Ben B. Pradhan

Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2.

Study Design. This is a prospective cohort study examining the results and radiographic characteristics of anterior lumbar interbody fusion (ALIF) using femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2 (rhBMP-2). This was compared to a historical control ALIF using FRAs with autologous iliac crest bone graft (ICBG). Objective. To determine whether the use of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs. Summary of Background Data. ALIF is a well-accepted procedure in reconstructive spine surgery. Advances in spinal surgery have produced a multitude of anterior interbody implants. The rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded allograft dowels. The FRA still remains a traditional alternative for anterior support. However, as a stand-alone device, the FRA has fallen into disfavor because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may be more attractive because of its simplicity and remodeling potential. It is important to understand the implications when rhBMP-2 is used with such structural allografts. Methods. A total of 36 consecutive patients who underwent ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP-2 was followed prospectively. After noticing suboptimal results, the senior author terminated this method of lumbar fusion. A total of 27 prior consecutive patients who received FRAs filled with autogenous ICBG were used for comparison. Analyzing sequential radiographs, flexion-extension radiographs, and computerized tomography with multiplanar reconstructions determined nonunions. Minimum follow-up was 24 months. Results. Pseudarthrosis was identified in 10 of 27 (36%) patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]). Statistical significance was not established because of the early termination of the treatment group (P > 0.3). Of interest, radiographs and computerized tomography revealed early and aggressive resorption of the FRAs when used with rhBMP-2. This preceded graft fracture and even disintegration, resulting in instability and eventual nonunion. Conclusion. The use of rhBMP-2 did not enhance the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a higher nonunion rate with rhBMP-2, although this was not significant with the numbers available. This result appears to be caused by the aggressive resorptive phase of allograft incorporation, which occurs before the osteoinduction phase.

Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment.

Study Design. A retrospective study of patients who underwent 1–3-level kyphoplasty procedures at a single institute. Objective. To examine and compare the effects of single and multilevel kyphoplasty procedures on local versus overall sagittal alignment of the spine. Summary of Background Data. Cement augmentation has been a safe and effective method in the treatment of symptomatic vertebral compression fractures (VCFs). In addition to providing rapid pain relief, balloon tamp kyphoplasty has reduced acute fractures, allowed controlled cement placement under lower pressure, and resulted in improvement of deformity. The restoration of normal overall spinal sagittal alignment in the elderly patient with a VCF and kyphotic deformity has obvious benefits. Although significant correction of local kyphosis (fractured vertebra) has been reported in the literature, to our knowledge, there have been no reports on whether this leads to an improved overall sagittal alignment. Methods. A total of 65 consecutive patients with symptomatic VCFs who underwent 1–3-level kyphoplasty procedures were included in the study. Preoperative and postoperative radiographs were analyzed to quantify local and overall spinal sagittal alignment correction. Preoperative and postoperative vertebral heights at the fractured levels were also measured and categorized into anterior, middle, or posterior vertebral heights. Results. Measurements revealed that kyphoplasty reduced local kyphotic deformity at the fractured vertebra by an average of 7.3° (63% of preoperative kyphosis). This result did not translate to similar correction in overall sagittal alignment. In fact, angular correction decreased to 2.4° (20% of preoperative kyphosis at fractured level) when measured 1 level above and below. The angular correction further decreased to 1.5° and 1.0° (13% and 8% of preoperative kyphosis at fractured level), respectively, at spans of 2 and 3 levels above and below. Average height gain was highest in the middle of the vertebral body (39% increase) compared to the anterior or posterior edges (19% and 3% increases, respectively). With multilevelkyphoplasty procedures, higher angular gains were seen over more vertebrae compared to the 7.3° for a single-level kyphoplasty: 7.8° over 2 levels and 7.7° over 3 levels for 2 and 3-level kyphoplasty procedures, respectively. Kyphoplasty was able to achieve higher angular reduction in thoracic versus lumbar fractures (8.5 vs. 6.4°, P < 0.01). The angular correction was also better maintained over adjacent segments in the thoracic spine. Conclusion. The majority of kyphosis correction by kyphoplasty is limited to the vertebral body treated. The majority of height gained after kyphoplasty occurs in the midbody. Higher correction over longer spans of the spine can be achieved with multilevel kyphoplasty procedures, in proportion to the number of levels addressed. Notwithstanding its well-published clinical efficacy, it is unrealistic to expect a 1 or 2-level kyphoplasty to improve significantly the overall sagittal alignment after VCFs.

Single-level lumbar spine fusion: a comparison of anterior and posterior approaches.

