Complications Following Use of rhBMP-2 in Anterior Lumbar Interbody Fusion

Proceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 81S–98S BMP during spinal fusion surgery and increased risk of cancer. A recent study examined pooled data from studies submitted to the FDA and found an association of BMP use with increased cancer risk. PURPOSE: We sought to determine whether use of BMP carried an increased risk of cancer in a large, independent cohort of patients undergoing lumbar fusions. Furthermore, we evaluated whether BMP is associated with an increased general risk of malignancy, or whether there are specific organs and tissues that are preferentially affected by the BMP used in spinal fusions. STUDY DESIGN/SETTING: Retrospective, cross-sectional, propensitymatched study. PATIENT SAMPLE: Reuter’s MarketScan database was used to identify 94,166 patients who had lumbar fusion between 2003 and 2009. OUTCOME MEASURES: Frequency of cancer diagnosis of any type and stratified by organ. METHODS: Of the 94,166 fusions performed, all patients with less than 2 years of pre-operative data, less than 2 years of postoperative follow-up or pre-existing cancer diagnosis codes (ICD-9-CM codes: 140-239.9) were excluded. The records of the remaining 9,367 patients were examined for use of BMP in their lumbar fusion surgery. Propensity score matching techniques were used to match 1344 patients who underwent spinal fusion with BMP to those who underwent spinal fusion without BMP. Cohorts were matched for age at the time of the procedure, gender, number of pre- and postoperative days, insurance type (Commercial, Medicaid, or Medicare), year of fusion and Charlson index (a frequently used measure of comorbidities). Additionally, these patients’ records were searched for ICD-9-CM cancer codes (140-239.9) stratified by organ.The primary outcome was all-type cancer risk at two or more years following operation. Logistic regression analysis was used to examine the association of BMP use with secondary outcomes including stratification by cancer type and impact of individual parameters (age, Charlson index, Insurance status). RESULTS: The study cohort comprised a matched set of 1344 patients who underwent fusion with BMP and 1344 without BMP. The average age in both groups was 50 years old and patients were followed for an average of 48 months after surgery. In this cohort, the all-type cancer risk was not significantly different (3.20% vs. 2.16%, p 5 0.0944). When examining tumor incidence in the total cohort (9367 patients) using a multivariate analysis, there was no significant difference between the two groups except for the diagnosis category ‘‘benign neoplasms’’ (2.60% vs. 1.53%, aOR 5 1.489, p 5 0.0473). This effect was not evident after adjusting for age, comorbidities, and insurance type and stratified by organ in the propensity matched cohort (2.60% vs. 1.71%, p 5 0.1112). CONCLUSIONS: In a large, independent, propensity matched cohort, the use of BMP in lumbar fusions was not associated with a significant increased cancer risk. BMP was associated with a higher rate of benign neoplasms, however this was not statistically significant after propensity matching. Further studies with larger sample sizes and longer followup are needed to evaluate further. FDA DEVICE/DRUG STATUS: rhBMP-2 (Approved for this indication). http://dx.doi.org/10.1016/j.spinee.2012.08.253

180. Complications Following Use of rhBMP-2 in Anterior Lumbar Interbody Fusion Daniel Lubelski1, Kalil G. Abdullah2, Amy S. Nowacki, PhD2, Matthew D. Alvin2, Michael P. Steinmetz, MD3, Edward C. Benzel, MD2, Thomas E. Mroz, MD2; 1Cleveland, OH, US; 2Cleveland Clinic Foundation, Cleveland, OH, US; 3MetroHealth Medical Center–Neurosurgery, Cleveland, OH, US BACKGROUND CONTEXT: rhBMP-2 has been used increasingly in spinal fusions. While initial studies extolled the product’s improvement of patients’ outcomes, recent investigations have revealed increased rates of urological complications, as well as wound infection, pseudoarthrosis, and reoperation, relative to the standard ALIF procedure.

91S

PURPOSE: To determine the complication profile associated with the use of rhBMP-2 in ALIF surgery. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: Two hundred sixty-seven ALIF patients, including 144 with rhBMP-2 and 123 without rhBMP-2. OUTCOME MEASURES: Urological complications (i.e. retrograde ejaculation), pseudoarthrosis, radiculitis, and reoperation. METHODS: We retrospectively reviewed the medical records of all patients who underwent ALIF with and without rhBMP-2 between January 2002 and August 2010. Patient demographic, operative, and complication information was analyzed. RESULTS: Of the 267 included ALIF patients, there were 144 with rhBMP-2 and 123 without rhBMP-2 that served as the control cohort. The mean follow-up was 20.2 months for the rhBMP-2 group and 32.5 months for the control group. In a sub-analysis of male patients, no difference was found regarding the number of urological complications in the rhBMP-2 group versus the control group (10% versus 6%, respectively; p50.5). Only one case of retrograde ejaculation was identified in the rhBMP-2 group; none were found in the control group. The rates of pseudoarthrosis, radiculitis, and reoperation were significantly higher in the rhBMP-2 group relative to the control (17% vs. 5%, 23% vs. 2%, and 22% vs. 5%, respectively). CONCLUSIONS: The use of rhBMP-2 with ALIF surgery, in this study, was not associated with an increased incidence ofurological complications and retrograde ejaculation. The higher rate of pseudoarthrosis, radiculitis, and reoperation confirm previous reports and should be considered by patients and surgeons before proceeding to operations with rhBMP-2. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. http://dx.doi.org/10.1016/j.spinee.2012.08.254

181. Complications with rhBMP-2 in Lateral Approach Spine Surgery William D. Smith, MD1, Christopher R. Brown, MD2, Juan S. Uribe, MD3, Luis Marchi, MD4, Leonardo Oliveira, MD4, Luiz H. Pimenta, MD, PhD4; 1 Western Regional Center for Brain & Spine Surgery, Las Vegas, NV, US; 2 Durham, NC, US; 3University of South Florida, Tampa, FL, US; 4S~ao Paulo, Brazil BACKGROUND CONTEXT: Recently, risks associated with the use of rhBMP-2 have been more closely examined in spine fusion. This has largely been attributed to an early inflammatory reaction (resorptive phase) which has led, in some studies, to increased rates of subsidence, osteolysis, and injury to neural structures. PURPOSE: This work examines cases of profound rhBMP-2-related complications in anterior lumbar interbody fusion performed using a lateral approach. STUDY DESIGN/SETTING: Cases of severe rhBMP-2 complications following extreme lateral interbody fusion (XLIFÒ, NuVasive, Inc.) were collected from four institutions. PATIENT SAMPLE: Out of 540 patients treated with XLIF and BMP from 2004 through 2011, six (6)(1.1%) cases of severe complication specific to the lateral approach following fusion with rhBMP-2 were identified. Cases with subsidence or other radiographic findings which could have caused the complications were excluded. OUTCOME MEASURES: BMP-related complications and their resolution. METHODS: Retrospective review of patients with a BMP-related complication following XLIF. RESULTS: Patient 1 L4-5 XLIF using BMP. Postoperative lower extremity motor evaluation was without deficit. By six weeks postoperative the patient developed right side quadriceps weakening. By three months postoperative, the patient was wheelchair bound, with no right quadriceps function (1/5 strength), confirmed by EMG. By 5 years postoperative,

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