, lateral bending and axial rotation but much smaller during extension. All tested interspinous implants had a similar effect on the flexibility: they strongly stabilized and reduced the intradiscal pressure in extension, but had almost no effect in flexion, lateral bending and axial rotation.

Intradiscal pressure, shear strain, and fiber strain in the intervertebral disc under combined loading

Study Design. Finite element study. Objective. To investigate intradiscal pressure, shear strain between anulus and adjacent endplates, and fiber strain in the anulus under pure and combined moments. Summary of Background Data. Concerning anulus failures such as fissures and disc prolapses, the mechanical response of the intervertebral disc during combined load situations is still not well understood. Methods. A 3-dimensional, nonlinear finite element model of a lumbar spinal segment L4–L5 was used. Pure unconstraint moments of 7.5 Nm in all anatomic planes with and without an axial preload of 500 N were applied to the upper vertebral body. The load direction was incrementally changed with an angle of 15° between the 3 anatomic planes to realize not only moments in the principle motion planes but also moment combinations. Results. Intradiscal pressure was highest in flexion and lowest in lateral bending. Load combinations did not increase the pressure. A combination of lateral bending plus flexion or lateral bending plus extension strongly increased the maximum shear strains. Lateral bending plus axial rotation yielded the highest increase in fiber strains, followed by axial rotation plus flexion or axial rotation plus extension. The highest shear and fiber strains were both located posterolaterally. An additional axial preload tended to increase the pressure, the shear, and fiber strains essentially for all load scenarios. Conclusions. Combined moments seem to lead to higher stresses in the disc, especially posterolaterally. This region might be more susceptible to disc failure and prolapses. These results may help clinicians better understand the mechanical causes of disc prolapses and may also be valuable in developing preventive clinical strategies and postoperative treatments.

Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion cage.

Study Design. A biomechanical in vitro subsidence test of different cervical interbody fusion devices was performed using a new testing protocol that simulates physiologic conditions. Objectives. To investigate the effect of simulated postoperative neck movements on the subsidence of the new WING cervical interbody fusion cage in comparison with two other cages and bone cement. Summary of Background Data. Cervical interbody fusion cages sometimes cause complications because of subsidence into the adjacent vertebrae with collapse of the intervertebral space. Complications such as cage dislocation or nonunion with instability also have been reported. To prevent such complications, the new WING cervical interbody fusion cage (Medinorm AG, Quierschied, Germany) has been developed. Its area of contact with the adjacent vertebrae is supposed to be large enough to resist excessive subsidence and small enough to prevent stress protection of the tissue growing in the cage. Methods. In this study, 24 human cervical spine specimens were tested after stabilization with either a WING, BAK/C, AcroMed I/F cage or bone cement. Then, in a new testing protocol, 700 pure-moment loading cycles (±2 Nm) were applied in randomized directions (lateral bending, flexion–extension, and axial rotation alone or in combination with each other) to simulate the patient’s neck movements during the first few postoperative days. Measurements of the subsidence depth (total height loss) in combination with flexibility tests (±2.5 Nm) were performed before cyclic loading and after 50, 100, 200, 300, 500, and 700 loading cycles. Results Cyclic loading caused subsidence in all four device groups, most distinct with BAK/C-cages (1.63 mm after 700 loading cycles) followed by the new WING (0.90 mm) and the AcroMed (0.82 mm) cages. No statistically significant difference could be found among the three cage designs. However, all three cage types showed a significantly higher subsidence depth than bone cement (0.48 mm;P = 0.023 between each of the three cage-types and bone cement). A moderate correlation between bone mineral density and subsidence depth could be found only in the BAK/C group (r2 = 0.495). A large subsidence depth after 700 loading cycles was associated with a large flexibility increase in the WING (r2 = 0.786) and AcroMed groups (r2 = 0.21), but with a small flexibility increase in the BAK/C group (r2 = 0.58). Conclusions. Postoperative neck movements caused subsidence in all cervical interbody implant types. The new WING cage and the AcroMed cage seemed to have a better resistance against subsidence than the BAK/C cage. However, all three cage types had a significantly higher subsidence tendency than bone cement.

Are the spines of calf, pig and sheep suitable models for pre-clinical implant tests?

