Abstract: We included reports for six studies of 656 participants that compared high- and low-intensity exercise programs; five studies exclusively recruited people with symptomatic knee osteoarthritis (620 participants), and one study exclusively recruited people with hip or knee osteoarthritis (36 participants). The majority of the participants were females (70%). No studies evaluated physical activity programs. We found the overall quality of evidence to be low to very low due to concerns about study limitations and imprecision (small number of studies, large confidence intervals) for the major outcomes using the GRADE approach. Most of the studies had an unclear or high risk of bias for several domains, and we judged five of the six studies to be at high risk for performance, detection, and attrition bias. Low-quality evidence indicated reduced pain on a 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale (mean difference (MD) -0.84, 95% confidence interval (CI) -1.63 to -0.04; 4% absolute reduction, 95% CI -8% to 0%; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 14 to 22) and improved physical function on the 68-point WOMAC disability subscale (MD -2.65, 95% CI -5.29 to -0.01; 4% absolute reduction; NNTB 10, 95% CI 8 to 13) immediately at the end of the exercise programs (from 8 to 24 weeks). However, these results are unlikely to be of clinical importance. These small improvements did not continue at longer-term follow-up (up to 40 weeks after the end of the intervention). We are uncertain of the effect on quality of life, as only one study reported this outcome (0 to 200 scale; MD 4.3, 95% CI -6.5 to 15.2; 2% absolute reduction; very low level of evidence). Our subgroup analyses provided uncertain evidence as to whether increased exercise time (duration, number of sessions) and level of resistance (strength or effort) have an impact on the exercise program effects. Three studies reported withdrawals due to adverse events. The number of dropouts was small. Only one study systematically monitored adverse effects, but four studies reported some adverse effects related to knee pain associated with an exercise program. We are uncertain as to whether high intensity increases the number of adverse effects (Peto odds ratio 1.72, 95% CI 0.51 to 5.81; - 2% absolute risk reduction; very low level of evidence). None of the included studies reported serious adverse events. We found very low-quality to low-quality evidence for no important clinical benefit of high-intensity compared to low-intensity exercise programs in improving pain and physical function in the short term. There was insufficient evidence to determine the effect of different types of intensity of exercise programs. We are uncertain as to whether higher-intensity exercise programs may induce more harmful effects than those of lower intensity; this must be evaluated by further studies. Withdrawals due to adverse events were poorly monitored and not reported systematically in each group. We downgraded the evidence to low or very low because of the risk of bias, inconsistency, and imprecision. The small number of studies comparing high- and low-intensity exercise programs in osteoarthritis underscores the need for more studies investigating the dose–response relationship in exercise programs. In particular, further studies are needed to establish the minimal intensity of exercise programs needed for clinical effect and the highest intensity patients can tolerate. Larger studies should comply with the Consolidated Standards of Reporting Trials (CONSORT) checklist and systematically report harms data to evaluate the potential impact of highest intensities of exercise programs in people with joint damage.

Plain-language summary: We identified six randomized controlled trails with 656 participants. Five studies (620 participants) enrolled people with knee osteoarthritis, and one study (36 participants) enrolled people with knee or hip osteoarthritis. The studies included more women (70%) than men. On a scale of 0 to 20 points (lower scores mean reduced pain), people who completed a high-intensity exercise program rated their pain 0.84 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People who performed a low-intensity exercise program rated their pain at 6.6 points. On a scale of 0 to 68 points (lower scores mean better function), people who completed a high-intensity exercise program rated their physical function 2.65 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People who performed a low-intensity exercise program rated their pain at 20.4 points. On a scale of 0 to 200 mm visual analog scale (higher score means better function), people who completed a high-intensity exercise program rated their quality of life 4.3 mm higher (6.5 mm lower to 15.2 mm higher) (2% absolute improvement) than people who performed a low-intensity exercise program. People who performed a low-intensity exercise program rated their quality of life at 66.7 mm. Two per cent more people had adverse effects with high-intensity exercise, or 17 more people out of 1000. • 39 out of 1000 people reported an adverse effect related to high-intensity exercise program • 22 out of 1000 people reported an adverse effect related to low-intensity exercise program Adverse events were not systematically monitored and and were incompletely reported by group. None of the included studies reported serious adverse events. Based on the evidence, people with knee osteoarthritis who perform high-intensity exercise may experience slight improvements in knee pain and function at the end of the exercise program (8 to 24 weeks) when compared with a low-intensity exercise program. We are uncertain as to whether high-intensity exercise improves quality of life or increases the number of people who experience adverse events. We graded the quality of evidence as low for pain and function and very low for quality of life. The small number of studies and participants included in some analyses reduced the robustness and precision of these findings. Adverse effects were poorly recorded. Very low quality evidence shows we are uncertain whether higher-intensity exercise programs may result in more side effects than lower-intensity exercise programs. Further research may change the result.