Artificial disc replacement: progress or hype?
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Arthroplasty, Replacement↗
Biomedical subjects
Howard S An
Publications and source records attributed to Howard S An.
Motion preservation technologies: alternatives to spinal fusion.
Spinal arthrodesis is a versatile and effective option in the management of instabilities, deformities, and painful spinal conditions. An increasing body of biomechanical and clinical evidence suggests that the relative immobility of fused spinal segments alters stress transfer, leading to adjacent-level degeneration. The development of nonfusion spinal prostheses has been driven by increasing concerns regarding these arthrodesis-related morbidities, including graft-site harvest, pseudarthrosis, and adjacent-level degeneration. Motion-sparing implants offer some theoretical advantages over fusion; however, judicious use of these products with careful patient selection is warranted until outcome studies can demonstrate their efficacy. In this article, we review the 3 major categories of nonfusion technologies: total disc replacement, prosthetic nuclear implants, and posterior stabilization devices.
Arthroplasty, Replacement↗
Transduced bovine articular chondrocytes affect the metabolism of cocultured nucleus pulposus cells in vitro: implications for chondrocyte transplantation into the intervertebral disc.
STUDY DESIGN: Biologic study on the effects of coculture of bovine articular chondrocytes transduced ex vivo with genes expressing bone morphogenetic proteins (BMPs) on nucleus pulposus (NP) cells. OBJECTIVE: To evaluate the effects of bovine articular chondrocytes transduced with adenoviruses expressing various BMPs on proteoglycan and collagen production, and cellular proliferation of NP cells in vitro. SUMMARY OF BACKGROUND DATA: Matrix synthesis by intervertebral disc cells is promoted by exposing the cells to growth factors or delivering genes that permit sustained expression of growth factors. We propose a novel therapeutic approach involving delivery of autologous chondrocytes, transduced ex vivo with bioactive proteins, to provide both the cells and proteins required to stimulate disc healing. METHODS: Adult bovine articular chondrocytes were transduced with adenoviruses (Ads) expressing either BMP-2, 4, 5, 7, 10, or 13 and plated as monolayers. Bovine NP cells encapsulated in alginate beads were cocultured, floating in the medium. Proteoglycan and collagen accumulation, and NP cell proliferation were measured after 6 days of coculture. As a positive control, beads were cocultured with articular chondrocytes in the presence of rhBMP-7. RESULTS: NP cells cocultered with articular chondrocytes transduced with BMPs-2, 4, 7, and 10 accumulated significantly (P < 0.05) more proteoglycan than when cocultured with chondrocytes transduced with AdGFP (control) [AdBMP-2: 23.6%; AdBMP-4: 27.0%; AdBMP-7: 129.1%; AdBMP-10: 102.1% increases respectively]. Collagen accumulation was significantly (P < 0.05) increased by NP cells cocultured with articular chondrocytes transduced with BMPs-2, 4, 5, and 7. [AdBMP-2: 104.6%; AdBMP-4: 40.6%; AdBMP-5: 58.6%; AdBMP-7: 55.5% increases respectively]. NP cells proliferated when cocultured with articular chondrocytes transduced with AdBMP-2 and -7. CONCLUSIONS: Bovine NP cells are stimulated to produce proteoglycans and collagen when exposed to chondrocytes transduced with genes for various BMPs. If applied to the treatment of disc degeneration, this strategy could provide the disc with not only metabolically active chondrocytes but also promote matrix replenishment by stimulating native NP cells.
Animals↗
Exposure to pulsed low intensity ultrasound stimulates extracellular matrix metabolism of bovine intervertebral disc cells cultured in alginate beads.
