Osteogenic protein-1 (OP-1, BMP-7) for stimulation of healing of closed fractures: evidence based medicine and pre-clinical experience

Blokhuis, Taco J.; Haarman, H. J. T. M.; Giltaij, Lex R.

doi:10.1007/978-3-0348-8121-0_7

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…Animal studies have documented that BMPs, carried by a collagen vector, favoured the deposition of new endochondral bone in several animal species [ 62 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Role of rhBMP-7, Fibronectin, And Type I Collagen in Dental Implant Osseointegration Process: An Initial Pilot Study on Minipig Animals

et al. 2021

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Background: The biological factors involved in dental implant osseointegration need to be investigated to improve implant success. Methods: Twenty-four implants were inserted into the tibias of six minipigs. Bone samples were obtained at 7, 14, and 56 days. Biomolecular analyses evaluated mRNA of BMP-4, -7, Transforming Growth Factor-β2, Interleukin-1β, and Osteocalcin in sites treated with rhBMP-7, Type 1 Collagen, or Fibronectin (FN). Inflammation and osteogenesis were evaluated by histological analyses. Results: At 7 and 14 days, BMP-4 and BMP-7 increased in the sites prepared with rhBMP-7 and FN. BMP-7 remained greater at 56 days in rhBMP-7 and FN sites. BPM-4 at 7 and 14 days increased in Type 1 Collagen sites; BMP-7 increased from day 14. FN increased the TGF-β2 at all experimental times, whilst the rhBMP-7 only did so up to 7 days. IL-1β increased only in collagen-treated sites from 14 days. Osteocalcin was high in FN-treated sites. Neutrophilic granulocytes characterized the inflammatory infiltrate at 7 days, and mononuclear cells at 14 and 56 days. Conclusions: This initial pilot study, in a novel way, evidenced that Type 1 Collagen induced inflammation and did not stimulate bone production; conversely FN or rhBMP-7 showed neo-osteogenetic and anti-inflammatory properties when directly added into implant bone site.

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“…Animal studies have documented that BMPs, carried by a collagen vector, favoured the deposition of new endochondral bone in several animal species [ 62 , 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Role of rhBMP-7, Fibronectin, And Type I Collagen in Dental Implant Osseointegration Process: An Initial Pilot Study on Minipig Animals

et al. 2021

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“…Currently, few therapeutic options exist for the enhancement of local bone repair. Bone morphogenetic proteins (BMP2 and BMP7) have been investigated as pharmacologic agents for enhancing fracture healing (3–6) . However, the cost effectiveness, degree of clinical benefit, and long‐term safety of these therapies have not been delineated.…”

Section: Introductionmentioning

confidence: 99%

A Novel, Non-Prostanoid EP2 Receptor-Selective Prostaglandin E2 Agonist Stimulates Local Bone Formation and Enhances Fracture Healing

Hua

et al. 2003

Journal of Bone and Mineral Research

105

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CP-533,536, a newly discovered, non-prostanoid EP2 receptor-selective PGE 2 agonist, stimulates local bone formation and enhances fracture healing in rat models.Introduction: There is a significant medical need for agents that can stimulate local bone formation and enhance fracture healing. We tested the effects of CP-533,536, a newly discovered, non-prostanoid EP2 receptor-selective prostaglandin E 2 (PGE 2 ) agonist, in stimulating local bone formation and enhancing fracture healing in rat models. Materials and Methods: In the first model, a single injection of CP-533,536 at doses of 0.3, 1, or 3 mg/kg to the proximal tibial metaphysis of 6-week-old male rats was given on day 1, and the local bone anabolic effect was determined on day 7. We then tested the effects of this compound in inducing bone formation on rat periosteum of the femur. A single dose of 0.3 mg of CP-533,536 incorporated in a poly-(D,L-lactide-co-glycolide) (PLGH) matrix was injected onto the periosteum of the femur in 3-week-old male rats, and local bone formation was determined on day 14. Finally, the ability of CP-533,536 in PLGH matrix in enhancing fracture healing was tested using the rat femoral fracture model. CP-533,536 in PLGH matrix at doses of 0.05, 0.5, or 5 mg was delivered to the local fracture site on the same day of fracture, and its efficacy was evaluated on day 21. Results and Conclusions: A single injection of CP-533,536 at doses of 0.3, 1, or 3 mg/kg to the proximal tibial metaphysis dose-dependently stimulated local lamellar bone formation on trabecular, endocortical, and periosteal surfaces, and thus increased bone mineral content and bone strength at the injected site. Similarly, a single injection of 0.3 mg of CP-533,536 incorporated in PLGH matrix onto the periosteum of the femur induced significantly local bone formation. In the rat femoral fracture model, 536 in PLGH matrix at doses of 0.05, 0.5, and 5 mg dose-dependently increased callus size, density, and strength compared with PLGH matrix alone. These results show that CP-533,536 stimulates new bone formation on trabecular, endocortical, and periosteal surfaces and enhances fracture healing. These data reveal that EP2 receptor-selective agonists provide therapeutic potential for local bone augmentation, bone repair, and bone healing in humans.

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“…However, in clinical trials BMP2 and BMP7 supported bone healing with an efficacy similar to autologous bone implants. It was initially shown that BMPs on bovine collagen carrier stimulate bone formation in animals, including rats, mice, rabbits, sheep, goats, dogs, and monkeys 64,82,[118][119][120][121][122] . In acute fracture clinical studies, bone loss was not demonstrated following administration of BMP2 and BMP7 104,106 .…”

Section: Commercial Bmp-based Bone Implantsmentioning

confidence: 99%

Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

Vukičević¹,

Perić²,

Oppermann³

et al. 2020

Rad Hrvatske akademije znanosti i umjetnosti

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Bone Morphogenetic Proteins (BMPs) are growth and differentiation factors within the TGFβ superfamily of proteins. They induce ectopic and orthotopic endochondral bone formation and are involved in the regulation of cell proliferation, differentiation, apoptosis and mesenchymal-epithelial interactions in critical morphogenetic processes of tissues beyond bone. BMP2 and BMP7 osteogenic devices have been approved for enhancing healing in patients with long bone defects and anterior spinal fusion procedures. However, due to a high price and various serious adverse events including heterotopic ossification, retrograde ejaculation and pain their clinical use have been limited. In this review we discuss the BMP discovery, biology and their use in clinical studies with particular reference to the newly developed BMP6 based autologous bone graft substitute (ABGS). A novel ABGS consisting of an autologous bone coagulum (ABC) carrier with dispersed BMP6 to initiate the differentiation of mesenchymal cells into endochondral bone. The ABC met the conditions for an optimal delivery system for BMP6 due to handling simplicity, without an immunogenic and inflammatory response at the implantation site. Addition of allograft or synthetic ceramics to ABGS demonstrated in animal models significantly increased volume

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Osteogenic protein-1 (OP-1, BMP-7) for stimulation of healing of closed fractures: evidence based medicine and pre-clinical experience

Cited by 4 publications

References 27 publications

Role of rhBMP-7, Fibronectin, And Type I Collagen in Dental Implant Osseointegration Process: An Initial Pilot Study on Minipig Animals

Role of rhBMP-7, Fibronectin, And Type I Collagen in Dental Implant Osseointegration Process: An Initial Pilot Study on Minipig Animals

A Novel, Non-Prostanoid EP2 Receptor-Selective Prostaglandin E2 Agonist Stimulates Local Bone Formation and Enhances Fracture Healing

Bone morphogenetic proteins: From discovery to development of a novel autologous bone graft substitute consisting of recombinant human BMP6 delivered in autologous blood coagulum carrier

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