There is a lot of interest in the spine community to develop a bone graft substitute to use during lumbar spinal fusion surgery procedures. This would eliminate the need to harvest the patient’s own bone, thus potentially reducing the risk and pain associated with the procedure and hopefully leading to a more reliable result (e.g higher fusion rates).

Spinal fusion surgery entails stopping the motion at a painful motion segment (the joint formed by two vertebral bodies). The theory is that if the joint does not move, it will not create pain. The fusion itself is achieved placing bone along or in between the vertebral bodies. As the bone grows, it fuses the vertebrae together and eliminates the motion at that segment of the spine.

ISSUES WITH CURRENT BONE GRAFT PROCEDURES FOR SPINE FUSION

The gold standard for bone graft used for lumbal spine fusion has been bone harvested from the patient’s pelvis, which is a surgical procedure performed at the time of the spine fusion surgery.

There are two main potential problems with harvesting bone from the patient’s pelvis:

· Graft site morbidity
Taking the bone graft from the patient’s pelvis is a surgical procedure. With proper surgical techniques, bone graft site morbidity can be decreased. There is, however, always the potential for a complication. Some of these potential complications include bleeding, infection, and chronic pain at the donor site.

· Failure to fuse (pseudoarthrosis or nonunion)
Even if the spine fusion operation is performed correctly, not every patient will obtain a solid fusion. Spinal instrumentation has to some extent reduced the risk of not getting a solid fusion, but there are some patient who are still at high risk for a pseudoarthrosis (e.g.) patients who have had multiple spine surgeries, who are obese, who smoke, or are having a multilevel spine fusion.

The above two issues, graft site morbidity and failure to fuse, are the two primary reasons there has been a great deal of interest in creating a bone graft substitute for use in a spine fusion procedure instead of using the patient’s own bone.

OBTAINING A SOLID SPINE FUSION

To achieve a solid spine fusion, three processes are necesaary:

· Osteoconduction - this refers to the scaffolding that is needed for new bone to grow on.

· Osteogenicity - this refers to the transmittal of live bone cells or osteoblasts.

· Osteoinduction - this is the process whereby proteins and growth factors induce the bone to grow.

AUTOGRAFT BONE (PATIENT’S OWN BONE)

Bone that is harvested from the patient (autologous bone graft, or autograft bone) has two of these properties because it has both the calcium scaffolding (osteoconduction) and it is estimated that some 15% of the bone cells survive the transplantation (osteogenicity). However, the third property – osteoinduction may not be sufficiently available in the patient’s own bone. Although small amounts of osteoinductive proteins are present in all bone matrix, since autograft is mineralized bone, these osteoinductive proteins are not exposed and may have very limited activity.

ALLOGRAFT BONE (CADAVER BONE)

Donor bone, which is bone from a cadaver and is referred to as allograft bone, has only the osteoconductive property. It does not contain bone cells or proteins, and has only a calcium scaffolding. Although donor bone seems to work well elsewhere in the spine (e.g. neck) it is not sufficient for a spine fusion in the lumbar spine (lower back). Allograft bone has been shown to not work well in a posterior lateral fusion, which is a common type of spine fusion, when compared with autologous bone graft (patient’s own bone). Sometimes allograft bone is used anteriorly (in the front of the spine) as an interbody device (bone dowel), but autologous bone harvested from the patient’s pelvis is almost always used along with it. The interbody device provides the structural support and the harvested bone graft from the patient’s pelvis is what eventually fuses.

Similar to the patient’s own bone, structural allograft bone comes fully mineralized so the osteoinductive proteins are not exposed and readily active. Recent developments have seen the advent of surfaced demineralize allograft that can combine the structural integrity of bulk allograft with the osteoinductivity of demineralized bone matrix (see explanation of demineralize bone matrix in the Bone graft substitutes section).

BONE GRAFT SUBSTITUTES FOR SPINE FUSION SURGERY

A third opinion, which is a newer area of development in spine fusion surgery, is the field of bone graft substitutes. There are several types of bone graft substitutes currently available for use as an adjunct to, or as a substitute for, the above two bone graft options.

