1. Intensive Diet and Exercise for Arthritis Eric Miller DO November 27 2013 JAMA 2013; 310(12):1263-1273

2. Leading cause of disability among older adults Knee Most frequent cause of mobility dependency and diminished quality of life Obesity is major risk factor Pharmaceutical treatment only yields 30% improvement in half of patients Destruction by both biomechanical and pro-inflammatory factors

3. Single center, blinded, Randomized Control Trial 18 months 3 groups Diet Exercise Diet & Exercise Results Knee joint compressive force IL-6 Clinical outcomes (pain, function, mobility and health related quality of life

4. 55 or older Community dwelling Kellgren-Lawerence grade 2-3 (mild-moderate) radiologic Pain on most days BMI 27-41, 79.3% >30 Sedentary < 30 minutes per week of formal exercise in the last 6 months 454 included 88% completed

5. Goal 10%, weight loss range 10-15% Diet 2 meal replacement shakes 3 rd meal weekly menu plan 500-750 kcal 15-20% protein Less than 30% fat 45-60% carbohydrates Plan for 800-100 kcal/day deficit Minimum 1100 kcal and 1200 kcal Weekly or biweekly monitoring Nutritional education sessions

6. 1 hour 3 days a week 6 months center based Afterward Home program Center based Combination 15 minute aerobic walking 20 minute strength training 15 minute 2 nd aerobic phase 10 minute cool down

7. Trained using behavioral techniques Social cognitive theory Group dynamics Additional counseling as needed

8. Baseline, 6 months, 18 months Tibiofemoral compressive force Blood sample 10 hour fast in D&E and E groups for IL-6 WOMAC for self reported pain SF-36 for HRQL Weight Height BMI Gait speed

10. Primary Outcomes IL-6 Knee compressive force Secondary Outcomes WOMAC pain & function SF-36

11. Diet and Diet & exercise lost significantly more weight than exercise p<.001 Diet -9.5% D&E -11.4% Exercise -2% Knee Load Diet -10% p=.007 95% CI D&E -9% Exercise -5% IL-6 p=.008 D p=.006 D&E p=.007

12. Pain and Function D&E 38% very little to no pain vs. 20-22% Vs. E p=.004 Vs. D p=.001 Function Vs. E p<.001 Vs. D p=.005 Mobility and HRQL Gait D&E vs. E 0.04m/s faster p=.003 Distance D&E Vs. E 21.3m p=.005 Vs. D 41.5m p<.001 Distance E vs. D 20.2m p=.009 SF-36 Physical D&E vs. E 2.81 units p=.005 Mental subscale no significant difference

13. Mean WOMAC Pain Scores Across the 18-Month Intervention PeriodThe Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale was used to measure self-reported pain while performing daily living activities in the last 48 hours due to knee osteoarthritis. Total scores range from 0 to 20; higher scores indicate greater pain. The estimates are based on the previously stated number of observations and multiply imputed values for the missing observations within each group adjusted for baseline body mass index, sex, and baseline values. P =.002 comparing the diet + exercise group with the diet group and exercise group. Error bars indicate 95% CIs. Figure Legend :

14. Weight change had significant dose response to: Knee compressive force IL-6 level Pain & function Weight loss greater in D&E and D vs. E Primary Outcomes Knee force decreased in all groups IL-6 D&E and D improved vs. E