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Two-year follow-up of a safety and efficacy study of osteoinductive protein–1 (recombinant human bone morphogenetic protein–7) as an adjunct to posterolateral lumbar fusion
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Proceedings of the NASS 16th Annual Meeting / The Spine Journal 2 (2002) 3S–44S
2000 were reviewed. Patients with the diagnosis of spinal osteomyelitis, discitis, epidural abscess and tuberculosis were identified, and the charts were examined in detail. In addition to demographic data, the following parameters were recorded: HIV risk factor, admission white blood cell count (WBC), absolute lymphocyte count, erythrocyte sedimentation rate, CD4 count, imaging studies, blood culture results, biopsy results, surgical procedure, antibiotic treatments and duration, length of stay, hospital charges and outcome. Results: For the 6-year period studied, there were 17,717 patient discharges with the diagnosis of HIV. Of these, 17 patients (0.095%) were also treated for a spinal infection. This included eight patients with discitis/ osteomyelitis, six patients with tuberculosis (TB) and three patients with an epidural abscess. Of the total number of patients discharged from our institution with these diagnoses, these patients represent 7% of all patients with discitis/osteomyelitis, 35% of patients with spinal TB and 5.5% of patients with epidural abscess. In the eight patients with disc discitis/osteomyelitis, the mean WBC was 8.4, mean absolute lymphocyte count 1,910 and mean CD4 count 339.6. Blood cultures were positive in one of six patients, and a biopsy/surgical specimen was positive in three of six patients. The organism identified in these patients was Staphylococcus aureus (sensitive to oxacillin). The remainder of these patients had positive findings on magnetic resonance imaging or nuclear medicine studies. All eight patients had clinical resolution of infection after 6 to 12 weeks of appropriate antibiotics. In contrast, in the six patients with spinal TB the mean WBC was 10.34, mean absolute lymphocyte count 823 (p.007) and mean CD4 count 57.2 (p.003). One of the six patients died during the admission. All were treated with antituberculosis medication protocols. The three patients with epidural abscesses had a mean WBC of 16.17, mean absolute lymphocyte count of 913.3 (p.007) and mean CD4 count of 20.67 (p.004). Two of three patients had a computed tomography–guided biopsy. The other was diagnosed by imaging and a positive blood culture. The two biopsies grew Nocardia species, and both of these patients died during the admission. The other patient had Group A streptococcus and was treated with a third-generation intravenous cephalosporin for 6 weeks with clinical improvement. There was no significant difference between the groups with regard to age, gender, race, HIV risk factor or length of hospital stay. Conclusion: Spinal infections in patients with HIV at our institution occur at a rate of 0.095%. This is more than the incidence in the general population but much less then originally suspected. Discitis/osteomyelitis occurs in the HIV patient with a mild to moderate decrease in the CD4 count. These patients would fall into the Center for Disease Control (CDC) class 2 (of 3) classification. The organism identified is consistent with that seen in the general population (S aureus), and the disease responds to appropriate antibiotics. Patients with markedly decreased CD4 counts (CDC class 3) were found to have spinal TB, and patients with the lowest CD4 counts developed epidural abscesses with more malignant species. The three in-hospital deaths occurred in the latter two groups. Although the CD4 count can be used as a predictor of the clinical course of the HIV patient with spinal infection, the identification of the organism still remains paramount in the treatment of this complex patient population. Two-year follow-up of a safety and efficacy study of osteoinductive protein–1 (recombinant human bone morphogenetic protein–7) as an adjunct to posterolateral lumbar fusion Tushar Ch. Patel, MD, Hopkinton, MA, USA; Alexander R. Vaccaro, MD, Philadelphia, PA, USA; Eeric Truumees, MD, Royal Oak, MI, USA; Jeffrey S. Fischgrund, MD, Southfield, MI, USA; Alan S. Hilibrand, MD, Philadelphia, PA, USA; Harry N. Herkowitz, MD, Southfield, MI, USA Introduction: Posterolateral intertransverse lumbar fusion is a commonly performed procedure for stabilization of the degenerated lumbar spine. A typical clinical scenario for which such fusions are used is the stabilization of a degenerative spondylolisthesis after decompression. In a recent large series reported in the literature, this type of fusion was noted to have a pseudarthrosis rate of up to 45% [1]. Measures to augment autograft fusions would thus be desirable. Materials and methods: Included are 2-year follow-up data to the study presented at the North American Spine Society (NASS) 2000 meeting. A pilot
