Purnendu Gupta

Potential use of Sox9 gene therapy for intervertebral degenerative disc disease.

Study Design. A new recombinant adenoviral vector expressing Sox9, a chondrocyte-specific transcription factor, was tested in a chondroblastic cell line and primary human intervertebral disc cells in vitro. Direct infection of intervertebral disc cells then was assessed in a rabbit model. Objectives. To deliver a potentially therapeutic viral vector expressing Sox9 to degenerative human and rabbit intervertebral discs cells, and to assess the effect of Sox9 expression on Type 2 collagen production. Summary of the Background Data. The concentration of competent Type 2 collagen, an essential constituent of the healthy nucleus pulposus, declines with intervertebral disc degeneration. Recent studies suggest that Sox9 upregulates Type 2 collagen production. Interventions that augment Type 2 collagen production by intervertebral disc cells may represent a novel therapeutic method for patients with degenerative disc disease. Methods. Adenoviral delivery vectors expressing Sox9 and green fluorescent protein were constructed using the AdEasy system. The chondroblastic cell line, HTB-94, and cultured human degenerated intervertebral disc cells were infected with the vectors. Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were performed to document increased Type 2 collagen expression. The AdSox9 virus then was injected directly into the intervertebral discs of three rabbits. After 5 weeks, the injected discs were evaluated histologically. Results. The AdSox9 virus efficiently transduced HTB-94 cells and degenerated human disc cells. Western blot analysis confirmed increased Sox9 production. Increased Type 2 collagen production was demonstrated in infected HTB-94 and human disc cells using both reverse transcriptase-polymerase chain reaction and immunohistochemical staining. In the rabbit model, cells infected with AdSox9 maintained a chondrocytic phenotype, and the architecture of the nucleus pulposus was preserved over a 5-week study period compared to control discs. Conclusions. A novel adenoviral vector efficiently increased Sox9 and Type 2 collagen synthesis in cultured chondroblastic cells and human degenerated disc cells. In a rabbit model, sustained Sox9 production preserved the histologic appearance of the nucleus pulposus cells in vivo. These findings suggest a potential role for Sox9 gene therapy in the treatment of human degenerative disc disease.

Spine loading characteristics of patients with low back pain compared with asymptomatic individuals.

Study Design. Patients with low back pain and asymptomatic individuals were evaluated while performing controlled and free-dynamic lifting tasks in a laboratory setting. Objective. To evaluate how low back pain influences spine loading during lifting tasks. Summary of Background Data. An important, yet unresolved, issue associated with low back pain is whether patients with low back pain experience spine loading that differs from that of individuals who are asymptomatic for low back pain. This is important to understand because excessive spine loading is suspected of accelerating disc degeneration in those whose spines are damaged already. Methods. In this study, 22 patients with low back pain and 22 asymptomatic individuals performed controlled and free-dynamic exertions. Trunk muscle activity, trunk kinematics, and trunk kinetics were used to evaluate three- dimensional spine loading using an electromyography- assisted model in conjunction with a new electromyographic calibration procedure. Results. Patients with low back pain experienced 26% greater spine compression and 75% greater lateral shear (normalized to moment) than the asymptomatic group during the controlled exertions. The increased spine loading resulted from muscle coactivation. When permitted to move freely, the patients with low back pain compensated kinematically in an attempt to minimize external moment exposure. Increased muscle coactivation and greater body mass resulted in significantly increased absolute spine loading for the patients with low back pain, especially when lifting from low vertical heights. Conclusions. The findings suggest a significant mechanical spine loading cost is associated with low back pain resulting from trunk muscle coactivation. This loading is further exacerbated by the increases in body weight that often accompany low back pain. Patient weight control and proper workplace design can minimize the additional spine loading associated with low back pain.

