Full-length spp24, but not its 18.5-kDa proteolytic fragment, inhibits bone-healing in a rodent model of spine fusion.

BACKGROUND: Growth factors like bone morphogenetic protein (BMP) are used as bone-graft substitutes to enhance bone growth in clinical situations. However, adverse reactions have been associated with BMP use. We developed a synthetic adjuvant therapy based on the sequence of a BMP-binding protein, secreted phosphoprotein-24 (spp24), which enhances the effects of BMPs and ameliorates the adverse reactions. Our hypothesis is that a natural proteolytic fragment of spp24 is identical to an osteogenic protein previously described independently by two investigators. To test this hypothesis, spp24 and a truncated form of spp24 were separately implanted with recombinant human BMP-2 (rhBMP-2) in a rodent model of spine fusion. METHODS: Two isoforms of spp24 were constructed with use of DNA recombinant technology. Spp24 with or without rhBMP-2 were added to collagen sponges and implanted bilaterally between L4 and L5 transverse processes. Radiographs were made biweekly, and spines were explanted after eight weeks. Gross evaluation, microquantitative computed tomography study, and histological analysis were performed to evaluate bone growth. RESULTS: Animals that received full-length spp24 and rhBMP-2 exhibited a complete obliteration of bone growth, while animals with the truncated form in combination with rhBMP-2 exhibited a mild inhibition to bone growth, with bone area measured from radiographs. Manual assessment and gross evaluation of all spines confirmed the results obtained from the bone-area measurements. Microquantitative computed tomography provided three-dimensional visual images of representative specimens, while histological staining of spine tissue displayed cellular evidence of bone formation. CONCLUSIONS: Results from this investigation confirm that the various isoforms of spp24 affect the bone-healing activity of rhBMP-2 in the rat spine fusion model. Thus, proteolytic modification of this protein is a likely mechanism for the regulation of BMP availability in the physiological environment. Future studies will define the roles of these proteins in controlling the activity of BMPs and other members of the transforming growth factor-beta family of cytokines. This information will increase the understanding of normal bone-healing, allowing for the engineering of more effective orthopaedic treatment.

Cost and use of conservative management of lumbar disc herniation before surgical discectomy.

BACKGROUND CONTEXT: Lumbar discectomy is one of the most common spine surgical procedures. With the exception of true emergencies (eg, cauda equina syndrome), lumbar discectomy is usually performed as an elective procedure after a prudent trial of nonoperative treatment. Although several studies have compared costs of definitive operative or nonoperative management of lumbar disc herniation, no information has been published regarding the cost of conservative care in patients who ultimately underwent surgical discectomy. PURPOSE: The purpose of this study was to determine the financial costs (and relative distribution of those costs) associated with the nonoperative management of lumbar disc herniation in patients who ultimately failed conservative care and elected to undergo surgical discectomy. STUDY DESIGN: This is a retrospective database review. PATIENT SAMPLE: The sample comprises patients within the database who underwent lumbar discectomy. OUTCOME MEASURES: The outcome measures were frequency of associated procedures and the costs of those procedures. MATERIALS AND METHODS: A search was conducted using a commercially available online database of insurance records of orthopedic patients to identify all patients within the database undergoing lumbar discectomy between 2004 and 2006. Patients were identified by American Medical Association Current Procedural Terminology code. The associated charge codes for the 90-day period before the surgery were reviewed and categorized as outpatient physician visits, imaging studies, physical therapy, injection, chiropractic manipulation, medication charges, preoperative studies, or miscellaneous charges. The frequency of each code and the percentage of patients for whom that code was submitted to the insurance companies were noted, as were the associated charges. RESULTS: In total, 30,709 patients in the database met eligibility criteria. A total of $105,799,925 was charged during the 90 days preoperatively, an average of $3,445 per patient. Average charge for discectomy procedure was $7,841. Charges for injection procedures totaled $16,211,246 or 32% of total charges, diagnostic imaging $15,648,769 (31%), outpatient visits $6,552,135 (13%), physical therapy visits $5,723,644 (11%), chiropractic manipulation $1,177,406 (2%), preoperative studies $426,976 (0.8%), medications $263,039 (0.5%), and miscellaneous charges $1,177,371 (2%). CONCLUSIONS: Charges for preoperative care of patients with lumbar disc herniation are substantial and are split almost evenly between diagnostic charges (outpatient visits, imaging, laboratory studies, and miscellaneous) and therapeutic charges (injections, physical therapy, chiropractic manipulation, and medications). Although a large number of patients will ultimately require surgical intervention, given that many patients will improve with nonoperative therapy, a trial of conservative management is appropriate. Additional studies to identify patients who may ultimately fail nonoperative treatment and would benefit from early discectomy would be beneficial.

