Posterolateral Lumbar Spinal Fusion Research Articles

Human perivascular stem cell-based bone graft substitute induces rat spinal fusion.

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair.

A Prospective Trial Comparing L4/5 Instrumented Posterolateral Fusion for Degenerative Spondylolisthesis Performed with Local Bone Graft Alone versus Posterior Iliac Crest Graft and Local Bone Graft versus Beta Tricalcium Phosphate and Local Bone Graft

Introduction Prospective randomized radiological comparative study on the status of fusion in single level instrumented posterolateral lumbar fusion in low-grade spondylolisthesis using local bone graft versus iliac crest bone graft and local bone versus β-tricalcium phosphate and local bone graft. Materials and Methods A total of 24 patients in three groups with degenerative low-grade spondylolisthesis with stenosis randomly underwent decompressive laminectomy and single level instrumented posterolateral fusion with either local bone only or iliac crest bone graft with local bone or β-tricalcium phosphate and local bone graft. Each group consisted of eight patients and was followed for a minimum of 2 years after which a CT scan was done to evaluate the fusion mass according to the Lenke et al classification system. Results At the end of 2 years, no pseudoarthrosis was observed in either of the three groups. In the local bone graft only group, four (50%) patients had a definite solid fusion mass while the remaining four (50%) had a probable solid fusion mass. In the iliac crest group, seven (87.5%) had a definite fusion mass while one patient had a probable fusion mass. In the β-tricalcium phosphate group, five (62.5%) patients had a definite fusion while three (37.5%) had a probable solid fusion mass. Although iliac crest graft remains as the gold standard, its associated donor site morbidity has limited its use. Hence, local bone graft or substitutes such as β-tricalcium phosphate are frequently used. However, there seems to be no significant advantage of β-tricalcium phosphate over iliac crest graft in terms of the fusion status. Conclusion Although iliac crest bone graft remains the gold standard in lumbar fusion procedures, its associated morbidity limit its usage. Hence, local bone alone or combined with β-tricalcium phosphate are frequently used. However, there is no significant advantage of β-tricalcium phosphate over the local bone graft or iliac crest graft in terms of the fusion status. Disclosure of Interest None declared References Sengupta DK, Truumees E, Patel CK, et al. Outcome of local bone versus autogenous iliac crest bone graft in the instrumented posterolateral fusion of the lumbar spine. Spine 2006;31(9):985–991 Herzog RJ, Marcotte PJ. Assessment of spinal fusion. Critical evaluation of imaging techniques. Spine 1996;21(9):1114–1118 Larsen JM, Rimoldi RL, Capen DA, Nelson RW, Nagelberg S, Thomas JC Jr. Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings. J Spinal Disord 1996;9(2):117–120 Zdeblick TA. A prospective, randomized study of lumbar fusion. Preliminary results. Spine 1993;18(8):983–991 Lenke LG, Bridwell KH, Bullis D, Betz RR, Baldus C, Schoenecker PL. Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 1992;5(4):433–442 Dimar JR II, Glassman SD, Burkus JK, Pryor PW, Hardacker JW, Carreon LY. Two-year fusion and clinical outcomes in 224 patients treated with a single-level instrumented posterolateral fusion with iliac crest bone graft. Spine J 2009;9(11):880–885 Dai LY, Jiang LS. Single-level instrumented posterolateral fusion of lumbar spine with beta-tricalcium phosphate versus autograft: a prospective, randomized study with 3-year follow-up. Spine 2008;33(12):1299–1304

Early-term and Mid-term Histologic Events During Single-level Posterolateral Intertransverse Process Fusion With rhBMP-2/Collagen Carrier and a Ceramic Bulking Agent in a Nonhuman Primate Model

We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic bulking agents in 3 different configurations. rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic bulking agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic bulking agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

Efficacy of rhBMP-2 Versus Iliac Crest Bone Graft for Posterior C1–C2 Fusion in Patients Older Than 60 Years

