EXercise as TReatment for osteoArthritis

Osteoarthritis (OA) of the knee is a chronic musculoskeletal disease, and a major cause of pain and disability worldwide. Exercise has previously demonstrated good effect in alleviating OA symptoms. However, optimal exercise modes in OA are currently unknown.

This study seeks to evaluate the effects of supplementary focused, knee extensor strength training in addition to neuromuscular exercise (NEMEX) and education in people with OA of the knee as performed in Good Life with osteoArthritis in Denmark (GLA:D ᵀᴹ).

Through a randomized design, study participants will either be allocated to 12 weeks (twice weekly) of NEMEX and education or 12 weeks (twice weekly) of NEMEX and education and focused, knee extensor strength training.

The primary outcome measurement for this study is the Knee injury and Osteoarthritis Outcome Score, subscale Activities of Daily Living (KOOS-ADL), which is a self-reported questionnaire on daily life activities. Other outcomes include parameters of maximal muscle strength and muscle power, muscle imaging, physical function, pain and self-reported health status.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases worldwide. In Denmark, it is estimated that approximately 900.000 people, or 1 out of 5 residents are suffering from OA in one or more joints. The annual socio-economic costs (treatment and loss of labour) as a direct consequence of OA in Denmark are estimated to 11.5 billion "Danish kroner" (DKK).

Osteoarthritis of the knee is the most frequently reported and disabling OA subgroup and is mainly reported in middle-aged adults (≥40 years) with an increasing prevalence with increasing age. Knee osteoarthritis is associated with knee pain, loss of lower limb muscle strength, activity limitations and reduced quality of life. Moreover, pain sensitization, i.e. increased responsiveness of nociceptive neurons, is another mechanism involved in pain and disability in knee-OA and may contribute to the frequently reported disparities between pain symptoms and radiographic signs of structural damage.

The current non-surgical treatment recommendations in Denmark as well as internationally include offering one or more of: Patient education, dietary advice, weight loss counselling and exercise. Exercise has proven to be a potent stimulus to improve function, and general quality of life in people with knee-OA. Moreover, exercise has been shown to reduce pain sensitization in knee-OA subjects with clinical signs of sensitization. However, there is still a paucity of information on the exact exercise mode for greatest beneficial effects in the knee-OA population.

Reduced lower limb muscle strength has repeatedly been suggested as one of the main working mechanisms behind knee-OA symptoms and quadriceps muscle strength is even suggested as a potential mediating factor in future knee joint space narrowing and longitudinal worsening of knee-joint pain. A recent systematic review revealed upper leg muscle strength along with joint proprioception to be two of the most potent mediating factors in symptomatic knee-OA.

In a randomized controlled trial (RCT) design, this study seeks to investigate potential added benefits of supplementing NEMEX and education with focused knee extensor strength training in patients with knee-OA. 90 patients deemed ineligible for knee replacement surgery will be recruited from the ambulatory setting at Naestved Hospital. By random allocation, patients will be recruited to either 12 weeks (twice weekly) of NEMEX and education + focused knee extensor strength training (intervention group) or 12 weeks (twice weekly) of NEMEX and education only (control group).

The main outcome is the change in KOOS-ADL from baseline to 12-week follow-up. Other outcomes include the remaining KOOS subscales, self-reported pain, health status, physical activity and patient satisfaction, knee extensor muscle power and knee extensor maximal contractile strength, pain sensitization, MRI assessed thigh muscle quality and physical function.

Eligibility Criteria:
Inclusion Criteria:

Patients with symptomatic and radiographically confirmed knee-OA who are found not eligible for knee replacement surgery by an orthopaedic surgeon in secondary health care.

Exclusion Criteria:

* Kellgren \& Lawrence score of \<2 on radiography
* Less than "mild" symptoms (mean score \>75 in 0-100 KOOS-ADL)
* Medication: Morphine for pain other than knee-joint pain
* Previous ipsilateral knee arthroplasty
* Rheumatoid arthritis
* Inability to comply with the protocol
* Inadequacy in written and spoken Danish