Use of osteogenic protein-1 in patients at high risk for spinal pseudarthrosis: a prospective cohort study assessing safety, health-related quality of life, and radiographic fusion

Invited submission from the Joint Section on Disorders of the Spine and Peripheral Nerves, March 2007

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Object

The capability of osteogenic protein (OP)–1 to induce bone formation has led to an increasing interest in its use in fusion surgery. This prospective study examines the safety and efficacy of OP-1 use in patients considered to be at a high risk for developing pseudarthrosis following reconstructive spinal surgery.

Methods

Outcome measures included documentation of adverse events, radiographic evaluation of fusion by an independent musculoskeletal radiologist blinded to treatment, the Oswestry Disability Index (ODI), and the 36-Item Short Form Health Survey (SF-36). The health-related quality of life (HRQOL) assessments (ODI and SF-36) were given at baseline and at 3, 6, 12, 18, and 24 months after the surgical OP-1 implant.

Results

The study consisted of 17 male and 13 female patients, with a mean age of 53 years (range 20–77 years). Fourteen patients underwent operations for cervical disease, and 16 for lumbar disease, with a median postoperative follow-up of 24 months (range 13–46 months). There were significant improvements in the physical health (from 28.7 ± 1.5 to 34.2 ± 3; p = 0.025) and mental health (from 43.7 ± 2 to 47.5 ± 3.1; p = 0.015) summary scores on the SF-36. The mean postoperative ODI score at 6, 9, 12, and 18 months was significantly lower than the baseline ODI score, after taking into consideration a 10-point measurement error (p = 0.0003, p = 0.003, p = 0.004, and p = 0.032, respectively). At 24 months, however, the differences in ODI scores were no longer significant. Of the 30 patients, 24 (80%) were deemed to have a solid fusion. There were no allergic reactions to OP-1 and no symptomatic postoperative hematomas.

Conclusions

Our results suggest that the use of OP-1 is safe and may contribute to high fusion rates, as demonstrated by radiographs, reduced levels of disability, and improved HRQOL in patients considered to be at a high risk for developing a nonunion after spinal reconstructive surgery.

Abbreviations used in this paper:BMI = body mass index; CT = computed tomography; HRQOL = health-related quality of life; MR = magnetic resonance; ODI = Oswestry Disability Index; OP = osteogenic protein; rhOP-1 = recombinant human OP-1; SF-36 = 36-Item Short Form Health Survey.

Article Information

Address correspondence to: Michael G. Fehlings, M.D., Ph.D., Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 4W449, Toronto, Ontario M5T 2S8, Canada. email: Michael.Fehlings@uhn.on.ca.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Bar graphs of norm-based SF-36 scores comparing preoperative (baseline) and postoperative assessments of physical and mental health summary scores and their domains (A), and physical and mental summary scores over time (B). Asterisks indicate significant differences (p < 0.05) even after the inclusion of a seven-point measurement error in comparisons with baseline values.

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    Bar graphs of the ODI component scores comparing preoperative (baseline) with postoperative assessment (A), and ODI assessment scores over time (B). Asterisks indicate significant differences (p < 0.05) after the inclusion of a 10-point measurement error in comparisons with baseline values.

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    Preoperative (A) and postoperative (B and C) radiographs obtained in a 24-year-old woman with a history of Klippel–Feil syndrome, juvenile rheumatoid arthritis, and immunosuppressant use. A: Image showing the development of C3–4 instability and transient quadriplegia after a diving injury. This injury was managed using combined anterior/posterior instrumentation as a staged procedure, resulting in solid fusion. The rhOP-1 implant was used to supplement the local autograft posteriorly. B and C: The absence of motion on extension (B) and flexion (C) dynamic radiographs was demonstrated at 36 months after spine fusion. This patient has a mild, asymptomatic C1–2 instability that has not required surgical intervention to date.

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    Preoperative axial (A) and mid sagittal (B) CT scans and postoperative radiographs (C and D) obtained in a 69-year-old man with L4–5 spondylolisthesis and intractable neurogenic bladder due to spinal stenosis who underwent lumbar surgical fusion using bone grafting and adjunctive rhOP-1. Evidence for a solid fusion without instrumentation-related problems was demonstrated on the 27-month follow-up radiographs (C and D).

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    Preoperative MR images (A and B) and postoperative radiographs (C and D) obtained in a 60-year-old woman with heterotopic ossification of soft tissues after surgical cervical fusion and reconstruction using bone grafting and rhOP-1. This patient developed atlantoaxial subluxation, Klippel–Feil deformity, C2–3 subaxial stable kyphosis, and C3–4 subaxial spondylosis with stenosis, as shown in the axial (A) and T2-weighted sagittal (B) images. The radiographic assessment performed 21 months after spine surgery (C and D) revealed a solid fusion and no instrumentation-related problems.

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