Degenerative Changes Following Spinal Fixation in a Small Animal Model
 
   

Degenerative Changes Following Spinal Fixation
in a Small Animal Model

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:
   Frankp@chiro.org
 
   

FROM:   J Manipulative Physiol Ther 2004 (Mar);   27 (3):   141–154

Gregory D Cramer, DC, PhD, Jaeson T Fournier, DC, MPH, Christopher C Wolcott, DC, Charles N.R Henderson, DC, PhD

Department of Research, National University of Health Sciences, 200 E Roosevelt Road, Lombard, IL 60148, USA. gcramer@nuhs.edu


OBJECTIVE:   The objective of this study was to evaluate changes of the lumbar vertebral column following fixation.

DESIGN:   Using an established small animal (rat) model of spinal fixation (hypomobility), 3 contiguous lumbar segments (L4, L5, L6) were fixed with a specially engineered vertebral fixation device. Spinal segments of control rats were compared with those of animals with 1, 4, or 8 weeks of fixation. Subgroups of these fixation animals subsequently had the fixation device removed for 1, 2, 4, 8, or 12 weeks to evaluate the effects of attempting to reestablish normal forces to the vertebral segments following hypomobility.

SETTING:   This Institutional Animal Care and Use Committee (IACUC) approved study was conducted in a university animal facility.

ANIMALS:   Eighty-seven animals (23 controls animals and 64 fixation animals) were used in this study.

MAIN OUTCOME MEASURES:   Outcome measures were degenerative changes of the vertebral bodies (VBs) and intervertebral disks (IVDs), zygapophysial (Z) joint osteophyte formation, and Z joint articular surface degeneration (ASD). Changes found in vertebral segments that were fixed (hypomobile) were compared with changes in adjacent nonfixed vertebral segments, and changes among fixation animals were compared with nonfixed controls.

MAIN RESULTS:   Very few degenerative changes were identified on the VBs and IVDs. Z joint changes were significant, both for osteophyte formation (analysis of variance [ANOVA], P <.0001) and ASD (ANOVA, P <.0001). Fixed segments had more degenerative changes than nonfixed segments for all Z joint parameters (ANOVA, P <.0001). Osteophyte formation and ASD were directly dependent on duration of fixation.

CONCLUSIONS:   These findings indicate that fixation (hypomobility) results in time-dependent degenerative changes of the Z joints.


From the Full-Text Article:

Discussion

Vertebral Body and Intervertebral Disk Degeneration

The reason for the low incidence of vertebral body (VB) and intervertebral disk (IVD) degeneration may be due to the success of the model in producing hypomobility rather than fusion. The results of biomechanical testing support the hypothesis that hypomobility (rather than fusion or no mobility) is created in this animal model. [11] In addition, when the dissected spines with the linked attachment devices (SAUs) still in place (FNR animals) were moved into flexion or extension by an investigator, slight movement was seen at the Z joints, but more motion was subjectively observed at the VBs and IVDs, which were further from the point of fixation. The vertical bars that were a part of the SAUs were important in the fixation process. These bars extended 12 mm posterior to the spinous processes. The horizontal linking bars used to create fixation were attached to the vertical bars by means of a bolt coursing through a hole in each vertical bar that was approximately 10 mm posterior to the spinous process (2 mm from the distal tip of the vertical bar). Therefore, the VBs and IVDs were a considerable distance from the point of fixation. The extremely low incidence of degenerative changes seen in the VBs and IVDs of this study supports the hypothesis that the fixation model used was truly a model of spinal hypomobility, which is thought to be a much more common clinical presentation than spinal fusion (found only in cases of ankylosis or arthrodesis).

Z Joints

Fixed segments versus nonfixed segments

The marked differences between fixed segments versus nonfixed segments for all Z joint parameters in the combined fixation group provide strong evidence that the fixation devices did produce a difference between the 2 types of segments (fixed versus nonfixed). This is further supported by the findings that for every Z joint parameter, there was no difference between corresponding segments in either the Cnull or Csau control groups. This latter finding indicates that neither the surgery nor the placement of the SAUs on the spinous processes resulted in the changes found in the fixed Z joints. Therefore, the differences found in the fixation groups of this study were most likely due to the linking of the SAUs (and the resultant hypomobility of the Z joints).


Fixation position

There were no differences found among the 3 different fixation configurations (Fn, fixed in neutral; Ff, fixed in flexion; and Fr, fixed in rotation) for any of the parameters of degeneration. This indicates that decreased vertebral motion alone (hypomobility) was more important in the development of degenerative changes than the position in which the vertebrae were fixed during the period of decreased motion.


Osteophytes

The data of Tables 5 and 6; Figure 4, A and B; and the results of the inferential analyses indicate that there was a threshold between 4 and 8 weeks of fixation when the osteophytes became so severe that there was very little return to normal even after a considerable length of time. This also corresponds to a preliminary report of biomechanical data of spine stiffness using this animal model. [11]


Articular Surface Degeneration

With respect to ASD, the data of Tables 7 and 8; Figure 6, A and B; and the results of the inferential analyses indicate that ASD occurred earlier than osteophytic formation, with a threshold of between 1 and 4 weeks of fixation. After this threshold was reached, the ASD became so severe that there was very little return to normal after removal of the linking bars. Therefore, ASD was found to occur first, followed by the development of osteophytes. These findings indicate that fixation resulted in reversible degenerative changes that became progressively more severe (and less apt to reverse) with time. For each type of degenerative change evaluated in this study, there appeared to be a rather distinct time threshold; after this threshold was reached, a decrease in degenerative changes–even after the linking devices were removed from the SAUs–was unlikely. This lack of remission, once a critical time threshold was reached, may be clinically significant and emphasizes the potential importance of maintaining intersegmental motion through the application of spinal manipulative therapy. Further study is needed to determine the effects of spinal manipulative therapy on the time thresholds of degenerative changes and its effectiveness in reducing hypomobility need to be studied in this animal model. Such studies are in progress.


