Publications by authors named "Carol Toth"

6 Publications

  • Page 1 of 1

In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model.

Spine J 2006 Sep-Oct;6(5):500-6. Epub 2006 Jul 26.

Rush University Medical Center, 1725 W. Harrison Street, Suite 1063, Chicago, IL 60612, USA.

Background Context: Prevention of osteoporotic vertebral fractures could help at-risk individuals avoid the pain and morbidity associated with these fractures. Currently, patients with osteoporosis are treated with systemic medications to reduce fracture risk. Although effective, these therapies do not eliminate fractures and also tend to have a gradual time-dependent effect on fracture risk. The mechanism of action of the bone morphogenetic protein (BMP) family theoretically makes these molecules candidates for rapidly enhancing local bone structure.

Study Design: An in vivo study analyzing the effects of BMP-7 (osteogenic protein 1 [OP-1]) treatment on osteopenic ovine vertebral architecture and biomechanics.

Purpose: We tested the hypothesis that local injection of OP-1 into osteopenic ovine vertebrae will improve bone mass and trabecular distribution, thereby reducing bone fragility and fracture risk. We specifically evaluated compressive biomechanics and morphology of osteopenic ovine vertebral bodies 6 months after local OP-1 treatment.

Study Design: In vivo animal study.

Methods: Skeletally mature sheep (n=24) underwent ovariectomy and were placed on low cation relative to anion diet. These interventions reduce bone density and induce skeletal fragility. After 6 months, sheep were randomly assigned to six treatment groups based on OP-1 dose (370 mg or 0 mg) and carrier with 4 animals/treatment group. Carriers A and B were poly-L-glycolic acid (PLGA) biospheres with different release kinetics (B allowing sustained BMP release); Carrier C was carboxymethylcellulose. After creating an 8-mm-diameter defect in the midvertebral body, sheep underwent intravertebral body implantation at two nonadjacent levels. Animals were euthanized 6 months after implantation and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Two-way analysis of variance was used to determine effects of OP-1 (alpha=0.05).

Results: An 81.9%, 333.2%, and 39.9% increase in stiffness was seen for OP-1 treated vertebra with Carriers A, B, and C respectively. Although these effects did not reach statistical significance, trends toward improvement were evident. Histology showed varied degrees of bony healing in the injection sites. Histomorphometrically, OP-1 treated vertebrae showed improvements in percent bone of up to 38% and star volume of up to 55% (with Carrier B). Improvements in whole vertebral body BMD were not detected for any treatment.

Conclusion: In this study, local OP-1 treatment showed a positive trend in improving mechanical strength and histomorphometric parameters of osteopenic vertebra, despite the absence of consistent change in BMD. Controlled slow release of OP-1 using PLGA microspheres appeared to be the most effective method of protein delivery. In conclusion, we feel that the pilot data suggest that the use of OP-1 in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.
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January 2007

Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatite.

J Biomed Mater Res A 2004 Dec;71(3):412-8

Stryker Orthopaedics, 325 Corporate Drive, Mahwah, New Jersey 07430, USA.

Solution precipitation of calcium and phosphate is a technique to generate hydroxyapatite [Peri-Apatitetrade mark (PA), Stryker Orthopaedics, Mahwah, NJ] on metal substrate. This study was carried out to determine the capacity of PA to adsorb osteogenic protein-1 (OP-1) and the time course of release, and to determine the osteoinductive activity of OP-1. The adsorption and release studies were conducted with (125)I-labeled OP-1- and PA-coated titanium alloy disks. The results indicate that the adsorption of OP-1 on the PA-coated disks is linear with the concentration of OP-1 up to 5 mg/mL. There is an initial release of 75% to 80% of adsorbed OP-1 within the first hour, and 92% of OP-1 is released in 3 days. The osteoinductive activity of OP-1 was determined in the rat intramuscular ectopic bone formation assay. A total of 24 titanium alloy disks were evenly divided into 3 groups with different treatments for implantation, plain disks (group A), disks coated with PA (group B), and disks coated with PA plus 40 microg OP-1 (group C). Osteogenic protein-1, 40 microg in solution, was injected into the muscle pouch in animals of group D (n = 8). The rats were sacrificed 3 weeks postoperatively and the implants were retrieved. Ectopic bone formation was evaluated with radiography and histology. Results demonstrated that OP-1 induced ectopic bone in all the animals of group C and group D. The titanium alloy disks were surrounded by trabecular bone and marrow tissue. None of the animals of group A or group B showed any evidence of osteoinduction. Our findings indicate that PA can deliver OP-1 directly to titanium alloy implants and maintain the osteoinductive activity of OP-1.
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December 2004

Osteogenic protein-1 enhances osseointegration of titanium implants coated with peri-apatite in rabbit femoral defect.

J Biomed Mater Res B Appl Biomater 2004 Nov;71(2):408-13

Stryker Orthopaedics, Mahwah, New Jersey, USA.

This study evaluated the effect of osteogenic protein-1 (OP-1) carried by Peri-Apatite (PA) on bone healing in the gap surrounding implants in a rabbit model. Cylindrical titanium implants (3 x 9 mm) were uniformly coated with PA precipitated from a calcium and phosphate solution. OP-1 solution containing 60 microg OP-1 was directly loaded on the implants immediately before implantation for the experimental group, whereas buffer solution was loaded on the implants for the control. The implant was placed in the distal femur and surrounded by a 1-mm gap. The implants were retrieved and examined 6 weeks after implantation. Mechanical testing (push-out) data showed that OP-1 enhanced implant fixation by 80%. Histomorphometric measurements indicated that bone ingrowth in the initial gap expressed as a percentage of the whole gap was significantly higher in the specimens treated with OP-1 than the control group (25.4% vs. 8.9%, p < 0.05). The percentage of the surface of implants, which was covered by bone, was significantly higher in the OP-1-treated group compared to the control group (65% vs. 25%, p < 0.05). This study suggests that OP-1 can be loaded on orthopedic implants through PA to enhance the osseointegration of orthopedic implant.
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November 2004

The use of OP-1 in femoral impaction grafting in a sheep model.