Few studies have specifically examined the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) in posterolateral lumbar spine fusion. The purpose of this study was to report the clinical outcomes in elderly patients treated with posterior C1-C2 fusion with iliac crest bone graft (ICBG) plus rhBMP-2/ACS vs ICBG alone. One hundred forty patients older than 60 years were enrolled in this prospective, randomized trial and underwent instrumented C1- C2 fusion. Patients were divided into 2 groups based on fusion material. The ICBG group comprised patients who received ICBG alone, and the rhBMP-2/ACS group comprised patients who received ICBG plus rhBMP-2/ACS. The groups were compared based on operative time, estimated blood loss, hospital length of stay, clinical results, perioperative complications, fusion rate, fusion time, and revision rate. There were no significant differences in operative time, estimated blood loss, length of stay, and intraoperative complications between the 2 groups. Improvements in visual analog scale scores and Japanese Orthopaedic Association scores over the 2-year follow-up period were similar between groups. The fusion rate was 82.4% (56 of 68) in the rhBMP-2/ACS group and 78.7% (52 of 66) in the ICBG group (P=.782). Mean fusion time was 11 days shorter in the rhBMP-2/ACS group (81.8±29.4 days) than in the ICBG group (92.9±23.7 days) (P=.034). There were more wound complications requiring treatment in the rhBMP-2/ACS group (n=6; 8.8%) than in the ICBG group (n=2; 3.0%), although this was not statistically significant (P=.118). The use of rhBMP-2/ACS for posterior C1-C2 fusion appears to result in a relatively shorter fusion time, but there may be an increased risk of posterior cervical wound complications.

Allogeneic mesenchymal progenitor cells for posterolateral lumbar spine fusion in sheep

Background contextOsteoconductive porous ceramic bone graft materials supplemented with mesenchymal precursor cells (MPC) derived from autologous bone marrow aspirates have been shown to stimulate successful interbody and posterolateral spine fusion in preclinical models. Recent advances in immunomagnetic cell sorting have enabled purification and isolation of pluripotent stem cells from marrow aspirates and have expanded stem cell technology to allogeneic cell sources. Allogeneic MPC technology combined with appropriate synthetic biomaterial carriers could provide both the osteogenic and osteoconductive components needed for successful posterolateral spine fusion without the need for autologous bone harvest or expensive recombinant protein technology. PurposeTo determine the safety and efficacy of a hydroxyapatite:tricalcium phosphate graft material supplemented with allogeneic mesenchymal precursor cells in posterolateral lumbar spine fusion using an ovine model. Study designSkeletally mature ewes underwent single-level instrumented posterolateral lumbar spine fusion using either autograft (AG), hydroxyapatite:tricalcium phosphate carrier (CP), or CP supplemented with allogeneic mesenchymal progenitor cells (MPCs). Three doses of MPCs were evaluated: 25 × 106 cells (low dose, LD), 75 × 106 cells (mid dose, MD), and 225 × 106 cell (high dose, HD). Animals survived for either 4 or 9 months. MethodsPlain radiographs were acquired and scored for bridging bone at regular intervals during healing to monitor fusion development. Hematology, coagulation, and serum chemistry were monitored at regular intervals throughout the study to monitor animal health. After necropsy, computed tomography, high-resolution radiography, biomechanical testing, organ pathology, bone histopathology, and bone histomorphometry were conducted to monitor the safety and ascertain the efficacy of MPC treatment. ResultsMPC treatment in this spine fusion model resulted in no observed adverse systemic or local tissue responses. Radiographically, fusion scores for MPC-treated animals were uniformly higher compared with those treated with carrier alone (CP) after 3 months and continued the same trend throughout 9 month of healing. Quantitative computed tomography confirmed better connectivity of the fusion for MPC treatment groups compared with CP. Biomechanical analyses were not able to differentiate between treatment groups. Histomorphometry results confirmed radiographic and quantitative computed tomography results; cell-supplemented treatment groups and autograft had equivalent amounts of bone within the fusion mass and less bony fusion tissue was found within the fusion mass in specimens from the CP treatment group. No conclusive effects of cell dose of fusion efficacy were noted. ConclusionsAdult allogeneic mesenchymal precursor cells delivered via a hydroxyapatite:tricalcium phosphate carrier were both safe and efficacious in this ovine spine fusion model. Results from this preclinical study support that allogeneic mesenchymal precursor cells produced fusion efficacy similar to that achieved using iliac crest autograft, thereby providing a safe and viable option to achieve successful posterolateral spine fusion.

