Purpose of study: To develop an experimental model of degenerative disc disease without direct intervention of the intervertebral disc (IVD). Our hypothesis was that inducing vertebral body damage at sites adjacent to the IVD would modify nutrient transport through the end plates and thus initiate degeneration in a manner relevant to degenerative disc disease in humans.Methods used: Vertebral body defects were created in lumbar motion segments of minipigs (10 experimental and 7 control levels, n=3). A high-speed drill with a diamond burr (3 to 5 mm diameter) was used to remove bone adjacent to the inferior and superior end plates of the experimental IVDs. A resorbable calcium phosphate bone cement was then packed into the defects. Spines were harvested at 3, 6 and 9 months and imaged in the sagittal plane with high-resolution magnetic resonance imaging (MRI; 7.1 T). Four blinded observers graded MRI appearance with the scheme of Thompson and coworkers (1990; 1 = nondegenerate, 5 = severely degenerate). In addition, MRI data sets were analyzed to determine changes in disc height and signal intensity for regions corresponding to the nucleus pulposus (NP) and anterior and posterior anulus fibrosus (AF). After imaging, individual motion segments were processed for routine histology (toluidine blue, hemotoxylin and eosin) and immunohistochemistry to detect matrix proteins including type II collagen and decorin.of findings: Higher MRI grades of degeneration were observed in all experimental IVD regions at 9 months after surgery. Reviewer grades were significantly higher for both NP (average of four graders = 1.8 vs. 3.8, control vs. experimental) and AF at 9 months after surgery (1.7 vs. 3.4). There was some evidence of end plate changes beginning at 3 months after surgery (1.5 vs. 2.3, control vs. experimental), which became quite dramatic at 9 months (1.4 vs. 4.5). No differences were noted in disc height between control and experimental IVDs at any region. However, decreases in MRI signal intensity (normalized to maximum values) were noted in experimental IVDs, particularly in the anterior AF (mean, 39%) and NP at 9 months (15%). Decreased signal intensity is a hallmark of IVD degeneration in the human, suggesting loss of hydration. Upon histological examination, there was evidence of inward bulging of the inner AF, end plate damage and decreased NP staining. Immunostaining demonstrated increased collagen type II in the experimental sections compared with controls, although few consistent changes were noted in the expression of decorin. Increases in the levels of both collagen type II and decorin have been demonstrated in other animal models of IVD degeneration and in human disease.Relationship between findings and existing knowledge: Overall, the changes observed in this experimental model confirm some key features of human IVD degeneration, including increased radiographic grade of degeneration, decreased MRI intensity and morphological and histological changes, such as increased staining for collagen type II and decreased staining of the NP. Holm and coworkers (1999) demonstrated that a controlled vertebral end plate defect will induce compositional and morphological evidence of disc degeneration in an animal model. Findings of the current study demonstrate that disruption of the vertebral body alone, without controlled violation of the end plate, may serve to initiate disc degeneration without direct, surgical injury of the IVD.Overall significance of findings: The mechanism for the onset of degeneration is not known but may relate to a role of vertebral body damage in altering nutrient transport across the end plate.Disclosures: No disclosures.Conflict of interest: William J. Richardson, grant research support, DePuy Orthobiologics.
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Dec 1, 2003
Hala Zreiqat + 3
Open Access