Becker's Spine Review

4 EXECUTIVE BRIEFING Dr. Buser agreed. "The FDA considers every osteobiologic to be a medical device. Class III is the most stringent and the most regulated, but only a handful of osteobiologics used in spinal fusion are Class III. Less evidence is needed for Class II which is 510(k) approval. Animal models are required, but post-market clinical studies are optional. The least stringent category, where CBAs are classified, is HCT/Ps. These products don't require any clinical evidence and the sterility requirements aren't as stringent as the other two classes." In recent years, sales of CBA products have decreased. "Physicians and value committees at hospitals and ambulatory surgery centers require more data and evidence to justify the use of higher-cost bone graft products," Dr. Bruder noted. "In terms of cost, you have first- and second-generation synthetics and then you have CBAs which are a big step up in expense, just below growth factor technologies. Many hospitals and doctors prefer to use a $3,000 synthetic treatment that's been cleared through a 510(k) with excellent animal data, rather than choosing a $4,000 CBA treatment that doesn't have good data to support the sale." Bone graft companies should have transparency in reporting safety data Safety issues are another contributor to decreased demand for CBAs. "I recently had a patient with a cell-based allograft that was contaminated with tuberculosis and it spread to their spine," Dr. Cook said. "With synthetics, the side effect profile is very small and there is pretty much zero infection risk. I now use synthetics for 99 percent of my cases. I tend to use MagnetOs since I've gotten better results than with other products and I find the handling properties easier to use." One "ideal" bone graft material doesn't exist — surgeons must educate themselves on the options and consider the characteristics of each case The pathology of a patient's condition is highly variable, as are patient risk factors. "No two patients are the same," Dr. Buser said. "Certain osteobiologics might be better or worse in a challenging environment. In addition, surgeons must look at the complexity of the surgery, a single-level procedure versus multi-level." The handling characteristics of different bone graft materials are also an important consideration. "The graft could be anything from a block of material to a wet piece of tissue paper, a moldable putty or granules that can be poured but don't hold their shape," Dr. Bruder said. "This is a serious challenge for surgeons. To make a meaningful decision, they must spend extra time educating themselves… not only on the different categories of grafts, but the specific products within each category." This means understanding the science that underpins the different graft categories and the specific products, as well as their associated economics. Surgeons must challenge the status quo, read the literature, challenge what sales reps say and ask for evidence and data. "It is confusing and tough for surgeons when someone asks them what level of evidence is needed to make a decision about a bone graft material," Dr. Buser said. "I think more clinical evidence on products is necessary, but not every single randomized controlled trial is generalizable. People should first read what FDA class the device is — that will help them understand whether the product has any clinical evidence, then they can dive deeper." Dr. Cook agreed that surgeons must do considerable research when selecting a bone graft material and not all of the information he would like is always available. "I always look at the research papers and clinical trials first," he said. "Personally, I like randomized controlled trials, but they aren't commonly done because they take time and are expensive. I also want to see the histology, including the actual histo slides and studies that have been performed." To help surgeons select the most appropriate bone graft material for each case, new tools have emerged like the AO Spine Knowledge Forum's BOnE (Bone Osteobiologics and Evidence) Classification and the AAOS Biologics Dashboard. The BOnE Classification categorizes every existing osteobiologic on the market, based on the level of evidence. "Our goal is to bring everyone to the table, remove the bias and find a way to help patients," Dr. Buser said. The AAOS Biologics Dashboard from the American Association of Orthopedic Surgeons is also designed to help surgeons better understand the products currently on the market, by aggregating existing evidence and making it easily accessible in a neutral fashion with agreed-upon guidelines from the stakeholders. The intersection of immunology, biology and bone is moving the needle in spinal fusion. Osteoimmunology is an emerging field of science based on the relationship of the immune system and the skeletal system to stimulate bony healing. "The goal is to see how modifications of the inflammatory environment and ecosystem can drive and support bone formation, using only synthetic bone graft products like MagnetOs," Dr. Bruder said. "We also now have the ability to create sub-micron surface technology and changes in architecture." These developments arm the scientific and clinical communities with a new set of tools to drive bone formation, as well as possibly other tissue types for use in tissue repair, regeneration, and healing. "I think we're at a very exciting time in the evolution of biology," Dr. Bruder said, "and I'm thrilled to be a part of it."n We help patients live fuller, more active lives by giving surgeons the technology they need to eliminate non-unions. We achieve this with a unique surface design called NeedleGrip that's proven to unlock the untapped power of the body's immune system by growing new bone throughout the graft - for more predictable fusions. *†1-3 MagnetOs bone graft, which features NeedleGrip Surface Technology, has been used to treat over 10,000 patients across the Globe. *Results from in vivo laboratory testing may not be predictive of clinical experience in humans. For important safety and intended use information please visit kurosbio.com. †MagnetOs has been proven to generate more predictable fusions than two commercially available alternatives in an ovine model of posterolateral fusion. 1. Van Dijk, et al. JOR Spine. 2018;e1039. 2. Van Dijk, et al. J Biomed Mater Res. Part B: Appl Biomater. 2019;107(6):2080-2090. 3. Van Dijk, et al. Clin Spine Surg. 2019;33(6):E276-E287.

• Cover