Vertebral Bone Resorption After Transforaminal Lumbar Interbody Fusion With Bone Morphogenetic Protein (rhBMP-2)

McClellan, John W.; Mulconrey, Daniel S.; Forbes, Robert; Fullmer, Nancy

doi:10.1097/01.bsd.0000211231.83716.4b

Cited by 185 publications

(109 citation statements)

References 17 publications

(21 reference statements)

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“…Numerous theories have been proposed to explain why complications from the use of rhBMP-2 occur, including the stimulation of inflammatory cytokines, angiogenic growth factors, and a potent osteolytic response. 16,35,36 Although none of these has been definitively proven, the effects are associated with the potent osteoinductivity of growth factors, which are utilized at concentrations one million-fold greater than those seen endogenously in humans. 17 Our data suggest that the use of TrioMatrix 1 , which perhaps relies on a more physiologic dose of BMP provided by its DBM component, may avoid these types of complications.…”

Section: Discussionmentioning

confidence: 99%

“…It is notable that animals in the rhBMP-2, Grafton 1 , and DBX 1 groups performed similarly to other studies utilizing the same doses of these products. 18,21,22,24 Because critics of rhBMP-2 use are concerned about the host inflammatory response demonstrated clinically in the cervical spine and lumbar interbody fusions, 10,11,16,17,34 TrioMatrix 1 was qualitatively and quantitatively evaluated in comparison to rhBMP-2 in a novel MR imaging protocol. Assessment 7 days after surgery demonstrated that the formation of an inflammatory response/fluid collection consistent with that described clinically after the use of rhBMP-2 was avoided with the use of TrioMatrix 1 .…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] In the lumbar spine, reports have demonstrated radiculitis, pseudarthrosis, seroma/hematoma formation, and heterotopic ossification with rhBMP-2 use. [13][14][15][16][17] DBMs, which are derived from human cadaveric bone through an acid extraction process, 18 have been associated with a widely variable osteoinductive potency in vivo. [18][19][20][21][22] Ceramic carriers have shown promise in their clinical use as bone graft extenders, 23 but when used alone, provide no exogenous osteoinductivity.…”

mentioning

confidence: 99%

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Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Hsu¹,

Polavarapu²,

Riaz³

et al. 2011

Journal Orthopaedic Research

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The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix 1 ; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 mg rhBMP-2 on ACS (positive control), TrioMatrix 1 , Grafton 1 (Osteotech, Inc., Eatontown, NJ), and DBX 1 (Synthes, Inc., West Chester, PA). Both TrioMatrix 1 and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton 1 , and DBX 1 groups. Notably, the use of TrioMatrix 1 as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix 1 . Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Hsu¹,

Polavarapu²,

Riaz³

et al. 2011

Journal Orthopaedic Research

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show abstract

“…Recombinant human bone morphogenetic protein-2 (rhBMP-2) in combination with an absorbable collagen sponge (ACS) requires a supraphysiologic dose that carries potential complications, including bone resorption, graft migration, hematoma formation, radiculitis, and heterotopic ossification. [5][6][7][8][9][10][11] Other growth factors, such as platelet-rich plasma, have shown a limited efficacy in promoting healing. 12 While some preclinical studies have investigated the potential of allogeneic mesenchymal stem cell (MSC) therapy, efficacy concerns have thus far prevented its introduction into clinical practice.…”

mentioning

confidence: 99%

A Comparative Evaluation of Factors Influencing Osteoinductivity Among Scaffolds Designed for Bone Regeneration

Hsu

Ghodasra

Ashtekar

et al. 2013

Tissue Engineering Part A

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Due to differing compositions, synthetic scaffolds developed for bone regeneration vary widely in efficacy. To quantify the impact of such differences on osteoinductivity, numerous parameters were examined. Absorbable collagen sponge (ACS), three ceramic-based carriers (#1-3) of varying compositions, mineralized allograft chips, and an experimental phosphoserine-rich nanofiber scaffold [S(P) gel] were compared in their ability to promote cell adhesion, proliferation/survival, growth factor binding/release, and osteogenic gene expression. Human preosteoblasts were found to adhere most efficiently to the S(P) gel, and the growth/survival was greatest on the S(P) and ACS scaffolds, with minimal growth seen on the allograft and Ceramic #3. In bone morphogenetic protein-2 (BMP-2) binding/release assays, ACS demonstrated a burst release pattern, whereas the allograft and the ceramics inefficiently released BMP-2. The S(P) gel showed the most ideal rates of growth factor binding and release. QPCR analyses showed significant differences in the CXCL12, CXCR4, and RANKL transcripts among the cells grown on these various scaffolds. Although some scaffolds showed an advantage over others in individual parameters, the nanofiber gel appears to provide the optimal balance in the factors important to osteoinductivity evaluated here.

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“…McClellan et al [61] Retrospective review of transforaminal lumbar interbody fusion with BMP Pradhan et al [72] A prospective cohort study of ALIF using femoral ring allografts and rhBMP-2 Boden et al [10] A prospective randomized clinical pilot study of the use of rhBMP-2 for posterolateral fusion Dimar et al [28] A prospective randomized study comparing the use of iliac crest bone grafts to that of rhBMP-2 for single-level posterolateral fusions…”

Section: Lumbar Spinementioning

confidence: 99%

An update on bone substitutes for spinal fusion

et al. 2009

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With the current advances in spinal surgery, an understanding of the precise biological mechanism of each bone substitute is necessary for inducing successful spinal fusion. In this review, the categories of bone substitutes include allografts, ceramics, demineralized bone matrix, osteoinductive factors, autogenous platelet concentrate, mesenchymal stem cells, and gene therapy. Further, clinical studies have been evaluated by their levels of evidence in order to elucidate the precise effect of the bone substitute employed and to establish clinical guidance. This article will review both clinical studies based on evidence and basic research in current advances in order to avoid as far as possible any chances of failure in the future and to understand cellular biology in novel technologies.

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Vertebral Bone Resorption After Transforaminal Lumbar Interbody Fusion With Bone Morphogenetic Protein (rhBMP-2)

Abstract: The benefit of rhBMP-2 to promote interbody fusion in the lumbar spine has been well documented. BMP has demonstrated an increased fusion rate and the ability to produce a robust fusion mass. rh-BMP-2's osseous remodeling potential may lead to bone resorption within the vertebral body.

Cited by 185 publications

References 17 publications

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

A Comparative Evaluation of Factors Influencing Osteoinductivity Among Scaffolds Designed for Bone Regeneration

An update on bone substitutes for spinal fusion

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