STUDY DESIGN: In vitro study on the effects of pulsed low intensity ultrasound on the cellular metabolism of bovine intervertebral disc cells. OBJECTIVE: To determine whether pulsed low intensity ultrasound has effects on cell proliferation and extracellular matrix metabolism by bovine intervertebral disc cells. SUMMARY OF BACKGROUND DATA: The application of pulsed low intensity ultrasound is known to be effective in stimulating fracture and cartilage repair. However, the effects of pulsed low intensity ultrasound on intervertebral disc cells are not known. METHODS: Cells of the nucleus pulposus and inner and outer anulus fibrosus were enzymatically isolated from bovine coccygeal tissue and precultured in alginate beads for 14 days. In the ultrasound group, pulsed low intensity ultrasound was administered to the culture for 20 minutes daily for an additional 20 days. The control group was cultured in the same way but without administration of ultrasound. Cell viability, DNA content, proteoglycan and collagen synthesis, and proteoglycan content at days 10 and 20 after the initiation of treatment were evaluated. Characterization of newly synthesized collagen and proteoglycan was performed. RESULTS: No significant differences in cell viability and DNA content were observed between the two groups. On day 20, proteoglycan synthesis was increased by the application of pulsed low intensity ultrasound in nucleus pulposus and inner and outer anulus fibrosus cells (24%-26% increase, P < 0.001). The application of pulsed low intensity ultrasound increased proteoglycan content in alginate beads containing inner and outer anulus fibrosus cells (P < 0.05). Collagen synthesis by cells isolated from all three zones of the intervertebral disc was increased by the application of pulsed low intensity ultrasound (16%-19% increase, P < 0.05-0.0001). CONCLUSIONS: The application of pulsed low intensity ultrasound stimulated extracellular matrix metabolism in intervertebral disc cells. Pulsed low intensity ultrasound may prove useful for the physical stimulation of cell metabolism for tissue engineering of intervertebral disc tissue.
Animals↗
Is autograft the gold standard in achieving radiographic fusion in one-level anterior cervical discectomy and fusion with rigid anterior plate fixation?
STUDY DESIGN: A review of 66 consecutive patients at a single institution who underwent one-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation with allograft or autograft. OBJECTIVES: To address the efficacy of allograft to autograft with primary respect to fusion rate and secondary attention to risk factors and clinical outcome in patients undergoing one-level ACDF with rigid anterior plate fixation. SUMMARY OF BACKGROUND DATA: Although autograft is considered the gold standard in achieving optimal fusion, when compared with allograft in noninstrumented one-level ACDF and in plated and nonplated multilevel ACDF, the efficacy of allograft to autograft in one-level ACDF with rigid anterior plate fixation is not thoroughly understood. METHODS: Sixty-six consecutive patients (mean age, 45 years) at a single institution who underwent one-level ACDF with rigid anterior plate fixation with allograft (n = 35) or autograft (n = 31) were reviewed for radiographic fusion (mean, 12 months), risk factors, and clinical outcome (mean, 17 months). Smokers entailed 33.3% of the patients, and 45.5% of all patients presented with a work-related injury. An independent blinded observer reviewed at last follow-up lateral neutral and flexion/extension plain radiographs for radiographic fusion and instrumentation integrity. Clinical outcome was assessed on last follow-up and rated according to the Odom criteria. The threshold for statistical significance was established at P < 0.05. RESULTS: Solid fusion was achieved in 63 patients (95.5%). Fusion was noted in 100% of the allograft patients, whereas 90.3% of the autograft cases achieved fusion. No statistically significant difference was noted between allograft to autograft with regard to fusion rate (P > 0.05). Three patients developed nonunions (1 smoker; 2 nonsmokers) and entailed Orion instrumentation. In the one patient who was a nonsmoker with a nonunion, slight screw penetration into the involved and uninvolved interbody spaces was noted. No other intraoperative, postoperative, or radiographic complication was noted. All of the nonunions occurred early in the series. Postoperatively, excellent results were reported in 19.7%, good results in 71.2%, and fair results in 9.1% of the patients. Satisfactory clinical outcome was noted in all nonunion patients. A nonstatistically significant difference was noted with regard to clinical outcome of fused and nonfused patients, demographics, and the presence of a work-related injury (P > 0.05). The impact of smoking was not a factor influencing fusion or clinical outcome in this series (P > 0.05). A statistically significant difference was noted in plate-type on fusion rate (P < 0.05). CONCLUSION: A 100% and 90.3% radiographic fusion rate was obtained for allograft and autograft in one-level ACDF procedures with rigid anterior plate fixation, respectively. Although autograft achieved a higher incidence of nonunion than allograft, this may be attributed to the use of autograft early in the experience of plate application and fixation in this series. The effects of smoking were not found to be a significant factor influencing fusion in these plated patients. In 90.9% of the patients, excellent and good clinical outcome results were reported. The use of allograft in one-level ACDF with rigid plate fixation yields similar and high fusion rates as autograft. The use of allograft bone eliminates complications and pitfalls associated with autologous donor site harvesting. However, the use of autograft is a viable alternative to avoid the risk of infection, disease transmission, and histocompatibility differences associated with allograft. The use of allograft or autograft bone in properly selected patients for one-level ACDF with rigid anterior plate fixation can result in high fusion rates with excellent and good clinical outcomes.
