Hans Joerg Meisel

Synthetic bone graft versus autograft or allograft for spinal fusion: a systematic review

The purpose of this review was to compare the efficacy and safety of synthetic bone graft substitutes versus autograft or allograft for the treatment of lumbar and cervical spinal degenerative diseases. Multiple major medical reference databases were searched for studies that evaluated spinal fusion using synthetic bone graft substitutes (either alone or with an autograft or allograft) compared with autograft and allograft. Randomized controlled trials (RCT) and cohort studies with more than 10 patients were included. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. The search yielded 214 citations with 27 studies that met the inclusion criteria. For the patients with lumbar spinal degenerative disease, data from 19 comparative studies were included: 3 RCTs, 12 prospective, and 4 retrospective studies. Hydroxyapatite (HA), HA+collagen, β-tricalcium phosphate (β-TCP), calcium sulfate, or polymethylmethacrylate (PMMA) were used. Overall, there were no differences between the treatment groups in terms of fusion, functional outcomes, or complications, except in 1 study that found higher rates of HA graft absorption. For the patients with cervical degenerative conditions, data from 8 comparative studies were included: 4 RCTs and 4 cohort studies (1 prospective and 3 retrospective studies). Synthetic grafts included HA, β-TCP/HA, PMMA, and biocompatible osteoconductive polymer (BOP). The PMMA and BOP grafts led to lower fusion rates, and PMMA, HA, and BOP had greater risks of graft fragmentation, settling, and instrumentation problems compared with iliac crest bone graft. The overall quality of evidence evaluating the potential use and superiority of the synthetic biological materials for lumbar and cervical fusion in this systematic review was low or insufficient, largely due to the high potential for bias and small sample sizes. Thus, definitive conclusions or recommendations regarding the use of these synthetic materials should be made cautiously and within the context of the limitations of the evidence.

ACDF Graft Selection by Surgeons: Survey of AOSpine Members:

Study Design: Cross-sectional survey study. Objective: To determine what are the most commonly used graft materials in anterior cervical discectomy and fusion and whether the choice of graft is affected by surgeon’s training, years in practice, geographic location, practice setting, or surgeon’s perceived difficulty in achieving fusion. Methods: A 23-question survey was sent out to 5334 surgeons using the Global AO Spine database. Response data was then stratified into surgeon training, years of practice, practice type, and global region. Results: Overall, surgeons believe that graft selection affects fusion rates (89.3% of surgeons) and affects time to fusion (86.0% of surgeons). The use of a cage is currently the most common structural graft component used worldwide at 64.1%. Of surgeons that use cages, the PEEK Cage makes up 84%. North American surgeons differ from this global trend and use composite allograft more commonly. The choice to add a nonstructural graft component was reported at 74%. This result was similar for performing multilevel fusions at 72.8%. The selection of nonstructural graft material depends on whether the type of surgery is considered simple or complex. Most surgeons are not satisfied with available literature comparing effectiveness of grafts but believed that there was sufficient evidence to support the use of their chosen graft. Conclusion: Almost all surgeons believe that fusion is important to anterior cervical discectomy and fusion surgery outcomes and that most surgeons believe graft choice affects fusion. However, this survey indicates that there is great variability in the type of graft material used by spine surgeons across the world.

Postoperative Complications Associated With rhBMP2 Use in Posterior/Posterolateral Lumbar Fusion:

