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

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p></jats:sec>

The use of bone morphogenetic proteins (BMP) and pseudarthrosis, a literature review

“…The rhBMP-7 has been documented as a potential treatment alternative for different diseases, including bone disease, stroke, inflammatory bowel disease, prostate cancer, and chronic renal disease 9 . More explicitly, rhBMP-7 plays an important role in bone formation by inducing differentiation of pluripotent mesenchymal cells into active osteoblasts, Furlan et al 9 concludes that it can induce a stable, mature, posterolateral spinal fusion mass more rapidly than an autologous bone graft, and the resulting fusion mass may be biomechanically stiffer in the early stages (up to 3 months) of healing.…”

Use of OP-1 (rhBMP-7) in posterolateral lumbar arthrodesis

“…Similarly, Jeppsson et al observed bony bridging at the fusion site in only one of four rheumatoid patients treated with wire fixation and rhOP-1 for atlantoaxial instability (34). On the other hand, Fehlings and coworkers have demonstrated fusion rates exceeding 80% using rhOP-1 in patients at high risk for pseudoarthrosis undergoing cervical or lumbar fusion (17,35). The initial randomized controlled trials of rhOP-1 compared use of rhOP-1 to autograft in a small number of patients (<40) undergoing posterolateral lumbar fusion (36)(37)(38)(39).…”

“…Both rhBMP-2 and rhOP-1 demonstrated efficacy in inducing bone formation in preclinical animal studies, which has spurred clinical investigation of their efficacy as bone graft substitute (13)(14)(15)(16). Moreover, other investigators have suggested that BMPs, including OP-1, may show promise in promoting fusion in patients with high-risk adverse medical conditions (17).…”

“…The primary outcome of 'overall success' was evaluated at 24 months; the definition was essentially the same as that used by Delawi et al in the present study. However, at 24 months, fusion was assessed using AP and flexion-extension radiographs and defined as new (17,39,41). The FDA reported seven patients developing cancer with use of rhOP-1 (32).…”

Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies

“…The authors suggested that some modification of either the surgical technique or the carrier may be required for extensive use of OP-1 in instrumented posterolateral lumbar fusion. Furlan et al 168 reported good fusion rates (80%) and improved health related quality of life (HRQOL) outcomes in a level III study using OP-1 and autograft in 30 patients with high risk of spinal pseudarthrosis. The data consisted of cases of lumbar or lumbosacral fusions as well as cervical and occipitocervical fusions for high risk cases such as previous failed fusions, rheumatoid arthritis, systemic lupus erythematosus, MaroteauxLamy syndrome, ankylosing spondylitis, steroid use, immunosuppression, heavy smokers and osteopenic or osteoporosis.…”