The quantification of low back disorder using motion measures : Methodology and validation

STUDY DESIGN Trunk angular motion features were used as a means to quantify the extent of a low back disorder in healthy people and patients with chronic low back disorders. OBJECTIVE To refine and validate a previously reported means of quantifying the extent of a low back disorder. SUMMARY AND BACKGROUND Many assessment tools of low back disorder are subjective. A quantitative assessment tool would facilitate the tracking of the recovery and help document the appropriateness of treatments. METHODS The trunk motion characteristics of 374 healthy people and 335 patients with chronic low back disorders of varying severity were documented as they flexed and extended their trunks in five different planes of motion. The trunk motion features were normalized as a function of age and gender. Four classification techniques were used to assess the ability of the quantitative motion measure to identify those with and without low back disorders. In addition, 31 patients were observed longitudinally to determine whether the motion measures agreed with observed changes in back pain symptoms. RESULTS The quantitative trunk motion measure distinguished between people with low back disorders and healthy people between 88% and 94% of the time, depending on which classification system was used. Sensitivity and specificity varied between 83% and 97%. The quantitative measure also showed promise as a means to distinguish between muscle-based and structure-based low back disorders. Prospective findings indicated that the quantification system agreed well with clinical observations of progress. CONCLUSIONS The quantification of trunk motion can serve as a measure of the extent of a low back disorder. When considered along with other clinical information, the ability to assess and treat low back disorders is enhanced.

Spine loading in patients with low back pain during asymmetric lifting exertions

BACKGROUND CONTEXT Recurrent low back pain (LBP) is a common and costly problem that might be related to increased spine loads in those with LBP. However, we know little about how the spine is loaded when those with LBP perform lifting exertions. PURPOSE Document spine loading patterns of patients with LBP performing symmetric and asymmetric lifting exertions compared with asymptomatic individuals performing the same tasks. STUDY DESIGN Spine loadings during lifting exertions that varied in asymmetric origin as well as horizontal and vertical distance from the spine were compared between asymptomatic subjects and patients with LBP. METHODS Sixty-two patients with LBP and 61 asymptomatic individuals performed a variety of lifting exertions that varied in lift origin horizontal and vertical position (region), lift asymmetry position and weight lifted. An electromyography-assisted model was used to evaluate spine loading in each subject during the lifting exertions. Differences in spine loading between the LBP and asymptomatic subjects were noted as a function of the experimental variables. RESULTS Patients with LBP experienced greater spine compression and shear forces when performing lifting tasks compared with asymptomatic individuals. The least taxing conditions resulted in some of the greatest differences between LBP and asymptomatic individuals. CONCLUSIONS Greater levels of antagonistic muscle coactivation resulted in increases in spine loading for patients with LBP. Specific lifting conditions that tend to exacerbate loading can be identified by means of physical workplace requirements. These findings may impact acceptable return-to-work conditions for those with LBP.

Longitudinal quantitative measures of the natural course of low back pain recovery.

Study Design. A prospective study was developed to quantify acute low back pain recovery. Objective. To compare traditional self-report measures of low back pain recovery with a quantitative measure of recovery. Summary of Background Data. The magnitude of low back disorders in society continues to be a problem. To prevent secondary injuries, an understanding of recovery must be gained by comparing the natural course of recovery using several outcome measures. Methods. For this study, 16 occupational and 16 nonoccupational patients with low back pain were recruited. Recovery was monitored prospectively every 2 weeks for 3 to 6 months, using subjective work status, pain symptoms, activities of daily living, and objective functional performance probability (trunk kinematics). Results. Return to work underestimated the percentage of subjects impaired, as compared with all other outcome measures. Symptoms, activities of daily living, and functional performance probability all showed similar patterns of recovery for 0 to 12 weeks. At 14 weeks, there was a lag in functional performance recovery. Both symptoms and activities of daily living indicated that 80% of the population was recovered, whereas functional performance indicated the figure to be 68%. Conclusion. This prospective study demonstrates the natural course of recovery using several outcome measures. The objective kinematic functional performance measure of recovery quantifies a different aspect of impairment not evaluated by traditional subjective measures. Use of several outcome measures may lead to a better understanding of low back pain recovery or residual impairment, which may minimize the risk of recurrent injury.