TYPES OF BONE GRAFT SUBSTITUTES FOR SPINE FUSION

There are several different types of bone graft substitutes that are either currently available or are in various stages of development for use in spine fusion surgery.

1. Demineralized Bone Matrix (DBM) has been readily available for over ten years. This is a manufactured product that includes demineralized pieces of cortical bone to expose the osteoinductive proteins contained in the matrix. These proteins include the family of bone morphogenetic proteins (BMP’s – see below) known to be able to induce new bone formation de novo. These activated demineralized bone particles are usually added to a substrate or carrier (e.g. glycerol or a polymer). DBM is mostly an osteoinductive product, but lacks enough induction to be used in its own in challenging healing environments such as posterolateral spine fusion. It is almost always used as a bone graft extender (not as a substitute) for posterolateral spine fusion surgery and is generally intended to allow the use of less autogenous bone.

Recently, a fiber-based (rather than particle-based) DBM formulation has been shown to enhance the healing success rate of spine fusions in the challenging rabbit and rhesus monkey models (Grafton Matrix DBM, made by Osteotech). This is the first commercially available DBM product that has been validated in a non-human primate spine fusion model and the first shown to increase the fusion success rate above that seen with autogenous bone graft. The increased activity is presumed to be related to more optimal preservation of the activity of the osteoinductive proteins as well as improved osteoconductivity provided by the fibers of bone as compared to that with standard particles. Several laboratories have shown this material to have superior activity in vivo in comparative studies.

Several papers have been presented at the North American Spine Society since 2000 that showed that some, but not all, brands of commercially available DBM do enhance bone growth in experimental tests. There is great variability between the efficacy (osteoinductivity) of different brands of DBM and few have been properly validated in stringent animal models. Because these materials are tissue rather than devices, clinical trials are not required and there are very limited human data available.

2. Bone Morphogenic Proteins (e.g BMP-2 or BMP-7) have been shown to be excellent at growing bone and there are several products being tested. Extensive animal testing has already been undertaken, and human trials are finished and in process for these products.

BMP-2 delivered on an absorbable collagen sponge (Infuse, made by Medtronic Sofamor Danek) has been used inside titanium fusion cages and resulted in fusion in 11 out of 11 patients in a pilot study and 99% of over 250 patients in a pivotal study. In July, 2002 the infuse brand of BMP received FDA approval for use in certain types of spine fusion. A pilot study with BMP-2 delivered on a ceramic carrier was recently published and reported a 100% successful posterolateral fusion rate. BMP-7 (OP-1) has reported 50-70% successful posterolateral lumbar fusion results in human studies to date. Studies with these and other BMP’s are underway.

It is important to note that use of BMP’s may add cost to an already very expensive operation. Not only will researchers need to show that it is safe over the long term and that it works, but they will need to show that it is cost effectie before it will earn widespread support in the medical community.

3. Bone graft substitute combined with the patient’s own bone marrow is another possible means to reduce bone graft site morbidity and enhance fusion rates.

Bone marrow contains osteoprogenitor cells (1/50,000-100,000 cells) and can be osteogenic, depending on how the bone marrow is isolated.

Extensive testing has been done in Europe on a product (Healos) that is a matrix made up of collagen with hydroxyappetite spun onto it. Microscopically it closely resembles bone and it works by absorbing harvested bone marrow before insertion. Therefore, with marrow it has both osteoconductive and osteogenic properties, yet it would eliminate the need for an open incision (to retrieve bone from the patient’s hip) as the patient’s bone marrow can be harvested with a needle. It also may be less expensive than BMP’s, although it may not be as effective. Animal studies have yielded conflicting results with respect to its success in posterolateral spine fusions.

Other strategies involving the concentration of bone marrow aspirate are being investigated as well. These strategies could increase the number of progenitor cells from marrow by approximately 5-fold, however, the actual number of progenitors would still be relatively small. This strategy has not been satisfactorily proven in primates to date.

Development of bone graft substitutes is currently one of the highest areas of interest in the spine community – for patients considering spine fusion, for spine surgeons and for companies developing the products. Judging by the amount of resources being devoted to the task of developing a safe and effective bone graft substitute, it is probably just a matter of time before a patient’s own bone will no longer need to be harvested as part of a fusion procedure.