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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anterior lumbar interbody arthrodesis is commonly performed for conditions involving infection, deformity, and instability. The purpose of this investigation was to determine the effective dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute inside a titanium threaded interbody fusion cage using a nonhuman primate model of laparoscopic anterior lumbar interbody arthrodesis. Eight adult rhesus monkeys underwent laparoscopic exposure of the lumbosacral spine followed by insertion of a hollow titanium threaded cylindrical cage (Sofamor-Danek, Memphis, TN, U.S.A.). Before insertion, the chamber of the cage was filled with a collagen sponge delivery vehicle soaked with either 0 mg/ml (sham, buffer only), 0.75 mg/ml (low dose), or 1.5 mg/ml (high dose) of rhBMP-2 (Genetics Institute, Cambridge, MA, U.S.A.). Fusions were evaluated in a blinded fashion with plain radiographs and computed tomography (CT) scans 12 and 24 weeks after surgery, and by manual palpation and histology after euthanasia 24 weeks after surgery. All five monkeys treated with a cage filled with rhBMP-2 obtained a solid fusion as assessed by manual palpation. The two monkeys that received no growth factor did not achieve solid fusions. Plain radiographs were of limited value, with fusions best assessed on sagittally reconstructed CT scans. Scans from the two animals treated without growth factor showed ingrowth of bone only into the outer edges of the cage, but not through the center. Scans from the rhBMP-2-treated animals demonstrated arthrodesis with continuous bone growth through the cage. Histologic analysis demonstrated normal mature trabecular bone surrounding and growing through the cages, which correlated with the CT scan findings. We conclude that rhBMP-2 delivered in a threaded titanium interbody cage can serve as a bone graft substitute in a nonhuman primate model. Sagittal reconstructed CT may be a better method to assess for fusion with this device.
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PMID:Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage. 958 64

There are drawbacks to using threaded cylindrical cages (e.g., limited area for bone ingrowth and metal precluding radiographic visualization of bone healing). To somewhat offset these drawbacks, a barbell-shaped cage has been designed. The central core of the barbell can be wrapped with collagen sheets infiltrated with bone morphogenetic protein. The obvious theoretical advantages of a barbell cage have to be weighed against potential biomechanical disadvantages. Our purpose was to compare the biomechanical properties of an anterior lumbar interbody reconstruction using 18-mm-diameter threaded cylindrical cages, with a reconstruction using barbell cages (18-mm diameter and 6 mm wide at both cylindrical ends, with a round 4-mm-diameter bar joining the two ends). Twelve cadaveric lumbar motion segments were tested. Three L5-S1 segments received two threaded cylindrical cages, and three L5-S1 segments received two barbell cages. Three L3-L4 segments received one threaded cylindrical cage, and three L3-L4 segments received one barbell cage. A series of biomechanical loading sequences were carried out on each motion segment, and stiffness curves were obtained. After the biomechanical testing, an axial compressive load was applied to the motion segments until failure. They were then radiographed and bisected through the disc, and the subsidence (or penetration) of the cage(s) in the cancellous bone of the vertebral bodies was measured. There was no difference in terms of stiffness between the motion segments with the threaded cylindrical cage(s) inserted and those with the barbell cage(s) inserted (p > 0.15). The average values of subsidence was 0.96 mm for the threaded cylindrical cage group and 0.80 mm for the barbell cage group (difference not significant: p = 0.38). The results suggest that a reconstruction using barbell cages is a biomechanically acceptable alternative to one using threaded cylindrical cages.
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PMID:Anterior lumbar interbody fusion using a barbell-shaped cage: a biomechanical comparison. 1158 37

The particular advantages of interbody cages include the beneficial effects on bone healing associated with the anterior column location (Wolff's Law), the stabilization potential in appropriate motion segments, the ability to restore anterior column height and foraminal volume, and the avoidance of the fusion disease phenomenon. These advantages do not depend on whether the approach of insertion is open or laparoscopic. The specific and demonstrated chief benefit of the laparoscopic approach to interbody cage insertion is the reduction in surgical morbidity. This is especially evident when the laparoscopic technique is combined with the use of bone morphogenetic protein (rhBMP-2). It is the author's belief that this significant diminution in patient morbidity drives the further acceptance of the laparoscopic approach in a manner similar to the evolution of arthroscopic orthopedic surgery and laparoscopic general surgery. The main disadvantage of the laparoscopic approach is the initial learning curve of the surgical team with the technique. The anterior approach to cage placement (open or laparoscopic) also is limited regarding the inability to decompress the spinal canal directly. It is recommended that the interbody cages be considered as only one option in the stabilization of symptomatic motion segments. With care in patient selection, their ability to function in a stand-alone configuration has been demonstrated successfully. To evolve to the laparoscopic placement technique of interbody cages, the access surgeon or spine surgeon should begin as part of a team with the open approach placing the particular instrumentation system they plan to use laparoscopically. Together, the access surgeon and spine surgeon team should attend a hands-on laparoscopic course for the specific instrumentation system. Finally, in terms of initial case selection, one should begin with nondeformity L5-S1 cases and, most importantly, allow time.
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PMID:Laparoscopic approaches to fusion of the lumbosacral spine: latest techniques. 1238 87