Functional Impairment as a Predictor of Spine Loading

Study Design. Spine loadings during a variety of lifting exertions were compared with individual torso kinematic abilities. Relationships were evaluated between these measures. Objective. To determine if trunk kinematic status (functional impairment) is indicative of spine loading increases in patients with low back pain (LBP) compared to asymptomatic individuals. Summary of Background Data. Recurrent LBP is a common and costly problem that may be related to increased spine loads in those individuals with LBP. Previous studies suggest that patients with LBP had greater loading than their asymptomatic counterparts when performing work. However, we know little about how to identify when a patient with LBP can resume lifting tasks without having exaggerated spine loading. Methods. Sixty-two patients with LBP and 61 who were asymptomatic were evaluated for signs of kinematic compromise (i.e., inability to generate normal trunk kinematic patterns) during a prelift test. All subjects were then asked to perform a variety of lifting exertions that varied in lift origin (region), lift asymmetry position, and weight lifted. An electromyography-assisted model was used to evaluate spine loading in each subject during the lifting exertions. Statistical models were used to assess the relationship between kinematic compromise and spine loading. Results. Patients with LBP had greater spine loading as well as greater kinematic compromise. The degree of kinematic compromise was related to the degree of spine loading increases in those individuals with LBP. A statistical model was developed that was able to describe 87% of the variability in compression, 61% in anteroposterior shear, and 65% in lateral shear. Conclusions. Those patients with greater kinematic compromise used higher levels of antagonistic muscle coactivation that not only reduced trunk motion but also resulted in increases in spine loading. Given the degree of kinematic compromise and the lifting task conditions, a method has been devised to predict the increase in spine loading above and beyond that of an asymptomatic individual when performing typical materials handling tasks.

Effect of torso flexion on the lumbar torso extensor muscle sagittal plane moment arms

BACKGROUND CONTEXT Accurate anatomical inputs for biomechanical models are necessary for valid estimates of internal loading. The magnitude of the moment arm of the lumbar erector muscle group is known to vary as a function of such variables as gender. Anatomical evidence indicates that the moment arms decrease during torso flexion. However, moment arm estimates in biomechanical models that account for individual variability have been derived from imaging studies from supine postures. PURPOSE Quantify the sagittal plane moment arms of the lumbar erector muscle group as a function of torso flexion, and identify individual characteristics that are associated with the magnitude of the moment arms as a function of torso flexion. STUDY DESIGN/SETTING Utilization of a 0.3 Tesla Open magnetic resonance image (MRI) to image and quantify the moment arm of the right erector muscle group as a function of gender and torso flexion. METHODS Axial MRI images through and parallel to each of the lumbar intervertebral discs at four torso flexion angles were obtained from 12 male and 12 female subjects in a lateral recumbent posture. Multivariate analysis of variance was used to investigate the differences in the moment arms at different torso flexion angles, whereas hierarchical linear regression was used to investigate associations with individual anthropometric characteristics and spinal posture. RESULTS The largest decrease in the lumbar erector muscle group moment arm from neutral to 45-degree flexion occurred at the L5-S1 level (9.7% and 8.9% for men and women, respectively). Measures of spinal curvature (L1-S1 lordosis), body mass and trunk characteristics (depth or circumference) were associated with the varying moment arm at most lumbar levels. CONCLUSIONS The sagittal plane moment arms of the lumbar erector muscle mass decrease as the torso flexes forward. The change in moment arms as a function of torso flexion may have an impact on prediction of spinal loading in biomechanical models.

Prospective functional evaluation of the surgical treatment of neurogenic claudication in patients with lumbar spinal stenosis.