Adult↗
A prospective cohort analysis of adjacent vertebral body bone mineral density in lumbar surgery patients with or without instrumented posterolateral fusion: a 9- to 12-year follow-up.
STUDY DESIGN: A prospective, cohort study of 11 patients who underwent either a posterior lumbar spinal fusion with instrumentation (n = 7) or a lumbar laminotomy and discectomy alone (n = 4) and who were evaluated by dual energy radiograph absorptiometry (DEXA) to determine bone mineral density (BMD) at the adjacent three cephalad vertebral levels. OBJECTIVES: To determine long-term BMD changes that occur at the adjacent three levels above an instrumented posterolateral lumbar fusion or an isolated laminotomy and lumbar discectomy. SUMMARY OF BACKGROUND DATA: No long-term prospective study has evaluated the affects of instrumented lumbar fusions on bone remodeling at adjacent vertebral levels. Several studies in animals and humans have reported a decrease in BMD at the adjacent level during the first 6 months after spinal fusion with a return to baseline at 1-year follow-up in up to 60% of patients. METHODS: DEXA was performed initially at a mean postoperative follow-up of 4 years (range, 2.3-5.5 years) and again at a mean of 10.8 years (range, 9.1-2.4 years). Eleven patients were divided into two groups: laminotomy and discectomy (n = 4) and instrumented posterior spinal fusion (n = 7). All patients underwent surgical procedures at the L4-L5 or L5-S1 levels with DEXA analysis being performed on the adjacent three cephalad levels. The discectomy group (mean age, 57.8 years) underwent lumbar hemilaminotomy without fusion whereas the other group (mean age, 60 years) underwent pedicle-screw instrumentation and posterolateral lumbar fusion. Peripheral sites, including the femoral neck, were included in the DEXA analysis to normalize for individual differences in bone mineral metabolism. RESULTS: At the mean 10.8-year follow-up, the fusion group was noted to have at the adjacent level, two levels cephalad, and three levels cephalad normalized BMDs of 1.47, 1.39, and 1.27, respectively. A 14.8%, 10.8%, and 9.5% increase respectively in normalized BMD was observed when compared with the mean 4-year fusion values (P < 0.05). This increase was also noted on comparative T-score, Z-score, and absolute BMD values (P < 0.05). The discectomy group when evaluated revealed no statistically significant change from the mean 4 to 10.8-year follow-up (BMD, normalized BMD, T-score, Z-score). No statistically significant difference was noted in hip BMD at the mean 4-year and 10.8-year follow-up (1.05 versus 1.03), suggesting that the effects were local. CONCLUSIONS: The local BMD adjacent to an instrumented lumbar fusion is increased at a mean of 10.8-years after surgery. There is a gradual decrease in BMD changes with increasing distance from the fusion level. Alterations in fusion site biomechanics and modulus mismatch between the host bone and the spinal instrumentation most likely result in chronic, localized bone remodeling with an increased BMD that decreases the greater the distance from the fusion mass.
Bone Density↗
Expressions of membrane-type I matrix metalloproteinase, Ki-67 protein, and type II collagen by chondrocytes migrating from cartilage endplate into nucleus pulposus in rat intervertebral discs: a cartilage endplate-fracture model using an intervertebral disc organ culture.
