title: The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study.
abstract: BACKGROUND
  Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stem cells. Osteogenic protein-1 (OP-1) Putty is a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft.
  
  
  METHODS
  A prospective, randomized, controlled, multicenter clinical pilot study.
  
  
  METHODS
  Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients).
  
  
  METHODS
  Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups.
  
  
  METHODS
  Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes.
  
  
  RESULTS
  At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty.
  
  
  CONCLUSIONS
  Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University and The Rothman Institute, 925 Chestnut Street, 5(th) Floor, Philadelphia, Pennsylvania, PA 19107, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Vaccaro
authors.forename: Peter G
authors.initials: PG
authors.lastname: Whang
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
authors.forename: Frank M
authors.initials: FM
authors.lastname: Phillips
authors.forename: D Greg
authors.initials: DG
authors.lastname: Anderson
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Albert
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hilibrand
authors.forename: Richard S
authors.initials: RS
authors.lastname: Brower
authors.forename: Mark F
authors.initials: MF
authors.lastname: Kurd
authors.forename: Anoop
authors.initials: A
authors.lastname: Appannagari
authors.forename: Milan
authors.initials: M
authors.lastname: Patel
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Fischgrund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007085:Ilium / Q000637:transplantation*; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications; D013123:Spinal Fusion / Q000379:methods*; D013130:Spinal Stenosis / Q000601:surgery; D013168:Spondylolisthesis / Q000601:surgery*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D019485:Bone Morphogenetic Proteins; C511401:osteogenic protein 1 putty, recombinant human