Posterolateral inter-transverse lumbar fusion in a mouse model

BackgroundSpinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described.PurposeTo present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass.MethodMicroCT reconstructions of the unfused mouse spine and human spine were compared to design a surgical approach. In phase 1, posterolateral lumbar spine fusion in the mouse was evaluated using 18 animals allocated to three experimental groups. Group 1 received decortication only (n = 3), Group 2 received 10 μg rhBMP-2 in a collagen sponge bilaterally (n = 6), and Group 3 received 10 μg rhBMP-2 + decortication (n = 9). The surgical technique was assessed for intra-operative safety, efficacy, access and reproducibility. Spines were harvested for analysis at 3 weeks (Groups 1, 2) and 1, 2, and 3 weeks (Group 3). In phase 2, a dose response study was carried out in an additional 18 animals with C57BL6 mice receiving sponges containing 0, 0.5, 1, 2.5, 5 μg of rhBMP-2 per sponge bilaterally.ResultsThe operative procedure via midline access was rapid and reproducible, and fusion of the murine articular processes was found to be analogous to the human procedure. Unlike reports from other species, decortication alone (Group 1) yielded no new bone formation. Addition of rhBMP-2 (Groups 2 and 3) yielded a significant bone mass that bridged the L4-L6 vertebrae. The subsequent dose response experiment revealed that 0.5 μg rhBMP-2 per sponge was sufficient to create a fusion mass.ConclusionWe describe a new approach for mouse lumbar spine fusion that is safe, efficient, and highly reproducible. The technique we employed is analogous to the human midline procedure and may be highly suitable for genetically modified mouse models.

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in posterolateral lumbar spine fusion: complications in the elderly

Study designRetrospective cohort study of 1430 patients undergoing lumbar spinal fusion from 2002 - 2009. Objective: The goal of this study was to compare and evaluate the number of complications requiring reoperation in elderly versus younger patients.Summary of background datarhBMP-2 has been utilized off label for instrumented lumbar posterolateral fusions for many years. Many series have demonstrated predictable healing rates and reoperations. Varying complication rates in elderly patients have been reported.Materials and methodsAll patients undergoing instrumented lumbar posterolateral fusion of ≤ 3 levels consenting to utilization of rhBMP-2 were retrospectively evaluated. Patient demographics, body mass index, comorbidities, number of levels, associated interbody fusion, and types of bone void filler were analyzed. The age of patients were divided into less than 65 and greater than or equal to 65 years. Complications related to the performed procedure were recorded.ResultsAfter exclusions, 482 consecutive patients were evaluated with 42.1% males and 57.9% females. Average age was 62 years with 250 (51.9%) < 65 and 232 (48.1%) ≥ 65 years. Patients ≥ 65 years of age stayed longer (5.0 days) in the hospital than younger patients (4.5 days) (p=0.005).Complications requiring reoperation were: acute seroma formation requiring decompression 15/482, 3.1%, bone overgrowth 4/482, 0.8%, infection requiring debridement 11/482, 2.3%, and revision fusion for symptomatic nonunion 18/482, 3.7%. No significant differences in complications were diagnosed between the two age groups. Statistical differences were noted between the age groups for medical comorbidities and surgical procedures. Patients older than 65 years underwent longer fusions (2.1 versus 1.7 levels, p=0.001).DiscussionDespite being older and having more comorbidities, elderly patients have similar complication and reoperation rates compared to younger healthier patients undergoing instrumented lumbar decompression fusions with rhBMP-2.

