Bernard A. Rawlins

Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression

Axial and radial specimens of non-degenerate and degenerate human anulus fibrosus (AF) were tested in confined compression to test the hypothesis that degeneration significantly affects the compressive properties of AF. Due to the highly oriented structure of AF, a secondary objective was to investigate anisotropic behaviors of AF in compression. Uniaxial swelling and stress relaxation experiments were performed on site-matched samples of anulus from the anterior outer region of L2-3 intervertebral discs. The experimental stress-relaxation behavior was modeled using the finite deformation biphasic theory and a finite-difference approximation scheme. Significant effects of degeneration but not orientation were detected for the reference stress offset, sigma(offset), and parameters describing the compressive stiffness (i.e. reference aggregate modulus, H(A0), and nonlinear stiffening coefficient, beta). Average values were 0.13+/-0.06 and 0.05+/-0.05 MPa for sigma(offset), 0.56+/-0.21 and 1.10+/-0.53 MPa for H(A0) and 2.13+/-1.48 and 0.44+/-0.61 for beta for all normal and degenerate specimens, respectively. No significant effect of degeneration or orientation were detected for either of the parameters describing the strain-dependent permeability (i.e. reference permeability, k0 and strain-dependent permeability coefficient, M) with average values for all specimens of 0.20+/-0.10 x 10(-15) m4/N-s and 1.18+/-1.30 for k0 and M, respectively. The loss of sigma(offset) was compensated with an elastic stiffening and change in the shape of the equilibrium stress-strain curve with H(A0) for degenerate tissues almost twice that of normal tissues and beta less than one sixth. The increase in reference elastic modulus with degeneration is likely related to an increase in tissue density resulting from the loss of water content. The significant effects of degeneration reported in this study suggested a shift in load carriage from fluid pressurization and swelling pressure to deformation of the solid matrix of the AF. The results also suggest that the highly organized and layered network of the anulus fibrosus, which gives rise to significant anisotropic effects in tension, does not play a major role in contributing to the magnitude of compressive stiffness or the mechanisms of fluid flow of the anulus in the confined compression configuration.

Combined Bone Morphogenetic Protein-2 and −7 Gene Transfer Enhances Osteoblastic Differentiation and Spine Fusion in a Rodent Model†

To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer.

The anisotropic hydraulic permeability of human lumbar anulus fibrosus. Influence of age, degeneration, direction, and water content

STUDY DESIGN Experimental investigation to determine the effect of intervertebral disc degeneration on the kinetic behavior of fluid in human anulus fibrosus. OBJECTIVES To measure the hydraulic permeability coefficient of anulus fibrosus specimens in the axial, circumferential, and radial directions to determine the anisotropic permeability behavior of nondegenerate and degenerate human intervertebral discs over a range of ages. SUMMARY OF BACKGROUND DATA Fluid, a major component of normal intervertebral discs, plays a significant role in their load-supporting mechanisms. Transport of fluid through the intervertebral disc is important for cell nutrition and disc viscoelastic and swelling behaviors. The hydraulic permeability coefficient is the most important material property governing the rate of fluid transport. However, little is known about the anisotropic behavior of this kinetic property and how it is influenced by disc degeneration. METHODS Using a permeation testing apparatus developed recently, testing was performed on 306 axial, circumferential, and radial anulus fibrosus specimens from the posterolateral region of 30 human lumbar (L2-L3) discs. A new method, flow-controlled testing protocol, was developed to measure the hydraulic permeability coefficient. RESULTS The hydraulic permeability coefficient of anulus fibrosus depended significantly on the disc degenerative grade (P = 0.0001) and flow direction (P = 0.0001). For the nondegenerate group (Grade I), the hydraulic permeability was significantly anisotropic (P < 0.05), with the greatest value in the radial direction (1.924 x 10(-15) m4/Ns) and the lowest value in the circumferential direction (1.147 x 10(-15) m4/Ns). This anisotropic kinetic (flow) behavior of anulus fibrosus varied with disc degeneration. For the Grade III specimen group, there was no significant difference in hydraulic permeability coefficient among the three major directions (P = 0.37). With disc degeneration, the hydraulic permeability coefficient was decreased in the radial direction and increased in the axial and circumferential directions. The variations of hydraulic permeability coefficient from nondegenerate discs (Grade I) to mildly degenerate discs (Grade II) in each direction were significant (P < 0.05). However, the changes in permeability from Grade II to Grade III groups were not significant (P > 0.05) except in the circumferential direction (3.8% increase; P < 0.05). CONCLUSIONS The hydraulic permeability of human nondegenerate anulus fibrosus is direction-dependent (i.e., anisotropic), with the greatest permeability in the radial direction. With disc degeneration, the radial permeability of anulus fibrosus decreases, mainly because of decreased water content, and the axial and circumferential permeability coefficients increase, mainly because of structural change, leading to more isotropic permeability behavior for Grade III discs.

