Advances in Fusion Biologics

More than 350,000 spinal fusions are performed in the U.S. each year ? a 200-fold increase over the past three decades. The indications for spinal fusion are everevolving and, in conjunction with progress in the design of spinal instrumentation, these numbers may continue to rise. However, despite advances in spinal instrumentation, the strength of an instrumented spine decreases as the implant fatigues. Thus, a successful fusion remains dependent upon bone healing as well as the use of some form of bone graft application.

Understanding the biology of bone healing is essential for the surgeon who is choosing between bone graft alternatives. Three essential ingredients are necessary to achieve a bone fusion: 1) osteogenic cells that lay down new bone; 2) scaffolding into which bone can grow (osteoconductivity); and 3) stimulants that attract bone-forming cells (osteoinductivity).

Autograft: the gold standard
Autograft bone, most commonly derived from the iliac crest and ribs, is the gold standard used to achieve bone fusion. The advantages of autograft are that it offers all three key ingredients needed to achieve bone fusion, it is histocompatible, and there is no risk of disease transmission. The issues related to autograft include variable quality and quantity of donor site bone, increased operating time and another potential surgical site for related operative complications, most commonly chronic pain. This complication has been reported in roughly one of three patients postoperatively and is one of the greatest arguments against the use of auto-harvested bone.

Allograft averts donor site morbidity
Cadaveric bone (or allograft) has the advantages of being readily available in the desired quantity and configuration and offers the obvious advantage of eliminating donor site morbidity. In the process of preparing allograft for safe use, the specimen must both be sterile and relatively non-immunogenic. The methods of preparing the bone ? either freezing or freeze-drying ? sacrifices both cellular and biological properties of the harvested bone, and freeze-drying has been shown to decrease its mechanical integrity. However, despite these issues, allograft essentially is utilized as a scaffold alone, maintaining most of its osteoconductive properties. The downside to using allograft is increased cost and decreased fusion rates compared with the use of autograft.

Bone graft complements
Oftentimes a surgeon needs to increase the volume of an autograft because of limited available quantities, so he or she turns to any number of osteoconductive synthetic scaffolds on the spine market. Calcium phosphate and calcium sulfate extenders mimic native bone in its porosity, serving as a matrix for bone deposition and growth. The disadvantages of many synthetics are their relative cost compared with autograft as well as resorption properties. Synthetic materials aren?t meant to replace autograft but act as extenders.

Demineralized bone matrix (DBM), created from demineralized bone particles combined with a carrier material, also can be utilized in conjunction with autograft as an extender. Although DBM maintains many osteoinductive properties, it is best used as a bone graft extender rather than as an autograft replacement. DBM comes in putty and gel forms and has the advantage of easy handling. Its increased cost is a disadvantage.

Several platelet-derived growth factors promote bone formation, and in vitro evidence suggests that these factors may promote the attraction of proliferative cells as well as assist with new capillary formation. Isolation and concentration of platelets from the patients own blood has been shown to increase the concentrate of growth factors three- to six-fold. Platelet concentrates are designed to enhance, rather than extend, bone graft usage.

Up-and-coming advances
Bone marrow is the primary source of osteoprogenitor stem cells, the only true osteogenic material.Marrow stem cells can be aspirated percutaneously and combined with osteoconductive carriers or extenders. The cells are concentrated using affinity column principles to increase the ratio of bone-forming stem Douglas Orr, M.D. cells to other more populous nucleated cells and then subjected to immediate selective retention. Theoretically, marrow stem cells can replace the need for cortical and cancellous autograft harvest. Advantages of stem cell technology are very low morbidity and cost.

Bone morphogenetic proteins (BMPs) represent a family of more than 20 proteins that stimulate the differentiation of stem cells into bone-forming cells, thus causing osteoinduction. BMPs rely on endogenous cells to form new bone and have been shown to express in the early stages of fracture healing. They attract stem cells from the local environment to prepare for bone growth then provide instructions to commence work in forming new bone. These activated cells release other bone growth-promoting signal proteins causing osteoblasts and osteoclasts to mature and begin the work of depositing calcium to generate strength.

Several BMPs (BMP 2, BMP 7 and BMP 14) have been shown either experimentally or clinically to induce bone formation in spinal fusion. Currently the only recombinant growth factor approved by the U.S. FDA is BMP 2 for use in anterior lumbar fusion within a device-specific cage. Studies have shown that BMP 2 is equivalent to autograft when used as approved by the FDA. BMP 2 truly represents bone graft replacement technology. However BMPs effectiveness as a replacement in other applications for spinal fusion has yet to be proved.