The effects of local insulin application to lumbar spinal fusions in a rat model

The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a time-released insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry. A time-released insulin implant may have similar effects when applied in a lumbar spinal fusion model. This study analyzes the effects of a local time-released insulin implant applied to the fusion bed in a rat posterolateral lumbar spinal fusion model. Our hypothesis was twofold: first, a time-released insulin implant applied to the autograft bed in a rat posterolateral lumbar fusion will increase the rate of successful fusion and second, will alter the local environment of the fusion site by increasing the levels of local growth factors. Animal model (Institutional Animal Care and Use Committee approved) using 40 adult male Sprague-Dawley rats. Forty skeletally mature Sprague-Dawley rats weighing approximately 500 g each underwent posterolateral intertransverse lumbar fusions with iliac crest autograft from L4 to L5 using a Wiltse-type approach. After exposure of the transverse processes and high-speed burr decortication, a Linplant (Linshin Canada, Inc., ON, Canada) consisting of 95% microrecrystalized palmitic acid and 5% bovine insulin (experimental group) or a sham implant consisting of only palmitic acid (control group) was implanted on the fusion bed with iliac crest autograft. As per the manufacturer, the Linplant has a release rate of 2 U/day for a minimum of 40 days. The transverse processes and autograft beds of 10 animals from the experimental and 10 from the control group were harvested atDay 4 and analyzed for growth factors. The remaining 20 spines were harvested at 8 weeks andunderwent a radiographic examination, manual palpation, and microcomputed tomographic (micro-CT) examination. One of the 8-week control animals died on postoperative Day 1, likely due to anesthesia. In the groups sacrificed at Day 4, there was a significant increase in insulinlike growth factor-I (IGF-I) in the insulin treatment group compared with the controls (0.185 vs. 0.129; p=.001). No significant differences were demonstrated in the levels of transforming growth factor beta-1, platelet-derived growth factor-AB, and vascular endothelial growth factor between the groups (p=.461, .452, and .767 respectively). Based on the radiographs, 1 of 9 controls had a solid bilateral fusion mass, 2 of 9 had unilateral fusion mass, 3 of 9 had small fusion mass bilaterally, and 3 of 9 had graft resorption. The treatment group had solid bilateral fusion mass in 6 of 10 and unilateral fusion mass in 4 of 10, whereas a small bilateral fusion mass and graft resorption were not observed. The difference between the groups was significant (p=.0067). Based on manual palpation, only 1 of 9 controls was considered fused, 4 of 9 were partially fused, and 4 of 9 were not fused. In the treatment group, there were 6 of 10 fusions, 3 of 10 partial fusions, and 1 of 10 were not fused. The difference between the groups was significant (p=.0084). Based on the micro-CT, the mean bone volume of the control group was 126.7 mm(3) and 203.8 mm(3) in the insulin treatment group. The difference between the groups was significant (p=.0007). This study demonstrates the potential role of a time-released insulin implant as a bone graft enhancer using a rat posterolateral intertransverse lumbar fusion model. The insulin-treatment group had significantly higher fusion rates based on the radiographs and manual palpation and had significantly higher levels of IGF-I and significantly more bone volume on micro-CT.

Improving the Clinical Evidence of Bone Graft Substitute Technology in Lumbar Spine Surgery

Bone graft substitutes have been used routinely for spine fusion for decades, yet clinical evidence establishing comparative data remains sparse. With recent scrutiny paid to the outcomes, complications, and costs associated with osteobiologics, a need to improve available data guiding efficacious use exists. We review the currently available clinical literature, studying the outcomes of various biologics in posterolateral lumbar spine fusion, and establish the need for a multicenter, independent osteobiologics registry.

The Effects of Local Insulin Application to Lumbar Spinal Fusions in a Rat Model

BACKGROUND CONTEXT: The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a timereleased insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry. A time-released insulin implant may have similar effects when applied in a lumbar spinal fusion model. PURPOSE: This study analyzes the effects of a local time-released insulin implant applied to the fusion bed in a rat posterolateral lumbar spinal fusion model. Our hypothesis was twofold: first, a time-released insulin implant applied to the autograft bed in a rat posterolateral lumbar fusion will increase the rate of successful fusion and second, will alter the local environment of the fusion site by increasing the levels of local growth factors. STUDY DESIGN: Animal model (Institutional Animal Care and Use Committee approved) using 40 adult male Sprague-Dawley rats. METHODS: Forty skeletally mature Sprague-Dawley rats weighing approximately 500 g each underwent posterolateral intertransverse lumbar fusions with iliac crest autograft from L4 to L5 using a Wiltse-type approach. After exposure of the transverse processes and high-speed burr decortication, a Linplant (Linshin Canada, Inc., ON, Canada) consisting of 95% microrecrystalized palmitic acid and 5% bovine insulin (experimental group) or a sham implant consisting of only palmitic acid (control group) was implanted on the fusion bed with iliac crest autograft. As per the manufacturer, the Linplant has a release rate of 2 U/day for a minimum of 40 days. The transverse processes and autograft beds of 10 animals from the experimental and 10 from the control group were harvested at Day 4 and analyzed for growth factors. The remaining 20 spines were harvested at 8 weeks and underwent a radiographic examination, manual palpation, and microcomputed tomographic (micro-CT) examination. RESULTS: One of the 8-week control animals died on postoperative Day 1, likely due to anesthesia. In the groups sacrificed at Day 4, there was a significant increase in insulinlike growth factor-I (IGF-I) in the insulin treatment group compared with the controls (0.185 vs. 0.129; p5.001). No significant differences were demonstrated in the levels of transforming growth factor beta-1,