Study Design: Retrospective database review. Objective: Posterior/posterolateral lumbar fusion (PLF) is an effective treatment for a variety of spinal disorders; however, variations in surgical technique have different complication profiles. The aim of our study was to quantify the frequency of various complications in patients undergoing PLF with and without human recombinant bone morphogenetic protein 2 (rhBMP2). Methods: We queried the orthopedic subset of the Medicare database (PearlDiver) between 2005 and 2011 for patients undergoing PLF procedures with and without rhBMP2. Complication and reoperation rates were analyzed within 1 year of the index procedure. Complications assessed include: acute renal failure, deep vein thrombosis, dural tear, hematoma, heterotopic ossification, incision and drainage, cardiac complications, nervous system complications, osteolysis, pneumonia, pseudarthrosis, pulmonary embolism, radiculopathy, respiratory complications, sepsis, urinary retention, urinary tract infection, mechanical, and wound complications. Chi-square analysis was used to calculate the complication differences between the groups. Results: Our data revealed higher overall complication rates in patients undergoing PLF with rhBMP2 versus no_rhBMP2 (76.9% vs 68.8%, P < .05). Stratified by gender, rhBMP2 males had higher rates of mechanical complications, pseudarthrosis, and reoperations compared with no_rhBMP2 males (P < .05), whereas rhBMP2 females had higher rates of pseudarthrosis, urinary tract infection, and urinary retention compared with no_rhBMP2 females (P < .05). Conclusion: Our data revealed higher overall complication rates in PLF patients given rhBMP2 compared with no_rhBMP2. Furthermore, our data suggests that rhBMP2-associated complications may be gender specific.

Trends Analysis of rhBMP Utilization in Single-Level Posterior Lumbar Interbody Fusion in the United States

Study Design: Retrospective study. Objectives: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spinal fusion surgery, but there is little information on rhBMP-2 utilization in single-level posterior lumbar interbody fusion (PLIF). The purpose of our study was to evaluate the trends and demographics of rhBMP-2 utilization in single-level PLIF. Methods: Patients who underwent single-level PLIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database, a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 100u2009000 patients searched in the database. Results: A total of 2735 patients had single-level PLIF. The average rate of single-level PLIF with rhBMP-2 maintained at a relatively stable level (28% to 31%) from 2005 to 2009, but decreased in 2010 (9.9%) and 2011 (11.8%). The overall incidence of single-level PLIF without rhBMP-2 (0.68 cases per 100u2009000 patients) was statistically higher (P < .01) compared to single-level PLIF with rhBMP-2 (0.21 cases per 100u2009000 patients). The average rate of single-level PLIF with rhBMP-2 utilization was the highest in West (30.1%), followed by Midwest (26.9%), South (20.5%), and Northeast (17.8%). The highest incidence of single-level PLIF with rhBMP-2 was observed in the age group <65 years (0.3 per 100u2009000 patients). Conclusions: To our knowledge, this is the first study to report on the demographics associated with rhBMP-2 use in single-level PLIF. There was a 3-fold increase in the rate of PLIF without rhBMP-2 compared to PLIF with rhBMP-2, with both procedures being mainly done in patients less than 65 years of age.

Analysis of Recombinant Human Bone Morphogenetic Protein-2 Use in the Treatment of Lumbar Degenerative Spondylolisthesis

Study Design Retrospective database review. Objective To identify trends of the recombinant human bone morphogenetic protein-2 (rhBMP-2) use in the treatment of lumbar degenerative spondylolisthesis (LDS). Methods PearlDiver Patient Record Database was used to identify patients who underwent lumbar fusion for LDS between 2005 and 2011. The distribution of bone morphogenetic protein use rate (BR) in various surgical procedures was recorded. Patient numbers, reoperation numbers, BR, and per year BR (PYBR) were stratified by geographic region, gender, and age. Results There were 11,335 fusion surgeries, with 3,461 cases using rhBMP-2. Even though PYRB increased between 2005 and 2008, there was a significant decrease in 2010 for each procedure: 404 (34.5%) for posterior interbody fusion, 1,282 (34.3%) for posterolateral plus posterior interbody fusion (PLPIF), 1,477 (29.2%) for posterolateral fusion, and 335 (22.4%) for anterior lumbar interbody fusion. In patients using rhBMP-2, the reoperation rate was significantly lower than in patients not using rhBMP-2 (0.69% versus 1.07%, pu2009<u20090.0001). Male patients had higher PYBR compared with female patients in 2008 and 2009 (pu2009<u20090.05). The West region and PLPIF had the highest BR and PYBR. Conclusions Our data shows that the revision rates were significantly lower in patients treated with rhBMP-2 compared with patients not treated with rhBMP-2. Furthermore, rhBMP-2 use in LDS varied by year, region, gender, and type of fusion technique. In the West region, the posterior approach and patients 65 to 69 years of age had the highest rate of rhBMP-2 use.

