Safety of Recombinant Human Bone Morphogenetic Protein-2 After Spinal Laminectomy in the Dog

Meyer, Ralph A.; Gruber, Helen E.; Howard, Brian A.; Tabor, Owen B.; Murakami, Takanori; Kwiatkowski, Timothy C.; Wozney, John M.; Hanley, Edward N.

doi:10.1097/00007632-200003151-00015

Cited by 4 publications

(7 citation statements)

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“…In several studies in which intertransverse fusion models were evaluated, high BMP-2 doses (up to 1500 g) were necessary to achieve intertransverse fusion. 3,8,9,19,31,36 In our study a small dose of BMP-2 (approximately 150 g) applied with a PDLLAcoated cage or a collagen sponge was able to accelerate anterior interbody bone matrix formation significantly.…”

Section: Bone Morphogenetic Protein-2mentioning

confidence: 49%

“…2,3,8,9,19,31,36,44 In the majority of animal studies investigators have used BMP-2 in an intertransverse process spinal fusion model. 3,8,9,19,31,36 Compared with this model, the biological environment of anterior interbody fusion provides a greater access to cancellous bone and bone marrow elements with osteogenetic potency. This favorable biological environment may therefore reduce the quantity of growth factors needed to achieve solid fusion, making the use of growth factors more economically feasible.…”

Section: Bone Morphogenetic Protein-2mentioning

confidence: 99%

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Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Kandziora¹,

Bail²,

Schmidmaier³

et al. 2002

Journal of Neurosurgery: Spine

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Object. Growth factors such as bone morphogenetic protein—2 (BMP-2) have been proven to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum method to deliver such growth factors remains a matter of discussion. The purpose of this study was to determine the safety and efficacy of a new poly(d,l-lactide) (PDLLA) carrier system for BMP-2 and to compare this carrier system with a collagen sponge carrier in a sheep cervical spine interbody fusion model. Methods. Thirty-two sheep underwent C3–4 discectomy and fusion: Group 1, titanium cage (eight animals); Group 2, titanium cage coated with a PDLLA carrier (eight animals); Group 3, titanium cage coated with a PDLLA carrier including BMP-2 (150 µg) (eight animals); and Group 4, titanium cage combined with a collagen sponge carrier including BMP-2 (150 µg) (eight animals). Blood samples, body weight, and temperature were assessed. Radiographs were obtained pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After the sheep were killed 12 weeks postoperatively, flexion—extension radiography was performed to evaluate fusion sites. Quantitative computerized tomography scans were obtained to assess bone mineral density (BMD), bone mineral content (BMC), and bone callus volume (BCV). Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral, and elastic zone were determined. Histomorphological and -morphometrical analyses were performed, and polychrome sequential labeling was used to determine the timeframe of new bone formation. There were no differences among the groups concerning blood counts, body weight, and temperature. Compared with the noncoated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus, as well as slightly higher values for BMC, BCV, and the bone volume/total volume ratio. In comparison with the cage-alone group, the BMP-2 groups showed significantly higher values for BMD and biomechanical stiffness. Histomorphological, -morphometrical, and polychrome sequential labeling analyses demonstrated greater progression of callus formation in the BMP-2 groups than in any other group. Compared with BMP-2 delivered using a collagen sponge carrier, BMP-2 application with a PDLLA carrier resulted in a higher BCV and a greater progression of interbody callus formation in the histomorphometrical analysis. Conclusions. The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a “real fusion” cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.

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Section: Bone Morphogenetic Protein-2mentioning

confidence: 49%

Section: Bone Morphogenetic Protein-2mentioning

confidence: 99%

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Kandziora¹,

Bail²,

Schmidmaier³

et al. 2002

Journal of Neurosurgery: Spine

View full text Add to dashboard Cite

show abstract

“…A large number of studies [24][25][26][27][28][29][30][31][32][33][34] in which dogs have been subjected to orthopedic techniques have revealed that BMPs can accelerate bone healing during craniofacial reconstruction, fracture and gap-defect repair, and spinal fusion in dogs. Treatment with mesenchymal stem cells has also received attention for its ability to enhance fracture and gap-defect repair in dogs.…”

mentioning

confidence: 99%

Effects of osteogenic inducers on cultures of canine mesenchymal stem cells

Volk¹,

Diefenderfer²,

Christopher³

et al. 2005

ajvr

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“…Larger doses of rhBMP have been associated with bone resorption, while ectopic bone formation has also been observed. Several studies [11][12][13]16 have documented ectopic bone formation in animal models although neurological sequelae were not observed, even with mild cord compression. In human studies, McKay and Sandhu 9 reported ectopic bone growth encroaching into the spinal canal following posterior lumbar interbody fusion without neurological deficit.…”

Section: Discussionmentioning

confidence: 99%

Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis

Lindley¹,

Dahdaleh²,

Menezes³

et al. 2011

PED

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Object Management of pediatric occipitocervical instability remains especially challenging. The off-label use of recombinant human bone morphogenetic protein (rhBMP)-2 for spinal fusion has increased with a well-documented increase in fusion rate in many case series. Unfortunately, recent reports have documented complications associated with rhBMP use in adult spinal fusions. Complications associated with the use of rhBMP in pediatric spinal surgery is less well understood. In this study the authors report on the fusion rate and complications associated with rhBMP in pediatric occipitocervical arthrodesis. Methods The authors reviewed the medical records of those patients 18 years old and younger who underwent dorsal occipitocervical fusion from January 2004 to December 2007 at the University of Iowa Hospitals and Clinics. Forty-eight patients were identified who received rhBMP-augmented fusion. The clinical outcome and complications of these fusions were analyzed. Results All 48 patients had fusion confirmed on lateral radiographs within 4–14 months with an average fusion time of 6.7 months. There were 6 complications, 5 of which included seroma formation. Two of 5 patients who developed postoperative seroma presented with symptoms suggesting brainstem compression and obstructive hydrocephalus requiring emergency reoperation. One patient developed heterotopic bone formation causing cervicomedullary compression requiring reoperation. Conclusions The use of rhBMP to augment autograft in occipitocervical fusion allows for a high rate of successful arthrodesis, but is associated with potentially life-threatening complications in pediatric patients.

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Safety of Recombinant Human Bone Morphogenetic Protein-2 After Spinal Laminectomy in the Dog

Cited by 4 publications

References 0 publications

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Effects of osteogenic inducers on cultures of canine mesenchymal stem cells

Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis

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