Lumbar Posterolateral Fusion Using Heparin‐Conjugated Fibrin for Sustained Delivery of Bone Morphogenic Protein‐2 in a Rabbit Model

We had devised a heparin-conjugated fibrin (HCF) system to deliver bone morphogenic proteins (BMPs) for a long-term period to enhance bone regeneration. In the present study, we tested the effectiveness of the delivery system for spinal fusion in a rabbit model. A total of 15 rabbits underwent posterolateral lumbar spine fusion with BMP-2 (50 µg per collagen sponge). The control group received only collagen sponges without BMP-2, another group (short-term delivery [SD] group) received collagen sponges filled with fibrin gel loaded with BMP-2, and the third group (long-term delivery [LD] group) received collagen sponges filled with HCF loaded with BMP-2. All animals were euthanized 8 weeks after surgery, and the fusion was assessed by radiographs, manual palpation, computed tomography, and mechanical testing. The fusion rate was significantly higher in the LD group using HCF than in the SD group or in the control group. Biomechanical testing showed the tensile strength was also significantly higher in the LD group using HCF than in other groups. The HCF system can provide a good option for the delivery of BMP-2 on posterolateral lumbar spine fusion.

腰椎後側方固定術後の隣接椎間に脊柱管狭窄と椎間関節嚢腫を生じた1例

腰椎後側方固定術後の隣接椎間に脊柱管狭窄と椎間関節嚢腫を生じた1例

Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Posterolateral Lumbar Spine Fusion: Complications in the Elderly

Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Posterolateral Lumbar Spine Fusion: Complications in the Elderly

Impact of total disc arthroplasty on the surgical management of lumbar degenerative disc disease: Analysis of the Nationwide Inpatient Sample from 2000 to 2008

Background:Spinal fusion is the most rapidly increasing type of lumbar spine surgery for various lumbar degenerative pathologies. The surgical treatment of lumbar spine degenerative disc disease may involve decompression, stabilization, or arthroplasty procedures. Lumbar disc athroplasty is a recent technological advance in the field of lumbar surgery. This study seeks to determine the clinical impact of anterior lumbar disc replacement on the surgical treatment of lumbar spine degenerative pathology. This is a retrospective assessment of the Nationwide Inpatient Sample (NIS).Methods:The NIS was searched for ICD-9 codes for lumbar and lumbosacral fusion (81.06), anterior lumbar interbody fusion (81.07), and posterolateral lumbar fusion (81.08), as well as for procedure codes for revision fusion surgery in the lumbar and lumbosacral spine (81.36, 81.37, and 81.38). To assess lumbar arthroplasty, procedure codes for the insertion or replacement of lumbar artificial discs (84.60, 84.65, and 84.68) were queried. Results were assayed from 2000 through 2008, the last year with available data. Analysis was done using the lme4 package in the R programming language for statistical computing.Results:A total of nearly 300,000 lumbar spine fusion procedures were reported in the NIS database from 2000 to 2008; assuming a representative cross-section of the US health care market, this models approximately 1.5 million procedures performed over this time period. In 2005, the first year of its widespread use, there were 911 lumbar arthroplasty procedures performed, representing 3% of posterolateral fusions performed in this year. Since introduction, the number of lumbar spine arthroplasty procedures has consistently declined, to 653 total procedures recorded in the NIS in 2008. From 2005 to 2008, lumbar arthroplasties comprised approximately 2% of lumbar posterolateral fusions. Arthroplasty patients were younger than posterior lumbar fusion patients (42.8 ± 11.5 vs. 55.9 ± 15.1 years, P < 0.0000001). The distribution of arthroplasty procedures was even between academic and private urban facilities (48.5% and 48.9%, respectively). While rates of posterolateral lumbar spine fusion steadily grew during the period (OR 1.06, 95% CI: 1.05-1.06, P < 0.0000001), rates of revision surgery and anterior spinal fusion remained static.Conclusions:The impact of lumbar arthroplasty procedures has been minimal. Measured as a percentage of more common lumbar posterior arthrodesis procedures, lumbar arthroplasty comprises only approximately 2% of lumbar spine surgeries performed in the United States. Over the first 4 years following the Food and Drug Administration (FDA) approval, the frequency of lumbar disc arthroplasty has decreased while the number of all lumbar spinal fusions has increased.