Complications Related to the Recombinant Human Bone Morphogenetic Protein 2 Use in Posterior Cervical Fusion

Study Design: A retrospective cohort study. Objective: To compare the complications between posterior cervical fusions with and without recombinant human bone morphogenetic protein 2 (rhBMP2). Summary of Background Data: Use of rhBMP2 in anterior cervical spinal fusion procedures can lead to potential complications such as neck edema, resulting in airway complications or neurological compression. However, there are no data on the complications associated with the “off-label” use of rhBMP2 in upper and lower posterior cervical fusion approaches. Materials and Methods: Patients from the PearlDiver database who had a posterior cervical fusion between 2005 and 2011 were identified. We evaluated complications within 90 days after fusion and data was divided in 2 groups: (1) posterior cervical fusion including upper cervical spine O-C2 (upper group) and (2) posterior cervical fusion including lower cervical spine C3–C7 (lower group). Complications were divided into: any complication, neck-related complications, wound-related complications, and other complications. Results: Of the 352 patients in the upper group, 73 patients (20.7%) received rhBMP2, and 279 patients (79.3%) did not. Likewise, in the lower group of 2372 patients, 378 patients (15.9%) had surgery with rhBMP2 and 1994 patients (84.1%) without. In the upper group, complications were observed in 7 patients (9.6%) with and 34 patients (12%) without rhBMP2. In the lower group, complications were observed in 42 patients (11%) with and 276 patients (14%) without rhBMP2. Furthermore, in the lower group the wound-related complications were significantly higher in the rhBMP2 group (23 patients, 6.1%) compared with the non-rhBMP2 group (75 patients, 3.8%). Conclusions: Our data showed that the use of rhBMP2 does not increase the risk of complications in upper cervical spine fusion procedures. However, in the lower cervical spine, rhBMP2 may elevate the risk of wound-related complications. Overall, there were no major complications associated with the use of rhBMP2 for posterior cervical fusion approaches. Level of Evidence: Level III.

A Retrospective Analysis of Complications Associated With Bone Morphogenetic Protein 2 in Anterior Lumbar Interbody Fusion

Study Design: Retrospective review. Objective: The aim of our study was to quantify the frequency of complications associated with recombinant human bone morphogenetic protein 2 (rhBMP-2) use in anterior lumbar interbody fusion (ALIF). Methods: The orthopedic subset of the Medicare database (PearlDiver) was queried for this retrospective cohort study using International Statistical Classification of Diseases 9 (ICD-9) and Current Procedure Terminology (CPT) codes for ALIF procedures with and without rhBMP-2 between 2005 and 2010. Frequencies of complications and reoperations were then identified within 1 year from the index procedure. Complications included reoperations, pulmonary embolus, deep vein thrombosis, myocardial infarction, nerve-related complications, incision and drainage procedures, wound, sepsis, pneumonia, urinary tract infections, respiratory, heterotopic ossification, retrograde ejaculation, radiculopathy, and other medical complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the statistical significance. Results: We identified a total of 41u2009865 patients who had an ALIF procedure. A total of 14u2009384 patients received rhBMP-2 while 27u2009481 did not. Overall, 6016 (41.8%) complications within 1 year from surgery were noted within the group who received rhBMP-2 and 12u2009950 (47.1%) complications within 1 year from surgery were recorded in those who did not receive rhBMP-2 (OR = 0.81, CI = 0.77-0.84). Overall, exposure to rhBMP-2 was associated with significantly decreased odds of complications with exception to reoperation rates (0.9% rhBMP-2 vs 1.0% no rhBMP-2; OR = 0.88, CI = 0.71-1.09) and radiculopathy (4.4% rhBMP-2 vs 4.3% no rhBMP-2; OR = 1.02, CI = 0.93-1.13). Conclusions: The use of rhBMP-2 in patients undergoing ALIF procedure was associated with a significantly decreased rate of complications. Further studies are needed to elucidate a true incidence of complication.