A Novel Regulatory Role for Stromal-derived Factor-1 Signaling in Bone Morphogenic Protein-2 Osteogenic Differentiation of Mesenchymal C2C12 Cells

Stromal-derived factor 1 (SDF-1) is a chemokine with important functions in development and postnatal tissue homeostasis. SDF-1 signaling via the G-protein-coupled receptor CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study we examined the contribution of SDF-1 signaling to osteogenic differentiation of mesenchymal C2C12 cells induced by bone morphogenic protein 2 (BMP2). Blocking SDF-1 signaling before BMP2 stimulation by treatment with siRNA, antibodies against SDF-1 or CXCR4, or the G-protein-coupled receptor inhibitor pertussis toxin strongly suppressed BMP2 induction of osteogenic differentiation in C2C12 cells, as evidenced by an early decrease in the expression of the myogenesis inhibitor Id1, the osteogenic master regulators Runx2 and Osx, the osteoblast-associated transcription factors JunB, Plzf, Msx2, and Dlx5, and later of the bone marker proteins osteocalcin and alkaline phosphatase. Similarly, blocking SDF-1/CXCR4 signaling strongly inhibited BMP2-induced osteogenic differentiation of ST2 bone marrow stromal cells. Moreover, we found that the interaction between SDF-1 and BMP2 signaling was mediated via intracellular Smads and MAPK activation. Our data provide the first evidence for a co-requirement of the SDF-1/CXCR4 signaling axis in BMP2-induced osteogenic differentiation of C2C12 and ST2 cells and, thus, uncover a new potential target for modulation of osteogenesis.

Partial lumbosacral kyphosis reduction, decompression, and posterior lumbosacral transfixation in high-grade isthmic spondylolisthesis: clinical and radiographic results in six patients.

Background. In an attempt to increase fusion while decreasing the neurologic risk associated with complete reduction of high-grade spondylolisthesis, the authors have used a technique of partial lumbosacral kyphosis reduction, posterior decompression, and pedicle screw transfixation of the lumbosacral junction. Objective. To determine if this technique is effective in treatment of high-grade spondylolisthesis. Study Design. A retrospective review of six patients with high-grade spondylolisthesis treated by this technique was performed. There were four female patients (ages 16 years [n=2], 23 years [n=1], and 29 years [n=1]) and two male patients (both 13 years of age) with spondylolisthesis ranging from Grade IV to Grade V. All patients presented with pain and radiculopathy. After surgery the patients were evaluated for resolution of symptoms, sagittal alignment, fusion, and satisfaction. The radiographic measurements included the slip angle, the percentage slip, and the sacral inclination. An SRS outcome score was also obtained on all six patients to evaluate postoperative outcome, in terms of pain control, self-image perception, and return to function. Results. The average length of follow-up was 42.6 months (range 24–60 months). All patients evidenced solid fusion by the 6-month follow-up (based on oblique radiographs showing lateral bridging bone masses). The slip angle was improved from 62° to 28° (P < 0.5), whereas there was no significant improvement in the percentage slip or the sacral inclination (89–80% and 28–37°, respectively). No progression of the slip angle or percentage slip was noted on the follow-up radiographs. Complications included two intraoperative dural tears that were identified and repaired. There were no neurologic complications. The SRS outcome instrument demonstrated good postoperative pain control, function, self-image, and satisfaction in all patients. Conclusion. In high-grade spondylolisthesis, this posterior approach is safe and effective in obtaining a solid arthrodesis, restoring sagittal balance, and improving function. These results reinforce the impression that it is the partial reduction of the slip angle, not the percentage slip, in high-grade spondylolisthesis that is important in obtaining optimal results.

Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone.

Study Design. Prospective study to assess the enhancement of spine fusion using a tissue engineering construct consisting of bone marrow cells genetically modified by adenovirus (Ad) vector-encoding bone morphogenetic protein-7 (BMP-7) seeded onto an allograft scaffold in a rat model. Objectives. To evaluate Ad transgene expression at the fusion site and the effect of AdBMP-7-treatment on fusion rates, mechanical stability, microscopic anatomy, and bone formation rates. Summary of Background Data. Nonunion is a major complication of spine fusion. Gene transfer may be an effective method for locally overexpressing BMP-7, a gene important for bone formation and regeneration to enhance allograft spine fusion. Materials and Methods. Bone marrow cells were treated with AdBMP-7 or Ad&bgr;gal (encoding the marker gene &bgr;-galactosidase), AdNull (with no gene), or no vector and implanted with allograft in a site of posterior spine fusion. Marker gene expression was assessed up to 14 days after administration. Fusions were evaluated at 8 weeks. Results. Ad gene expression was maximal on day 3, waning to background levels by 14 days. With AdBMP-7 treatment, radiographic fusion rate was 70% and mechanical fusion rate was 80%versus 0% by either parameter in control groups. Fused AdBMP-7-treated spines had a 2.5-fold to 3.0-fold lower range of motion and 1.7-fold to 1.9-fold lower hysteresis than controls. Fusion masses of AdBMP-7-treated spines had the microscopic appearance of normal trabecular bone and showed a 23-fold higher uptake of fluorochrome indicating increased bone formation. Conclusions. Addition of AdBMP-7-modified marrow cells can enhance allograft spine fusion.

Clinical Value of Routine Preoperative Magnetic Resonance Imaging in Adolescent Idiopathic Scoliosis: A Prospective Study of Three Hundred and Twenty-seven Patients

Background: The prevalence of intraspinal pathology associated with scoliosis has been reported to be as high as 26% in some series1, and, on the basis of this finding, preoperative magnetic resonance imaging is used in the screening of patients with adolescent idiopathic scoliosis. However, this practice continues to be highly controversial. In order to better resolve this issue, we performed what we believe to be the largest prospective study to evaluate the need for preoperative magnetic resonance imaging in patients with adolescent idiopathic scoliosis requiring arthrodesis of the spine. Methods: A total of 327 consecutive patients with adolescent idiopathic scoliosis were evaluated between December 1991 and March 1999. All patients in the study presented with an adolescent idiopathic scoliosis curve pattern and had a complete physical and neurologic examination. Magnetic resonance imaging of the brain and the spinal cord were performed as part of their preoperative work-up. Results: Seven patients had an abnormality noted on magnetic resonance imaging. These abnormalities included a spinal cord syrinx in two patients (0.6%) and an Arnold-Chiari type-I malformation in four (1.2%). One patient had an abnormal fatty infiltration of the tenth thoracic vertebral body. No patient required neurosurgical intervention or additional work-up. All patients who underwent spinal arthrodesis with segmental instrumentation tolerated the surgery without any immediate or delayed neurologic sequelae. Conclusions: The fact that magnetic resonance imaging did not detect any important pathology in the large number of patients in this study strongly suggests that magnetic resonance imaging is not indicated prior to arthrodesis of the spine in patients with an adolescent idiopathic scoliosis curve pattern and a normal physical and neurologic examination.

