Effect of Energy Restriction and Exercise for Knee Osteoarthritis

Effect of Short-term Negative Energy Balance With or Without Exercise on Systemic Biomarkers in Patients With Knee Osteoarthritis

The investigators are looking at the effects of energy restriction, with or without exercise on markers of inflammation in individuals with knee osteoarthritis. There will be a 4 week 'wash-in' period where participants will maintain their normal lifestyle, followed by a 4 week 'intervention period' where participants will be randomised into either the diet alone group or the diet plus exercise group.

Knee Osteoarthritis is a condition that causes pain, reduced physical function and quality of life. Long-term studies have shown that exercise and substantial weight loss can cause improvements in these factors. Individuals with knee Osteoarthritis might have changes in their joint that can be seen with x-ray images. However, this is not guaranteed, and imaging does not always detect changes that occur with interventions that cause improved symptoms. As a result, there is interest in biological markers (biomarkers) as another way of monitoring Osteoarthritis. These markers can be examined in biological tissues, with samples measured in blood easier to obtain than those taken from the fluid within the joint itself. Historically, Osteoarthritis was thought of as a disease caused by mechanical factors but we are now aware that inflammation also plays a part. Therefore, the investigators aim to test a short -term diet/exercise intervention that has been show to improve inflammation in other populations, in individuals with knee osteoarthritis. Importantly, this will allow the investigators to see if reducing food intake alone or doing this with regular exercise can improve outcomes without substantial weight loss. The investigators will ask individuals to participate in one of two groups where they will first be asked to continue their normal lifestyle for 4 weeks to check the stability of outcomes. The investigators will then ask individuals to either reduce their food intake by 5000 calories per week, or do this while also completing moderate intensity cycling exercise 5 times a week for 4 weeks. At the start and end of each period the investigators will collect a blood sample to assess markers of inflammation and disease related processes. The investigators will also conduct questionnaire measurements, tests of physical function and experimental pain and scan participants to establish body composition.

Reduced calorie intake by 5000kcals per week over 4 weeks with the addition of five 30 minute exercise sessions per week on a cycle ergometer. The exercise in intensity will be progressive and perceptually based and monitored by the investigators.

Participants caloric intake will be reduced by 5000kcal per week over 4 weeks. Participants will also be asked to perform 5x30 minute cycling exercise sessions at home. Each week the intensity of exercise will be increased (week 1 = RPE 12, week 2 = RPE 13, week 3 = RPE 14, week 4 = RPE 15)

Measured in pg/ml via electrochemiluminescence Interleukin-1 Beta Interleukin-1Receptor Antagonist Interleukin- 4 Interleukin- 6 Interleukin- 8 Interleukin- 10 Interleukin- 13 Interleukin-17A Interleukin-18 Tumor Necrosis Factor- alpha

Pain, Symptoms, Activity of daily living, Sport/Rec, Quality of Life subscales. Each subscale has a minimum score of 0% and a maximum score of 100%, with lower values representing worse outcomes.

Mobility, Self-care, Usual activities, Pain/discomfort and Anxiety/depression. Each of the five dimensions comprising the EQ-5D descriptive system is divided into five levels of perceived problems: LEVEL 1: indicating no problem LEVEL 2: indicating slight problems LEVEL 3: indicating moderate problems LEVEL 4: indicating severe problems LEVEL 5: indicating unable to/extreme problems A unique health state is defined by combining one level from each of the five dimensions.

Physical functioning, Bodily pain, Role limitations due to physical health problems, Role limitations due to personal or emotional problems, Emotional well-being, Social functioning, Energy/fatigue, and General health perceptions. Scores for each domain range from 0 to 100, with a higher score defining a more favourable health state.

mmol/L Glucose Non-Esterified Fatty Acids Triglycerides Total cholesterol Low Density Lipoprotein Cholesterol High Density Lipoprotein Cholesterol

Inclusion Criteria: Male or post-menopausal females Clinically diagnosed with knee Osteoarthritis including radiographic confirmation Oxford Knee Score ≥20 to ≤35 for index knee Aged 45-69 years BMI ≥27.5kg/m2 to ≤40.0 kg/m2 Daily physical activity level <2.00 Exclusion Criteria: Inability to undertake cycling exercise safely Use of prescribed anti-inflammatory medication Current smoker (or having quit <6months ago) Has a diagnosis of diabetes or other metabolic disorder Use of other medications that might interfere with study outcomes Recent (within last 3 months) change in body mass of >5% Currently engaged in an ongoing programme of physiotherapy treatment Currently on waiting list or having had surgery for Osteoarthritis on the index knee (prior OA related surgery permitted on other knee as long as this is greater than 12 months prior to enrolment) Having had major hip/knee surgery within preceding 12 months Individuals with a blood pressure of greater than 180/110 Currently pregnant or intending to become pregnant during the study