Back pain and total hip arthroplasty: a prospective natural history study.

BACKGROUND: Many patients with degenerative joint disease of the hip have substantial degeneration of the lumbar spine. These patients may have back and lower extremity pain develop after THA and it may be difficult to determine whether the source of the pain is the hip or spine. QUESTIONS/PURPOSES: We therefore: (1) identified the incidence/prevalence of pain in the lower back in a group of patients with end-stage arthritis of the hip undergoing THA; (2) described the natural history of low back pain in this cohort undergoing THA; and (3) determined factors that were predictive of persistent low back pain after THA. METHODS: We administered a detailed questionnaire and a diagram of the human body on which the patients could draw the site of their pain, to 344 patients preoperatively, at 6 weeks, 6 months, and 1-year after THA. Before the THA, 170 patients (49.4%) reported pain localized to the lower lumbar region, whereas 174 patients did not have low back pain. RESULTS: Low back pain was variable in location. Postoperatively, the low back pain resolved in 113 (66.4%) of the 170 patients. Thirty-seven of the remaining 57 patients had known spine disorders. Thirty-five of the 174 patients (20%) without prior low back pain had low back pain develop within 1 year postoperatively. The low back pain improved in 17 of these 35 patients; 12 of the remaining 18 patients had preexistent spine disorders. Pain radiating below the knee was associated most closely with preexisting spine disorders. CONCLUSIONS: Hip and spine arthritis often coexist. Most patients who presented with hip arthritis and lower lumbar pain experienced resolution or improvement of their pain after THA. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Degenerative spondylolisthesis versus spinal stenosis: does a slip matter? Comparison of baseline characteristics and outcomes (SPORT).

STUDY DESIGN: As-treated analysis of the Spine Patient Outcomes Research Trial. OBJECTIVE: To compare baseline characteristics and surgical and nonoperative outcomes between degenerative spondylolisthesis (DS) and spinal stenosis (SPS) patients. SUMMARY OF BACKGROUND DATA: DS and SPS patients are often combined in clinical studies despite differences in underlying pathology and treatment. METHODS: The DS cohort included 601 patients (369 [61%] underwent surgery), and the SPS cohort included 634 patients (394 [62%] underwent surgery). Baseline characteristics were compared between the 2 groups. Changes from baseline for surgical and nonoperative outcomes were compared at 1 and 2 years using longitudinal regression models. Primary outcome measures included the SF-36 bodily pain and physical function scores and the Oswestry Disability Index. RESULTS: The DS patients included more females (69% vs. 39%, P < 0.001), were older (66.1 year vs. 64.6 years, P = 0.021), and were less likely to have multilevel stenosis (35% vs. 61%, P < 0.001) compared with the SPS patients. There were no significant baseline differences on any of the main outcome measures. DS patients undergoing surgery were much more likely to be fused than SPS patients (94% vs. 11%, P < 0.001) and improved more with surgery than SPS patients on all primary outcome measures (DS vs. SPS): physical function (+30.4 vs. +25.3, P = 0.004 at 1 year; + 28.3 vs. +21.4, P < 0.001 at 2 years), bodily pain (+32.3 vs. +27.5, P = 0.006 at 1 year; +31.1 vs. +26.1, P = 0.003 at 2 years), and Oswestry Disability Index (-25.9 vs. -21.0, P < 0.001 at 1 year; -24.7 vs. -20.2, P < 0.001 at 2 years). Patients treated nonoperatively improved less than those treated surgically, and there were no significant differences in nonoperative outcomes between the 2 cohorts. CONCLUSION: Overall, DS and SPS patients had similar baseline characteristics. However, DS patients improved more with surgery than SPS patients. Future studies should probably not combine these heterogeneous patient populations.

Osteogenic potential of adult human stem cells of the lumbar vertebral body and the iliac crest.

