1st Day-5th Talk: “Growth Factors in Orthopedics” by Jack Chen, M.D.

Dr. Chen joins us from the Orthopedic Specialty Institute Medical Group of Orange County. The current technology to treat most orthopedic injuries is surgery (i.e. spinal surgery and trauma surgery), but these procedures are invasive and can have severe implications for the patients. The main talking point of Dr. Chen’s discussion is the use of BMP (Bone Morphogenic Proteins) as an additional therapy in some patients with orthopedic conditions.

As previously discussed, mesenchymal stem cells can differentiate into a number of different cell types (stroma, muscle, osteoblasts, chondrocytes, fibroblasts, and adipocytes). These mesenchymal cells can come from a number of sources, such as: peripheral blood, all mesenchymal tissues, endosteum, muscle, and bone. BMP functions as a differentiation factor for the mesenchymal cells and stimulates bone cell proliferation. BMPs are primarily used clinically as a bone graft substitute. They also have a contemporary use in orthopedic trauma surgery to treat open fractures and non-union injuries. Open fractures can often lead to amputation if they are not properly reconstructed using nails and pins and a piece from muscle tissue (i.e. abdominal or otherwise) to cover the wound in the absence of sufficient soft tissue supply.
Dr. Chen asked the question: “What if we placed BMP at the site of the fracture at the time of wound closure?” A randomized, controlled, single-blinded study was conducted in 450 patients with open tibia fractures. The control group received the current standard of care and the experimental group was treated with BMP in addition to the standard protocol. The results were measured based on the need for secondary intervention after the patients were treated. Some of the advantages of using BMP in these situations included: a 44% reduction in secondary intervention in the patients treated with BMP, faster fracture healing, fewer hardware failures, fewer infections, and faster wound healing. The main disadvantage of using BMP is that it is costly.

In spine surgery, fusions are performed to address deformity, instability and pain. Dr. Chen presented a number of figures to demonstrate where BMP may be a beneficial therapeutic, such as: scoliosis, spondylolisthesis, osteomyelitis, discogenic pain associated with degenerative disc disease, and lumbar degenerative disc disease. Nine studies were conducted using BMP- 2 (Infuse) and 3 studies were conducted using BMP-7 (OP-1). All of the studies used allograft bone as a control. Another randomized prospective study included 131 patients where 79 were treated with BMP-2 and 52 were in the ICBG control group. All patients received a follow-up exam in a minimum of 24 months. With a p value less than 0.001, there was a 96% increase observed in the fusion rate of the patients treated with BMP versus only a 71% fusion rate in the control group. The patients treated with BMP also endured a shorter average length of surgery, less blood loss, and a shorter hospital stay compared to the patients in the control group. According to the Oswestry Disability Index, patients treated with BMP showed improvement in the SF-36 physical component score and a low-back and leg pain score.

So the bottom line is, of course, is it worth the money to use BMP? The cost of using this therapy is approximately an additional $5580 per case. However, the estimated savings in hospital stay costs, OR time, and additional follow-up care as a result of using BMP is approximately $3300. 1000 spine fusions will cost approximately $5,950,025 dollars and the use of BMP will add about $1,790,000 to this number. However, the savings due to reduced hospital stay time, OR time, fewer revisions, and less sick days that the patient must incur results in an actual savings of $4,392,630.

Dr. Chen discussed several future directions for this line of research. For example, instead of fusing the spine, what about regenerating the disc? A lab study with OP-1 (BMP-7) showed that annular puncture induces disc degeneration. The question is, can injection of BMP reverse the degeneration? A study was conducted in rabbits with an annular puncture to begin addressing this issue. The sample size consisted of 66 rabbits; 33 were in the control group and 33 were treated with BMP. 4 weeks after the puncture, the subjects in the experimental group were injected with OP-1 dissolved in lactose and the control group was injected with lactose alone as a placebo. The studies in the animal models are promising as there were significant increases in proteoglycan and collagen production in the subjects treated with OP-1 upon biochemical analysis. It has been speculated that the addition of FGF-1may provide even more benefit.
In summation, BMP is FDA approved and is currently used for open tibia fractures and spine fusions. Current research focuses on the use of BMP to regenerate degenerated discs.