Comparisons with other studies
Quite opposite to previously published studies on exercise in knee osteoarthritis we found no improvement in pain or function. Possible reasons for this include our study group having moderate to severe osteoarthritis compared with mild to moderate in most previous studies, being younger than previously studied groups and the intervention being of comparably high intensity.
It has been suggested that the responsiveness to exercise is modified by the loss of joint space width . The homogeneity of this study population, with regard to radiographic changes, provided us the possibility to study the effects of exercise on patients with moderate to severe radiographic knee osteoarthritis. Can significant improvements of pain or self-reported function be expected in patients with radiographic knee osteoarthritis corresponding to Kellgren & Lawrence grade 3 or more? In this study, no improvements were seen on group level in pain or function. However, regular exercise in general is important to prevent diseases caused by inactivity , and thus patients with knee osteoarthritis should be encouraged to exercise. In clinical practice, patients with severe knee osteoarthritis should have treatments based on individual preferences and different stages of motivation .
It can be argued that the exercise intensity was too high for this group with moderate to severe knee osteoarthritis. Even though the intensity of each exercise was individually adapted, all individuals exercised at a minimum of 60% of HR max. It has been suggested that pain during exercise might be a protective mechanism in knee osteoarthritis, i.e. an increase in pain from too intensive exercises may restrain patients from further joint loading, which otherwise could cause further cartilage damage . Patients in the current study were told to reduce the exercise intensity if pain during exercise was perceived as worse than 'acceptable', or persisted more than 24 hours.
It is suggested that the different degrees of varus-valgus laxity should be taken into account in exercise interventions, to enhance the functional outcome [34, 35]. Severe knee osteoarthritis is associated with a hip-knee-ankle malalignment and an increase in varus-valgus laxity compared to healthy knees . It is possible that varus-valgus laxity mediated the effect of exercise on pain since all patients had radiographic changes corresponding to Kellgren and Lawrence grade III or more. Malalignment may cause increased joint loads, and greater quadriceps strength might further increase joint load by the muscles compressing the articular surfaces .
Younger patients are usually more physically active than elderly , and have higher demands on level of physical function and physical performance at work or leisure time. Thus, moderate to severe knee osteoarthritis might be perceived as more disabling by younger individuals compared to elderly. Our study population was younger (<65 years) and comprised more men (49%) than most other populations with knee osteoarthritis described in randomized controlled trials of exercise [13–15, 39, 40], which might have reduced the effect on self-reported function in the present study.
This study showed no significant differences on self-reported pain and function either between or within groups. A post-hoc analysis was performed to study the possibility that the benefit from exercise was larger in subjects with worse pain at baseline. Fifteen patients in the exercise group were compared to 13 from the control group who had worse than total group median pain score (KOOS Pain 58 on a 0–100, worst to best scale) at baseline. The groups had comparable patient characteristics. The changes seen in these subgroups were however not different from the changes seen in the total groups.
A possible limitation could be lack of power. A post-hoc analysis was performed to estimate the number of patients needed to show a clinically significant difference of 11 ± 15 KOOS-points . The standard deviation of 15 is supported by results from randomized controlled trials of glucosamine supplementation  and a nutritional supplement  for knee osteoarthritis, where significant group differences were found in KOOS pain and ADL subscales. The number of subjects in each treatment arm in these RCT:s ranged from 15 to 27. The standard deviations in KOOS subscales have not previously been determined in exercise interventions.
Only one of the five KOOS subscales showed a statistical significant improvement, and it can not be excluded that this result could be due to chance. The improvement of the KOOS subscale Quality Of Life in the exercise group was of doubtful clinical significance, however the improvement persisted over time, and is in accordance with previous findings of impact from exercise on mental health aspects in patients with knee osteoarthritis [31, 43, 44]. Group dynamics, support, or attention received may possibly have influenced the quality of life more than the exercise itself in the present study. Psychosocial factors are important determinants of physical function , and our results suggest that supervised exercises and follow-up are important, and that quality of life should be evaluated in osteoarthritis interventions.