The kinematic relationships of the upper cervical spine.

STUDY DESIGN: A retrospective radiographic study. OBJECTIVE: To elucidate the kinematic relationships of the upper cervical spine. SUMMARY OF BACKGROUND DATA: To our knowledge, few reports have described the kinematic relationships of the upper cervical spine in patients with general age-related cervical spondylosis. METHODS: We performed Kinetic magnetic resonance imaging for 295 consecutive patients experiencing neck pain without neurologic symptoms. Subjects with rheumatoid arthritis, traumatic history, and severe degenerative changes in the upper cervical spine were excluded. Anterior atlantodens interval (AADI) and the cervicomedullary angle in 3 different postures were measured, and the variations in each value between flexion and neutral (F-N), neutral and extension (N-E), and flexion and extension (F-E) were calculated. The subjects were classified into 3 groups according to the space available for the cord values (A: or=15 mm). RESULTS: AADI significantly increased from extension to flexion posture, however, no significant differences were observed in every posture among the groups. F-N variation in AADI showed no significant differences among the groups; however, N-E variation between Groups A and C and between Groups B and C and F-E variation between Groups A and C showed significant differences. The cervicomedullary angle significantly increased from flexion to extension posture, however, no significant differences were observed in every posture among the groups. Angle variations among the groups showed no significant differences, except for F-N angle variation between Groups B and C. None of the variations in AADI and the cervicomedullary angle were significantly correlated. CONCLUSION: Our results suggest that only the kinematics of the atlantoaxial movement, especially the posterior movement, was greatly affected by the narrowing of space available for the cord. The central atlantoaxial joint may be closely related to the mechanisms for protecting the spinal cord by restriction of the atlantoaxial movement.

Cervical segmental motion at levels adjacent to disc herniation as determined with kinetic magnetic resonance imaging.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: To investigate the effects of cervical disc herniation on kinematics at adjacent vertebral motion segments. SUMMARY OF BACKGROUND DATA: Kinetic magnetic resonance imaging (kMRI) is an alternative method to conventional MRI, which allows evaluation of the cervical spine in a more physiologic, weight-bearing position, and acquisition of images in flexion, extension, and neutral alignment. kMRI has previously been used to evaluate the effects of disc degeneration on cervical kinematics. METHODS: A total of 407 patients with neck pain without prior history of surgery were evaluated using kMRI. Translational motion, angular variation, and disc height were measured at each segment from C2-C3 through C7-T1. Other factors including the degree of disc degeneration, age, gender, and vertebral segment location were analyzed in order to determine any predisposing risk factors for segmental instability adjacent to disc herniations. RESULTS: Spinal levels above the disc herniation exhibited, on average, a 7.2% decrease in translational motion per mm of disc herniation (P = 0.0113), without significant change in angular motion. Levels below the herniation demonstrated a 5.2% decrease in angular motion per mm of disc herniation (P = 0.0236) without significant change in translational motion. The degree of disc degeneration had no significant effect on adjacent level motion. Disc herniation had no significant impact on disc height at adjacent levels, although disc degeneration correlated with decreased disc height above and increased disc height below. CONCLUSION: Although disc height, translational motion, and angular variation are significantly affected at the level of a disc herniation, no significant changes are apparent in adjacent segments. Our results indicate that herniated discs have no effect on ROM at adjacent levels regardless of the degree of disc degeneration or the size of disc herniation, suggesting that the natural progression of disc degeneration and adjacent segment disease may be separate, unrelated processes within the cervical spine.

Lumbar segmental mobility according to the grade of the disc, the facet joint, the muscle, and the ligament pathology by using kinetic magnetic resonance imaging.