Multicenter human clinical studies of patients undergoing anterior lumbar fusion have been conducted using recombinant bone morphogenetic protein or rhBMP-2 on an absorbable collagen sponge, marketed as INFUSE Bone Graft, or autograft implanted in the LT-CAGE Lumbar Tapered Fusion device. An integrated analysis of multiple clinical studies was performed using an analysis of covariance to adjust for preoperative variables in a total of 679 patients. Of these patients, 277 had their cages implanted with rhBMP-2 on an absorbable collagen sponge and 402 received autograft transferred from the iliac crest. The patients treated with rhBMP-2 had statistically superior outcomes with regard to length of surgery, blood loss, hospital stay, reoperation rate, median time to return to work, and fusion rates at 6, 12, and 24 months. Oswestry Disability Index scores and the Physical Component Scores and Pain Index of the SF-36 scale at 3, 6, 12, and 24 months showed statistically superior outcomes in the rhBMP-2 group.
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PMID:Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered fusion device. 1267 64

An economic model was developed to compare costs of stand-alone anterior lumbar interbody fusion with recombinant human bone morphogenetic protein 2 on an absorbable collagen sponge versus autogenous iliac crest bone graft in a tapered cylindrical cage or a threaded cortical bone dowel. The economic model was developed from clinical trial data, peer-reviewed literature, and clinical expert opinion. The upfront price of bone morphogenetic protein (3380 dollars) is likely to be offset to a significant extent by reductions in the use of other medical resources, particularly if costs incurred during the 2 year period following the index hospitalization are taken into account.
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PMID:A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in single-level anterior lumbar fusion. 1457 25

Beta-tricalcium phosphate (beta-TCP) combined with recombinant human bone morphogenetic protein-2 (BMP-2) was examined as a substitute for autograft for packing into interbody fusion cages in the canine lumbar spine model. Discectomy and interbody cage fusion were performed at three disc spaces in eight dogs. Examination of microradiographs and histological sections of the lumbar spine at 16 weeks postsurgery revealed three fusions in the autograft cages (Group A), three in the beta-TCP cages (Group B), and five in the beta-TCP-BMP-2 cages (Group C). The mean percentage of trabecular bone area in the cages was 51.9% in Group A, 48.8% in Group B, and 65.6% in Group C. Mean percentage of trabecular bone formation and mechanical stiffness were highest in the cages filled with beta-TCP and BMP-2. Combination of BMP to beta-TCP may act as an osteoconductive and osteoinductive bone graft substitute in clinical spine surgery.
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PMID:Beta-tricalcium phosphate combined with recombinant human bone morphogenetic protein-2: a substitute for autograft, used for packing interbody fusion cages in the canine lumbar spine. 1520 57

The use of bone morphogenetic protein-2 (rhBMP-2) in spinal fusion has increased dramatically since an FDA approval for its use in anterior lumbar fusion with the LT cage. There are several reports of its use in transforaminal lumbar interbody fusion, posterolateral fusion, and anterior cervical fusion. Reports on adverse effects of rhBMP-2 when used in spinal fusion are scarce in literature. An Institutional Review Board approved retrospective study was conducted in patients undergoing anterior spinal fusion and instrumentation following diskectomy at a single center. Forty-six consecutive patients were included. Twenty-two patients treated with rhBMP-2 and PEEK cages were compared to 24 in whom allograft spacers and demineralized bone matrix was used. Patients filled out Cervical Oswestry Scores, VAS for arm pain, neck pain, and had radiographs preoperatively as well at every follow up visit. Radiographic examination following surgery revealed end plate resorption in all patients in whom rhBMP-2 was used. This was followed by a period of new bone formation commencing at 6 weeks. In contrast, allograft patients showed a progressive blurring of end plate-allograft junction. Dysphagia was a common complication and it was significantly more frequent and more severe in patients in whom rhBMP-2 was used. Post operative swelling anterior to the vertebral body on lateral cervical spine X-ray was significantly larger in the rhBMP-2 group when measured from 1 to 6 weeks after which it was similar. These effects are possibly due to an early inflammatory response to rhBMP-2 and were observed to be dose related. With the parameters we used, there was no significant difference in the clinical outcome of patients in the two groups at 2 years. The cost of implants in patients treated with rhBMP-2 and PEEK spacers was more than three times the cost of allograft spacers and demineralized bone matrix in 1, 2, and 3-level cases. Despite providing consistently good fusion rates, we have abandoned using rhBMP-2 and PEEK cages for anterior cervical fusion, due to the side effects, high cost, and the availability of a suitable alternative.
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PMID:Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. 1738 22

