Focus Area: Osteoarthritis

Osteoarthritis (OA), the most common form of arthritis, has a disabling impact on the lives of millions of people around the world. Knee OA, in particular, results in as much chronic disability as cardiovascular disease and is more debilitating than any other medical condition, yet few prevention strategies exist due to limited knowledge of what causes it to progress.

Dr. Leena Sharma, MD: Solovy/Arthritis Research Society research professorAt Northwestern University Feinberg School of Medicine, investigators have made great strides in identifying factors responsible for knee OA outcomes. A leader in the field, Leena Sharma, MD, Solovy/Arthritis Research Society professor of medicine, and her multidisciplinary team are widely known for their seminal and more than decade-long work studying the role of local mechanical factors in the natural history of knee osteoarthritis and the decline of function in persons with the condition.

“Most OA treatments and interventions currently available provide symptom relief, but none effectively prevent or delay disease progression,” says Dr. Sharma, principal investigator for three active National Institutes of Health (NIH)-funded grants, one of which is a competing renewal. “Our ultimate goal is to help identify targets for intervention that might change the disease course and help prevent function decline and disability.”

Using a Biomechanical Approach

A rheumatologist who helped to develop and worked in an orthopaedic / rheumatologic collaborative clinic during her junior faculty years, Dr. Sharma brings a unique perspective to her research. She leads the first natural history study of knee OA to focus on mechanical factors, examining their effect on joint structural outcomes (such as cartilage loss) using state-of-the-art radiographic and magnetic resonance imaging (MRI)-based protocols, and on function and disability outcomes. Based at Feinberg, the Mechanical Factors in Arthritis of the Knee (MAK) study, supported by an NIH-funded Multidisciplinary Clinical Research Center (MCRC) in Rheumatology grant and two R01 grants, has yielded major findings since 1997, when it began.

Over the years, the MAK study group has pinpointed several key factors that influence the progression of disease in knee OA, including knee alignment (varus and valgus versus neutral) and meniscal damage (tears and extrusions). “Another very interesting factor we have identified that contributes to the maintenance of good functional status over time, in addition to muscle strength and aerobic exercise, is greater self-efficacy,” says Sharma. “Individuals who believe in their ability to perform movements and functional tasks do better than those who do not. This belief is an important predictor of how well people with knee OA are able to maintain good function.”

The MAK study’s biomechanical approach to understanding knee OA disease progression has focused in recent years on better understanding how certain forces distributed across the knee during movement, such as walking, affect the joint. The MAK-2 study, for example, found that knees with a thrust (an outward or inward movement of the knee during the weight-bearing portion of gait) were more likely to experience OA progression. A greater hip abduction movement during gait at the baseline evaluation (a factor related to hip strength) was associated with a lower risk of knee OA progression over the next 18 months.

Researchers at Feinberg are investigating whether individuals with stronger hip muscles have a slower rate of knee OA progression.Now in its third cycle, the MAK study builds on this groundbreaking work by zeroing in on the potentially beneficial role of hip muscles in knee osteoarthritis progression. Currently recruiting 250 participants, Dr. Sharma’s team will examine whether people with stronger hip muscles—particularly hip abductor and external rotator strength—have a slower rate of knee OA progression, physical function decline, and disability development over a two-year period. Recent findings support that hip muscle forces may help modify joint loading and consequently provide knee joint protection in persons with osteoarthritic knees. Using advanced imaging techniques including MRI and specialized radiographic protocols, the MAK-3 study will also feature a comprehensive quantitative gait analysis component utilizing Feinberg’s state-of-the-art gait laboratory directed by Steven Gard, PhD, research associate professor, Department of Physical Medicine and Rehabilitation, to gain a more realistic picture of forces sustained by the osteoarthritic knee during ambulation.

“Quantitative gait analysis allows us to look more closely at the mechanical factors that are in play as people walk—the most common activity that humans undertake,” explains Dr. Sharma. “Having this component as a part of our study and utilizing the resources at Northwestern adds a greater level of sophistication to our data analysis and will help advance our efforts to aid in the development of physical and rehabilitative therapies for persons with knee OA.” To date, the MAK-3 study has enrolled 160 patients.

Circling Back to the Patient

The research of the MAK study group has resulted in numerous publications, providing the clinical and scientific communities with the foundation for the development of effective interventions and treatments for knee OA. Recognizing achievements in the field of OA, the Osteoarthritis Research Society International—a leading scientific group dedicated to the study of OA—honored Dr. Sharma with its Clinical Research Award in 2009. While participants in the MAK studies contribute at a macro-level to improvements in the clinical care of knee OA, they also personally benefit at a micro-level from the clinical expertise of Dr. Sharma and others in the Division of Rheumatology. A patient-focused newsletter informs all participants of study findings, and clinical researchers provide participants with feedback at the time of evaluation, ensuring that the division’s research, indeed, translates into care that helps patients.