Naturally occurring BMP is found within the bone itself; however, it is only available in small amounts. To provide clinically useful and reproducible amounts of isolated, human BMP, it cannot be economically extracted from donor bone and must be manufactured (genetically engineered).
The preferred method for manufacturing rhBMP-2 is by a process called recombination. Scientists isolated the gene for one protein (BMP-2) from the bone tissue and used well-established molecular biology techniques to create genetically engineered cells. These cells then produce large quantities of rhBMP-2. A similar process is used to manufacture other proteins, like insulin. The recombinant form of rhBMP-2 is identical to the natural form in both its chemistry and its ability to heal bone.
During surgery, rhBMP-2 is soaked onto a collagen sponge that is designed to resorb, or disappear, over time. As the sponge dissolves, the rhBMP-2 stimulates the cells to produce new bone and ultimately, to heal. After a few weeks, the rhBMP-2 also goes away, but it has completed its task to initiate the normal bone healing process. In the spine, the BMP grows bone in the disc space to join or fuse the vertebrae to reduce back pain and stabilize the spine. In certain tibial fractures, rhBMP-2 has been shown to help heal broken bones.
How does rhBMP-2 work?
Surgeons in the operating room prepare the rhBMP-2 (InFUSE™ Bone Graft) by combining the protein in powder form with saline solution and a collagen sponge about the size of a thumbnail. The sponge is then implanted into a titanium spinal fixation cage that itself is inserted in place of a damaged disc.
Cells that encounter the protein are prompted to start a process called osteogenesis, or bone creation. After a shortened healing period, bone grows through the collagen sponge and around parts of the cage, fusing the vertebrae together.
Traditional Spinal Fusion vs. rhBMP-2 Spinal fusion surgery involves the joining or fusing of one or more vertebrae to reduce pain and stabilize the spine. Traditionally, spinal fusion requires the transplant of bone chips from a patient's pelvis to the spinal vertebrae to help "fuse" them together. Although this procedure can be very effective for the treatment of certain spinal disorders, the bone transplantation procedure (bone grafting) can prolong surgery and increase blood loss, hospital stay, recovery time, and recovery pain. Nearly 40% of patients who have had bone grafting experience some discomfort even two years after surgery. Moreover, the bone grafting technique does not always reliably result in successful fusion of the vertebrae because of occasional inadequate bone growth. Since rhBMP-2 stimulates a patient’s own cells to make more bone, it eliminates the need for bone grafts from the hip. As a result, it is less invasive and less painful.
History of rhBMP-2
The process of stimulating bone growth within the body is known as osteoinduction. One of the pioneers in the science of osteoinduction was Dr. Marshall Urist, Professor Emeritus of the Department of Orthopaedic Surgery at the UCLA School of Medicine. More than 35 years ago, Dr. Urist discovered that the proteins that directed bone to heal itself were contained within its own matrix, or substance. It was not until 1988 that these proteins were individually identified and genetically reproduced. Thereafter, it was quickly discovered that rhBMP-2 could, by itself, direct the repair and regeneration of bone in various parts of the skeleton. In several laboratory experiments performed from 1993 to 1997, rhBMP-2 was shown to effectively stimulate bone growth along spinal vertebrae.
In 1997, rhBMP-2 was used for the first time in patients undergoing spinal fusion. In this initial clinical trial, all eleven patients who had been implanted with rhBMP-2 achieved successful fusion within 6 months from the time of surgery. In fact, 10 of these 11 patients had achieved their fusions within 3 months of surgery. Because these patients did not require bone grafting from the pelvis, their hospital stays were shorter and their post-surgical pain was less than typically seen with traditional bone grafting techniques. These promising initial findings were then studied in several larger clinical trials throughout the United States.
The latest study, which won the Volvo Award for Spine Research from the International Spine Society (May 2002) demonstrated that patients who were implanted with rhBMP-2 (InFUSE™) were able to achieve consistent spinal fusion even without the use of metal implants (rods and screws). These patients had shorter surgical time, less blood loss and less postoperative pain.
rhBMP-2 (InFUSE™) is produced by Medtronic Sofamor Danek, headquartered in Memphis, Tenn. Their website is located at www.medtronicsofamordanek.com.
invested over 20 years of research in developing OP-1 (Osteogenic Protein-1, BMP-7), a naturally occurring osteoinductive protein that has demonstrated the ability to stimulate, repair, and regenerate bone*. Stryker offers OP-1 products for trauma and spine indications and is developing products based on BMP-7 for a number of clinical specialties including degenerative disc disease, osteoarthritis, and sports medicine. The long-term goal is to establish a family of skeletal repair products based on BMP-7 that will address the needs of a broad range of surgical specialties.
An Overview of OP-1 Products
OP-1 Putty and OP-1 Implant are currently approved in the United States under Humanitarian Device Exemptions (HDE) for revision posterolateral lumbar spine fusion and for the treatment of long bone nonunion fractures, respectively. OP-1 Implant is approved in 28 additional countries, including Australia, Canada, and the European Union. Approximately 40,000 patients have been treated globally with OP-1 products.
The active ingredient in OP-1 products is recombinant human bone morphogenetic protein-7 (rhBMP-7 or Osteogenic Protein 1), a recombinant version of a naturally occurring growth factor that belongs to a class of proteins known as bone morphogenetic proteins (BMPs) that are the only known proteins capable of inducing the formation of new bone. Stryker’s recombinant biotechnology process allows human OP-1/BMP-7 to be produced and delivered on a purified Type I bone collagen carrier that provides an osteoconductive scaffold on which new bone can grow.
Features & Benefits
OP-1, which has been in development for over 20 years, is the subject of 350 papers supporting its use in approved indications. As an alternative to autograft, OP-1 products have the potential to reduce:
- Operating room time
- Blood loss
- Hospital stays
- Osteomyelitis (infections)
- Donor site morbidity
INFUSE® Bone Graft
The active ingredient in INFUSE® Bone Graft is rhBMP-2 (recombinant human bone morphogenetic protein-2). Bone morphogenetic protein is a manufactured version of a naturally occurring protein found in small quantities in the bone. The purpose of the protein is to stimulate natural bone healing.
During surgery, the rhBMP-2 protein solution is soaked onto a collagen sponge, which is designed to resorb, or disappear, over time. The sponge keeps the solution from moving away from the broken bones and acts as a scaffold for the formation of the new bone.