A prospective evaluation of patients with lumbar spinal stenosis undergoing operative treatment was performed using treadmill-bicycle functional testing as well as Oswestry and Visual Analog Pain scales for self-assessment. Thirty-two patients undergoing spinal stenosis decompression with and without a concomitant spinal fusion were prospectively evaluated, preoperatively and a minimum of 2 years postoperatively. Surgical treatment was demonstrated to produce significant improvement in walking ability, and to a lesser degree, in the ability to bicycle 2 years postoperatively. Improvement in patient function demonstrated on the Oswestry questionnaire correlated with decreased pain observed on the Visual Analog Pain scale. The treadmill-bicycle test appears to be a useful tool for the differential diagnosis of neurogenic claudication and may be used as an objective test of postoperative outcome.

The Lordotic Effect of the Osi Frame on Operative Adolescent Idiopathic Scoliosis Patients

Study Design. A prospective evaluation of adolescent idiopathic scoliosis patients undergoing operative treatment on the Orthopedic Systems Incorporated (OSI; Jackson) frame. Objectives. To investigate prospectively thoracic, thoracolumbar, and lumbar sagittal alignments in patients with adolescent idiopathic scoliosis who undergo an instrumented posterior spinal fusion on the OSI frame. Summary of Background Data. In several studies, it has been shown that patient positioning on various operative frames is an important component of ultimate lumbar sagittal alignment. However, these studies have all concentrated on the lumbar spine, and no sagittal plane alignment data in adolescent idiopathic scoliosis patients have been reported in the thoracic and thoracolumbar junction as it relates to intraoperative positioning, correction maneuvers, and correlative postoperative results. Methods. Thirty‐nine patients with operative adolescent idiopathic scoliosis treated with an instrumented posterior spinal fusion on the OSI frame were prospectively evaluated. Standing preoperative, intraoperative, and postoperative long‐cassette lateral radiographs were reviewed with regional and segmental Cobb measurements of the thoracic, thoracolumbar junction, and lumbar spine obtained. Results. Thoracic kyphosis (T1‐T12) measured +34° before surgery, +28° during surgery, and +30° after surgery. Thus, a statistically significant decrease was noted in thoracic kyphosis secondary to prone positioning on the OSI frame (P < 0.05). Thoracolumbar spine measurements from T10 to L2 also showed a lordotic trend from +2° before surgery, to −4° during surgery, to −8° after surgery, which was also statistically significant (P < 0.05). Total lumbar lordosis from T12 to S1 remained relatively unchanged from −60° before surgery, to −59° during surgery, to −60° after surgery. However, segmental lumbar lordosis measured from T12 to the lowest instrumented vertebra showed a statistically significant increase in lordosis from −17° before surgery, to −19° during surgery, to −23° after surgery (P < 0.05). Those patients in whom lumbar pedicle screws were used (vs. hooks alone) had the greatest increase in lumbar instrumented lordosis. Conclusions. Performing adolescent idiopathic scoliosis correction on the OSI frame tends to decrease thoracic kyphosis, increase thoracolumbar lordosis, and increase segmental instrumented lumbar lordosis, while it maintains total lumbar lordosis.

Localized oxygen use of healthy and low back pain individuals during controlled trunk movements.

Individuals who have low back pain (LBP) have significantly different motion characteristics than healthy individuals. However, the cause of these differences is unknown. Oxygen use of the erector spinae muscle was examined while simultaneously monitoring motion characteristics to determine whether oxygen use differed between healthy and LBP individuals. Thirty volunteers were classified as healthy, structural, or muscular-based LBP. A near-infrared spectrometer monitored oxygen use and blood volume in the lumbar region. Results showed significant differences in oxygen use but not blood volume between healthy and LBP subjects with muscular-based disorders. Inability of the muscular group to use oxygen in a manner similar to the healthy group indicates different processes at the tissue level, indicating that differences in oxygen use may provide insight into why motion patterns differ between healthy and LBP groups.