Pre-clinical in vitro tests are needed to evaluate the biomechanical performance of new spinal implants. For such experiments large animal models are frequently used. Whether these models allow any conclusions concerning the implant’s performance in humans is difficult to answer. The aim of the present study was to investigate whether calf, pig or sheep spine specimens may be used to replace human specimens in in vitro flexibility and cyclic loading tests with two different implant types. First, a dynamic and a rigid fixator were tested using six human, six calf, six pig and six sheep thoracolumbar spine specimens. Standard flexibility tests were carried out in a spine tester in flexion/extension, lateral bending and axial rotation in the intact state, after nucleotomy and after implantation. Then, the Coflex interspinous implant was tested for flexibility and intradiscal pressure using another six human and six calf lumbar spine segments. Loading was carried out as described above in the intact condition, after creation of a defect and after implantation. The fixators were most easily implantable into the calf. Qualitatively, they had similar effects on ROM in all species, however, the degree of stability achieved differed. Especially in axial rotation, the ROM of sheep, pig and calf was partially less than half the human ROM. Similarly, implantation of the Coflex interspinous implant caused the ROM to either increase in both species or to decrease in both of them, however, quantitatively, differences were observed. This was also the case for the intradiscal pressure. In conclusion, animal species, especially the calf, may be used to get a first idea of how a new pedicle screw system or an interspinous implant behaves in in vitro flexibility tests. However, the effects on ROM and intradiscal pressure have to be expected to differ in magnitude between animal and human. Therefore, the last step in pre-clinical implant testing should always be an experiment with human specimens.

Do early stages of lumbar intervertebral disc degeneration really cause instability? Evaluation of an in vitro database

Early stages of intervertebral disc degeneration are postulated to cause instability. In the literature, however, some authors report the opposite. These contradictory positions are probably supported by the mostly small number of segments which are investigated. The aim of this project therefore was to investigate the influence of intervertebral disc degeneration on lumbar spine rotational stability using a large data set. The flexibility data from all spine specimens tested in our institute so far were collected in a large in vitro database. From this database, all lumbar spine specimens were selected, which had been tested for flexibility under pure moment loads of ±7.5 N m and for which radiographs were accessible. 203 segments met these criteria. Their radiographic degree of disc degeneration was determined on a scale from 0 (no degeneration) to 3 (severe degeneration) and their influence on the respective range of motion and neutral zone was examined. The different lumbar levels differ in flexibility, which increases the variability of the data if pooled together. To minimise this effect a statistical model was fitted. The model-based mean estimates showed a decrease of the range of motion from grade 0 to 3 in flexion/extension (by 3.1°, p 0.05). The neutral zone was affected in a similar way but to a smaller degree (p > 0.05). In conclusion, the results indicated that early stages of intervertebral disc degeneration do not necessarily cause rotational instability. In contrast, stability increased in flexion/extension and lateral bending. Only in axial rotation stability tended to decrease.

Primary stabilizing effect of interbody fusion devices for the cervical spine: an in vitro comparison between three different cage types and bone cement

Abstract Interbody fusion cages are small hollow implants that are inserted into the intervertebral space to restore physiological disc height and to allow bony fusion. They sometimes cause clinical complications due to instability, subsidence or dislocation. These are basic biomechanical parameters, which influence strongly the quality of a fusion device; however, only few data about these parameters are available. Therefore, the purpose of the present study was to investigate the primary stabilizing effect of four different cervical fusion devices in in vitro flexibility tests. Twenty-four human cervical spine segments were used in this study. After anterior discectomy, fusion was performed either with a WING cage (Medinorm AG, Germany), a BAK/C cage (Sulzer Spine-Tech, USA), an AcroMed cervical I/F cage (DePuy AcroMed International, UK) or bone cement (Sulzer, Switzerland). All specimens were tested in a spine tester in the intact condition and after implantation of one of the four devices. Alternating sequences of pure lateral bending, flexion-extension and axial rotation moments (± 2.5 Nm) were applied continuously and the motions in each segment were measured simultaneously. In general, all tested implants had a stabilizing effect. This was most obvious in lateral bending, where the range of motion was between 0.29 (AcroMed cage) and 0.62 (BAK/C cage) with respect to the intact specimen (= 1.00). In lateral bending, flexion and axial rotation, the AcroMed cervical I/F cages had the highest stabilizing effect, followed by bone cement, WING cages and BAK/C cages. In extension, specimens fused with bone cement were most stable. With respect to the primary stabilizing effect, cages, especially the AcroMed I/F cage but also the WING cage and to a minor extent the BAK/C cage, seem to be a good alternative to bone cement in cervical interbody fusion. Other characteristics, such as the effect of implant design on subsidence tendency and the promotion of bone ingrowth, have to be determined in further studies.