study was designed to evaluate the safety and efficacy of osteoinductive protein-1 (OP-1, also known as recombinant human bone morphogenetic protein [BMP-7]) in lumbar fusion. Twenty-two patients with the diagnosis of symptomatic spinal stenosis and single-level degenerative spondylolisthesis in the lower lumbar spine (L3–S1) were enrolled (NASS 2000). The patients were randomized to either an OP-1 group or a control group. The OP-1 group received 3.5 mg of OP-1 in a putty carrier per side and iliac crest autograft. The control group received iliac crest autograft alone. Outcomes were measured clinically using the Oswestry score and dynamic radiographs evaluated independently by two blinded radiologists using digital calipers. Results: Two-year results indicate the preservation of fusion in OP-1–treated patients. No acute or long-term adverse effects related to the use of OP-1 were noted in the treatment group. Discussion: Despite the small number of patients enrolled in this pilot study, OP-1 appears to be a safe and effective adjunct to iliac crest autograft in human posterolateral lumbar fusion. Two-year results indicate preservation of fusion in OP-1–treated patients, and the lack of acute and long-term adverse effects speak to the safety of OP-1 in posterolateral fusions. At 2 years, the OP-1 group had a higher radiographic fusion rate than the autograft group. This correlated well with the greater clinical success experienced by the OP-1 group, as measured by improvement in the Oswestry score. None of the previously reported device-related complications related to the use of BMPs in animal studies, such as exuberant bone growth with subsequent neural impingement, ectopic ossification or spinal stenosis, were seen in the treatment group. Conclusion: OP-1 appears to be a safe and effective adjunct to iliac crest autograft in human posterolateral lumbar fusion. The dose, 3.5 mg per side, and the carrier, biodegradable putty, appear to provide a safe and effective means of delivering the bone morphogenetic protein OP-1 to the human lumbar spine. Reference [1] Fischgrund. Spine 1997. Recombinant human bone morphogenetic protein–2 with tapered cages: a prospective, randomized lumbar fusion study Matthew F. Gornet, MD, St. Louis, MO, USA; J. Kenneth Burkus, MD, Columbus, GA, USA; Curtis A. Dickman, MD, Phoenix, AZ, USA; Thomas A. Zdeblick, MD, Madison, WI, USA Introduction: Anterior lumbar interbody fusion (ALIF) is an effective treatment for patients with symptomatic degenerative disc disease. Results from a small series of patients undergoing ALIF with tapered cages demonstrated that recombinant human bone morphogenetic protein–2 (rhBMP-2) promotes osteoinduction and fusion. To further evaluate the clinical performance of rhBMP-2 with tapered metal cages for lumbar fusion procedures, a larger multicenter study was initiated. This paper reports the clinical and radiographic outcomes at 12 months for this clinical trial. Methods: This prospective, randomized, nonblinded study enrolled 281 patients at 16 investigational sites. Patients were randomized into two groups. The control group was treated with autogenous iliac crest bone graft with a tapered metal cage (LT-CAGE device, Medtronic Sofamor Danek). The rhBMP-2 group received rhBMP-2 on a collagen sponge carrier (InFUSE Bone Graft, Medtronic Sofamor Danek) with the LT-CAGE device. Patient demographics: Preoperatively, all patients had symptomatic, single-level degenerative disc disease and had complaints of disabling low back and/or leg pain. All had symptoms lasting at least 6 months and had failed nonoperative treatments. All patients underwent an ALIF procedure through an open approach. The control group consisted of 136 patients (68 men, 68 women) with an average age of 42.3 years, and the rhBMP-2 group consisted of 145 patients (79 men, 66 women) with an average age of 43.3 years. In the control group, 35.3% used tobacco within 6 months before surgery compared with 32.4% in the rhBMP-2 group. The percentage of patients with pending litigation was 15.4% and 13.1% in the control group and rhBMP-2 group, respectively. The percentage of patients seeking workers compensation was 33.8% for both groups. Clinical and radiographic outcome measurements: Clinical outcomes were assessed using several methods including Oswestry Low Back Pain
