Effective Doses of Recombinant Human Bone Morphogenetic Protein-2 in Experimental Spinal Fusion

Sandhu, Harvinder S.; Kanim, Linda E.A.; Kabo, J. Michael; Toth, Jeffrey M.; Zeegen, Erik N.; Liu, D.; Delamarter, Rick B.; Dawson, Edgar G.

doi:10.1097/00007632-199609150-00012

Cited by 206 publications

(91 citation statements)

References 19 publications

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“…To manufacture an osteoinductive artificial bone graft substitute, cytokines retaining osteoinductive activity (e.g., BMPs) have been combined with collagen and used to obtain spinal fusion in experimental animals or in human cases [1,4,5,17,25,26,35,36]. This experimental study was designed to achieve solid posterior interspinous lumbar fusion more effectively and less invasively than before with proper use of rhBMP-2 in combination with synthetic carrier materials.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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Introduction As a powerful bone-inducing cytokine, rhBMP-2 has been used as a bone graft substitute in combination with animal-derived collagen to achieve interbody or posterolateral spinal fusion. Successful interspinous process fusion using rhBMP-2 in combination with synthetic carrier materials would offer a safe, minimally invasive spinal fusion option for the treatment of spinal disorders. The aims of the present study were to achieve interspinous process fusion by implanting rhBMP-2-retaining degradable material instead of bone grafting and to evaluate efficacy for vertebral stabilization. Materials and methods A polymer gel (200 mg), btricalcium phosphate powder (400 mg), and rhBMP-2 (0, 30, 60 or 120 lg) were mixed to generate a plastic implant, which was then placed during surgery to bridge the L5-6 interspinous processes of 58 rabbits. Control animals received implants either without rhBMP-2 or with autogenous bone chips from the iliac crest. L5-6 vertebrae were recovered 8 weeks postoperatively. Interspinous process fusion was evaluated by radiography, biomechanical bending test, intradiscal pressure (IDP) measurement, and histology. Results In bending tests, strength of fusion was significantly greater in BMP60 and BMP120 groups than in sham, BMP0, BMP30 or autogenous bone groups. IDP at L5-6 was significantly reduced in BMP60 and BMP120 groups compared to sham, BMP0, BMP30, and autograft groups. Histologically, coronal sections of the fusion mass showed a bone mass bridging both spinous processes. ConclusionSolid interspinous process fusion was achieved in rabbit models by 8 weeks after implanting the biodegradable bone-inducing material. These results suggest a potential new less-invasive option without bone grafting for the treatment of lumbar disorders.

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Section: Discussionmentioning

confidence: 99%

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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“…number of experiments have suggested that bone morphogenetic protein (BMP) may be used to enhance bone fusion in the posterior part of the spine and perhaps even to act as a bone substitute 1,2 . In a number of recent studies, gene-therapy techniques have been used as an alternative to BMP to achieve bone formation in various animal models [3][4][5] .…”

Section: Discussionmentioning

confidence: 99%

Thoracoscopic Intradiscal Spine Fusion Using a Minimally Invasive Gene-Therapy Technique

Riew

Lou

Wright

et al. 2003

The Journal of Bone and Joint Surgery-American Volume

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“…At present, only BMP-2 and BMP-7 are produced commercially as a therapy to enhance bone healing with BMP-7 called osteogenic protein 1 (OP-1). BMP-2 and OP-1 both promote bone formation in a variety of experimental models (rat [8,13,25,46,47,56], rabbit [3,10,29,48], sheep [15,20], dog [9,19,32,35,40,43]). Although these proteins are now used clinically, most of the information on their effects is known from these and other experimental studies.…”

Section: Introductionmentioning

confidence: 99%

“…However, patient morbidity from graft collection in human orthopaedics is well-documented [17,40,41]. Bone graft collection in veterinary orthopaedics also is associated with patient morbidity at the donor site [45].…”

Section: Introductionmentioning

confidence: 99%

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

Gilley

Wallace

Bourgeault

et al. 2009

Clin Orthop Relat Res

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Glucocorticoids inhibit bone remodeling and fracture healing. We sought to determine whether osteogenic protein 1 (OP-1) can overcome this inhibition in a closed fracture model in the rat. Time-released prednisolone or placebo pellets were implanted subcutaneously; closed femoral fractures were created 2 weeks later in rats. Fractures received sham, OP-1 and collagen, or collagenonly implants. Femurs were harvested at 3, 10, 21, 28, and 42 days postfracture. Fractures were examined radiographically for amount of hard callus; mechanically for torque and stiffness (also expressed as a percentage of the contralateral intact femur); and histomorphometrically for amount of cartilaginous and noncartilaginous soft callus, hard callus, and total callus. Glucocorticoid administration inhibited fracture healing. The application of a devitalized Type I collagen matrix mitigated the inhibitory effects of prednisolone on fracture healing However, further increases in indices of fracture healing were observed when OP-1 was added to the collagen matrix compared with collagen alone. OP-1 and collagen was more effective than collagen alone.

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Effective Doses of Recombinant Human Bone Morphogenetic Protein-2 in Experimental Spinal Fusion

Abstract: No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human bone morphogenetic protein-2.

Cited by 206 publications

References 19 publications

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Thoracoscopic Intradiscal Spine Fusion Using a Minimally Invasive Gene-Therapy Technique

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

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