Strength Training for ARthritis Trial

Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with
knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk
factor for it. However, while all published treatment guidelines, supported by Level-1
evidence, recommend muscle strengthening to combat sarcopenia and improve muscle quality in
knee OA patients, previous strength-training studies either used intensities or loads below
recommended levels or were generally short, lasting only 6 to 24 weeks. Consequently, they
had low-to-modest effect sizes, could not detect changes in disease progression, did not
address underlying OA mechanisms, and provided little lasting clinical benefit. The positive
effects of long-term, structured exercise are known to persist even years after supervised
treatment terminates.

The efficacy of high intensity strength training in improving OA symptoms, slowing
progression, and affecting the underlying mechanisms has not been examined due to the
unsubstantiated belief that it might exacerbate symptoms. Our preliminary data clearly show
excellent tolerance for high-intensity strength training as well as reduced pain and
increased function among older adults with knee OA. Similar studies in healthy older adults
found improvements in thigh muscle mass and decreases in thigh fat mass with minimal
alteration in total body weight after 16-18 weeks of training. We now propose an 18-month,
high-intensity strength-training intervention for older adults with knee OA, focused on
improving thigh composition (more muscle and less fat). We hypothesize that in addition to
short-term clinical benefits, combining greater duration with high intensity will alter thigh
composition sufficiently to attain long-term changes in knee-joint forces, decrease
inflammatory cytokines, lower pain levels, and slow OA progression, which has yet to be
convincingly demonstrated for any OA treatment. These are important benefits that are not
achievable with shorter interventions.

Participants will be randomized to one of 3 groups: high-intensity strength training;
low-intensity strength training; or attention control. The primary clinical aim is to compare
the interventions' effects on knee pain, and the primary mechanistic aim is to compare their
effects on knee-joint compressive forces during walking, a mechanism that affects the OA
disease pathway. Secondary aims will compare intervention effects on additional clinical
measures of disease severity (e.g., function, mobility); disease progression, measured by
xray; thigh muscle and fat volume, measured by CT; components of thigh muscle function,
including hip abductor strength and quadriceps strength, power, and proprioception;
additional measures of knee-joint loading; and inflammatory and OA biomarkers.

Inclusion Criteria:

- Mild to Moderate Knee Osteoarthritis

Exclusion Criteria:

- BMI ≥20 kg/m2 and ≤44.9 kg/m2

- Knee varus malalignment

- Participation in formal strength training for more than 30 min/week in the past 6
months.