AAOS Bulletin - February, 2006

Symposium focuses on disc degeneration

Leading clinicians, researchers suggest new directions for research, treatment

By Gunnar B.J. Andersson, MD, PhD; Howard S. An, MD; Theodore R. Oegema Jr., PhD; Lori Setton, PhD

Designed to develop a consensus on future directions for cooperative research and strategies for rapidly translating basic research into patient care, the 2005 AAOS research symposium on intervertebral disc degeneration (IDD) attracted leading clinicians and scientists from around the world. The three-day conference, held near Chicago in September, addressed the present state of intervertebral disc degeneration and emerging areas that affect the field. It was the latest in a series of annual research events sponsored by the AAOS with the National Institutes of Health.

IDD Moderators: (Left to right) Ian A.F. Stokes, PhD; Edward N. Hanley, Jr., MD; Dawn Elliott, PhD; Scott Boden, MD; Gunnar B.J. Andersson, MD, PhD; Howard S. An, MD; Lori Setton, PhD; Theodore R. Oegema, Jr. PhD; Peter J. Roughley, PhD; Bruce Caterson, PhD.

The symposium was organized by Gunnar B.J. Andersson, MD, PhD, chairman of the AAOS Research Committee and the department of orthopaedic surgery at Rush University Medical Center (RUMC); Howard S. An, MD, director of spine surgery and spine fellowship programs at RUMC; Theodore R. Oegema Jr., PhD, chairman of the biochemistry department at RUMC; and Lori Setton, PhD, associate professor of biomedical engineering and orthopaedic surgery, Duke University, with support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Orthopaedic Research Society (ORS). We recruited a group of 22 specialists to address the biology, biomechanics, mechanism of pain, modeling and treatment of intervertebral disc degeneration. The outcomes of the symposium presentations and breakout sessions will appear in a special supplement in a future issue of the Journal of Bone and Joint Surgery.

“We assembled a group of specialists for a very unique opportunity to pool knowledge and establish where the scientific community stands on disc degeneration,” said Dr. Andersson in the opening session. Canadian researcher and ORS member Tapio Videman, MD, made the initial presentation, pointing out that the lack of standardized, universally accepted definitions of disc degeneration is partly because of the limited knowledge of the process.

Jeffrey N. Katz, MD, MSc, of Harvard Medical School, covered the socioeconomic impact of IDD, which is estimated to cost $50 million to $100 million annually, primarily in lost wages. He also noted that just 5 percent of those affected are responsible for 75 percent of all costs. Other presenters included Sally Roberts, PhD, director of spinal research at Hunt Orthopaedic Hospital, Oswestry, Great Britain, and Victor M. Haughton, MD, of the University of Wisconsin.

Disc biology

Dr. Oegema and Peter J. Roughley, PhD, of Quebec’s Shriners Hospital, led a session examining the biology of the intervertebral disc and the degeneration process. Featured presenters included Irving M. Shapiro, PhD, of Thomas Jefferson University, Philadelphia, who discussed the role of cells in disc degeneration; Dick K. Heinegård, MD, of Sweden’s University of Lund, who presented on the role of matrix, and Jill Urban, PhD, of Oxford University in Great Britain, who covered the role of nutrition.

Biomechanics of IDD

The second session—on the biomechanics of IDD—was moderated by Dr. Setton and Dawn M. Elliott, PhD, of the University of Pennsylvania. In his opening remarks, Raghu N. Natarajan, PhD, of RUMC, discussed the modeling changes that occur in the mechanical response of intervertebral discs with degeneration. Suggesting that “The biphasic nature of the disc is an important factor in load transfer and stress distribution,” Dr. Natarajan called for the use of both analytical models and in vitro and in vivo experimental models to develop a complete understanding of IDD.

IDD Symposium Organizers: Theodore R. Oegema Jr., PhD; Lori Setton, PhD; Gunnar B.J. Andersson, MD, PhD. (Not pictured: Howard S. An, MD)

James C. Iatridis, PhD, of the University of Vermont, spoke on the mechanical effects of disc metabolism, and said that “Future studies evaluating the influence of mechanical loading on disc metabolism are necessary to develop a more quantitative and predictive relationship between mechanical loading and disc remodeling.”

Noting that “Recent studies have demonstrated that whole body mechanical factors may have only a small role in low back pain and disc degeneration and highlighted a dominant genetic predisposition,” Neil A. Duncan, B.Eng., PhD, of the University of Calgary, Alberta, Canada, discussed cell deformation and the micromechanical environment in the intervertebral disc. Dr. Setton concluded the session by examining the mechanobiology of the intervertebral disc.

Pain and IDD

James N. Weinstein, DO, MS, chairman of the department of orthopaedic surgery at Dartmouth-Hitchcock Medical Center and the AAOS Council on Academic Affairs, moderated a discussion on the mechanism of pain and IDD, along with Björn L. Rydevik, MD, PhD, of Sweden’s Sahlgrenska University Hospital.

