Efficacy Of Bone Morphogenetic Protein-2 Research Articles

Bone Morphogenetic Protein-2 (BMP-2) and Vascular Endothelial Growth Factor (VEGF) Transfection to Human Periosteal Cells Enhances Osteoblast Differentiation and Bone Formation

Periosteum has been demonstrated to contain mesenchymal progenitor cells differentiating to osteoblasts, and both bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) may play important roles in cell-based approaches to bone regeneration. The purpose of this study was to evaluate the feasibility and efficacy of BMP-2 and/or VEGF on periosteal cell differentiation to osteoblasts in vitro and ectopic bone formation in vivo. Human periosteum-derived cells were transfected with BMP-2, VEGF, BMP-2 + VEGF, or vehicle as a control by non-viral gene transfer and then cultured and implanted to nude mice intramuscularly. Real-time polymerase chain reaction analysis of the culture revealed that transgenes for BMP-2 and BMP-2 + VEGF induced more mRNA expression of alkaline phosphatase, collagen type I, and osteocalcin than VEGF and vehicle treatments; additionally, alizarin red S staining, alkaline phosphatase staining, and alkaline phosphatase activity were significantly higher in the BMP-2 + VEGF transgene than in the other versions. After implantation, ectopic bone was observed at 4 weeks and greatly increased at 8 weeks in all groups. In particular, the combination of BMP-2 and VEGF formed significantly more bone at 4 weeks, and VEGF transfection resulted in more blood vessels relative to the conditions without VEGF. Thus, VEGF might enhance BMP2-induced bone formation through modulation of angiogenesis.

The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion

Background context There is mounting evidence supporting the efficacy of bone morphogenetic protein (BMP) for both anterior interbody and posterolateral lumbar fusion. However, the relative cost of BMP remains an important concern for physicians, hospitals, and payers. Purpose The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft (ICBG) supplemented with graft extenders. Study design/setting A prospective randomized controlled trial of rhBMP-2/ACS (Infuse Bone Graft; Medtronic Sofamor Danek, Memphis, TN) versus ICBG±graft extender for lumbar spine fusion in patients over 60 years old. Patient sample One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion randomized between receiving rhBMP-2/ACS or ICBG. Outcome measures All health-care costs over the first 3 months after surgery. Methods As part of a prospective randomized trial of rhBMP-2/ACS versus ICBG±graft extender for lumbar spine fusion, all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare, Louisville, KY. A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care. Results Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest. The mean hospital cost for the index admission was $24,736 for the rhBMP-2/ACS group and $21,138 for the ICBG group. Mean inpatient physician costs were $5,082 in the rhBMP-2/ACS group and $5,316 in the ICBG group. Costs associated with posthospital rehabilitation averaged $4,906 in the rhBMP-2/ACS group versus $6,820 in the ICBG group. Total payer expenditure for the 3-month perioperative period averaged $33,860 in the rhBMP-2/ACS group and $37,227 in the ICBG group. Conclusions The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS. In contrast, the payer in a Diagnosis-Related Group (DRG) model achieves a net savings, based primarily on the decreased payment for inpatient rehabilitation, but also on decreased hospital reimbursement, physician costs, and other outpatient services.

565. Acceleration of Fracture Healing with Adenovirally Transduced Human BMP-2 and -6 Genes in Horse Metatarsal Osteotomy and Ostectomy Models

Introduction; Treatment of delayed or nonunion fractures can be challenging. Bone morphogenetic protein-2 (BMP-2) is one of the most studied growth factors associated with bone healing, and successful induction of bone formation by BMP-2 has been demonstrated both in vitro and in vivo. The less investigated member of BMP family, BMP-6, currently received attention because it may contribute bone formation by an alternative mechanism compared to other BMPs. This study was to compare the efficacy of BMP-2 and -6 genes transduced by adenoviral vector (Ad) in an acceleration of bone healing using two different sizes of unstable fracture models using horses.

Effects of osteogenic inducers on cultures of canine mesenchymal stem cells

To examine age-related efficacy of bone morphogenetic protein (BMP)-2, ascorbate, and dexamethasone as osteogenic inducers in canine marrow-derived stromal cells (MSCs). Samples of femoral bone marrow obtained from 15 skeletally immature (< 1 year old) and 4 skeletally mature (> 1.5 years old) dogs. First-passage canine MSC cultures were treated with 100 microg of ascorbate phosphate/mL, 10(-7)M dexamethasone, 100 ng of BMP-2/mL, or a combination of these osteoinducers. On day 6, cultures were harvested for quantitation of alkaline phosphatase (ALP) activity and isolation of RNA to prepare cDNA for real-time polymerase chain reaction analyses of osteoblast markers. Early markers of osteogenesis were induced in canine MSCs by BMP-2 but not dexamethasone. In young dogs, the combination of BMP-2 and ascorbate yielded the highest ALP mRNA concentrations and activity. This combination also induced significant increases in mRNA for osteopontin and runt-domain transcription factor 2. In comparison to MSCs from immature dogs, those from mature dogs had diminished ALP activity in response to BMP and ascorbate. Results for cultures treated with 3,4-dehydroproline suggested that ascorbate-induced production of extracellular matrix was important for maximal BMP-2 response in canine MSCs. BMP-2 was capable of inducing markers of osteogenesis in short-term cultures of canine MSCs. In MSCs obtained from skeletally immature dogs, ascorbate was required for maximal effects of BMP These results define optimal conditions for stem cell osteogenesis in dogs and will facilitate development of stem cell-based treatments for dogs with fractures.

