Jeffrey Fischgrund

The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model.

Study Design. A study on the efficacy of recombinant human bone morphogenetic protein 2 (rhBMP‐2) in a nonhuman primate anterior interbody fusion model. Objectives. To investigate the efficacy of rhBMP‐2 with an absorbable collagen sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Summary of Background Data. RhBMP‐2 is an osteoinductive growth factor capable of inducing new bone formation in vivo. Although dosage studies using rhBMP‐2 have been performed on species of lower phylogenetic level, they cannot be extrapolated to the primate. Dosage studies on nonhuman primates are essential before proceeding with human primate application. Methods. Six female adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7‐S1 interbody lumbar fusion. All six sites were assigned randomly to one of two fusion methods: 1) autogenous bone graft within a single freeze‐dried smooth cortical dowel allograft cylinder (control) or 2) rhBMP‐2‐soaked absorbable collagen sponges within a single freeze‐dried smooth cortical dowel allograft cylinder also soaked in rhBMP‐2. The animals underwent a baseline computed tomography scan followed by 3‐ and 6‐month postoperation scans. Anteroposterior and lateral radiographs of the lumbosacral spine were performed monthly. After the monkeys were killed, the lumbar spine fusion sites were evaluated. Histologic evaluation of all fusion sites was performed. Results. The three monkeys receiving rhBMP‐2‐ soaked collagen sponges with a freeze‐dried allograft demonstrated radiographic signs of fusion as early as 8 weeks. The control animals were slower to reveal new bone formation. The computed tomography scans revealed extensive fusion of the L7‐S1 lumbar vertebrae in the group with rhBMP‐2. A pseudarthrosis was present in two of the control animals. Conclusions. This study was able to document the efficacy of rhBMP‐2 with an absorbable collagen sponge carrier and a cortical dowel allograft to promote anterior interbody fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5 mg/mL concentration). The rate of new bone formation and fusion with the use of rhBMP‐2 and cortical dowel allograft appears to be far superior to that of autogenous cancellous iliac crest graft with cortical dowel allograft.

A Pilot Study Evaluating the Safety and Efficacy of OP-1 Putty (rhBMP-7) as a Replacement for Iliac Crest Autograft in Posterolateral Lumbar Arthrodesis for Degenerative Spondylolisthesis

Study Design. A prospective, randomized, controlled, multicenter clinical study was conducted. Objective. To compare the clinical and radiographic outcomes of patients treated with OP-1 (BMP-7) Putty to autogenous iliac crest bone graft for one-level uninstrumented posterolateral fusion of the lumbar spine following decompressive laminectomy for the treatment of symptomatic degenerative spondylolisthesis with spinal stenosis. Background. Preclinical studies have demonstrated that osteoinductive recombinant human osteogenic protein1 in the form of OP-1 Putty is successful at achieving a posterolateral fusion in rabbits and dogs without any significant safety concerns. Methods. Thirty-six patients with degenerative lumbar spondylolisthesis and symptoms of neurogenic claudication were randomized (2:1) to either OP-1 Putty (3.5 mg of OP-1 per side) or autogenous iliac crest bone graft for one-level uninstrumented posterolateral fusion following a decompressive laminectomy. Enrollment in the study was complete when 24 OP-1 Putty patients and 12 autograft patients had been randomized and treated. A patient administered Oswestry scale and SF-36 scale were used to determine clinical outcomes. Independent, blinded neuroradiologists reviewed both static and dynamic radiographs to determine fusion status. Results. At the 1-year follow-up, 32 patients were available for clinical analysis and 29 patients were available for radiographic review. Clinical success as measured on the Oswestry scale was achieved by 18 of 21 (86%) OP-1 Putty patients and 8 of 11 (73%) autograftpatients. SF-36 pain index scores showed similar results. Fourteen of 19 (74%) OP-1 Putty patients and 6 of 10 (60%) autograft patients achieved a successful posterolateral fusion fulfilling all fusion criteria. Of the 29 evaluable patients, 15 were both clinical and radiographic successes, 5 were radiographic successes but were clinicalfailures, 1 patient was both a radiographic and clinical failure, and 8 patients were radiographic failures but were clinical successes. No systemic toxicity, ectopic bone formation, recurrent stenosis, or other adverse events related to the OP-1 Putty implant were observed. Conclusion. Although the posterolateral spine is a challenging fusion environment in patients with degenerative spondylolisthesis, successful radiographic fusion was obtained using OP-1 Putty at a rate that was similar to autograft given the number of patients in this study. Importantly, there were no apparent adverse consequences related to the use of the OP-1 Putty implant in this patient population.

