A literature review of bone graft substitutes for spinal fusion was undertaken from peer reviewed journals to form a basis for guidelines on their clinical use. A PubMed search of peer reviewed journals between Jan 1960 and Dec 2009 for clinical trials of bone graft substitutes in spinal fusion was performed. Emphasis was placed on RCTs. Small and duplicated RCTs were excluded. If no RCTs were available the next best clinical evidence was assessed. Data were extracted for fusion rates and complications. Of 929 potential spinal fusion studies, 7 RCTs met the inclusion criteria for BMP-2, 3 for BMP-7, 2 for Tricalcium Phosphate and 1 for Tricalcium Phosphate/Hydroxyapatite (TCP/HA). No clinical RCTs were found for Demineralised Bone Matrix (DBM), Calcium Sulphate or Calcium Silicate. There is strong evidence that BMP-2 with TCP/HA achieves similar or higher spinal fusion rates than autograft alone. BMP-7 achieved similar results to autograft. 3 RCTs support the use of TCP or TCP/HA and autograft as a graft extender with similar results to autograft alone. The best clinical evidence to support the use of DBMs are case control studies. The osteoinductive potential of DBM appears to be very low however. There are no clinical studies to support the use of Calcium Silicate. The current literature supports the use of BMP-2 with HA/TCP as a graft substitute. TCP or HA/TCP with Autograft is supported as a graft extender. There is not enough clinical evidence to support other bone graft substitutes. This study did not require ethics approval and no financial support was received

Introduction:. Several reports showed superior fusion rates, as high as 100%, using rhBMP-2 with ALIF cages. This has led to the widespread off-label use of rhBMP-2 in several other lumbar fusion procedures. There is paucity of reports analysing the clinic-radiological outcome of using rhBMP-2 to promote bone union in cases of symptomatic pseudoarthosis following lumbar spine fusion. Methods:. 52 consecutive patients who underwent revision spinal surgery for symptomatic pseudoarthosis utilizing rhBMP-2 between 2008 and 2013 were included in the study. Demographic, and surgical data were collected from medical records. Functional outcomes were recorded using the ODI. All patients had preoperative fine-cut CT scan to confirm pseudoarthosis. Postoperative CT-scan at 6 months was routinely done to confirm fusion. Results:. Average age at time of revision surgery was 54years (range 28–73). Average follow up was 3 years 5 months (range 2–5 years). Overall fusion rate of 92.3% (48/52) was achieved. The average ODI has improved from 56% preoperatively to 49% postoperatively. We had 1 infection case, and 5 complications related to metalwork. One case with neuronal complications was recorded. No rhBMP-2 related complications. There was no record of heterotopic bone formation in the spinal canal or the neuroforamen. Conclusion:. Recombinant BMP-2 is a safe and effective adjunct to revision lumbar spinal fusion surgery to alleviate back pain symptoms from pseudoarthosis. The limitations of the study include: retrospective review, lack of matched cohort utilising iliac crest bone graft, and relatively short follow-up

We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage.

Cite this article: Bone Joint J 2013;95-B:217–23.

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years.

Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height.

Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.