As reported by Orthopedics Today, June 5, 2008.
Four Factors Critical in Ensuring Success of Bone Graft Substitutes
No Matter What Type of Bone Graft Material Is Used, Patients Do Best When These Elements Are Present
By Karen Zabel
Patients receiving bone graft substitutes will do best if surgeons keep in mind four key factors, according to Jay R. Lieberman, M.D.
He said no matter what type of bone repair situation you are facing these factors must be assessed:
- Are there bioactive factors present?
- Is there an adequate matrix?
- Are there responding cells? and
- Is there an adequate blood supply?
“The presence or absence of these four elements will influence the success of the procedure. If they are not present, then the surgeon must provide them,” he told Orthopedics Today.
In a review of available bone graft materials, presented at the Annual Advances in Arthritis, Arthroplasty and Trauma meeting, Lieberman, an Orthopedics Today Editorial Board Member, noted that each has its benefits and drawbacks.
“It is important to remember that allograft chips are osteoconductive, which means that they act as a scaffold on which new bone can form,” he said.
“A combination of morcellized cancellous material and cortical chips seems to work best. This graft needs to be placed in an environment that has a good blood supply and progenitor cells must be present,” he added.
Demineralized Bone Matrix
Lieberman said there is a huge variation in the biologic potential of demineralized bone matrixes (DBMs).
“They have not been rigorously studied and I would not use any DBM that had not been successfully used in animal studies,” he said. “Of course, just because it works in a rat does not mean it will work in a human, but if it does not work in a rat, it probably will not have a significant biologic effect in a human.”
Different DBMs have different carriers resorbing at different rates, which Lieberman said “probably affects” the material’s ability to act as a scaffold for new bone formation.
“They have no intrinsic strength,” he said. “Again, you do not want to put these materials in a compromised environment or you will not have success."
“Also, DBMs have minimal osteoinductive activity in humans. Although some package inserts may claim that they are osteoinductive,” he added. “They may be osteoinductive in lower animals, but they are not in humans.”
Ceramics may be either synthetic or derived from marine coral. In either case, the key factor in their use and success is their pore interconnectivity, Lieberman said.
“Biomechanically, they are brittle and have minimal hoop or sheer strength, and their bioresorption is variable,” he said. “They are most frequently used for tibial plateau fractures at this point. And again, you have to use it in the right environment to get a good result.”
Platelet-rich plasma (PRP) is an attractive concept because it is derived from whole blood, Lieberman said. “And as we all know, platelets play a critical role in fracture repair.”
He said when platelets enter the fracture site, they release growth factors that can enhance angiogenesis and stimulate cell proliferation.
“Unfortunately, no one has really studied this thoroughly because they are not FDA regulated, therefore the growth factor doses are unknown and we do not know the variability between patients,” he added. “For example, is the growth factor dose the same for a 25-year-old man as for a 75-year-old man, or a 65-year-old postmenopausal woman? Further study is necessary.”
PRP should be used with a matrix, although not DBM, he said.
“An animal study has shown that DBM combined with PRP can actually inhibit bone formation,” Lieberman noted. “If you use a PRP, you probably want to use it with allograft chips.”
Lieberman said bone marrow aspirate is one of his favorite graft materials, despite the fact that its use has fallen off somewhat during the last several years.
“I like it because it is an osteogenic material and it is easy to harvest,” he said. “The bone marrow contains progenitor cells, which can respond to any signal that you put in, and it also contains bioactive factors."
“The main challenge is the variability in the cellular yield in older patients versus younger patients, but probably having some stem cells is better than having none,” he noted.
Bone Morphogenic Protein
Bone morphogenic protein (BMP) acts by stimulating the differentiation of mesenchymal cells to an osteochondroblastic lineage, and is FDA-approved for fresh tibia fractures and spinal fusion, Lieberman said.
Marketed under the name InFUSE (Medtronic, Inc.), Lieberman said the product is the most potent osteoinductive agent currently on the market. “According to the manufacturer, a single dose has more BMP than naturally occurs in 100 healthy humans,” he noted. “I only want enough BMP to heal one not-so healthy human, and that’s the problem: To make it work, you have to use large doses."
“Obviously, we need to optimize the carrier, because the way the cells respond to BMP released from a collagen carrier is not very efficient” he added. “Having said that, it has a lot of clinical potential and can be very effective when used in the right circumstances.”
No matter what type of a procedure is being performed, and whichever graft material is being used, Lieberman emphasized the need to remember, in each case, the four critical elements.
For More Information
- Jay Lieberman, M.D., can be reached at New England Musculoskeletal Institute, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030; Phone: 860-679-2640; Email: firstname.lastname@example.org. He is a consultant for Smith & Nephew Orthopaedics.