Proceedings of the NASS 16th Annual Meeting / The Spine Journal 2 (2002) 3S–44S
2000 were reviewed. Patients with the diagnosis of spinal osteomyelitis, discitis, epidural abscess and tuberculosis were identified, and the charts were examined in detail. In addition to demographic data, the following parameters were recorded: HIV risk factor, admission white blood cell count (WBC), absolute lymphocyte count, erythrocyte sedimentation rate, CD4 count, imaging studies, blood culture results, biopsy results, surgical procedure, antibiotic treatments and duration, length of stay, hospital charges and outcome. Results: For the 6-year period studied, there were 17,717 patient discharges with the diagnosis of HIV. Of these, 17 patients (0.095%) were also treated for a spinal infection. This included eight patients with discitis/ osteomyelitis, six patients with tuberculosis (TB) and three patients with an epidural abscess. Of the total number of patients discharged from our institution with these diagnoses, these patients represent 7% of all patients with discitis/osteomyelitis, 35% of patients with spinal TB and 5.5% of patients with epidural abscess. In the eight patients with disc discitis/osteomyelitis, the mean WBC was 8.4, mean absolute lymphocyte count 1,910 and mean CD4 count 339.6. Blood cultures were positive in one of six patients, and a biopsy/surgical specimen was positive in three of six patients. The organism identified in these patients was Staphylococcus aureus (sensitive to oxacillin). The remainder of these patients had positive findings on magnetic resonance imaging or nuclear medicine studies. All eight patients had clinical resolution of infection after 6 to 12 weeks of appropriate antibiotics. In contrast, in the six patients with spinal TB the mean WBC was 10.34, mean absolute lymphocyte count 823 (p.007) and mean CD4 count 57.2 (p.003). One of the six patients died during the admission. All were treated with antituberculosis medication protocols. The three patients with epidural abscesses had a mean WBC of 16.17, mean absolute lymphocyte count of 913.3 (p.007) and mean CD4 count of 20.67 (p.004). Two of three patients had a computed tomography–guided biopsy. The other was diagnosed by imaging and a positive blood culture. The two biopsies grew Nocardia species, and both of these patients died during the admission. The other patient had Group A streptococcus and was treated with a third-generation intravenous cephalosporin for 6 weeks with clinical improvement. There was no significant difference between the groups with regard to age, gender, race, HIV risk factor or length of hospital stay. Conclusion: Spinal infections in patients with HIV at our institution occur at a rate of 0.095%. This is more than the incidence in the general population but much less then originally suspected. Discitis/osteomyelitis occurs in the HIV patient with a mild to moderate decrease in the CD4 count. These patients would fall into the Center for Disease Control (CDC) class 2 (of 3) classification. The organism identified is consistent with that seen in the general population (S aureus), and the disease responds to appropriate antibiotics. Patients with markedly decreased CD4 counts (CDC class 3) were found to have spinal TB, and patients with the lowest CD4 counts developed epidural abscesses with more malignant species. The three in-hospital deaths occurred in the latter two groups. Although the CD4 count can be used as a predictor of the clinical course of the HIV patient with spinal infection, the identification of the organism still remains paramount in the treatment of this complex patient population. Two-year follow-up of a safety and efficacy study of osteoinductive protein–1 (recombinant human bone morphogenetic protein–7) as an adjunct to posterolateral lumbar fusion Tushar Ch. Patel, MD, Hopkinton, MA, USA; Alexander R. Vaccaro, MD, Philadelphia, PA, USA; Eeric Truumees, MD, Royal Oak, MI, USA; Jeffrey S. Fischgrund, MD, Southfield, MI, USA; Alan S. Hilibrand, MD, Philadelphia, PA, USA; Harry N. Herkowitz, MD, Southfield, MI, USA Introduction: Posterolateral intertransverse lumbar fusion is a commonly performed procedure for stabilization of the degenerated lumbar spine. A typical clinical scenario for which such fusions are used is the stabilization of a degenerative spondylolisthesis after decompression. In a recent large series reported in the literature, this type of fusion was noted to have a pseudarthrosis rate of up to 45% [1]. Measures to augment autograft fusions would thus be desirable. Materials and methods: Included are 2-year follow-up data to the study presented at the North American Spine Society (NASS) 2000 meeting. A pilot
