ARRA IMPACT REPORT:
Public Health Burden
Osteoarthritis (OA) is the most common form of arthritis and the major cause of physical
disability in older people. An estimated 12.1 percent of the U.S. population (nearly
27 million Americans) age 25 and older have OA. By 2030, about 72 million
Americans will have passed their 65th birthday and will be at high risk for the
Genetic, Cellular, and Mechanical Influences
Whether damaged by injury or through normal activities, cartilage
(the tough but flexible tissue that covers the ends of bones at a joint) does
not heal well. However, if scientists understand the molecular and physical
processes that influence joint development, maintenance, and deterioration, they
may be able to develop drugs that repair cartilage or halt disease progression. ARRA
funds supported fundamental research in this area through the following projects:
- Using advanced, high throughput research techniques to map the signaling pathways and molecular regulators that control gene expression during OA onset and progression.2 ARRA funding has allowed new staff to be hired and research technicians to be retained. It also has enabled the investigators to expand their mouse facilities and create another OA mouse model.
- Establishing mouse models that researchers can use to study to cartilage healing.3,4 When researchers bred mice that rapidly recovered from a minor injury to their ear (a procedure akin to ear piercing) with other mice that healed more slowly, they found that the mice that could quickly heal were able to regenerate cartilage in the knee and were less susceptible to OA. Another mouse model of OA that was developed with ARRA funds appeared to have normal bones and joints as juveniles, but the animals developed OA upon reaching young adulthood.
- Determining which molecules in the fluid that lubricates the knee joint are important for joint health or OA progression, and monitoring how the loss of lubrication leads to joint damage.5
- Developing strategies to monitor and maintain cartilage and meniscal (a type of cartilage) tissue development during movement and weight-bearing activities. 6,7,8 Such research is an essential component of efforts to create tissue replacements that can survive and function in the complex and demanding mechanical environment of the body.
Discovering and Testing Treatments
At present, OA drug therapies may relieve pain, but do not stop
joint destruction and disease progression. Even surgeries to repair torn
ligaments and other soft tissues of an injured joint fail to prevent
post-traumatic OA. Therefore, researchers are exploring a multi-pronged approach
to prevent OA from developing and to slow its progression if it occurs. The
overall goal is to help patients live with less pain and improved function, and
to ensure that surgical options are available to patients who need them. Examples
of ARRA-funded research include:
- Developing compounds that could prevent post-traumatic OA.9,10 A series of rat studies have shown that injecting a lubricating protein into a joint shortly after injury can prevent the lasting damage that leads to OA. Additional ARRA-supported research on animals and tissue samples suggest other strategies for preserving cartilage after it is damaged.
- Testing whether a commonly used surgical technique reduces knee pain by removing pressure from cartilage.11
- Uncovering clues related to metal-on-metal hip implants.12 The discovery that the lubricating layer that forms on metal-on-metal hip implants has more in common with the lubrication of a combustion engine than that of a natural joint provides an avenue for investigators to pursue as they develop new implants.
- Testing the effectiveness of a telephone- and nurse-based system that extends OA pain management beyond doctors' offices.13 The research project, supplemented by ARRA funds, has produced a wealth of information about how to quantify pain due to OA.
Assessing OA Risk
reduce their risk of developing OA if they maintain a healthy weight, exercise
regularly, and do not smoke. As researchers develop additional interventions to
prevent OA onset or slow its progression, the ability to identify people who
will benefit most from these new therapies will become even more important. Examples of ARRA-funded research to identify people at risk of
- Finding genetic alterations that increase susceptibility to knee OA.14 The discovery of genetic variants that protect against or increase a person’s risk of developing OA is likely to suggest targets for the development of disease-modifying agents. Moreover, investigators could use genetic markers to identify appropriate participants for clinical trials.
- Discovering proteins or other substances in the blood or urine that indicate cartilage damage or repair following an injury.15 The ability to monitor patients’ recovery with markers of post-traumatic OA could guide physical therapy regimens for patients. Integrating the markers into clinical trials of drugs to promote healing and prevent OA also could improve studies’ efficiency.
Contributing NIH Institutes & Centers
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)