Bone graft substitutes for spine fusion
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.
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Demineralized Bone Matrix (DBM) has been readily available for over ten years. This is a manufactured product that includes pieces of cortical bone that are demineralized (removal of calcium and phosphate) to expose the osteoinductive proteins contained in the matrix. These proteins include the family of bone morphogenetic proteins (BMPs—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 on 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.
Article continues belowRecently, 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.
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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 to 70% successful posterolateral lumbar fusion results in human studies to date. Studies with these and other BMP’s are underway. OP-1 is approved only as a Humanitarian Device Exemption which means that safety has been documented, but not efficacy.
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 effective before it will earn widespread support in the medical community. -
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 to 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 five-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 sage 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.
