Opinion: Bone morphogenic proteins and their impact


By Jeffrey C Wang

In the mid-1960s Marshall Urist, MD, a professor of Orthopaedic Surgery at the University of California, Los Angeles, discovered that he could stimulate bone formation in his animal work. This lead to his discovery of the bone morphogenetic proteins, which has evolved into a larger field of biologics that has significantly impacted orthopaedic surgery as well as spine surgery in particular. His discoveries represent the beginning of an era which has evolved into the current stage where biologics are an increasingly important part of the treatment of spinal disorders and certainly there are several commercial products available for use by surgeons today. Today, we have a better understanding of the different realms of the biologics and seek to understand the degenerative pathway through basic science research to better understand and develop novel treatments.

One of the most exciting and, currently, one of the most controversial biological products are the recombinant bone morphogenetic proteins otherwise known as BMPs, which have been widely used in orthopaedic surgery as well as spine surgery to promote bone growth as well as spinal fusion. Early studies utilising the BMPs isolated from allograft bone were conducted as UCLA and were used in a variety of treatments ranging from oral, maxillofacial and dental procedures to spinal procedures to orthopaedic nonunions in long bones. Many publications from the early BMPs have been published in literature with varying degrees of success.

With the advent of the recombinant bone morphogenetic proteins and the utilisation of single proteins such as rhBMP2 or rhBMP7, several specific studies regarding these single proteins have been conducted in both long bones as well as in spinal fusion. The only FDA approved usage of the BMPs for spine is rhBMP2 for use in anterior lumbar fusion in the lower lumbar spine with the use of tapered threaded titanium cages. Studies showing successful fusion rates comparable to autogenous bone has allowed surgeons to use it in this application as a bone graft replacement. This is especially attractive given the potential donor site morbidity from the harvesting of iliac crest bone graft which can lead to a significant number of donor site problems including continued pain which can be difficult to treat. Prospective studies have been performed with the BMPs in different models of long bone fractures and nonunions as well as in other areas of spinal fusion for the cervical spine as well as the posterior lumbar spine. Unfortunately, with the increased usage, especially in the cervical spine, there have been several studies reporting the potential complications that can occur.

Specifically, when used in anterior cervical fusions, there can be a significant amount of soft tissue swelling with high rates of dysphasia or airway issues from the soft tissue reaction when used in this area. Other reports when used in the posterior cervical spine or in the posterior lumbar spine have demonstrated that serious fluid collections can occur from the significant inflammation and can lead to problems with compression of the nerves from this fluid collection as well as potentially a radiculitis from a direct inflammation of the lumbar nerve roots when placed in proximately to the nerve roots themselves. Wide reports of these potential complications, especially with the cervical spine, led to a public health notification from the FDA in July 2008 where it was warned that potential life-threatening complications can occur when rhBMP2 as well as rhBMP7 are used in the cervical spine. These complications have resulted in surgeons critically evaluating the off-label usage of any of the BMPs because of the significant potential complications as well as the added risk factors potentially from a legal aspect. When treating patients, it is important to minimize complications and therefore the judicious use of the BMPs needs to be maintained especially when using them in an off-label application. Patients need to be counseled for the potential complications and they truly need to understand that these can be life threatening. In addition, with the enormous rise in costs of healthcare and the expense involved in utilizing these recombinant proteins, if they are to used and especially if they are to be used in an off-label situation, care must be taken.

Jeffrey C Wang is professor of orthopaedics and neurosurgery,UCLA School of Medicine, UCLA Spine Center, California, US.