The Safety of OP-1 for Lumbar Fusion with Decompression - a Canine Study

Paramore, Christopher G.; Lauryssen, Carl; Wadlington, Van R.; Palmer, Cheryl A.; Brix, Amy E.; Cartner, Samuel C.; Hadley, Mark N.

doi:10.1097/00006123-199905000-00134

Cited by 97 publications

(39 citation statements)

References 16 publications

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“…Paramore et al implanted BMP-7 into the epidural space of dogs after laminectomy and posterolateral fusion. Animals demonstrated bone formation adjacent to their spinal cords causing mild spinal cord compression (Paramore et al 1999). Novel carriers need to contain the BMP, prevent ectopic and heterotopic bone formation and utilize lower, safe and costeffective dosages.…”

Section: Dose and Concentrationmentioning

confidence: 99%

Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Current challenges in BMP delivery

2009

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Recombinant human bone morphogenetic proteins (rhBMPs) have been extensively investigated for developing therapeutic strategies aimed at the restoration and treatment of orthopaedic as well as craniofacial conditions. In this first part of the review, we discuss the rationale for the necessary use of carrier systems to deliver rhBMP-2 and rhBMP-7 to sites of bone tissue regeneration and repair. General requirements for growth factor delivery systems emphasizing the distinction between localized and release-controlled delivery strategies are presented highlighting the current limitations in the development of an effective rhBMP delivery system applicable in clinical bone tissue engineering.

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Section: Dose and Concentrationmentioning

confidence: 99%

Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Current challenges in BMP delivery

2009

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“…In another canine model of dural perforation, Paramore, et al, 48 studied the safety of rhBMP-7 (rhOP-1) use. After laminectomy, the dura was opened to simulate an intraoperative dural rent.…”

Section: Animal Models Of Bmp Safetymentioning

confidence: 99%

“…Although placement of rhBMP-2 5 or bovine whole BMP extract 13 in the posterolateral location in an animal laminectomy model did not result in any significant encroachment of bone into the laminectomy defect, undesired bone formation was seen directly over the laminectomy defect with placement of rhBMP-2 36 or rhBMP-7. 48 Other models have induced spinal stenosis by direct implantation of BMP over the ligamentum flavum. 37,40 In the setting of dural laceration in animal models, significant intradural bone formation and calcification of the spinal cord was seen with rhBMP-7 48 , but not with rhBMP-2, 36 although the studies were not of similar design.…”

Section: 41mentioning

confidence: 99%

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Bone morphogenetic proteins and spinal fusion

Walker¹,

Wright²

2002

FOC

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Bone morphogenetic proteins (BMPs) have increasingly become a focus of research in the laboratory, with animal models, and in human clinical trials for the treatment of spinal disorders. Basic science research has elucidated the putative mechanism of action of BMPs, and the efficacy of BMPs in inducing bone formation has been evaluated in multiple animal models of anterior and posterior spinal fusion. Not only has BMP been shown to improve the quality and amount of bone formation when used as a supplement to autograft, it has also been shown to promote superior fusion in the absence of autograft, even in high-risk fusion models involving the use of nicotine or nonsteroidal antiinflam-matory agents. Both completed and ongoing clinical trials have demonstrated the efficacy of recombinant BMP, leading to the first BMP product being approved for clinical use earlier this year. Animal models and clinical trials have also been used to evaluate the safety of BMPs. Although few complications have been reported, BMPs can induce heterotopic bone formation, especially when placed adjacent to exposed neural elements. Potentially more serious, antibody formation has been seen in up to 38% of patients in some clinical trials. No clinical sequelae have been reported despite the development of antibodies against BMP, a naturally occurring human protein implicated in processes other than osteoinduction. The future directions of biological manipulation of the osteoinduction process include further understanding of the interactions of the BMP subtypes, the interactions of BMP with its receptors, and exploring other molecules capable of osteoinduction.

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“…Further efforts led to cloning of BMP-2 and BMP-7 (OP-1), members of the transforming growth factor-beta (TGF-beta) superfamily, and expression of recombinant human forms of these proteins (11,12). 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).…”

mentioning

confidence: 99%