This study is a retrospective review of 122 patients who underwent single-level lumbar spine fusion. The objectives were to directly compare perioperative morbidity and early results of single-level anterior interbody versus posterolateral intertransverse process lumbar spine fusion and to provide objective findings that may be useful in selecting surgical method. Lumbar spinal fusion is a well-recognized surgical treatment of intractable low back pain resulting from DDD or spondylolisthesis. Assessments of techniques, results, and outcomes have been published, but detailed head-to-head comparisons of anterior versus posterior approaches with objective operative and postoperative data are not available in the literature. A retrospective review of 122 patients who underwent either an anterior interbody or posterolateral intertransverse process (average follow-up 22 and 26 months, respectively) single-level instrumented lumbar spinal fusion was performed. Surgical, perioperative, and follow-up data were obtained directly from medical records. The findings compared included estimated blood loss, need for blood transfusion, number of units transfused, operative time, number of days in hospital, need for transitional facility care, complications, need for further surgery, radiographic fusion, and clinical results. There was significantly less blood loss, need for transfusion, amount of blood transfused, operative time, and hospital stay for patients with anterior fusion procedures (p < 0.01). There was no significant difference in need for transitional facility care, complication rates, and given follow-up period in radiographic fusion rate and clinical outcome. Clinical results were significantly worse for those undergoing revision versus primary fusion (p < 0.01). The anterior approach to single-level lumbar fusion is associated with less morbidity than the posterolateral approach. This may in turn affect surgical outcome and hospital cost. However, both approaches to single-level lumbar fusion produce similar early fusion rates and clinical results. Revision fusions had poor early results regardless of approach.

Controlling bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth using fibrin glue.

Study Design. An in vitro and in vivo study. Objective. To evaluate the ability of fibrin glue to limit diffusion of recombinant human bone morphogenetic protein (rhBMP)-2 and its ability to protect spinal nerves from rhBMP-2 stimulated bone growth. Summary of Background Data. Studies have shown bone morphogenetic protein (rhBMP-2) stimulated bone growth can encroach on the spinal canal and nerves, causing neural compression. More recently, rhBMP-2 use in the cervical spine has been associated with life-threatening swelling. Fibrin glue has been used as a biologic carrier but has not been evaluated for its ability to limit rhBMP-2. Methods. In phase 1 of the study, rhBMP-2 soaked absorbable collagen sponges (ACS) were encapsulated in fibrin glue and immediately incubated in physiologic lactated ringers solution at 38°C. Samples of solution were tested for rhBMP-2 concentration. In phase 2 of the study, rats were surgically treated with laminectomy and placement of rhBMP-2/ACS versus laminectomy and placement of fibrin glue before placement of rhBMP-2/ACS. After 8 weeks, animals were euthanized and imaged using micro-computerized tomography. Results. The diffusion study showed a significant limitation in rhBMP-2 diffusion when encapsulated in fibrin glue. The laminectomy study revealed blockage of bone formation by fibrin glue and protection of the spinal canal. Conclusions. Fibrin glue can limit the diffusion of rhBMP-2, and, thus, it can be used to help protect the spinal canal and nerve roots from rhBMP-2 stimulated bone growth.

Ketorolac and spinal fusion: does the perioperative use of ketorolac really inhibit spinal fusion?

Study Design. Retrospective review. Objective. To evaluate the effect of postoperative use of ketorolac (Toradol) on spinal fusion in humans. Summary of Background Data. The value of parenteral ketorolac in postoperative analgesia has been well documented across surgical specialties. However, some studies have shown that ketorolac may adversely affect osteogenic activity and fracture healing. Methods. A total of 405 consecutive patients who underwent primary lumbar posterolateral intertransverse process fusion with pedicle screw instrumentation were included in this retrospective study. A subtotal of 228 patients received Toradol after surgery for adjunctive analgesia. Each patient received a mandatory dose of 30 mg intravenously every 6 hours for 48 hours. The same surgeon performed the fusion procedure on all of these patients. Historical controls included 177 patients who did not receive Toradol after surgery. The minimum follow-up period was 24 months. Nonunions were diagnosed by analyzing sequential radiographs, flexion-extension radiographs, and computed tomography with multiplanar reconstructions. The gold standard of surgical exploration was performed in symptomatic patients with diagnostic ambiguity or nonunions diagnosed by imaging. Results. There were no smokers in the study population. Pseudarthrosis was identified in 12 of 228 patients (5.3%) who received Toradol after surgery, and in 11 of 177 patients (6.2%) who did not. There was no significant difference detected in the nonunion rates between the two groups (P > 0.05, &khgr;2 method). Conclusion. Use of ketorolac after spinal fusion surgery in humans, limited to 48 hours after surgery for adjunctive analgesia, has no significant effect on ultimate fusion rates.

Evidence-informed management of chronic low back pain with watchful waiting

The management of chronic low back pain (CLBP) has proven very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Biomechanical analysis in a human cadaveric model of spinous process fixation with an interlaminar allograft spacer for lumbar spinal stenosis: Laboratory investigation.