STUDY DESIGN: Marrow was aspirated from the vertebral body (VB) and iliac crest (IC) of patients undergoing lumbar spinal surgery, following an approved protocol. Progenitor cells were isolated using standard culture conditions and their osteogenic potential evaluated. OBJECTIVE: To evaluate the osteogenic potential of mesenchymal stem cells (MSCs) isolated from the bone marrow of the human VB. SUMMARY OF BACKGROUND DATA: IC marrow grafting during cervical discectomy and fusion procedure is associated with donor site morbidity. Since the VB contains marrow cells, it may be possible to circumvent this problem by using this tissue for osseous graft supplementation. However, there is paucity of information concerning the osteogenic potential of non-IC-derived progenitor cells. Herein, we address this issue. METHODS: Marrow samples from VB of patients undergoing lumbar spinal surgery were collected; marrow was also harvested from the IC. Progenitor cells were isolated and the number of colony forming unit-fibroblastic (CFU-F) determined. The osteogenic potential of the cells was characterized using biochemical and molecular biology techniques. RESULTS: Both the VB and IC marrow generated small, medium, and large sized CFU-F. Higher numbers of CFU-F were obtained from the VB marrow than the IC (P < 0.05). Progenitor cells from both anatomic sites expressed comparable levels of CD166, CD105, CD49a, and CD63. Moreover, progenitor cells from the VB exhibited an increased level of alkaline phosphatase activity. MSCs of the VB and the IC displayed similar levels of expression of Runx-2, collagen Type I, CD44, ALCAM, and ostecalcin. The level of expression of bone sialoprotein was higher in MSC from the IC than the VB. VB and IC cells mineralized their extracellular matrix to a similar extent. CONCLUSIONS: Our studies show that CFU-F frequency is higher in the marrow of the VB than the IC. Progenitor cells isolated from both sites respond in a similar manner to an osteogenic stimulus and express common immunophenotypes. Based on these findings, we propose that progenitor cells from the lumbar vertebral marrow would be suitable candidate for osseous graft supplementation in spinal fusion procedures. Studies must now be conducted using animal models to ascertain if cells of the VB are as effective as those of the IC for the fusion applications.

Failure of standard imaging to detect a cervical fracture in a patient with ankylosing spondylitis.

STUDY DESIGN: Retrospective case study of 38-year-old male with ankylosing spondylitis who presented with a Brown-Séquard syndrome following a fall and an occult fracture on initial spinal imaging studies. OBJECTIVE: To review the recommended imaging protocol in a patient with ankylosing spondylitis and a suspected cervical spine fracture. SUMMARY OF BACKGROUND DATA: Plain radiographic imaging using orthogonal views can detect the majority of spinal fractures. However, fracture identification is particularly difficult in patients with ankylosing spondylitis. Of the various contemporary imaging methods, [magnetic resonance imaging (MRI), computed tomography (CT), nuclear scanning] high-definition multidetector CT scanning is the most useful in identifying subtle fractures, but in metabolic bone diseases the utility of these methods is unknown. METHODS: Retrospective radiographic evaluation of imaging studies of ankylosing spondylitis patient with occult fracture by five spine surgeons and neuroradiologists, followed with detailed review and interpretation of literature concerning present radiology techniques and methods to isolate occult fractures. RESULTS: Initial imaging studies, including plain radiographs of the spinal axis, cervical and thoracic single-detector CT with reconstructed images, and MRI, were unremarkable in detecting an occult cervical spine fracture in a patient with ankylosing spondylitis and a spinal cord injury following a fall. The patient was placed empirically in a halo orthosis and a high definition multidetector CT scan was obtained. This study demonstrated a transverse fracture through the fused C6-C7 spinal level. CONCLUSION: Occult fractures in ankylosing spondylitis may not be apparent on routine plain radiographic and MRI studies. In the setting of ankylosing spondylitis, a high index of suspicion must be maintained in all patients presenting with spinal pain following even minor trauma. High-resolution multidetector CT imaging appears to be more sensitive and accurate in the diagnosis of fractures in this patient subgroup than other contemporary imaging methods.

Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy.