STUDY DESIGN: Immunohistochemistry was performed in organ-cultured intact and cartilage endplate (CE)-fractured rat intervertebral discs (IVDs). OBJECTIVES: To demonstrate biologic events associated with migration of chondrocytes from hyaline CE into nucleus pulposus (NP). SUMMARY OF BACKGROUND DATA: It was recently revealed that the transition from a notochordal NP to a fibrocartilaginous NP in the rabbit IVD is accomplished exogenously by chondrocytes migrating from CEs into the NP. This observation has not been studied in other animal models, and the biologic events associated with chondrocyte migration have not been elucidated in the literature. METHODS: IVDs including cranial and caudal CEs were obtained from 4-week, 6-month, 12-month, and 18-month old Wistar rats. To accelerate chondrocyte migration, CEs of IVDs were fractured and cultured for 48 hours. IVDs without CE-fracture were used as a control for each age group. Expressions of membrane-type I matrix metalloproteinase (MT1-MMP, as a marker for cell migration and extracellular matrix digestion) and Ki-67 protein (as a proliferation marker) and pericellular deposition of type II collagen (as a marker for fibrocartilaginous matrix) by the chondrocytes migrating from CE into NP were examined immunohistochemically. RESULTS: In the control groups, chondrocyte migration limited only along the periphery of the notochordal NP and no chondrocytes were inside the NP proper. However, all the IVDs in the CE-fracture groups showed direct and more extensive migration of chondrocytes from CEs into the NP proper. The migrating chondrocytes in both control and CE-fracture groups expressed MT1-MMP and Ki-67 protein and deposited type II collagen in the NP. CONCLUSIONS: This report demonstrates the chondrocyte migration from CE into NP in the organ-cultured rat IVDs. This phenomenon is accelerated in the presence of CE fracture. The chondrocytes migrating from CEs into the NP expressed MT1-MMP and Ki-67 protein and deposited type II collagen. These biologic strategies probably enable chondrocytes of the hyaline CE to migrate into the ectopic NP region, replace notochordal cells, and change the notochordal tissue into fibrocartilage. These results suggest that similar biologic mechanisms may be involved in the natural transition from the notochordal NP to the fibrocartilaginous NP in other animal models, including human.
Animals↗
An autocrine or paracrine Fas-mediated counterattack: a potential mechanism for apoptosis of notochordal cells in intact rat nucleus pulposus.
STUDY DESIGN: Immunohistochemistry and in situ nick end-labeling (TUNEL) were performed in rat lumbar intervertebral discs. OBJECTIVES: To demonstrate the mechanism of notochordal cell death in the nucleus pulposus (NP). SUMMARY OF BACKGROUND DATA: With age, notochordal cells gradually disappear in the NP. We hypothesized that this phenomenon might be related to Fas-mediated apoptosis. MATERIALS AND METHODS: Expressions of Fas; Fas ligand (FasL); caspase 3, 8, 9, 10; Ki-67 protein; and TUNEL were examined in 4-week-, 6-month- and 12-month-old rat NPs. Apoptosis (TUNEL-positive) and proliferation potential (Ki-67-positive) indexes of notochordal cells were calculated and compared among age groups. RESULTS: Notochordal cells constitutively expressed both Fas and FasL. Among their downstream initiator (caspase 8, 9, and 10) and executioner (caspase 3) caspases tested, caspase 9 and 3 were expressed. Proliferation potential of the notochordal cells was the highest at 4 weeks (1.96 +/- 1.3%) and decreased to a significantly lower level at 6 (0.81 +/- 0.68%) and 12 months (0.8 +/- 0.37%; P = 0.03 and 0.01, respectively). In contrast, apoptosis of the notochordal cells was the lowest at 4 weeks (3.52 +/- 1.07%) and increased to a significantly higher level at 6 (19.38 +/- 10.99%) and 12 months (21.51 +/- 16.99%; P < 0.001 in both comparisons). CONCLUSIONS: Fas-mediated mitochondrial caspase 9 pathway is constitutively present in the rat notochordal cells. The constitutive expression of Fas, FasL and its downstream caspases, as well as the homogeneity ofnotochordal cell population suggests an autocrine or paracrine Fas-mediated counterattack to be a potential mechanism for apoptosis of rat notochordal cells. A regulated negative balance of notochordal cell proliferation against apoptosis is likely to involve the disappearance of notochordal cells in the rat NP. This information on the mechanism for apoptosis of notochordal cells could be important in the investigation of intervertebral disc development as well as aging and perhaps degeneration.
Aging↗
Differential effects of fibronectin fragment on proteoglycan metabolism by intervertebral disc cells: a comparison with articular chondrocytes.