Joyce A. DeLeo, PhD, director of the Neuroscience Center at Dartmouth-Hitchcock Medical Center, addressed the basic science of pain, noting that “Future investigation into the discovery and development of novel, nonopioid drug therapy may provide needed options for the millions of patients who suffer from chronic pain syndromes, including pain originating from peripheral nerve, nerve root, spinal cord, bone muscle and discs.”

John M. Cavanaugh, MD, winner of the 1995 Kappa Delta Award for research on the neurophysiology of low back pain, spoke on facet osteoarthritis and pain. The nervous system’s response to IDD was reviewed by Helena Brisby, MD, PhD, of Sahlgrenska University Hospital in Sweden. “Disc deterioration also influences other spinal structures such as facet joints, ligaments and muscles, which are possible pain generators,” said Dr. Brisby. “Disc degeneration may thereby be responsible for the development of chronic low back pain without being the actual pain focus.”

In his discussion of biologic markers in disc degeneration, A. Robin Poole, PhD, DSc, director of the Joint Diseases Laboratory in Montreal’s Shriners Hospital for Children, pointed out that “Biomarkers of skeletal turnover offer the opportunity to gain new insights into spinal pathology and its treatment.”

Modeling in IDD

Ian A.F. Stokes, PhD, research professor in the departments of orthopaedics and rehabilitation and mechanical engineering at the University of Vermont, and Scott D. Boden, MD, director of the Emory Orthopaedics & Spine Center, Atlanta, guided the session on modeling in disc degeneration.

According to Jeffrey Lotz, PhD, director of the Orthopaedic Bioengineering Laboratory at the University of California San Francisco, animal models suggest that three primary factors accelerate IDD: disc nutrition, load history and genetic predisposition. Other studies suggest that discogenic pain results from a synergistic combination of innervation, inflammation and biomechanical instability.

James D. Kang, MD, director of the Ferguson Laboratory for Spine Research at the University of Pittsburgh Medical Center, reviewed the ability of gene product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and future trends in this field. Dr. An closed the session with a discussion of the relevance of in vivo and in vitro models in disc degeneration.

Treating IDD

The final session—on treating IDD—was moderated by Edward N. Hanley Jr., MD, chairman of the department of orthopaedic surgery at Carolinas Medical Center, Charlotte, N.C., and Bruce Caterson, PhD, of the Connective Tissue Biology Laboratory at Cardiff University in Wales. Christopher H. Evans, PhD, ORS president and director of the Center for Molecular Orthopaedics at Harvard Medical School, addressed biologic treatments such as the use of recombinant or natural proteins that increase matrix accumulation and assembly, enhance the number of disc cells or in other ways lead to restoration of the native, healthy disc.

Dr. Hanley discussed disc replacement surgeries and Joshua J. Jacobs, MD, chairman of the AAOS Council on Research and Scientific Affairs and ORS president-elect, addressed complications with wear particles. Dr. Jacobs called for both basic science investigations and long-term clinical outcome studies to understand and optimize the performance of materials used in joint replacement.

Vijay K. Goel, PhD, chairman of the University of Toledo (Ohio) bioengineering department, detailed testing protocols for the evaluation of spinal implants. Noting that a full battery of testing protocols may include biocompatibility, biomechanical and clinical performance, device durability, stability tests and animal studies, Dr. Goel presented testing strategies in use or under development for evaluating the safety and efficacy of spinal instrumentation.

Participants also identified a need for further consideration of indications in patient selection and the need for a standardized grading system. They called for an increased focus on educating the public on the prevention of disc disease. Overall, stronger links between biologics, mechanics and pain need to be established to advance the diagnosis, management and treatment of IDD.

The proceedings from the symposium will serve to enrich the knowledge and future work of all participants, as well as achieve the greater goal of educating the musculoskeletal community and the practicing clinician about intervertebral disc degeneration. According to S. Tim Yoon, MD, of Emory Orthopaedics & Spine Center in Atlanta, “The meeting was highly productive and we were able to establish strong, focused research priorities for advancement in the field of IDD.”

Visit the AAOS/NIH research symposia Web site for additional information.

Fast facts on disc degeneration

By age 50, everyone has evidence of disc degeneration on magnetic resonance images.

Disc degeneration starts early and is present in more than one-third of people in their 20s.

The causes of disc degeneration remain uncertain. There is a strong association between increasing age and progressive degeneration.

Occupational factors were previously thought to play the major role, but recent studies indicate the importance of heredity. Environmental factors such as smoking influence the prevalence as well.

In general, degenerative disc changes are not by themselves symptom producing.

Over time degenerative changes may lead to secondary clinical problems such as disc herniations, degenerative spinal stenosis and degenerative spondylolisthesis.

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