STUDY DESIGN: The kinematic study of human lumbar spinal movements. OBJECTIVE: To investigate how disc degeneration and the degeneration of facet joint, ligaments, and paraspinal muscles are associated with lumbar segmental mobility. SUMMARY OF BACKGROUND DATA: Previous studies revealed relationship between spinal motion and osteoarthritic changes of facet joint as well as disc degeneration; however, little is known about the association of disc, facet joint, ligament, and muscle degeneration with lumbar segmental motion characteristics. METHODS: The 1580 lumbar motion segments from 316 patients (200 male, 116 female) underwent Kinetic magnetic resonance imaging, which were used to assess disc degeneration (grade I-V) and facet joint degeneration (grade 1-4), interspinous ligament (ISL) degeneration (grade 1-4), ligamentum flavum hypertrophy (LFH), and fatty degeneration of muscles. Segmental translational and angular motion in the flexion, extension, and neutral postures were digitally automatically measured by MR analyzer. RESULTS: Grade II (46.77%) disc, grade 1 (48.35%) facet joint degeneration, and grade 1 (64.1%) ISL were most common. LFH was most common in L4-L5 (49/330, 14.8%). In younger age (<35), grade I disc and grade 1 facet joint were predominant compared with the older age (35< or = and <45) in which grade III, IV, and V disc and grade 2 facet joint were predominant (P < 0.05). Translational motion increased significantly in high grade of disc and facet joint (except grade V disc and grade 4 facet joint) and with LFH in L1-L5 (P < 0.05). Angular motion significantly decreased in grade V disc, grade 4 ISL, and without LFH in L1-L5 (P < 0.05). According to muscle fatty degeneration, translational and angular motions were not significantly changed. CONCLUSION: Our results support that facet joint degeneration is followed by disc degeneration according to age. Increased translational movements of the lumbar segments occurred in severe disc degeneration accompanied by facet joint degeneration or the presence of LFH even if the movements were stabilized in the advanced status. Therefore, the current status of the intervertebral discs, facet joints, and ligamentum flavum should be taken into consideration when evaluating stability within the lumbar spine.

Kinetic magnetic resonance imaging analysis of abnormal segmental motion of the functional spine unit.

OBJECT: The authors conducted a retrospective observational study using kinetic MR imaging to investigate the relationship between instability, abnormal sagittal segmental motion, and radiographic variables consisting of intervertebral disc degeneration, facet joint osteoarthritis (FJO), degeneration of the interspinous ligaments, ligamentum flavum hypertrophy (LFH), and the status of the paraspinal muscles. METHODS: Abnormal segmental motion, defined as > 10 degrees angulation and > 3 mm of translation in the sagittal plane, was investigated in 1575 functional spine units (315 patients) in flexion, neutral, and extension postures using kinetic MR imaging. Each segment was assessed based on the extent of disc degeneration (Grades I-V), FJO (Grades 1-4), interspinous ligament degeneration (Grades 1-4), presence of LFH, and paraspinal muscle fatty infiltration observed on kinetic MR imaging. These factors are often noted in patients with degenerative disease, and there are grading systems to describe these changes. For the first time, the authors attempted to address the relationship between these radiographic observations and the effects on the motion and instability of the functional spine unit. RESULTS: The prevalence of abnormal translational motion was significantly higher in patients with Grade IV degenerative discs and Grade 3 arthritic facet joints (p < 0.05). In patients with advanced disc degeneration and FJO, there was a lesser amount of motion in both segmental translation and angulation when compared with lower grades of degeneration, and this difference was statistically significant for angular motion (p < 0.05). Patients with advanced degenerative Grade 4 facet joint arthritis had a significantly lower percentage of abnormal angular motion compared to patients with normal facet joints (p < 0.001). The presence of LFH was strongly associated with abnormal translational and angular motion. Grade 4 interspinous ligament degeneration and the presence of paraspinal muscle fatty infiltration were both significantly associated with excessive abnormal angular motion (p < 0.05). CONCLUSIONS: This kinetic MR imaging analysis showed that the lumbar functional unit with more disc degeneration, FJO, and LFH had abnormal sagittal plane translation and angulation. These findings suggest that abnormal segmental motion noted on kinetic MR images is closely associated with disc degeneration, FJO, and the pathological characteristics of interspinous ligaments, ligamentum flavum, and paraspinal muscles. Kinetic MR imaging in patients with mechanical back pain may prove a valuable source of information about the stability of the functional spine unit by measuring abnormal segmental motion and grading of radiographic parameters simultaneously.

Radiographic parameters of segmental instability in lumbar spine using kinetic MRI.

OBJECTIVE: To investigate the effectiveness of radiographic parameters on segmental instability in the lumbar spine using Kinetic magnetic resonance imaging (MRI). METHODS: Segmental motion, defined as excessive (more than 3 mm) translational motion from flexion to extension, was investigated in 309 subjects (927 segments) using Kinetic MRI. Radiographic parameters which can help indicate segmental instability include disc degeneration (DD), facet joint osteoarthritis (FJO), and ligament flavum hypertrophy (LFH). These three radiographic parameters were simultaneously evaluated, and the combinations corresponding to significant segmental instability at each level were determined. RESULTS: The overall incidence of segmental instability was 10.5% at L3-L4, 16.5% at L4-L5, and 7.3% at L5-S1. DD and LFH at L3-L4 and FJO and LFH at L4-L5 were individually associated with segmental instability (p<0.05). At L4-L5, the following combinations had a higher incidence of segmental instability (p<0.05) when compared to other segments : (1) Grade IV DD with grade 3 FJO, (2) Grade 2 or 3 FJO with the presence of LFH, and (3) Grade IV DD with the presence of LFH. At L5-S1, the group with Grade III disc and Grade 3 FJO had a higher incidence of segmental instability than the group with Grade I or II DD and Grade 1 FJO. CONCLUSION: This study showed that the presences of either Grade IV DD or grade 3 FJO with LFH at L4-L5 were good indicators for segmental instability. Therefore, using these parameters simultaneously in patients with segmental instability would be useful for determining candidacy for surgical treatment.