J Orthop Res 2004 Sep;22(5):1008-15

Department of Orthopaedics and Trauma, University of Adelaide and Royal Adelaide Hospital, L4 Bice Building, Adelaide, South Australia 5000, Australia.

The aim of this pilot study was to examine bone graft incorporation in femurs impacted with allograft bone alone (control group) or with allograft containing the bone morphogenetic protein OP-1 (BMP-7) (OP-1 group) in a sheep model of cemented hemiarthroplasty. Two sheep in each group were sacrificed at 6, 18 and 26 weeks. Successful bone graft incorporation was evident in both groups by six weeks but in the OP-1 group, there had been more extensive resorption of the graft. There was one case of excessive stem subsidence in the OP-1 group at six weeks. By 18 weeks, there was remodelling and trabeculation of the new bone in the OP-1 group, but this appeared less advanced in the control group. By 26 weeks, there was remodelling of bone in the graft bed. The results of this small study suggest that OP-1 promotes initial graft resorption, thus hastening bone graft incorporation and remodelling in femoral impaction grafting. The one case of stem subsidence may be associated with the early resorption seen in the OP-1 group and reinforces the need for further studies, examining dose response and using precise measures of stem movement, before this BMP is used in femoral impaction grafting at revision hip arthroplasty.
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September 2004

Successful transpedicular lumbar interbody fusion by means of a composite of osteogenic protein-1 (rhBMP-7) and hydroxyapatite carrier: a comparison with autograft and hydroxyapatite in the sheep spine.

Spine (Phila Pa 1976) 2002 Dec;27(23):2697-705

Trauma and Reconstructive Surgery, Würzburg University Hospital, Germany.

Study Design: Transpedicular lumbar interbody fusion (TLIF) was performed in a sheep model comparing three treatment groups: a composite of osteogenic protein (OP)-1 and hydroxyapatite carrier (HA), HA without OP-1, and autograft.

Objective: To evaluate the efficacy of the composite of OP-1 and HA (HA-OP-1) in achieving reliable TLIF.

Summary Of Background Data: Anterior fusion techniques directly address disc-related problems and achieve primary axial stability. However, they are characterized by high morbidity. Alternatively, the theoretically advantageous posterior TLIF technique using autograft fails clinically because it lacks compressive stability.

Methods: In 36 sheep, lumbar vertebrae L4 to L6 were instrumented posteriorly. Endoscopically assisted TLIF of L4 to L5 was performed. In 12 sheep, the defect was filled with injectable HA-OP-1. Another 12 sheep were treated with HA and another 12 with autograft. Animals were killed at 8 weeks and evaluated by radiologic, histologic, and histomorphometric analysis and by fluorochrome labeling.

Results: Only 10 autograft sheep were available for evaluation. Radiologically and histologically, TLIF with HA-OP-1 led to a fusion rate of 10 in 12 compared with autograft (one in 10 fused) and HA (two in 12 fused) ( = 0.0016). Semiquantitative radiologic and histologic scoring also revealed significant differences with superiority of HA-OP-1 ( = 0.0011). Compared with HA, HA-OP-1 presented significantly more ossification at the bone-cement interface ( = 0.0003) and less cement resorption ( = 0.0209). In four of 12 HA sheep, excessive resorption was responsible for local aseptic inflammation.

Conclusions: Biointegration of the osteoconductive HA does not occur, because shear forces cause early HA fracture, subsequent fragmentation, and gross resorption (initiating severe inflammation in four of 12 sheep). In contrast, osteoinductive effects of HA-OP-1 enable bio-integration, resulting in full osseous composite sheathing and solid fusion. By use of this composite, TLIF is successfully applied in sheep. Harvesting autograft and the anterior approach are avoided.
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December 2002

Recombinant human osteogenic protein-1 (bone morphogenetic protein-7) as an osteoinductive agent in spinal fusion.

Spine (Phila Pa 1976) 2002 Aug;27(16 Suppl 1):S59-65

Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Study Design: The data related to spinal applications of osteogenic protein-1 presented at national meetings or published in peer-reviewed literature are reviewed.

Objectives: To review the available data related to the use of osteogenic protein-1 for spinal arthrodesis. REVIEW OF BACKGROUND DATA: Osteogenic protein-1 (bone morphogenetic protein-7) is a member of the bone morphogenetic protein family and has shown strong osteoinductivity in vivo.

Methods: The background related to osteogenic protein-1 for spinal applications and the known studies presented at national meetings or published in the peer-reviewed literature are reviewed.

Results: Osteogenic protein-1 is able to achieve solid bony fusion of the spine in both the anterior and posterolateral environments in animal studies and has a good safety profile. Early human trials appear to be promising.

Conclusions: Animal studies support the ability of osteogenic protein-1 to enhance or replace autograft for spinal arthrodesis in both the posterolateral and interbody environment. Human trials ultimately will provide data to clarify the optimal role of osteogenic protein-1 in human spinal surgery.
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August 2002