Representatives and leaders from AAOS, the Orthopaedic Research Society (ORS), and the Orthopaedic Research and Education Foundation (OREF) met with National Institutes of Health (NIH) Director Francis Collins, MD, PhD, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Director Stephen Katz, MD, PhD, and other NIAMS leaders to highlight the impact and value of orthopaedic care. The collaborative presentation, which was delivered on April 5, focused on how federal funding boosts orthopaedic research, positively impacts society, and reduces the burden of musculoskeletal disease. In addition, it illustrated how NIH-funded research has changed the practice of orthopaedics and spotlighted opportunities for future advancements.

Cohort studies, clinical trials provide answers

The presentation illustrated the impact of NIH research funding on sports medicine, describing successes in five NIH-funded cohort and randomized clinical trials (Table 1). Results of a Multicenter Orthopaedic Outcomes Network trial and the Multicenter ACL Revision Study on anterior cruciate ligament (ACL) surgery showed that avoiding allograft in specific ages can help prevent group failures. The Meniscal Tear in Osteoarthritis Research study demonstrated that most patients with meniscus tears and early to moderate osteoarthritis (OA) can be treated with physical therapy without surgery. Quantitative magnetic resonance imaging has been shown to identify potentially reversible early articular cartilage subsurface matrix changes reflective of “pre-OA” after ACL injury and can be a potent imaging biomarker for development of OA prevention strategies. The Bridge Enhanced ACL Repair trial is looking toward a future with the potential to heal the ACL with a novel tissue-engineered scaffold versus traditional replacement with graft.

Large studies are key to advancing orthopaedic care

Joan Bechtold, PhD, director of the biomechanics laboratory at Hennepin County Medical Center in Minneapolis, described the outcomes of the OA Initiative (OAI), an NIH-funded program developed by leadership of NIAMS and the National Institute on Aging (NIA). The OAI identified the need to establish objective and measurable standards for the onset and progression of OA by which new drugs can be evaluated. Its goal was to create research resources to aid in identification and evaluation of biomarkers as candidates for surrogate endpoints for OA. The development of a prospective, natural history cohort resulted in nearly 500 publications from public-private partnerships. Current successes resulting from NIH’s commitment to the OAI include the OAI biological specimen archive and genome-wide association study data for the entire cohort of 4,796 participants. Large initiatives such as this enable new, high-quality patient and basic science studies in orthopaedics. Continued NIH funding of the OAI and other large trials is key to developing new preventive measures and treatments in arthritis, including cartilage replacement, prevention strategies for posttraumatic OA, and biologics.

Erin Ransford/AAOS staff

Harnessing stem cells and regenerative medicine to restore mobility

NIH’s investment in and the public’s demand for biologics and regenerative medicine are significant. However, marketing unproven cell therapies directly to consumers as “stem cell” treatments is a public health issue that has led to recent calls for action by AAOS; NIAMS; the American Association for the Advancement of Science; and the National Academies of Sciences, Engineering, and Medicine. Constance Chu, MD, professor of orthopaedic surgery at Veterans Affairs Palo Alto Health Care System in California, discussed the research needs and opportunities in biologics and highlighted increasing patient interest in regenerative medicine, following a recent study that showed that the demand for cell therapies is highest for orthopaedic conditions (Fig. 1, see online version of the article).

Knee OA, for example, is a common, serious, and disabling condition that lacks adequate treatment options prior to joint replacement for end-stage disease. Many patients with OA look to biologics, such as stem cell treatments, to obtain nonopioid pain relief and nonsurgical repair of damaged joints. However, it is unknown whether stem cells can achieve such effects. Establishing an infrastructure to perform appropriately designed clinical trials to answer these questions for orthopaedic conditions is critically important to health promotion and disease prevention. This is, in large part, because of the loss of mobility that patients with orthopaedic problems like OA often experience.

In recognition of the importance of exercise to public health, the Molecular Transducers of Physical Activity Consortium (MoTrPAC), a national research consortium studying the molecular changes that occur during and after exercise in humans, was established through the NIH director’s common fund. MoTrPAC is managed by a cross-agency working group that includes NIAMS, NIA, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Biomedical Imaging and Bioengineering, and the NIH Office of Strategic Coordination. The initiative’s goal is to advance the understanding of how physical activity improves and preserves health. As such, it highlights the need to investigate regenerative and biological solutions to orthopaedic problems that severely limit patient mobility.

Funded orthopaedic surgeons had highest grant impact

Funding and supporting researchers are key to scientific advancement. ORS President Gloria Matthews, DVM, PhD, underscored that surgeon-scientists drive translational discovery. In recent years, declining NIH funding rates have disproportionately affected surgeon-scientists (a decrease of $2.7 million from 2006 to 2016). Despite lower grant funding levels for surgeons nationwide, grant impact was higher in orthopaedics than in other disciplines. Additionally, orthopaedic surgeon-scientists have a higher conversion rate from NIH K awards to NIH R01 Awards (Fig. 2, online).

Opportunities abound with research funding

Joshua Jacobs, MD, past-president of AAOS and ORS and current OREF trustee, described an increase in NIH funding success with previous OREF support among orthopaedic surgeons and researchers. “Grants awarded by the OREF lead to an NIH funding rate that is nearly triple the 18 percent national average success rate for NIH funding applications,” he said, noting that 46 percent of OREF Career Development Grant recipients have received subsequent NIH grant funding.

Funding musculoskeletal research presents an abundance of opportunities for advancing the prevention and treatment of orthopaedic conditions. Dr. Jacobs foresees a joint replacement that lasts 30 years, with progression in nanotechnology, smart materials, and precision medicine. Regenerative medicine can impact injury treatments, neoplasia, congenital diseases, and degenerative diseases. Continued and additional research funding will lead to advancements in biologic treatments and preventive strategies for orthopaedic injuries, degenerative disk disease, fragility fractures, and osteoporosis. Orthopaedic surgeons are also taking a lead in researching opioid-limiting perioperative pain-management protocols.

NIH launches HEAL initiative

On April 4, NIH launched the Helping to End Addiction Long-term (HEAL) initiative, which doubles funding for research on opioid addiction and misuse. HEAL will promote research across the NIH institutes and agencies. One of the top-cited issues by HEAL includes “[launching] a longitudinal study to follow patients after acute onset of musculoskeletal pain and after surgery to identify biomarkers that might predict which individuals are more likely to transition from acute to chronic pain.” Additional information on HEAL and opportunities for funding can be found at nih.gov/research-training/medical-research-initiatives/heal-initiative.

AAOS, ORS, and OREF plan to continue collaborative initiatives to advance federal funding of orthopaedic research and work to promote the scientific advancements that have led to breakthroughs in clinical care.

Kurt Spindler, MD, is vice chairman of research at the Orthopaedic and Rheumatologic Institute, director of orthopaedic clinical outcomes, academic director of the Cleveland Clinic Sports Health in Ohio, and chair of the AAOS Research Development Committee. Erin Ransford is manager of research advocacy at AAOS.

References

1. Hegde V, Johansen D, Park HY, et al: The relationship between OREF grants and future NIH funding success. J Bone Joint Surg Am. 2017;99:e87.