Positron emission tomography-CT study on posterolateral lumbar spinal fusion with recombinant human bone morphogenetic protein-2/allograft composite in a rabbit model

Objective To investigate revascularization and osteogenesis of the fusion masses in rabbits undergoing posterolateral lumbar spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2)/allograft composite. Methods Forty-five adult male New Zealand white rabbits were randomly divided into 3 even groups. The rabbits in each group undergoing intertransverse process fusion at L4 and L5 respectively with rhBMP-2/allograft composite (group A), autograft (group B) and allograft (group C). 18F-NaF was injected into every rat at 2nd, 4th and 6th weeks after surgery. Whole-body radionuclide scan by PET-CT was done for all rats to evaluate the uptake values (SU V) in fusion areas. Results The SUVs for autograft and composite groups were superior to that for allograft group at 2nd, 4th and 6th weeks ( P ＜0. 05). The SUV for composite group was significantly higher than that for autograft group at the 4th and 6th weeks ( P ＜0. 05), but similar to that for autograft group at the 2nd week ( P ＞ 0. 05) . Conclusion Since the rhBMP-2/allograft composite can not only promote the bone formation but also improve the blood supply in the posterolateral lumbar spinal fusion, it may serve as a substitute material for autografts. Key words: Bone morphogenetic proteirs; Spinal fusion; Lumbar vertebrae; Tomography,spiral computed

Effects of low-intensity pulsed ultrasound stimulation on porous hydroxyapatite blocks for posterolateral fusion of lumbar spine in rabbits

The effects of porous hydroxyapatite blocks (PHABs) and an adjunct low-intensity pulsed ultrasound stimulation (LIPUS) on the fusion rate in a rabbit spinal posterolateral fusion (PLF) model were evaluated. Twenty rabbits underwent PLF with autograft and PHABs were randomly assigned to two groups: treated group with 20 min LIPUS daily and untreated control group for 4 weeks until euthanasia. The fused motion segments were subjected to manual palpation, gross observation, and radiographic investigation before histomorphologic and scanning electron microscopic analyses. Statistical differences between the LIPUS group and the control group are found in the fusion rate, bone density gray scale, trabecular bone formation, osteoblast-like cells, chondrocytes and positive expression of BMP-2 and TGF-β1 in the junction zone (significance level p<0.05). The results suggest that LIPUS can increase fusion rates and accelerate bone in-growth into PHAB. Hence, PHAB and LIPUS may be used together to increase fusion rates in a rabbit spinal fusion model with a promising extension to human application.

Complications with recombinant human bone morphogenetic protein-2 in posterolateral spine fusion associated with a dural tear