Treatment of Osteonecrosis of the Femoral Head with Core Decompression and Human Bone Morphogenetic Protein

A retrospective evaluation was done of 15 patients (17 hips) with symptomatic osteonecrosis of the hip treated with core decompression combined with an allogeneic, antigen-extracted, autolyzed fibula allograft and 50 mg of partially purified human bone morphogenetic protein and noncollagenous proteins. The average duration of clinical followup of the patients was 53 months (range, 26-94 months). The osteonecrotic involvement of the hip was classified by plain radiographs using a modification of the Ficat staging system and MRI evaluations. Fifteen hips were classified as Ficat Stage IIA, one hip (one patient) was classified as Ficat Stage IIB, and one hip (one patient) was classified as Ficat Stage III. Fourteen hips had involvement of 50% or less of the femoral head and 2/3 or less involvement of the weight-bearing surface of the femoral head, based on a magnetic resonance imaging evaluation. The procedures were a clinical success in 14 of 15 hips (93%; 13 patients) with Stage IIA disease. Three of 17 hips (three patients) had radiographic progression (Ficat Stages IIA, IIB, and III) of the femoral head and were converted to total hip replacements. Only one of seven hips (six patients) with 50% or less involvement of the femoral head and between 1/3 and 2/3 of the weightbearing surface of the femoral head developed radiographic progression of the femoral head. There was no radiographic progression in the 3 hips with less than 1/3 involvement of the weightbearing surface of the femoral head. Further evaluation of the potential efficacy of bone morphogenetic protein is required in randomized trials.

Cortical bone grafts used to culture bone cells to be used for increasing efficacy of bone morphogenetic proteins in tissue engineered bone substitutes

Introduction: Mostly cancellous endocondral bone has been utilized for culturing of cells in vitro. We report here a technique to acquire small particle sized membraneous bone chips perfectly suited for cell culturing viable bone-like cells. The problems that are encountered with the clinical use of BMP is usually the lack of responding cells in the implanted site, therefore the use of patients’ own cells could enhance the efficacy of BMPs and related proteins with different biomaterials.

Clinical Efficacy of Bone Morphogenetic Proteins

Clinical Efficacy of Bone Morphogenetic Proteins

Bone morphogenetic proteins and spinal fusion

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 antiinflammatory 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.

Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles

The efficacy of bone morphogenetic protein (BMP) for bone reconstruction has been widely studied in numerous animal experiments, but insufficient information exists about its ability to regenerate bone in primates. The purpose of this study was to evaluate the effects of recombinant human BMP-2 (rhBMP-2) on bone formation in alveolar bone defects in the mandibles of young primates. Marginal bone defects were created in the mandibles of nine 5-year-old rhesus monkeys and rhBMP-2 permeated in a polylactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defects. The resected bone treated with rhBMP-2 regenerated completely at 12 weeks postoperatively, and remodelling and consolidation of new bone were seen histologically. This study provides evidence of considerable bone regeneration in alveolar defects after surgical implantation of rhBMP-2 in non-human primates. This technique may be an effective alternative to autogenous bone grafts for reconstructive surgery in clinical practice.

Efficacy of bone morphogenetic protein (BMP) with osteopromotive membranes--an experimental study in rat mandibular defects.

The effect of bone morphogenetic protein (BMP) on healing of standardized bone defects was studied with and without the placement of osteopromotive membranes. Two different bovine BMP (bBMP) preparations were tested. These contained primarily collagen as a carrier. Standardized transosseous bone defects, 5 mm in diameter, were created in mandibles of rats. If left untreated, such "critical size defects" never heal during the lifetime of the animal, whereas covering with an osteopromotive membrane is known to cause complete healing of the defects in 6 weeks. The bBMP was implanted in defects and were either covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX) or were left uncovered. Control defects did not receive any bBMP and were either covered with membrane or were left uncovered. Histological evaluation was made after 12 d and 24 d of healing, respectively. Implantation of bBMP alone was associated with formation of voluminous amounts of new bone, resulting in essentially complete defect healing at 24 d. However, the combination of membrane and bBMP was clearly less effective in stimulating bone healing, being only about as efficient as when using membranes alone. It was concluded that whereas both bBMP preparations were strongly osteoinductive, no further improvement of bone healing was when the membrane technique was supplemented with bBMP, compared to membrane alone. An explanation may be that the presence of an e-PTFE membrane prevents the degradation of the carrier material in the preparations, thus strongly reducing the availability of bBMP.