STUDY DESIGN: This in vitro study used the alginate bead culture system to probe for differences in the effects of fibronectin fragment on cell proliferation and proteoglycan metabolism by different populations of intervertebral disc cells and articular chondrocytes. OBJECTIVE: To compare the effects of fibronectin fragment on cell proliferation, and proteoglycan synthesis and degradation by cells from the nucleus pulposus, the anulus fibrosus, and articular cartilage. SUMMARY OF BACKGROUND DATA: In articular cartilage, the administration of fibronectin fragment stimulates cartilage degeneration. Fibronectin fragment levels were increased in human intervertebral discs with increased disc degeneration. Fibronectin fragment injected into the central region of the rabbit intervertebral disc induced a progressive degeneration of that disc. METHODS: Bovine tails and metacarpophalangeal joints from 14- to 18-month-old animals were used. Alginate beads containing cells isolated from intervertebral discs and articular cartilage were cultured with (1-100 nmol/L) or without (control) fibronectin fragment in the presence of 10% fetal bovine serum. In these cultures, deoxyribonucleic acid and proteoglycan contents, as well as the rate of proteoglycan synthesis were determined. Proteoglycan degradation was measured in cultures with or without 10 nmol/L fibronectin fragment. RESULTS: In articular chondrocytes, fibronectin fragment strongly suppressed proteoglycan synthesis and stimulated proteoglycan degradation; the total proteoglycan content was diminished in a dose-dependent manner. Compared to articular chondrocytes, nucleus pulposus cells responded to fibronectin fragments in a similar, although less pronounced manner. On the other hand, anulus fibrosus cells treated with fibronectin fragment did not show any significant effects on proteoglycan degradation. A slight but statistically significant up-regulation of proteoglycan synthesis was observed at 10 nmol/L fibronectin fragment in outer anulus fibrosus cells. However, total proteoglycan content was decreased significantly at high concentrations of fibronectin fragment. CONCLUSIONS: Fibronectin fragment has different effects on cell proliferation, proteoglycan synthesis, degradation, and accumulation by articular chondrocytes and intervertebral disc cells. The different effects of fibronectin fragment in those different cell types suggest metabolic differences between these cells, and may further suggest differences in pathways of fibronectin fragment signaling as well as a differential need of these cells to be involved in tissue remodeling in which both anabolic and catabolic pathways might be altered.
Animals↗
Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits.
STUDY DESIGN: A study of the disc height and biochemical changes in the rabbit intervertebral disc after injection of osteogenic protein-1 into the nucleus pulposus. OBJECTIVES: To evaluate the in vivo effects of osteogenic protein-1 administered intradiscally to the intervertebral disc of rabbits. SUMMARY OF BACKGROUND DATA: Growth factors, such as osteogenic protein-1 and transforming growth factor-beta, have the ability to stimulate synthesis of proteoglycan and collagen in vitro. No attempts have yet been made to determine the effects of these growth factors in an in vivo model. METHODS: Twenty-four New Zealand adolescent white rabbits were divided evenly into two subject groups. In one group, three consecutive intervertebral discs were injected with saline; whereas in the other group, they were injected with osteogenic protein-1 in saline. At 2, 4, and 8 weeks after the injection, the intervertebral disc heights of the injected specimens were measured by lateral plain radiographs and compared with preinjection measurements. The change in disc height was expressed as the percent disc height index compared with the preinjection value. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, proteoglycan, and collagen contents. RESULTS: At 2 weeks after the injections, the mean disc height index of the osteogenic protein-1-injected discs was 15% greater than that of the saline group. The increase in disc height with osteogenic protein-1 injection was still statistically significant at the 4- and 8-week time points. The proteoglycan content of the nucleus pulposus in discs injected with osteogenic protein-1 was higher than that in the saline group at the 2-week time point. The osteogenic protein-1-induced effect on the proteoglycan content was also present at the 4- and 8- week time intervals; however, these increases were not statistically significant. There were no significant differences in the DNA content, normalized to noninjected control, of the nucleus pulposus between the saline and osteogenic protein-1 groups. However, a significant increase in the DNA content of the anulus fibrosus in the osteogenic protein-1 group, compared with that of the anulus fibrosus in the saline group, was observed after 4 weeks. CONCLUSION: To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.
Age Factors↗
A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration.
STUDY DESIGN: An in vivo study to radiographically and histologically assess a new method of induction of disc degeneration. OBJECTIVE.: To establish a reproducible rabbit model of disc degeneration by puncturing the anulus with needles of defined gauges and to compare it to the classic stab model. SUMMARY OF BACKGROUND DATA: New treatment approaches to disc degeneration are of great interest. Although animal models for disc degenerative disease exist, the quantitative measurement of disease progression remains difficult. A reproducible, progressive disc degeneration model, which can be induced in a reasonable time frame, is essential for development of new therapeutic interventions. METHODS: The classic anular stab model and the new needle puncture model were used in the rabbit. For the needle puncture model, 3 different gauges of needle (16G, 18G, and 21G) were used to induce an injury to the disc to a depth of 5 mm. Radiographic and histologic analyses were performed; magnetic resonance images were also assessed in the needle puncture model. RESULTS: Significant disc space narrowing was observed as early as 2 weeks after stabbing in the classic stab model; there was no further narrowing of the disc space. In the needle puncture model, all needle sizes tested induced a slower and more progressive decrease in disc height than in the classic stab model. The magnetic resonance imaging supported the results of disc height data. CONCLUSIONS: The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.
