Intensive Diet and Exercise for Improving Knee Osteoarthritis in Obese and Overweight Older Adults

OA, the most common form of arthritis, occurs in about 21 million Americans. Of all the
weight-bearing joints, the knee is most commonly affected by OA. Knee OA leads to physical
changes to the entire joint structure, including cartilage, neighboring bone, and ligaments.
Such structural changes to the knee alter joint function during movement, resulting in pain.
The pain typically leads to less physical activity, leading to weight gain, followed by
impaired physical function and disability.

Excessive body weight adds to the compressive forces on the knee joint and is a risk factor
for OA. While there is no cure for OA, weight loss is the best nonpharmacologic way to slow
OA progression. The amount of weight loss necessary to alter OA progression is unknown. The
purpose of this study is to compare the effects of significant dietary restriction, exercise,
and a combination of both in reducing knee inflammation and compressive forces in obese and
overweight adults with knee OA. The study will also examine how diet and exercise affect
everyday function and pain levels, as well as the extent of weight loss necessary for slowing
OA disease progression.

This study will last 18 months. Four, 2-hour screening visits will include various
questionnaires, physical exams, physical performance tests, x-rays, and blood and urine
collection. Half of the participants will also undergo additional x-rays, magnetic resonance
imaging (MRI), and a CT scan. Eligible participants will be randomly assigned to one of three
intervention groups:

- Group 1 participants will follow a calorie-restricted diet

- Group 2 participants will follow an exercise regimen

- Group 3 participants will follow a calorie-restricted diet and an exercise regimen

Group 1 and 3 participants will aim to lose at least 10% of their body weight and drop to the
next lower body mass index (BMI) class level; Group 2 participants will aim to maintain their
weight. Group 1 and 3 participants will follow the prescribed diet, which will include
traditional healthy food and up to two meal replacement supplements. Initially, the diet will
be set to result in an overall loss of 800 to 1000 calories per day. Body weight will be
monitored during weekly nutritional education and behavioral sessions. For the first 6
months, Group 1 and 3 participants will attend one individual session and three group
sessions per month. During Months 7 through 18, participants will attend group sessions once
every two weeks and individual sessions once every 3 months. Throughout the study,
participants will record food and beverage intake in daily logs that will be collected
monthly.

Group 2 and 3 participants will partake in three, 60-minute exercise sessions per week for
the duration of the study. The exercise sessions will incorporate aerobic exercise and
resistance training. Participants will also be encouraged to exercise at home. Body weight
will be monitored monthly.

Follow-up evaluations for all participants will occur at Months 6 and 18, during which most
of the screening procedures will be repeated. The Month 6 follow-up will include two study
visits, and the Month 18 follow-up will include three study visits. Group 2 participants will
be offered dietary counseling at the end of the study.

Inclusion Criteria:

- Grade II to III radiographic tibiofemoral OA of one or both knees

- Body mass index (BMI) of 27 to 37

- Sedentary lifestyle, defined as not participating in more than 30 minutes of formal
exercise per week within the 6 months prior to study entry

Exclusion Criteria:

- Significant comorbidity that may pose a safety risk to the participant or otherwise
interfere with the study. More information about this criterion can be found in the
protocol.

- Previous acute knee injury

- Knee injection within 1 month of study entry

- Knee surgery within 6 months of study entry

- Knee OA other than tibiofemoral OA

- Unwilling or unable to change eating and physical activity habits due to environment

- Cannot speak or read English

- Excess alcohol use (21 or more drinks per week)

- Unable to finish the 18-month study or unlikely to comply with the study

- Unable to undergo MRI of the knee

- Significant cognitive impairment