Comparison of OP-1 Putty (rhBMP-7) to Iliac Crest Autograft for Posterolateral Lumbar Arthrodesis : A Minimum 2-Year Follow-up Pilot Study

Study Design. A prospective, randomized, controlled, multicenter clinical study. Objective. To compare the safety and clinical and radiographic outcomes of OP-1 (BMP-7) Putty to autogenous iliac crest bone graft in a population of patients undergoing laminectomy and posterolateral fusion for symptomatic lumbar stenosis associated with degenerative spondylolisthesis. Summary of Background Data. Although the existing preclinical and clinical data suggest that OP-1 is able to achieve osteoinduction and clinical fusion in a variety of situations, the efficacy of this recombinant protein in a clinical spine fusion population has not been fully elucidated. This study directly compares the efficacy and safety of OP-1 putty to autograft bone for arthrodesis in patients with symptomatic stenosis in association with degenerative spondylolisthesis. Methods. Thirty-six patients with degenerative lumbar spondylolisthesis and symptoms of neurogenic claudication underwent laminectomy, bilateral medial facetectomy, and posterolateral fusion using either iliac crest autograft or OP-1 Putty. Oswestry scores and SF-36 questionnaires were used to determine the clinical response to treatment. Independent, blinded neuroradiologists reviewed both static and dynamic radiographs to determine the fusion status. Successful fusion was declared whenthe presence of continuous bridging bone between the transverse processes was observed and less than 5° of angular motion and 2 mm of translational movement was measured using digital calipers. Results. Efficacy data were tabulated for 27 patients at the 24-month time point and an additional 4 patients (without evaluable 24-month results) at the 36-month time point. One patient was not evaluable for radiology, so the data reflect clinical information for 31 patients and radiology for 30 patients. Clinical success, defined as a 20% improvement in the preoperative Oswestry score, was achieved by 17 of 20 (85%) OP-1 Putty patients and 7 of 11 (64%) autograft patients. A successful posterolateral fusion was achieved in 11 of 20 (55%) OP-1 Putty patients and 4 of 10 (40%) autograft patients. SF-36 scores showed similar clinical improvement in both groups. No systemic toxicity, ectopic bone formation, recurrent stenosis, or other adverse events specifically related to the use of the OP-1 Putty implant were observed. Conclusion. This study represents the first clinical trial to demonstrate the safety and similarity of OP-1 Putty as a replacement for autogenous bone graft in the posterolateral fusion environment with a minimum of 2-year follow-up. OP-1 Putty was able to achieve osteoinduction leading to a radiographically solid fusion in the absence of autogenous iliac crest bone graft in 55% of the patients at 24 and 36 months. These results compare favorably to the historical fusion rates reported for uninstrumented arthrodesis in this challenging clinical scenario.

A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP—osteogenic protein 1, in the form of OP-1 putty—combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5° of angular motion and less than or equal to 2xa0mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.

Anterior cervical interbody fusion with rhBMP-2 and tantalum in a goat model

BACKGROUND CONTEXTnTricortical autogenous iliac crest has long served as the gold standard for arthrodesis after cervical discectomy. The added morbidity resulting from bone graft harvest may be eliminated by the use of a biocompatible synthetic bone graft substitute with osteoconductive abilities, and when used with an osteoinductive agent, such as recombinant bone morphogenic protein (rhBMP)-2, it may facilitate arthrodesis similar to autograft.nnnPURPOSEnTo determine by radiographic and histologic analysis whether tantalum with and without rhBMP-2 can facilitate bony ingrowth and arthrodesis in an animal model.nnnSTUDY DESIGN/SETTINGnSingle-level anterior cervical discectomy and fusion was performed using a tantalum bone graft substitute with and without rhBMP-2 in a previously established goat model for anterior cervical fusion.nnnMETHODSnEight goats underwent single-level anterior cervical discectomy and stabilization with a porous tantalum implant. There were four goats in each experimental group. Group A underwent anterior cervical stabilization with tantalum alone, whereas in Group B rhBMP-2 was added to the tantalum implant. The goats were sacrificed at 12 weeks, and their cervical spines were removed for histologic and radiological analysis.nnnRESULTSnOnly one of four goats in Group A had any bony ingrowth into the tantalum. Three of four goats in Group B demonstrated bony ingrowth. The average extent of bony ingrowth at the perimeter of the tantalum in Group A was 2.5% compared with 12.5% in Group B. Similarly, the volume of bony ingrowth within the tantalum was 2.5% in Group A and 10% in Group B. The difference was not statistically significant.nnnCONCLUSIONSnThe data in this pilot study suggest that tantalum may function as a synthetic osteoconductive bone graft substitute. The addition of rhBMP-2 may facilitate osteoinduction within a synthetic osteoconductive implant. The sample size in this study was too small for statistical significance. The present animal model as used in this study was inadequate for cervical arthrodesis where rigid implant fixation is desired.