Animals↗
Update on bone morphogenetic proteins and their application in spine surgery.
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Animals↗
Open vertebral cement augmentation combined with lumbar decompression for the operative management of thoracolumbar stenosis secondary to osteoporotic burst fractures.
Osteoporotic burst fractures with neurologic symptoms are typically treated with neural decompression and multilevel instrumented fusion. These large surgical interventions are challenging because of patients' advanced ages, medical co-morbidities, and poor fixation secondary to osteoporosis. The purpose of this retrospective clinical study was to describe a novel technique for the treatment of osteoporotic burst fractures and symptomatic spinal stenosis via a limited thoracolumbar decompression with open cement augmentation [vertebroplasty (VP) or kyphoplasty (KP)]. Indications for decompression and cement augmentation were intractable pain at the level of a known osteoporotic burst fracture with symptoms of spinal stenosis. As such, 25 patients (mean age, 76.1 years) with low-energy, osteoporotic, thoracolumbar burst fractures (7 males, 18 females; 39 fractures) were included. In all cases, laminectomy of the stenotic level(s) was followed by vertebral cement augmentation (9 VP; 16 KP). When a spondylolisthesis at the decompressed level was present, instrumentation was applied across the listhetic level (n = 9). Clinical outcome (1 = poor to 4 = excellent) was assessed on last clinical follow-up (mean, 44.8 wks). In addition, a modified MacNab's grading criteria was used to objectively assess patient outcomes postoperatively. Radiographic analysis of sagittal contour was assessed preoperatively, immediately postoperatively, and at final follow-up. The average time from onset of symptoms to intervention was 19 weeks (range, 0.3-94 wks). A mean of 1.6 fractures/patient was augmented (range, 1-3 fractures) and 2.8 levels were decompressed (range, 1-6 levels). No statistical difference in anatomic distribution or number of fractures between the VP and KP groups or in the instrumented versus noninstrumented patients was noted (P > 0.05). An overall subjective outcome score of 3.4 was noted. Twenty of 25 patients were graded as excellent/good according to the modified MacNab's criteria. The choice of augmentation procedure or use of instrumentation did not predict outcome (P = 0.08). Overall, 1.7 degrees of sagittal correction was obtained at final follow-up. One patient was noted to have progressive kyphosis after KP. The use of a limited-posterior decompression and open cement augmentation via VP or KP is a safe treatment option for patients who have osteoporotic burst fractures and who are incapacitated from fracture pain and concomitant stenosis. After thoracolumbar decompression, open VP/KP provides direct visualization of the posterior vertebral body wall, allowing for safe cement augmentation of burst fractures, stabilizing the spine, and obviating the need for extensive spinal reconstruction. Although clinically successful, this technique warrants careful patient selection.
Aged↗
Low-dose interleukin-1 partially counteracts osteogenic protein-1-induced proteoglycan synthesis by adult bovine intervertebral disk cells.
