How Do Bone Grafts Work?

Osteogenic Stimulation
Since only living cells can make new bone, the success of any bone grafting procedure is dependent on having enough bone forming or "osteogenic" cells in the area. In some situations, the healthy tissues around the graft site will contain a sufficient number of bone-forming cells. However, in many clinical settings, the number of bone-forming cells in the surrounding tissues may be limited. Areas of scarring, previous surgery or infection, bone gaps, and areas previously treated with radiation therapy are all likely to be deficient in bone forming cells.

Currently, bone-forming cells can be added to a graft site from two sources. Traditionally, healthy bone is removed from an area where it is unlikely to cause a disability and then transferred into the graft site. It has recently become more accepted to transfer bone-forming cells using bone marrow, which can be obtained with a needle, without surgery. Bone marrow can be injected into a graft site or mixed with other components as a composite graft. Both transplantation of a patient's bone and transplantation of just the bone marrow are referred to as "autografts" or "autogenous bone grafts".

When bone marrow or other graft materials are delivered by injection, this method is defined as "minimally invasive bone grafting."

Osteoconductive Stimulation
"Osteo" means "bone". Osteoconduction refers to the ability of some materials to serve as a scaffold on which bone cells can attach, migrate (meaning move or "crawl"), and grow and divide. In this way, the bone healing response is "conducted" through the graft site, just as we say that electricity is conducted through a wire. Osteogenic cells generally work much better when they have a matrix or scaffold to attach to.

Osteoconductive materials make it more likely for bone cells to fill the entire gap between two bone ends. They also serve as a spacer, which reduces the ability of tissue around the graft site from growing into the site. Osteoconductive materials are a very important addition to the tools available to the Orthopaedic Surgeon. They do not induce healing better than transfer of the patient's own bone. In fact, in many settings they work poorly. However, when used appropriately, these materials can offer an effective alternative to many patients. This can save many patients from the extra surgery needed to transplant their own bone.

Many materials are available as osteoconductive materials, and more are being developed. These include processed human bone ("allograft bone"), purified collagen, several calcium phosphate ceramics, and synthetic polymers. Choosing if and when these materials are appropriate requires both knowledge of their effects on cells and knowledge of the mechanical handling of these materials. Some materials are reabsorbed by the body, while other materials may stay in the graft site for many years. A knowledgeable surgeon must balance these factors.

Osteoinductive Stimulation
Induction of bone formation refers to the capacity of many normal chemicals in the body to stimulate primitive "stem cells" or immature bone cells to grow and mature, forming healthy bone tissue. Most, but not all of these signals are protein molecules called, as a group, "peptide growth factors" or "cytokines". Many of these growth factors are present in normal human bone. For this reason, methods have been developed to process human bone and prepare bone matrix which retains the normal growth factors, but limit, if not eliminate, the risk of transmitting diseases or viruses. "Allograft Bone" processed in this way is currently the only approved way in which surgeons can use an osteoinductive stimulus.

This has been an intense area of research in the past 30 years. This work is now poised to provide Orthopaedic Surgeons, and their patients with a new important tool for bone healing, which may reduce the need for bone transplant procedures. Much interest has centered on a group of proteins called Bone Morphogenetic Proteins (BMPs), which have a powerful effect in stimulating new bone formation.

In the long run, as more is known about how these growth factors may be used, BMPs will not be the only option for osteoinduction. Many other growth factors are now known to have specific effects on the growth, migration, and development of bone cells, and other cells in healing bone. Some of the factors which are most likely to have clinical value in the future are: Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factors (FGFs), Parathyroid Hormone Related Peptide (PTHrp), Insulin-like Growth Factors (IGFs), and Transforming Growth Factor-Beta (TGF-B). Several of these are under active investigation at The Cleveland Clinic Foundation, though none of this work has yet advanced to the point of offering these as treatment options to patients.