RHEUMATOID ARTHRITIS OF THE CERVICAL SPINE

Rheumatoid arthritis most often affects the cervical spine, resulting in clinical and radiographic findings. For most patients with rheumatoid arthritis the cervical involvement represents a relatively benign process, but, in a small percentage of these patients, a progressive instability pattern develops that may compromise neural or vascular structures. The rate of neural compromise because of cervical instability ranges from 11% to 58%. The clinical manifestation may be radiculopathy, myelopathy, quadriplegia, and, in extreme instances, sudden death.

Technique and results of fixation to the sacrum with iliosacral screws

This article describes the technique of iliosacral screw fixation, as well as a retrospective review of 28 consecutive patients who had spine fusion to the sacrum with iliosacral screws, with a munimum follow-up of 2 years. The study included 6 male and 22 female patients. Average age at teh time of surgery was 43 years, and mean follow-up time was 3.5 years. There were no neurologic complications at final follow-up evaluation. Ninety-five percent of the patients had radiographic evidence of fusion. Three patients required iliosacral screw removal because of suboptimal intraoperative Kirschner-wire placement. Optimal intraoperative radiographic evaluation for accurate iliosacral screw placement is recommended. The use of iliosacral screws is also a useful addition to the armamentarium of the spine surgeon when fixation to the sacrum is required.

Functional and radiographic outcomes after surgery for adult scoliosis using third-generation instrumentation techniques.

Study Design. Retrospective radiograph and chart review of 28 patients with adult idiopathic scoliosis undergoing primary corrective surgery. Clinical and radiographic parameters were assessed before surgery, after surgery, and at a 2-year follow-up assessment. A self-perceived outcome questionnaire was administered to the study patients at a minimum 2-year follow-up assessment. Objective. To assess patient outcomes after surgery for adult scoliosis using traditional radiographic parameters along with a self-perceived outcomes questionnaire. Summary of Background Data. The clinical and radiographic results and the outcomes for the surgical treatment of adult idiopathic scoliosis have not been established in the literature with respect to the use of modern third-generation instrumentation techniques. Most studies reviewing the surgical treatment of adult idiopathic scoliosis look primarily at Harrington instrumentation techniques. Methods. Records and radiographs were reviewed retrospectively for all the patients (n = 54) undergoing primary corrective surgery for adult idiopathic scoliosis between December 30, 1994 and December 30, 1997. Of the 54 patients reviewed, 28 (52%) met the following inclusion criteria: age exceeding 20 years, primary surgery, fusion above the sacrum, availability of medical records along with preoperative, postoperative, and 2-year follow-up radiographs. Additionally, a self-perceived outcomes questionnaire was administered to these patients at a minimum 2-year follow-up assessment. Results. All the patients were women (28/28). The indications for surgery were pain and progression in 54% (15/28) and pain in 29% (8/28) of the patients. The average preoperative major curve measurement was 65° (range, 38–98°). The average postoperative major curve measurement was 24° (range, 5–59°), for a correction of 64%. The average follow-up curve measurement was 27° (range, 3–60°), for a correction of 61%. Whereas 71% of the cases were anteroposterior, 29% were posterior only. There was one intraoperative complication among the 28 patients and four postoperative complications in 3 of the 28 patients. The self-perceived outcome questionnaires were available for 83% (23/28) of the patients. Definite or probable relief of symptoms was reported in 74%(17/23). Improved ability to sleep was reported in 61% (14/23), and ability to return to their usual job was reported in 57% (13/23). Satisfaction with the results of surgery was reported in 87% (20/23). Conclusions. Surgery for adult idiopathic scoliosis using third-generation instrumentation techniques provides significant clinical improvement, scoliosis correction, maintenance of sagittal alignment, and patient satisfaction, with an acceptable complication rate.