Background context Potential complications related to ectopic bone formation, as seen with transforaminal lumbar interbody fusion, have always been a concern with the use of bone morphogenetic proteins (BMPs). Although less clearly anticipated, complications related to the proinflammatory effects of recombinant human bone morphogenetic protein-2 (rhBMP-2), such as swelling and edema in the cervical spine, have been observed as well. Until recently, risks related to intradural exposure to BMP have not been widely considered. However, a recent animal study reports “in the presence of a SCI and/or dural tear, rhBMP-2 diffuses intrathecally and activates a signaling cascade in all major CNS cell types, which may increase glial scarring and impact neurologic recovery.” Although this study was conducted at the spinal cord level, the observation generates obvious concerns for the much more common scenario of a dural tear associated with lumbar decompression and fusion. Purpose The purpose of this study was to look for any indication of neurologic injury or impaired neurologic recovery in patients treated with rhBMP-2 for lumbar fusion complicated by dural tear. Study design/setting Propensity score matched case-control study. Patient sample From consecutive series of 1,037 patients who underwent decompression and posterolateral lumbar spine fusion using rhBMP-2/absorbable collagen sponge between 2003 and 2006, intraoperative dural tear was reported in 58 cases (5.59%). Outcome measures Preoperative and 2-year postoperative Oswestry Disability Index, Short Form-36 (SF-36), leg pain, and back pain scores. Methods Fifty-eight cases in which decompression and posterolateral spinal fusion were complicated by dural tear, where propensity score matched to a group without dural tear, based on age, smoking status, number of surgical levels and preoperative Oswestry Disability Index, SF-36 Physical Composite Summary score, SF-36 Mental Composite Summary (MCS) score, and back and leg pain scores. The patients with a dural tear were then compared with the matched cohort with regard to baseline and 2-year patient-based outcome measures. Particular attention was given to indices of leg pain that might reflect an influence of rhBMP-2 on neurologic function or impaired neurologic recovery. Results No patient in the group with a dural tear and three patients in the group without a dural tear complained of new onset radiculopathy postoperatively, with one requiring oral steroids. The radiculopathy resolved within 6 months postoperatively in all three patients. Statistically significant improvement was observed in all health-related quality of life (HRQOL) measures, except SF-36 MCS, at both 1 and 2 years postoperatively in both groups. There were no significant differences in any HRQOL parameter between the groups with or without a dural tear at either 1 or 2 years postoperatively. In particular, the leg pain improvement, 2.2 points in the group with a dural tear and 2.4 points in the group without a dural tear, was statistically equivalent. Conclusions The data suggests fairly convincingly that the presence of a repairable dural tear is not necessarily an impediment to the use of rhBMP-2 in posterolateral fusion. Further studies are needed to address the less common clinical scenario of BMP use in conjunction with spinal cord injury, as studied in the animal model that prompted this investigation. Finally, avoidance of BMP use may still be prudent in the setting of an unrepairable dural tear.

Formation of Painful Seroma and Edema After the Use of Recombinant Human Bone Morphogenetic Protein-2 in Posterolateral Lumbar Spine Fusions

The use of bone morphogenetic proteins for fusion augmentation in spine surgery has increased dramatically in recent years. Information is continually emerging regarding the effectiveness and safety profile of these compounds. We have noted an increased incidence in sterile seroma formation and painful edema after the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for posterolateral lumbar fusion. We present a retrospective review to determine the incidence of seroma formation and to discuss its clinical implications. We retrospectively reviewed the operative reports of patients who underwent posterolateral lumbar fusion with the addition of rhBMP-2. We identified all patients who required surgical exploration of a postoperative sterile seroma. Of the 130 patients who underwent posterolateral lumbar fusion with rhBMP-2, 6 (4.6%) were returned to the operating room for exploration of a sterile seroma. The total amount of rhBMP-2 delivered to the posterolateral space per patient was 2.1 to 14.7 mg (mean, 8.4 mg per patient). The patients were returned to the operating room 5 to 13 days (mean, 7.7 days) after their initial surgery, and infection was ruled out in all cases by intraoperative cultures. There seems to be an increased incidence of formation of sterile seroma and painful edema in the lumbar region after posterolateral fusion with rhBMP-2. This report, along with other series highlighting the potential complications of bone morphogenetic proteins, suggests that more caution should be used when these compounds are used. Further studies are required to better define the risks and benefits of using bone morphogenetic proteins for spine surgery.