Minimally invasive spine surgery in the treatment of thoracolumbar and lumbar spine trauma

Thoracolumbar and lumbar trauma account for the majority of traumatic spinal injuries. The mainstay of current treatments is still nonoperative therapy with bracing. Classic treatment algorithms reserved absolute surgical intervention for spinal trauma patients with neurological compromise or instability. Relative indications included incapacitating pain and obesity/body habitus making brace therapy ineffective. In the past decade, minimally invasive surgical (MIS) techniques for spine surgery have been increasingly used for degenerative conditions. These same minimally invasive techniques have seen increased use in trauma patients. The goal of minimally invasive surgery is to decrease surgical morbidity through decreased soft-tissue dissection while providing the same structural stability afforded by classic open techniques. These minimally invasive techniques involve percutaneous posterior pedicle fixation, vertebral body augmentation, and utilization of endoscopic and thoracoscopic techniques. While MIS techniques are somewhat in their infancy, an increasing number of studies are reporting good clinical and radiographic outcomes with these MIS techniques. However, the literature is still lacking high-quality evidence comparing these newer techniques to classic open treatments. This article reviews the relevant literature regarding minimally invasive spine surgery in the treatment of thoracolumbar and lumbar trauma.

Hidden blood loss during posterior spine fusion surgery

BACKGROUND CONTEXTnPosterior spine fusion is associated with significant intra- and postoperative blood losses. When referring to the total blood loss during spine surgery, the standard is to measure the intraoperative bleeding plus the postoperative drainage. This ignores the hidden blood loss that was found to be significant in other fields of surgery.nnnPURPOSEnThe purpose of this study was to examine whether posterior spine fusion carries a substantial hidden blood loss.nnnSTUDY DESIGN/SETTINGnA prospective study.nnnPATIENT SAMPLEnWe prospectively studied 114 patients undergoing instrumented posterior spinal fusion at one center between January 2011 and April 2011.nnnOUTCOME MEASURESnTotal blood loss, visible blood loss, and hidden blood loss.nnnMETHODSnFor each patient, the hidden blood loss was calculated by deducting the observed perioperative blood loss from the calculated total blood loss based on the hematocrit changes. We compared the percentage of the hidden blood loss out of the total blood loss for primary versus revision posterior spine fusion.nnnRESULTSnPrimary decompression and posterior fusion patients had a mean total true loss of 1,439 mL. Their calculated hidden loss was 600 mL, 42% of the total loss. After revision posterior spinal fusion surgery, the mean total blood loss was 1,606 mL. The mean visible loss was 975 mL, and the mean hidden loss was 631 mL, 39% of the total loss. Thus, there was no statistical difference in the hidden blood loss between primary and revision posterior spinal fusion surgeries (p>.05). We did not find a significant difference in the percentage of the hidden blood loss between patients who underwent one, two, or three or more levels of surgery.nnnCONCLUSIONSnAfter posterior spinal fusion, there may be a large amount of the hidden blood loss.

Passive reduction of spondylolisthesis on the operating room table: a prospective study

Translational motion of low-grade spondylolisthesis is traditionally assessed with lateral flexion and extension radiographs. Maximum motion in an unanesthetized patient may be limited by patient cooperation, pain, or muscle spasm. Twenty-four patients with degenerative or isthmic spondylolisthesis were assessed with preoperative lateral flexion and extension radiographs. A lateral radiograph was obtained on the operating room table after administering an anesthetic, exposing the spine, and performing a laminectomy. The percentage slip decreased from 24 to 15 to 6% on flexion, extension, and intraoperative lateral radiographs, respectively (p < 0.001). The amount of reduction did not correlate with disc height, slip angle, slip level, or type of spondylolisthesis. Many low-grade spondylolisthesis deformities reduce almost completely on the operating table. Translational motion of spondylolisthesis is greater than preoperative flexion and extension radiographs indicate.

Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study

AbstractPurposeTo evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP.MethodsA total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47xa0years (range 25–69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2xa0weeks, 6xa0weeks and 3, 6 and 12xa0months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3xa0months.ResultsAt 3xa0months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (pxa0=xa00.019, per-protocol population). A responder analysis based on ODI decrease ≥xa010 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3xa0months.ConclusionPatients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3xa0months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain.Graphical abstractnThese slides can be retrieved under Electronic Supplementary Material.