A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats.

BACKGROUND CONTEXT: Recombinant bone morphogenetic proteins (rhBMPs) have been used successfully in clinical trials. However, large doses of rhBMPs were required to induce adequate bone repair. Collagen sponges (CSs) have failed to allow a more sustained release of rhBMPs. Ongoing research aims to design carriers that allow a more controlled and sustained release of the protein. E-Matrix is a injectable scaffold matrix that may enhance rhBMP activity and stimulate bone regeneration. PURPOSE: The purpose of this study was to test E-Matrix as a carrier for rhBMPs in a CS and examine its feasibility in clinical applications by using a rat spinal fusion model. PATIENT SAMPLE: A total of 80 Lewis rats aged 8-16 weeks were divided into nine groups. STUDY DESIGN/SETTING: Rat spinal fusion model. OUTCOME MEASURES: Radiographs were obtained at 4, 6, and 8 weeks. The rats were sacrificed and their spines were explanted and assessed by manual palpation, high-resolution microcomputed tomography (micro-CT), and histologic analysis. METHODS: Group I animals were implanted with CS alone (negative control); Group II animals with CS containing 10microg rhBMP-2 (positive control); Group III animals with CS containing 3microg rhBMP-2; Group IV animals with CS containing 3microg rhBMP-2 and E-Matrix; Group V animals with CS containing 1microg rhBMP-2; Group VI animals with CS containing 1microg rhBMP-2 and E-Matrix; Group VII animals with CS containing 0.5microg rhBMP-2; Group VIII animals with CS containing 0.5microg rhBMP-2 and E-Matrix; and Group IX animals with CS and E-Matrix without rhBMP-2. RESULTS: Radiographic evaluation, micro-CT, and manual palpation revealed spinal fusion in all rats in the BMP-2 and E-Matrix groups (IV, VI, and VIII) and high-dose BMP-2 groups (II and III). Four spines in the 3microg rhBMP-2 group (V) fused, and one spine in the 0.5microg rhBMP-2 group (VII) exhibited fusion. No spines were fused in Groups I (CS alone) and IX (E-Matrix alone). The volume of new bone in the area between the tip of the L4 transverse process and the base of the L5 transverse process in Group IV was equivalent to the volumes observed in Group II. CONCLUSION: E-matrix enhances spinal fusion as a carrier for rhBMP-2 in a rat spinal fusion model. The results of this study suggest that E-Matrix as a growth factor carrier may be applicable to spinal fusion and may improve rhBMP-2's activity at the fusion site.

Kinematic analysis of the relationship between sagittal alignment and disc degeneration in the cervical spine.

STUDY DESIGN: Retrospective analysis using kinetic magnetic resonance images (MRIs). OBJECTIVE: To investigate the relationship of changes in the sagittal alignment of the cervical spine on the kinematics of the functional motion unit and disc degeneration. SUMMARY OF BACKGROUND DATA: Normal lordotic alignment is one of the most important factors contributing to effective motion and function of the cervical spine. Loss of normal lordotic alignment may induce pathologic changes in the kinematics and accelerate degeneration of the functional motion unit. However, the relationship of altered alignment on kinematics and degeneration has not been evaluated. METHODS: Kinetic MRIs in flexion, neutral, and extension were performed. Study participants were classified into 5 groups based on the C1-C7 Cobb angle of sagittal alignment--Group A: Kyphosis (n = 19), Group B: Straight (n = 29), Group C: Hypolordosis (n = 38), Group D: Normal (n = 63), and Group E: Hyperlordosis (n = 52).Intervertebral disc degeneration was graded (Grades 1-5), and the kinematics of the functional spinal unit were obtained. RESULTS: When the alignment shifted from normal to less lordotic, the translational motion and angular variation tended to decrease at all levels. The contribution of the C1-C2, C2-C3, and C3-C4 levels to total angular mobility tended to be higher in Group C than Group D. However, the contribution of the C4-C5, C5-C6, and C6-C7 levels tended to be lower in Group C than in Group D. The grade of disc degeneration associated with loss of lordosis tended to be higher than that associated with normal alignment at the C2-C3 and C3-C4 levels. CONCLUSION: The present study demonstrated that the changes in sagittal alignment of the cervical spine affect the kinematics. Consequently, it may cause changes in the segment subjected to maximum load for overall motion and accelerate its degeneration.