OBJECTIVE: Because mesenchymal stem cells can differentiate into chondrocyte-like cells, we ask the question, can mesenchymal stem cells commit to the nucleus pulposus phenotype? BACKGROUND: Back pain, a significant source of morbidity in our society, is linked to degenerative changes of the intervertebral disc. Absence of suitable graft tissue limits therapeutic approaches for repair of disc tissue. For this reason, there is considerable interest in developing "tissue engineering" strategies for the regeneration of the nucleus pulposus. METHODS: Rat mesenchymal stem cells were immobilized in 3-dimensional alginate hydrogels and cultured in a medium containing transforming growth factor-beta1 under hypoxia (2% O2) and normoxia (20% O2). Mesenchymal stem cells were examined by confocal microscopy to evaluate their viability and metabolic status after labeling with Celltracker green, a thiol sensitive dye, and Mitotracker red, a dye sensitive to the mitochondrial membrane potential. Flow cytometry, semiquantitative reverse transcription polymerase chain reaction and Western blot analysis were carried out to evaluate phenotypic and biosynthetic activities and the signaling pathways involved in the differentiation process. RESULTS: Under hypoxic conditions, mesenchymal stem cells formed large aggregates and exhibited positive Celltracker and Mitotracker signals. Glucose transporter-3, matrix metalloproteinase-2, collagen type II and type XI, and aggrecan mRNA and protein expression was upregulated, whereas there was no change in the levels of decorin, biglycan, fibromodulin, and lumican. Hypoxia maintained the expression of CD44 (hyaluronan receptor), ALCAM (CD166), and endoglin (transforming growth factor-beta receptor). Likewise, expression of beta3 and alpha2 integrin was upregulated. Transforming growth factor-beta treatment increased MAPK activity and Sox-9, aggrecan, and collagen type II gene expression. Basal levels of the phosphorylated MAPK isoform ERK1/2, but not p38, were higher under hypoxic conditions than normoxia, and its activation was further augmented by treatment of cells with transforming growth factor-beta. In hypoxia, transforming growth factor-beta sustained phosphorylated p38 expression for an extended time period. Pharmacological inhibition of ERK1/2 and p38 enzymatic activity resulted in a decrease in Sox-9, aggrecan, and collagen type II mRNA levels. CONCLUSIONS: Our results indicate that hypoxia and transforming growth factor-beta drive mesenchymal stem cell differentiation towards a phenotype consistent with that of the nucleus pulposus. Measurement of selected signaling molecules and response to specific inhibitors suggest involvement of MAPK signaling pathways. It is concluded that mesenchymal stem cells could be used to repopulate the damaged or degenerate intervertebral disc.

An organ culture system for the study of the nucleus pulposus: description of the system and evaluation of the cells.

STUDY DESIGN: The goal of this study was to develop a methodology to maintain intervertebral discs in organ culture, thereby preserving tissue architecture and metabolic function in a three-dimensional environment. METHODS: Using a microdissection technique, intervertebral discs were removed from rat lumbar vertebrae. The discs were maintained in organ culture, and cell viability was evaluated histochemically and using probes that measured mitochondrial function and thiol status. The biosynthetic activity of the cells was evaluated by Western blot and RT-PCR analysis. RESULTS: The in vitro organ culture system maintained the vitality of the nucleus pulposus cells. Cells exhibited a high membrane potential for 1 week. When cells were exposed to carbonyl cyanide 4-trifluoromethoxy phenylhydrazone, a known protonophore, the fluorescence was lost, indicating that the staining was specific for viable cells. In many cells, Celltracker Green, probe for reduced thiols, colocalized with the membrane potential. Histologic studies revealed that in culture for 1 week, normal nucleus pulposus structure was maintained; after this time period, alterations were observed. We evaluated the two tissues for characteristic phenotypic markers HIF-1alpha and MMP-2. We noted that the nucleus pulposus expressed these proteins. The RT-PCR profile at 7 days indicated that the cells also expressed collagen type II, aggrecan, and decorin. DISCUSSION: Three factors contributed to success in maintaining the vitality of the nucleus pulposus in vitro. First, the cells were confined within the disc itself; second, the medium was hyperosmotic; third, the medium was supplemented with transforming growth factor-beta. The fluorescence measurement provided a rapid method for evaluation of the status of nucleus pulposus cells. Histologic analysis confirmed that the cells remained viable for at least 1 week. Viability in terms of biosynthetic activity was further confirmed using RT-PCR and Western blot analysis. We conclude that short-term intervertebral disc organ culture can be used as a suitable in vitro model to study effects of environmental factors linked to disc degeneration and/or regeneration.