study was designed to evaluate the safety and efficacy of osteoinductive protein-1 (OP-1, also known as recombinant human bone morphogenetic protein [BMP-7]) in lumbar fusion. Twenty-two patients with the diagnosis of symptomatic spinal stenosis and single-level degenerative spondylolisthesis in the lower lumbar spine (L3–S1) were enrolled (NASS 2000). The patients were randomized to either an OP-1 group or a control group. The OP-1 group received 3.5 mg of OP-1 in a putty carrier per side and iliac crest autograft. The control group received iliac crest autograft alone. Outcomes were measured clinically using the Oswestry score and dynamic radiographs evaluated independently by two blinded radiologists using digital calipers. Results: Two-year results indicate the preservation of fusion in OP-1–treated patients. No acute or long-term adverse effects related to the use of OP-1 were noted in the treatment group. Discussion: Despite the small number of patients enrolled in this pilot study, OP-1 appears to be a safe and effective adjunct to iliac crest autograft in human posterolateral lumbar fusion. Two-year results indicate preservation of fusion in OP-1–treated patients, and the lack of acute and long-term adverse effects speak to the safety of OP-1 in posterolateral fusions. At 2 years, the OP-1 group had a higher radiographic fusion rate than the autograft group. This correlated well with the greater clinical success experienced by the OP-1 group, as measured by improvement in the Oswestry score. None of the previously reported device-related complications related to the use of BMPs in animal studies, such as exuberant bone growth with subsequent neural impingement, ectopic ossification or spinal stenosis, were seen in the treatment group. Conclusion: OP-1 appears to be a safe and effective adjunct to iliac crest autograft in human posterolateral lumbar fusion. The dose, 3.5 mg per side, and the carrier, biodegradable putty, appear to provide a safe and effective means of delivering the bone morphogenetic protein OP-1 to the human lumbar spine. Reference [1] Fischgrund. Spine 1997. Recombinant human bone morphogenetic protein–2 with tapered cages: a prospective, randomized lumbar fusion study Matthew F. Gornet, MD, St. Louis, MO, USA; J. Kenneth Burkus, MD, Columbus, GA, USA; Curtis A. Dickman, MD, Phoenix, AZ, USA; Thomas A. Zdeblick, MD, Madison, WI, USA Introduction: Anterior lumbar interbody fusion (ALIF) is an effective treatment for patients with symptomatic degenerative disc disease. Results from a small series of patients undergoing ALIF with tapered cages demonstrated that recombinant human bone morphogenetic protein–2 (rhBMP-2) promotes osteoinduction and fusion. To further evaluate the clinical performance of rhBMP-2 with tapered metal cages for lumbar fusion procedures, a larger multicenter study was initiated. This paper reports the clinical and radiographic outcomes at 12 months for this clinical trial. Methods: This prospective, randomized, nonblinded study enrolled 281 patients at 16 investigational sites. Patients were randomized into two groups. The control group was treated with autogenous iliac crest bone graft with a tapered metal cage (LT-CAGE device, Medtronic Sofamor Danek). The rhBMP-2 group received rhBMP-2 on a collagen sponge carrier (InFUSE Bone Graft, Medtronic Sofamor Danek) with the LT-CAGE device. Patient demographics: Preoperatively, all patients had symptomatic, single-level degenerative disc disease and had complaints of disabling low back and/or leg pain. All had symptoms lasting at least 6 months and had failed nonoperative treatments. All patients underwent an ALIF procedure through an open approach. The control group consisted of 136 patients (68 men, 68 women) with an average age of 42.3 years, and the rhBMP-2 group consisted of 145 patients (79 men, 66 women) with an average age of 43.3 years. In the control group, 35.3% used tobacco within 6 months before surgery compared with 32.4% in the rhBMP-2 group. The percentage of patients with pending litigation was 15.4% and 13.1% in the control group and rhBMP-2 group, respectively. The percentage of patients seeking workers compensation was 33.8% for both groups. Clinical and radiographic outcome measurements: Clinical outcomes were assessed using several methods including Oswestry Low Back Pain