OBJECTIVE: Low back pain associated with degenerative disk disease is a common clinical problem that has enormous socioeconomic impact in today's aging population. As an alternative to the surgical removal of the diseased intervertebral disk, the direct application of a purified growth factor into the intervertebral disk may provide physiatrists a valuable tool to halt or slow down disk degeneration. Our goal here is to determine if low levels of interleukin-1 (IL-1), a proinflammatory cytokine present in the degenerating disk, could interfere with the potentially beneficial effects of growth factors on proteoglycan synthesis. New knowledge gained from this study will prove useful in the development of new treatment modalities that take advantage of the stimulatory effects of growth factors such as osteogenic protein-1 (OP-1). DESIGN: This was an in vitro study of proteoglycan accumulation and synthesis by cells from the nucleus pulposus, inner annulus fibrosus, and outer annulus fibrosus in the bovine intervertebral disk. RESULTS: In cells cultured with serum and no additional exogenous growth factor, treatment with low-dose IL-1 does not result in a significant decrease in proteoglycan synthesis. However, in the case of cells stimulated with OP-1, treatment with IL-1 resulted in a statistically significant decrease in sulfur-35-proteoglycan synthesis by cells derived from all three zones of the bovine intervertebral disk (nucleus pulposus, 60.3% [P < 0.0001]; inner annulus fibrosus, 18.4% [P = 0.0330]; outer annulus fibrosus, 12.3% [P = 0.0255]). Proteoglycan accumulation over the 12-day culture period also decreased significantly (nucleus pulposus, 26.8% [P < 0.0001]; inner annulus fibrosus, 15.8% [P = 0.0276]; outer annulus fibrosus, 16.8% [P = 0.0102]). It is worth noting that cells cultured in the presence of both OP-1 and IL-1 synthesized proteoglycan at a faster rate than cells cultured in the presence of IL-1 alone (nucleus pulposus, 58.5% [P < 0.0001]; inner annulus fibrosus, 39.7% [P = 0.0055]; outer annulus fibrosus, 45.1% [P = 0.0164]). Likewise, cells treated with OP-1 and IL-1 accumulated more proteoglycan in their newly formed matrix than cells cultured in the presence of IL-1 alone (nucleus pulposus, 65.3% [P < 0.0001]; inner annulus fibrosus, 60.5% [P = 0.0034]; outer annulus fibrosus, 19.4% (P = 0.0840]). CONCLUSIONS: Intervertebral disk cells that are stimulated by the growth factor OP-1, to increase the rate at which they produce a proteoglycan-rich matrix become more susceptible to the inhibitory effects of the proinflammatory cytokine IL-1 on the rate of proteoglycan synthesis and accumulation in the matrix over time. This notwithstanding, IL-1 at the low dose used did not totally obliterate the stimulatory effects of OP-1 on matrix formation. Consequently, this growth factor may remain partially effective in stimulating disk repair in vivo even when proinflammatory cytokines such as IL-1 are present.
Animals↗
Artificial disc replacement: the new solution for discogenic low back pain?
As we develop an increased understanding of DDD (e.g., pain generators, natural history, associated facet disease), so too will our ability to provide patients with effective care increase. Cautious optimism should be the attitude of surgeons treating patients with ADR. Issues such as implant design, wear debris, the role of ADR in osteoporosis, revision strategies, the patient selection will play important roles in the clinical success of ADR. the various topics discussed in this text will require careful additional scientific scrutiny prior to unconstrained endorsement of this evolving technique.
Arthroplasty, Replacement↗
Growth factors and treatment of intervertebral disc degeneration.
STUDY DESIGN: Literature review. OBJECTIVE: To review the most recent findings of the effects of growth factors on the intervertebral disc and, further, to discuss trends in the biologic repair of the degenerated intervertebral disc. SUMMARY OF BACKGROUND DATA: Since early in 1990, advancements in molecular biology and cell culture technology have enabled researchers to accumulate knowledge about the in vitro actions of growth factors on intervertebral disc cells. More recently, the use of growth factors for the biologic regeneration of the intervertebral disc is of increasing interest to the orthopedic field, and indeed, some preliminary in vivo studies have proven their efficacy. METHODS: Based on a literature search conducted using available databases, such as the National Library of Medicine, as well as data presented at scientific conferences held in the past 2 years, primarily in the United States, the current status of biologic therapy for disc degeneration using growth factors was summarized. RESULTS: With increasing evidence to support the feasibility of biologically regenerating intervertebral disc tissues, the clinical application of growth factors has become more plausible. The effects of growth factors on the metabolism of intervertebral disc cells or tissues have been extensively studied using in vitro approaches. More recently, the efficacy of an injection of growth factor protein to reverse disc regeneration has been shown in vivo using a small animal disc degeneration model. The confirmation of those effects and a detailed dose-response study, as well as a long-term safety study, in a large animal model is highly anticipated. Hopefully, the expansion of the clinical use of improved imaging techniques for the early detection of disc degeneration and promising results about the effects of growth factors on intervertebral disc regeneration will benefit the human population in the near future. CONCLUSIONS: The results from these in vitro and in vivo studies reviewed here clearly suggest the potential usefulness of growth factor injections as a new approach to restore intervertebral disc degeneration at an early stage.
Animals↗
Introduction: disc degeneration: summary.
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Animals↗