Bone Morphogenetic Protein-2 and Bone Marrow Aspirate With Allograft as Alternatives to Autograft in Instrumented Revision Posterolateral Lumbar Spinal Fusion

Retrospective cohort study. Compare the efficacy of rhBMP-2 and bone marrow aspirate with allograft (BMAA) as alternatives to autograft in instrumented revision posterolateral lumbar fusion (PLF). The use of autogenous bone graft is the current gold standard in revision PLF; however, this practice is associated with significant donor-site morbidity. Revision PLF pose the additional challenges of a less than ideal fusion environment and a limited quantity of autogenous bone graft. rhBMP-2 and BMAA have been shown to be acceptable bone graft substitutes in several primary orthopedic procedures. The role of these bone graft substitutes in instrumented revision PLF has yet to be determined. Sixty-two patients (125 levels) who underwent instrumented revision PLF with a minimum 2-year follow-up were included. Group 1 contained 24 patients (13 single- [group 1A] and 11 multilevel [group 1B]) who underwent instrumented revision PLF using rhBMP-2 on an absorbable collagen sponge. Group 2 included 18 patients (7 single- [group 2A] and 11 multilevel [group 2B]) with procedures using BMAA. Group 3 consisted of 20 patients (10 single- [group 3A] and 10 multilevel [group 3B]) with procedures using autograft. Demographic, surgical, and clinical data were collected from medical records. Time to solid fusion mass formation, fusion rate, complications, and clinical outcomes were evaluated. The progression of the fusion mass was evaluated by reviewing radiographs. A diagnosis of nonunion was based on exploration during an additional revision surgery or evidence of nonunion on dynamic radiographs or computerized tomography. Clinical outcomes were assessed using a visual analog scale (VAS) before surgery and at 6-week, 6-, 12-, and 24-month follow-ups. Overall fusion rate was 93.5% (58/62). All single-level revision PLF achieved solid fusion. Groups 1B and 3B achieved 100% fusion, (11/11) and (10/10), respectively;whereas group 2B had a fusion rate of 63.6% (7/11). Group 1 also developed a solid fusion mass earlier than the other groups. There was a significant decrease between preoperative and 2-year postoperative VAS scores in all groups, but no significant difference among groups. Three patients in group 2 required an additional revision surgery. rhBMP-2 may be an appropriate alternative to autogenous bone graft in both single- and multilevel revision PLF, whereas BMAA may be appropriate as a substitute in single-level revision PLF. The use of BMAA in single-level revisions may be a more cost-effective option than rhBMP-2.

Variability Across Ten Production Lots of a Single Demineralized Bone Matrix Product

Demineralized bone matrix is an osteoinductive allograft derived from processed bone that is commonly mixed with autogenous bone in fusion procedures to treat diseases of the spine. An increasing number of demineralized bone matrix-based products are commercially available for spinal fusion procedures, but osteoinductive variability has been found not only across different products but also among production lots from the same demineralized bone matrix formulation. The purpose of this study was to assess the lot-to-lot variability across a single demineralized bone matrix-based product in terms of both extracted bone morphogenetic protein (BMP) concentrations (in vitro) and fusion performance in rats (in vivo). The goal was also to determine whether the in vitro measures could sufficiently and accurately predict the in vivo fusion performance of different demineralized bone matrix-based product lots. BMP-2 and BMP-7 were extracted from ten production lots of InterGro DBM Putty and quantified with use of ELISA (enzyme-linked immunosorbent assay). A posterolateral lumbar spinal fusion was performed on forty athymic rats with implantation of a demineralized bone matrix-based product. Fusion success was determined at eight weeks with use of radiographs and manual palpation of the segments. Logistic regression was used to determine the predictive abilities of BMPs. Significant lot-to-lot variability was found in terms of both BMP concentrations (22 to 110 pg of BMP-2 per milligram of product and 44 to 125 pg of BMP-7 per milligram of product) and in vivo rates of fusion (0% to 75%; p < 0.04 for all). BMP-2 and BMP-7 concentrations correlated positively with each other across lots (r = 0.77, p < 0.0001). Most notably, extracted amounts of BMP-2 and BMP-7 each predicted in a dose-dependent manner the in vivo fusion performance in rats (R(2) = 0.32, p < 0.01 for BMP-2, and R(2) = 0.22, p < 0.009 for BMP-7). Assays for demineralized bone matrix-extracted BMP-2 and BMP-7 levels may be feasible and sufficient for predicting spinal fusion performance of individual production lots from the same demineralized bone matrix-based product.