We examined the effect of the extracellular bone morphogenetic protein (BMP) 2 and 7, which are up-regulated in the prostate adenocarcinomas of the conditional Pten deletion mouse model, on primary cultures of cancer-associated fibroblasts (CAF) derived from these tumors. In the CAF, we show that BMP2 or BMP7, but not transforming growth factor beta-1, can strikingly stimulate secretion of stromal cell-derived factor-1 (SDF-1), also known as CXCL12. The CAF cells express type I and type II BMP receptors as well as the receptor for SDF-1, CXCR4. SDF-1 activation is associated with BMP-induced Smad phosphorylation, and the stimulatory effect is blocked by BMP antagonist, noggin. The findings that BMP treatment can increase SDF-1 pre-mRNA levels in a time-dependent manner and actinomycin D treatment can abolish stimulatory effect of BMP suggest a transcriptional modulation of SDF-1 by BMP signaling. Using a human microvascular endothelial cell line, we show that SDF-1 present in the conditioned medium from the stimulated CAF can significantly induce tube formation, an effect relating to angiogenic function. Furthermore, we found that BMP2 can also protect the CAF from serum starvation-induced apoptosis independent of SDF-1, implying that BMP may induce other factors to sustain the survival of these cells. In short, this report establishes a novel BMP-SDF-1 axis in the prostate tumor along with a new prosurvival effect of BMP that when considered together with our previously described oncogenic properties of BMP indicate a circuitry for heterotypic cell interactions potentially critical in prostate cancer.
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PMID:A novel bone morphogenetic protein signaling in heterotypic cell interactions in prostate cancer. 1817 12

Although dysregulation of bone morphogenetic protein (BMP) signaling has been linked to various types of cancers, the relationship between abnormal activation of these signaling pathways and tumorigenesis is not clear. The purpose of the current study was to clarify how BMP2 is involved in colon cancer aggressiveness. The data showed that SW480 and DLD-1 cells displayed different responses to short- and long-term exposure to BMP2. During the first 24 h of exposure to BMP2, these cells were growth-inhibited, whereas surviving cells became resistant to growth inhibition, showing epithelial-to-mesenchymal transformation (EMT) and enhanced motility and invasiveness. Interestingly, in highly metastatic mesenchymal colon carcinoma cells (CT26), blockade of BMP2 signaling by BMP2 siRNA prevented EMT, motility and invasiveness; rather, blockade of BMP2 signaling caused a mesenchymal-to-epithelial transition (MET). The levels of phosphorylated Akt were very different between the two cell types; the BMP2-sensitive SW480 and DLD-1 cells had much higher levels of expression than the BMP2-resistant SW480 and DLD-1 and CT26 cells. CT26 cells, following exposure to BMP2 and activation of Akt, escaped the EMT-induced cellular motility and invasiveness. Moreover, LY294002 treatment of BMP2-sensitive SW480 cells blocked cell growth and enhanced motility and invasiveness. Together, these results suggest that suppression of the PI3 kinase/Akt pathway is correlated with the development of BMP2 resistance and invasion in BMP2-induced EMT in colon cancer.
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PMID:Inhibition of PI3 kinase/Akt pathway is required for BMP2-induced EMT and invasion. 1963 99

Local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute in spinal fusion was Food and Drug Administration approved on July 2, 2002. Its commercial trade name is INFUSE Bone Graft. It was cleared as a combination biologic device after petitioning the FDA in the early 1990s with the argument that rhBMP-2's effects were only local and not systemic. The protein is applied to a type I collagen sponge at the time of surgery. After a minimum of 15 minutes to allow binding, the collagen sponge is rolled up and placed into a titanium spinal fusion cage. Two of the rhBMP-2 loaded cages are implanted into an intervertebral spinal disc space to promote bone growth across the disc, i.e., spinal fusion. Fusion stops motion at the treated level and ultimately reduces back pain originating from the degenerated disc. This same product was FDA approved for a tibia long bone fresh fracture bone grafting application in August 2004, and for sinus elevation and alveolar defects associated with extraction sockets in March 2007. In addition, a new carrier is under clinical evaluation that will offer longer rhBMP-2 sustained release and compression resistance, further expanding the clinical utility of rhBMP-2.
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PMID:Local sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). 1996 55


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