In spine, not only is the regulatory environment challenging…so is the disc environment. With so many hurdles to cross, it’s amazing that biologics for use in the spine have progressed. But they have. Says Dr. Jeffrey Wang, Chief of the UCLA Spine Service and Director of the UCLA Spine Surgery Fellowship, “Ten years ago the field was 75% traditional rods and plates and 25% biologics. Now it has reversed and we are in a transition period where we’re focusing more on biologics than devices. This is in part because people are increasingly aware of the potential impact of biologics. Even in educational courses we used to relegate biologics to a small section at the end of the course or lecture and people were generally bored by it. The lectures were dry and back then the clinical applications were too far in the future for people to get their heads around it.”

But the visionary of this field saw things clearly early on. Explains Dr. Wang, “I credit Dr. Marshall Urist of UCLA with advancing biologics for the spine. Dr. Urist, the father of biologics in orthopedics, discovered BMPs and changed surgeons’ and patients’ lives forever. Now with the clinical use of BMPs and more emphasis on biologics we know that many more applications are not far off. In basic science labs around the country we are moving at a faster rate, so if there is a promising growth factor or gene we can make better progress than we could in the 60s or 70s. Computers are now smaller and faster, and the technology we use to develop BMPs is speedier. When Urist worked on BMPs in his animal study, he found extracts of human bone and had to work on this for a long time. Now if you see such a phenomenon in the lab you can jump right on in.”

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As always, the fundamental questions apply…“Does it work?” and “How much does it cost?” Dr. Wang: “In spinal fusion we are defining the use of different BMPs. BMP-2 has been used off label more so than on; we have used it all throughout the spine and it’s changed how we do fusion. We now rarely take the patient’s own bone; typically we are using a bone substitute. Having BMPs out there raised the bar for weaker biologics for fusion. In the past when companies had demineralized bone matrix (DBM) with osteoinductive proteins, people assumed it would work. Having BMPs available has meant that companies have to test DBM better and show how it is more effective than BMPs. In the allograft world DBM is not as regulated but that is changing. For awhile, as long as you had basic science studies to support it you could mix DBM and sell it. Now people are saying, ‘If I don’t use BMPs and use something else it may work, but how much will it cost? Is it worth it to get a better fusion?’ BMPs range in cost from $3,000 to $5,000, depending on the size of the kit. But it is a well-studied protein. DBM is not as well studied and they are still charging $1,000 to $1,500 for a 10cc vial.”

And the most exciting area of spine biologics? “Disc regeneration,” says Dr. Wang. “With degenerative disc disease (DDD) we’re dealing with an arthritic disc. The new frontier in biologics involves both trying to regenerate the disc or prevent DDD; a lot of companies and basic science labs are working on these issues. Many things are being tried, including growth factors, different genes, and injecting stem cells into the disc. A large trial has been started where OP-1 (BMP-7) was injected into the degenerated disc. They only injected the growth factor, not genes or cells, but it is the first foray into trying to prevent degeneration. The trial is ongoing at several centers in the U.S.; the results are not out yet. I think that growth factor injection is probably not going to be the final treatment. It is a great first step, but growth factors won’t stay around long enough to continue to prevent disc arthritis; repeated injections would be needed. Once we identify the proper growth factor we may be able to put the gene for the growth factor in the disc. Theoretically, that will last longer. It is widely believed that in the future, success will mean a combination of the right genes, growth factors, and stem cells…and even using biomechanical devices for later stages of DDD where the biomechanics are altered.”

And what is holding up progress? Blood flow and cash flow, among other things. “The environment in the disc itself is difficult,” says Dr. Wang. “The ph level is low so cells find it hard to survive. There is no blood supply so nutrients in the disc find it hard to grow cells or regenerate the disc. And as degeneration progresses the biomechanics change, the disc space collapses, and you have more instability. As for funding, government and industry grants have decreased. Industry is cutting back research funding out of concern that it would seem some surgeons are being paid inappropriately. Competition is increasing because the available money is decreasing. Innovative people are reaching into areas outside spine, outside orthopedic surgery, and partnering with people who have good preliminary data. The day of the lone wolf is gone.”

And if those hurdles aren’t enough, orthopedists themselves can present somewhat of a problem. “The biggest challenge,” states Dr. Wang, “is that this is a dry area of basic science that can’t always hold surgeons’ attention. While the possibilities are exciting, getting there involves a lot of detailed work for long periods of time. A lot of surgeons want the Cliff Notes version because it’s not so captivating to study the minutiae of, say, gene sequencing and viral vectors. Put it like this: A Porsche is sexy, but I don’t want to change the oil. Then there is the need to have collaborations. Many surgeons don’t have the connections for such work. And of course, many surgeons are busy enough with their practices. Unless there are other doctors in the practice who can spend the time teaching you, you probably won’t go take classes because you’re running a practice.”

But eventually orthopedic surgeons will be surrounded by biologics. And it will partly come from the people in their waiting rooms holding printouts. Says Dr. Wang, “Patients are more sophisticated now and are asking outright for BMP. When I tell them that the FDA hasn’t approved it for their condition, oftentimes they still demand it. Many patients know that if you use their own bone they can have donor site pain, so they have researched the issue and know their options. On the industry side, companies are advertising because the bar has been raised. As for surgeons, sometimes the doctor in a small town doesn’t have as much competition and contracts for reimbursement are better. The hospital has no competition so it is faring better. But when they use BMP the hospital loses money.”

Dr. Wang’s final comments? “It is important for surgeons to be critical and take the time to understand the scientific evidence in favor of the products they use. If you are going to work with biologics, know how to properly use them to avoid complications. Sometimes there is an attitude à la ‘I’m just going to throw it in there.’ That is what happened with BMP in the cervical spine. In the first years there were five studies showing a high rate of complications, such as swelling and problems breathing and swallowing. Biologics is a delicate area that needs to be thoroughly understood and studied prior to being undertaken.”