Surgeons may find superior outcomes using orthobiologics for difficult fractures

Biologic agents may offer better results than current gold standards.

NEW ORLEANS — Orthobiologics may yield better results than previous gold standards for difficult fractures, according to an investigator.

In a symposium on orthobiologics at the American Orthopaedic Foot and Ankle Society (AOFAS) Specialty Day Meeting, Scott D. Boden, MD, provided a spine surgeon’s perspective on topics relevant to the progress of foot and ankle surgery. The Specialty Day presentations were part of the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons.

Boden, the Spine Section Editor on the Orthopedics Today Editorial Board, said that iliac crest bone graft, once considered the gold standard for difficult healing situations, while acting as an osteoconductive and osteogenic material, is probably not osteoinductive because the bone is fully mineralized.

“And the reason I bring that out [is] that there are clinical opportunities for us with orthobiologics to actually get a better result than we would with the old gold standard,” Boden said.

He said orthopedic surgeons must adopt a more sophisticated way of thinking about difficult healing situations. They cannot rely on the assumption that “all growth factors must be good,” he said. Although several growth factors and cytokines are critical to bone formation, he noted that few of them possess osteoinductive abilities.

Key concepts

Boden highlighted some key concepts and lessons learned regarding bone morphogenetic proteins (BMPs).

“First, all orthobiologics and all BMPs are not created equal,” Boden said. He noted that the highest levels of osteoinductivity have been seen with BMP-2, BMP-6 and BMP-9, and that intermediate levels have been seen with BMP-4 and BMP-7.

He also noted that a 15,000-fold dose increase from cell culture to human is needed to achieve a consistent bone formation response. “That does not mean it is good or bad, it is just a fact of life.”

Local side effects

Boden warned against administering too high of a BMP dose due to possible local side effects, including sterile fluid formation, transient bone resorption and osteoclastic activity induction.

He said that the first generation BMPs were designed to be used in ectopic bone or near cortical bone. “When people started using them [near] cancellous bone, which may be something you would see more often in foot and ankle, what they found is that some of the higher doses and concentrations stimulated a little bit too much osteoclastic activity,” Boden said.

He concluded, “Lastly, I think BMPs can work in humans. The key is dose and carrier, fine tuning for the location and the use, being cognizant of local side effects and, most importantly, we as clinicians need to know when to use the big guns and when to stick with the small fire.” — by Thomas M. Springer

Reference:

• Boden SD. A spine surgeon’s perspective: orthobiologics: osteoinductive/osteopromotive growth factors. Presented during the symposium, Orthobiologic: Cross Pollinations at the American Orthopaedic Foot and Ankle Society Specialty Day Meeting, part of the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons. March 13. New Orleans.

• Scott D. Boden, MD, is director of Emory University Spine Center. He can be reached at 59 Executive Park South, Suite 3000, Atlanta, GA 30329; 404-778-7143; e-mail: scott.boden@emoryhealthcare.org.

Growth factors and cytokines, which are critical to bone formation, have a well-documented temporal relationship to each other in facilitating the osseous healing process after the onset of an injury or fracture. While I do concur with Dr. Boden that very few growth factors possess the unique osteoinductive ability of being able to form bone independently, the more critical interaction is probably between the triad of cells, matrix and the environment of the growth factors. Absence of any one of these components often cannot be compensated via augmentation of one “growth factor,” such as BMPs, rhPDGF etc.

I do agree with Dr. Boden that the highest level of osteoinductivity in vitro has been seen with BMP-2, BMP-6 and BMP-9 with intermediate levels in BMP-4 and BMP-7, as reported by Cheng and colleagues in 2003; however, the clear delineation observed in vitro has not been substantiated in vivo. The BMPs, like many other growth factors, have a known effect upon the osteoblastic and osteoclastic aspect of bone remodeling. This fine balance between the competing processes will drive either the injury site to undergo bone formation or resorption, which is clearly affected by the parameters of dose, temporal release, and type of carrier.

As the moderator of the AOFAS symposium Orthobiologic: Cross Pollinations, I felt these dynamic lectures demonstrated the critical need for closer interactions of the thought leaders of orthobiologics across our field, since each specialty actually have similar problems, issues and questions based upon their respective anatomic area of interest. Overall, the winners for AOFAS Specialty Day were not only the members, but more importantly the patients who will benefit from this cutting edge technology.

— Sheldon S. Lin, MD
Director of Foot and Ankle Division
University of Medicine & Dentistry of New Jersey, Newark, NJ

Reference:

• Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg (Am). 2003; 85(8):1544-1552.