The minimally effective dose of bone morphogenetic protein in posterior lumbar interbody fusion: a systematic review and meta-analysis.

BACKGROUND CONTENT: The risks and benefits of recombinant human bone morphogenetic protein-2 (BMP) in posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) have been widely reported. However, the BMP dose associated with such reports varied widely. Additionally, data on the location of BMP placement on complications and fusion are lacking. PURPOSE: To determine the minimally effective dose (MED) of BMP which results in optimal fusion rates while minimizing complications; to determine the effects of the location of BMP placement has on fusion rates and complications. STUDY DESIGN: Systematic review and meta-analysis. STUDY SAMPLE: Adult patients undergoing PLIF/TLIF for degenerative indications. OUTCOME MEASURES: Rates of radiculitis, fusion, osteolysis, heterotopic bone formation, and new cancer diagnosis. METHODS: PubMed, Embase, and Cochrane Database were used to identify studies published between January 1, 2011 and April 30, 2019 reporting BMP usage in adult patients who underwent PLIF/TLIF degenerative indications. A qualitative and quantitative synthesis was performed to evaluate the MED of BMP and the effect of location of BMP placement on fusion and complications. Complications were defined as osteolysis, heterotopic bone growth, radiculitis, and rate of new cancer diagnosis. Complications and fusion outcomes were each pooled according to commercially available BMP doses. Additionally, complications and fusion outcomes were pooled according to 4 location groups (interbody cage only, interbody cage + posterolateral gutter [PLG], cage + interspace, and interspace + PLG). Heterogeneity was assessed with Q and I2 statistics. RESULTS: Twenty-two articles, totaling 2,729 patients were included. Sixteen studies reported fusion and 15 reported complications. Among fusion studies, the mean BMP/level ranged from 1.28 to 12 mg/level. Among complication studies, the mean BMP/level ranged from 6.7 to 23.6 mg/level. The pooled overall fusion rate was 94.0% (91.4-95.8 confidence intervals). There was no significant difference in fusion and complication rates between different BMP doses. Thirteen studies included data on the location of BMP placement with 1,823 patients. At each BMP location, the fusion rate was not significantly different across the dose ranges (1.28-12 mg/level). We found the fusion rate to be marginally higher in the interspace + PLG group compared to the other groups. When BMP was placed in the interbody cage there was a mild increase in the rate of osteolysis compared to other placement locations. CONCLUSIONS: Fusion and complication rates did not differ significantly between different doses of BMP with the lowest MED for fusion as low as 1.28 mg/level. The location of BMP placement does not significantly affect fusion or complication rates.

Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions: Six Hundred Ninety Patients in a Dose-Finding Longitudinal Cohort Study.

STUDY DESIGN: Retrospective longitudinal cohort. OBJECTIVE: We sought to demonstrate the minimally effective bone morphogenetic protein (BMP) dose to achieve fusion in minimally invasive transforaminal lumbar interbody fusions. SUMMARY OF BACKGROUND DATA: Multiple studies have been conducted, which used a wide range of BMP doses for lumbar fusions highlighting associated risks and benefits. There is, however, a paucity in the literature in determining the minimally effective dose. METHODS: Consecutive patients who underwent transforaminal lumbar interbody fusion from 2009 to 2014 were reviewed. Fusion was determined by a combination of computed tomography and dynamic x-ray by independent radiologists. We used backward stepwise multiple logistic regression with fusion as the dependent variable to determine whether BMP dose/level was a significant predictor for fusion. To determine the minimally effective dose of BMP/level, separate logistic regressions for different BMP dose ranges and sensitivity analyses were used. A P value ≤0.025 was considered significant. RESULTS: There were 1102 interspaces among 690 patients. Average BMP dose was 1.28 mg/level. Overall fusion was 95.2% with a mean follow-up of 19 months. BMP dose/level was a significant predictor for fusion. Odds of fusion increased by 2.02 when BMP dose range was increased from (0.16-1 mg/level) to (1.0-2 mg/level), but fusion odds did not increase when BMP dose increased to more than 2 mg/level. CONCLUSION: BMP dose/level was a significant predictor for fusion. There was a significant increase in odds of fusion when BMP dose increased from 0.16 to 1 mg/level to 1.0 to 2 mg/level. No benefit from increasing the dose more than 2 mg/level was found, suggesting 1.0 mg/level to be the minimally effective BMP dose. LEVEL OF EVIDENCE: 3.

Surgical management of penetrating spinal cord injury primarily due to shrapnel and its effect on neurological outcome: a literature review and meta-analysis.

OBJECTIVE This study was performed to determine whether decompression of penetrating spinal cord injury (SCI) due to explosive shrapnel leads to greater neurological recovery than conservative management. METHODS In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search using PubMed/MEDLINE, Web of Science, Google Scholar, and the Defense Technical Information Center public site was conducted on May 2, 2016. Studies that described penetrating SCI with shrapnel as an etiology, included surgical and/or conservative management, and demonstrated admission and follow-up neurological status were eligible for inclusion in this study. Odds ratios were calculated for the overall effect of surgical treatment on neurological recovery. Funnel plots were used to evaluate publication bias. RESULTS Five case series (Level IV evidence) met the study criteria, and 2 of them had estimable odds ratios for use in the Forest plot analysis. Among the patients from all 5 studies, 65% were injured by shrapnel, 25% by high-velocity bullet, 8% by low-velocity bullet, and 2% by an unknown cause. A total of 288 patients were included in the overall odds ratio calculations. Patients were stratified by complete and incomplete SCI. The meta-analysis showed no significant difference in outcomes between surgical and conservative management in the complete SCI cohort or the incomplete SCI cohort. Overall rates of improvement for complete SCI were 25% with surgery and 27% with conservative treatment (OR 1.07, 95% CI 0.44-2.61, p = 0.88); for incomplete SCI, 70% with surgery and 81% with conservative treatment (OR 1.67, 95% CI 0.68-4.05, p = 0.26). CONCLUSIONS This study demonstrates no clear benefit to surgical decompression of penetrating SCI due predominantly to shrapnel. There is a considerable need for nonrandomized prospective cohort studies examining decompression and stabilization surgery for secondary and tertiary blast injuries.