Roundtable Discussion on Musculoskeletal Biology and Diseases

Monday, November 17, 2008 (historical)

NIH Campus, Building 45, Room D
(Natcher Building Conference Center)
Bethesda, Maryland

Co-Chairs:
Stephen I. Katz, M.D., Ph.D., NIAMS
James Panagis, M.D., M.P.H., NIAMS
Joshua Jacobs, M.D., Rush University Medical Center

Introduction

The topic of the roundtable, "Musculoskeletal Biology and Diseases," encompasses about one-fourth of the Institute's extramural research portfolio and includes four scientific programs at NIAMS:

  • Cartilage and Connective Tissue
  • Musculoskeletal Development, Tissue Engineering, and Regenerative Medicine
  • Orthopaedics, and
  • Osteoarthritis Initiative and Diagnostic Imaging

To facilitate the discussion, eight scientific categories were identified, based upon the content of the currently funded scientific projects in the aforementioned programs:

  • Developmental biology
  • Imaging
  • Implant science and devices
  • Injuries and repair
  • Joint structure and function
  • Osteoarthritis
  • Spinal disorders, and
  • Tissue engineering and regenerative medicine

The roundtable discussion expanded on the feedback compiled by participants, as well as input that was submitted via a web-based Request for Comments. In particular, the panel focused on what they viewed to be the most promising areas of science.

Discussion

Within the category of musculoskeletal biology and diseases, the field of tissue engineering and regenerative medicine was widely viewed as a promising area. While some participants acknowledged the recent advances in the field and related opportunities, the discussion centered on the aspects of the scientific environment that would significantly affect the success of these breakthroughs. It was observed that the field of tissue engineering and regenerative medicine required the ability to assess the effectiveness of various methods of replacing or repairing the function of whole tissues. Competitive evaluation of functional outcome measures would help to elucidate those approaches that have the most promise for advancing beyond the laboratory and into the clinic. Such assessment would require better tools, such as biomarkers and animal models, as well as a scientific community prepared for the consequent translational research. To best position the field, interdisciplinary research teams of scientists, engineers, and clinicians would be required to collaborate with industry and federal agencies. In addition, infrastructure, including large-scale registries with informatics and computational analysis capabilities, will be critical.

In particular, stem cells were identified as a very promising tool in the field of tissue engineering and regenerative medicine. However, it was conceded that a greater understanding of stem cells and their developmental processes, especially the environment in which they exist and would be applied, was needed. This included better knowledge of how biological, chemical, and mechanical conditions affect stem cell behavior. Systems biology approaches, including cells and integrated environments, would help promote these areas. Methods to monitor stem cells, such as improved imaging techniques and well-defined biomarkers, are also critical. Large animal models need to be developed and shared, as well as reliable cell sources and uniform handling protocols. Finally, coordination among scientists studying stem cells is required.

Opportunities were also noted in genetics and genomics, particularly in the hope that a patient's genetic code could assist in determining the best approach to treating musculoskeletal conditions. The roundtable participants stressed the importance of well-planned studies to provide validated phenotypic data for cases and controls to the broad scientific community.

The development of advanced biomedical imaging techniques, both in patients and in large animal models, was also identified as a promising area. Much of the discussion centered on the need for better image interpretation and registration, as well as computational methods to relate tissue properties to images. It was suggested that partnerships with industry may provide the environment to promote the use of new technologies for functional and disease-specific imaging.

A discussion involving the opportunities in osteoarthritis focused primarily on the need for well-coordinated clinical studies and clinical trials. Planning becomes paramount and outside-the-box thinking (like studies that begin patient tracking at early adulthood) is required. This field could also benefit from the insights that result from collaboration between biomedical disciplines. The establishment of improved outcome measures and clinical studies that track osteoarthritis risk factors were encouraged. It should be recognized that these studies require long-term monitoring and large numbers of subjects, due to the significant variance across conditions such as time, severity, and risk.

Inflammation and pain are also worth considerable attention. Just as researchers should distinguish between inflammation and damage, they should note acute versus chronic pain conditions. Understanding the genetics and genesis of pain may help to predict responses. Biomarkers, localized identification, and proper management are also goals for studies in pain.

In order to develop the best hypotheses for treatments of clinical diseases of the musculoskeletal system, our understanding of bone quality must be advanced. Participants commented on the need for better predictors of bone health that would take into account the roles of collagen and bone marrow nutrient transport, and include computational analysis of bone structure down to the cellular level. Improved predictors would not only help the understanding and treatment of diseases such as osteoarthritis, but it would be useful in implant surgery and fracture healing. However, scientific efforts to improve bone health must be combined with strong public outreach messages that promote healthy lifestyle habits in the community, as well as physician awareness of appropriate clinical practice.

Also discussed was the topic of general clinical research. It was strongly emphasized by many participants that scientists and clinicians should be exposed to each other's work through training and collaboration. These interactions should be incentivized by government agencies and professional societies, and be made a top priority by academic institutions.

Non-NIH Participants

ELISSEEFF, Jennifer H., Ph.D.
Associate Professor of Biomedical Engineering and Orthopedic Surgery
Director, Biomaterials and Tissue Engineering Laboratory
Johns Hopkins University

JACOBS, Joshua, M.D. (Co-Chair)
The Crown Family Professor and Chairman, Department of Orthopaedic Surgery
Rush University Medical Center

JORDAN, Joanne, M.D., M.P.H.
Chief, Division of Rheumatology, Allergy and Immunology
Director, Thurston Arthritis Research Center
University of North Carolina at Chapel Hill

LOTZ, Jeffrey C., Ph.D.
Professor, Department of Orthopaedic Surgery
Director, Orthopaedic Bioengineering Laboratory
University of California, San Francisco

MUSCHLER, George F., M.D.
Department of Biomedical Engineering
Lerner Research Institute
The Cleveland Clinic Foundation

RIMNAC, Clare, Ph.D.
Wilbert J. Austin Professor of Engineering
Director, Musculoskeletal Mechanics and Materials Laboratory
Case Western Reserve University

SAH, Robert L., M.D., Sc.D.
Director, Cartilage and Tissue Engineering Laboratory
Department of Bioengineering
University of California, San Diego

SERRA, Rosa, Ph.D.
Associate Professor
Department of Cell Biology
University of Alabama at Birmingham

SPINDLER, Kurt, M.D.
Kenneth Schermerhorn Professor of Orthopaedics
Vice Chairman for Clinical Affairs
Director, Vanderbilt Sports Medicine Center
Vanderbilt University Medical Center

SNYDER-MACKLER, Lynn, A.T.C., S.C.S., Sc.D.
Professor, Department of Physical Therapy
University of Delaware

WANG, James H-C., Ph.D.
Associate Professor, Department of Orthopaedic Surgery, Department of Bioengineering, Department of Mechanical Engineering and Materials Science
Director, MechanoBiology Laboratory
University of Pittsburgh

WRIGHT, Timothy, Ph.D.
Professor, Applied Biomechanics
Department of Orthopaedics
The Hospital for Special Surgery