OBJECT Traditional posterior pedicle screw fixation is well established as the standard for spinal stabilization following posterior or posterolateral lumbar fusion. In patients with lumbar spinal stenosis requiring segmental posterior instrumented fusion and decompression, interlaminar lumbar instrumented fusion (ILIF) is a potentially less invasive alternative with reduced morbidity and includes direct decompression assisted by an interlaminar allograft spacer stabilized by a spinous process plate. To date, there has been no biomechanical study on this technique. In the present study the biomechanical properties of the ILIF construct were evaluated using an in vitro cadaveric biomechanical analysis, and the results are presented in comparison with other posterior fixation techniques. METHODS Eight L1-5 cadaveric specimens were subjected to nondestructive multidirectional testing. After testing the intact spine, the following conditions were evaluated at L3-4: bilateral pedicle screws, bilateral laminotomy, ILIF, partial laminectomy, partial laminectomy plus unilateral pedicle screws, and partial laminectomy plus bilateral screws. Intervertebral motions were measured at the index and adjacent levels. RESULTS Bilateral pedicle screws without any destabilization provided the most rigid construct. In flexion and extension, ILIF resulted in significantly less motion than the intact spine (p < 0.05) and no significant difference from the laminectomy with bilateral pedicle screws (p = 0.76). In lateral bending, there was no statistical difference between ILIF and laminectomy with unilateral pedicle screws (p = 0.11); however, the bilateral screw constructs were more rigid (p < 0.05). Under axial rotation, ILIF was not statistically different from laminectomy with unilateral or bilateral pedicle screws or from the intact spine (p > 0.05). Intervertebral motions adjacent to ILIF were typically lower than those adjacent to laminectomy with bilateral pedicle screws. CONCLUSIONS Stability of the ILIF construct was not statistically different from bilateral pedicle screw fixation following laminectomy in the flexion and extension and axial rotation directions, while adjacent segment motions were decreased. The ILIF construct may allow surgeons to perform a minimally invasive, single-approach posterior decompression and instrumented fusion without the added morbidity of traditional pedicle screw fixation and posterolateral fusion.

Computed tomography assessment of the accuracy of in vivo placement of artificial discs in the lumbar spine including radiographic and clinical consequences

Study Design. Prospective cohort study of 52 patients who had undergone artificial lumbar disc replacement. Objectives. To evaluate the implantation accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis migration, and the clinical consequences of implant position. Summary of Background Data. Accuracy of spinal prosthesis implantation has not been evaluated rigorously, especially with a mini-incision approach. It is unknown if the inexact placement of a mobile device in the spine has any biomechanical, radiographic, or clinical repercussions. Methods. A total of 52 consecutive patients were treated using standard methods of disc implantation with an intervertebral prosthesis. Computed tomography scans were performed within 3 days and again at 6 to 24 months. An independent radiologist analyzed the images for prosthesis position, rotation, migration, and facet changes. Results were compared with clinical outcome, measured by the Visual Analog Scale and Oswestry Disability Index. Results. Deviation of the prosthesis from the center position was under 1.2 mm, and rotation off of midline was under 12°. Follow-up CT scans showed no migration or facet changes. Regression analysis showed no correlation of prosthesis position with clinical outcome. Conclusions. Current prosthetic disc implantation methods, with minimally invasive access techniques, are relatively accurate. Although there can be deviation of the prosthesis from ideal placement, no repercussions were attributable.

Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

BACKGROUND Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. METHODS Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1×) or 0.90 mg (7×). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. RESULTS Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1× and the 7× rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-to-marked resorption at the 7×-dose level and less resorption at the 1×-dose level. Both dose (p < 0.0007) and time (p < 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. CONCLUSIONS In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. CLINICAL RELEVANCE Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption.

P114. Mass Effect versus Biologic Inhibition of rhBMP-2 Activity by Cellular Environment (Inorganic Polyethylene Beads versus Fibroblasts) – Implications on Use of BMP for Salvage of Fusion or Devices

increases varied for the 2 donors and for agg and col2. Rabbit NP cell gene expression was not affected by rhGDF-5. CONCLUSIONS: To our knowledge, this is the first report on the relative dose-dependent effects of rhGDF-5 on human and rabbit IVD cells and the first to investigate the effects of rhGDF-5 on rabbit IVD cell gene expression. Indicators of anabolic activity for human and rabbit AF cells and human NP cells increased with rhGDF-5 over the entire dose range, but rabbit NP cells were not responsive to any dose of rhGDF-5. In considering these differences, however, it is important to note that cell populations of human and rabbit NP are different (more notochordal cells in the rabbit NP) and that cells were at various stages of dedifferentiation, due to monolayer expansion, prior to alginate bead encapsulation. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.