Time Thresholds for Degenerative Changes

Osteophytic formation and ASD were not significantly different in fixation versus control animals before 8 weeks and 4 weeks of fixation, respectively. One reason for the lack of difference between control and fixation groups in these earlier time frames can be attributed to a relative reduction of degenerative findings in the subgroups of animals that had the fixation devices removed for varying periods. This also supports the notion that the degenerative changes were reversible up to a certain time threshold, after which degenerative changes remained relatively constant (ie, were found to remain throughout the 12-week postfixation survival time of this study). Articular surface degeneration changes that showed no signs of reversal occurred between 1 and 4 weeks of fixation (hypomobility); osteophytic changes that showed no signs of reversal occurred between 4 and 8 weeks of fixation in the rat. These findings suggest that inducing motion into hypomobile segments as early as possible and before this threshold is reached may be clinically important. Estimating the human equivalent of the ages of the animals and the time span for the formation of degenerative changes in this study would be purely speculative and could be misleading.


Fixation No Release Animals

A direct relationship was found between duration of fixation and development of degenerative changes in the Z joints in the FNR animals (with 2 exceptions in the single 8-week fixation animal). These results support those presented above. That is, as the time of fixation increased, ASD and osteophytic changes increased.


Future Work

Future work is planned to evaluate the effects of spinal adjusting (mobilization of previously fixed segments) to determine if this changes the time profile found in this study. In addition, further work is being done to evaluate the development of adhesions within the Z joints following fixation (hypomobility). The Z joints of the rat have very large synovial folds that attach to the Z joint capsule. This is similar to the anatomy of human Z joints, which also have prominent synovial folds. [15, 16]. Putative Z joint adhesions would course from the articular cartilage of the cephalad and caudad articular facets to these synovial folds. Because the capsules (and the large synovial folds) were removed in this investigation, Z joint adhesions could not be investigated in this study. Work on the same animal model is currently being conducted in our laboratory to evaluate horizontal sections of the Z joints under light microscopy. Horizontal sections allow the Z joint capsules and synovial folds to remain intact, thus allowing for evaluation of any adhesions attaching the articular cartilage to the synovial folds.


Conclusion

Degenerative changes were found in the Z joints following spinal fixation in this animal model. In addition, degenerative changes of the articular surfaces preceded the slower formation of new bone required for the development of osteophytes. The average severity of the degenerative changes (degeneration severity parameters) supports the findings from the total number of osteophytes per animal and facetal surfaces showing signs of degeneration per animal (degeneration occurrence parameters). These results support the hypothesis that degenerative changes follow hypomobility of the Z joints and are consistent with the theoretical model shown in Figure 1. Future studies are planned to evaluate the effects of spinal adjusting on the time profiles of the degenerative changes found in this study and on the development of adhesions following fixation (hypomobility) of the Z joints.

We conclude that Z joint changes occur following spinal fixation in this rat model, and the amount and severity of degeneration is time-dependent with a threshold of between 4 and 8 weeks for the development of osteophytic changes that showed no signs of reversal and between 1 and 4 weeks for ASD changes of a similar magnitude.


Figure 1
Theoretical model of hypomobility and reversal via manipulation. Steps 1 and 2 outline the hypothesis that degenerative changes may occur in hypomobile Z joints. Some of the reasons for the development of hypomobility in the Z joints include prolonged sitting (as in certain occupations) with little or no exercise, prolonged standing with little or no exercise, or repetitive motions (for example, some assembly line tasks). Repetitive motions allow some joints to move, while others remain relatively stationary. Some of the degenerative changes referred to in step 2 are frequently described as adhesions. Other changes are described as thickening of the Z joint capsule and degenerative changes of the Z joint articular processes and facetal surfaces. Steps 3 through 5 portray a hypothesis of the mechanism of action of chiropractic adjusting on hypomobile (fixed) Z joints.

Figure 2
Specially designed and engineered external linking system used in this study. Left, linking system from a dorsal (top) view; right, same system from right lateral view. Notice SAUs fit over the lower 3 lumbar spinous processes. VFD, Vertebral fixation device; SAU, saddle-shaped spinal attachment units.

Figure 4
A and B, Z joint osteophyte formation on external surfaces of 2 L5 cephalad articular processes for the degeneration severity parameter. A is from a control animal (Cnull, 8-week), and B is from an 8-week fixation animal. Large white arrows (A) show smooth cephalad edge of articular process with no signs of osteophyte formation; Arrowheads (B) outline a +3 osteophyte. C and D, Internal surfaces of 2 L5 cephalad articular processes demonstrating Z joint articular cartilage degeneration for the degeneration severity parameter. C is from a control animal (Csau, 1-week), and D is from a 4-week fixation animal. Notice that hyaline articular cartilage of the control animal (C) is quite smooth, while that of the 4-week fixation animal (D) has marked roughening, pitting, and remodeling. The remodeling is so marked in D that the ventral portion of the articular process (bottom) is out of the plane of maximum focus. In addition, subchondral bone is exposed on dorsal portion of the articular process (hyaline articular cartilage has eroded). Arrows show deep pits within Z joint articular cartilage and subchondral bone. H, Hyaline cartilage on Z joint facet of cephalad articular process; S, subchondral bone.



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