Trends, Costs, and Complications of Anterior Cervical Discectomy and Fusion With and Without Bone Morphogenetic Protein in the United States Medicare Population

Study Design: Retrospective database review. Objectives: After the Food and Drug Administration approved bone morphogenetic protein–2 (BMP) in 2002, BMP was used off-label in the cervical spine to increase bone growth and bony fusion. Since then, concerns have been raised regarding complication rates and safety. This study was conducted to examine the use of BMP in anterior cervical discectomy and fusion (ACDF) in the Medicare population and to determine risk of complications and associated costs within 90 days of surgery. Methods: Patients who underwent ACDF were identified using Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision Procedure codes (ICD9-P). Complications were identified using ICD9 diagnostic codes. Charges were calculated as amount billed, and reimbursements were calculated as amounts paid by Medicare. Data for these analyses came from a nationwide claims database. Results: A total of 215u2009047 patients were identified who had ACDF from 2005 to 2011. For the majority of the procedures (89.0%), BMP was not used. BMP use rose from 11.84% in 2005 to a peak of 16.73% in 2007 before decreasing to 12.01% in 2011. BMP was used 16% more in women than men. BMP use was the highest in the West (13.6%) followed by Midwest (11.8%), South (10.6%), and Northeast (7.5%). There was a higher overall complication rate in the BMP group (2.1%) compared with the non-BMP group (1.9%) (odds ratio [OR] = 1.11, 95% CI = 1.01-1.22). The BMP group also had a higher rate of wound complications (0.98% vs 0.76%, OR = 1.29, 95% CI = 1.12-1.48). In this study population, there was no difference in dysphagia/hoarseness, neurologic, medical, or other complications. During the 90-day perioperative period, BMP surgeries were charged at 17.6% higher than non-BMP surgeries. Conclusions: The use of BMP in ACDF in the Medicare population has decreased since a peak in 2007. The rate of wound and overall complications for BMP use with ACDF was higher than without. Our results regarding dysphagia/hoarseness did not show a statistically meaningful difference, which is in contrast with many other studies. Charges associated with BMP use were higher during the 90-day perioperative period.

Trends and Cost of Posterior Cervical Fusions With and Without Recombinant Human Bone Morphogenetic Protein-2 in the US Medicare Population:

Study Design: Retrospective database review. Objective: To analyze and report the trends and cost of posterior cervical fusions (PCFs) with and without off-label recombinant human bone morphogenetic protein-2 (rhBMP-2) in the Medicare population. Methods: Patient records from the PearlDiver database were retrospectively reviewed from January 1, 2005, to December 31, 2012, to distinguish individuals who underwent a PCF with or without rhBMP-2. Total numbers, incidence, age, gender, geographic region, reimbursement, and length of stay were analyzed and summarized. Results: The combined total of non-rhBMP-2 (n = 39u2009479; 85.51%) and rhBMP-2 PCF (n = 6692; 14.49%) procedures performed between 2005 and 2012 was 46u2009171. In general, the number of PCFs without rhBMP-2 consistently increased over time, while the number of PCFs with rhBMP-2 had only a slight increase from 2005 to 2012. On average, PCFs without rhBMP-2 were associated with

Complication Rates in Posterior Lumbar Interbody Fusion (PLIF) Surgery With Human Bone Morphogenetic Protein 2: Medicare Population

1197 higher cost than those with rhBMP-2, but the average length of stay was similar (6 days). From 2005 to 2012, the average cost for procedures with and without rhBMP-2 increased by