Exercise for Lower Limb Osteoarthritis
Exercise for Lower Limb Osteoarthritis
The literature search yielded 3796 articles, from which we selected 177 full text articles for critical reading (Figure 1). Of the 177 articles, 115 did not meet the inclusion criteria and were excluded. Sixty randomised controlled trials (8218 patients) with usable outcome data met the inclusion criteria and were included. Appendix 2 details the characteristics of the included trials. The trials were published between 1989 and 2012. The maximum length of follow-up ranged from 4 weeks to 79 weeks (median 15 weeks). Most of the trials were from the US (n=17, 28%), followed by the UK (n=9, 15%) and Australia (n=8, 13%). Trials recruited participants mostly from local communities. Most of the trials recruited patients with knee osteoarthritis (n=44, 73%), two investigated hip osteoarthritis (4%), and 14 (23%) recruited a mix of patients with osteoarthritis of the hip, knee, or other joints.
(Enlarge Image)
Figure 1.
Study selection of trials examining exercise in treatment of lower limb osteoarthritis
We assessed risk of bias in all included trials (see Appendix 3 for summary and graph). The generation of the allocation sequence was adequate in most trials (n=42, 60%). Allocation concealment was adequate in almost half of the trials (n=25, 42%). Thirty one trials (52%) masked outcome assessors to treatment allocation. The potential risk of bias likely to be introduced by incomplete data was high in 10 trials (18%). The risk of selective reporting bias was low in most trials (n=53, 88%).
Trial sequential analysis showed that as of 2002 enough evidence had been accrued to show significant benefit of exercise intervention over no exercise control for both pain and functional improvement (see Appendix 4). The cumulative z curve for pain and function crossed the trial sequential monitoring boundaries, implying that there is firm evidence for a beneficial effect of exercise interventions over no exercise in people with lower limb osteoarthritis.
There were 13 comparisons (12 exercise interventions plus no exercise controls) in the network of eligible exercise intervention comparisons for pain (see Appendix 5). Most trials included a no exercise control group (n=54, 90%). The commonest comparison was no exercise control versus strengthening exercise (n=12, 20%), followed by no exercise control versus combined exercise (flexibility plus strengthening plus aerobic exercise) (n=10, 17%). No comparison had undue influence or contribution to the effect estimates in the entire network. The weighted percentage contributions of each comparison were fairly equally distributed in the entire network of evidence. Analysis based on direct versus indirect comparisons showed no evidence of inconsistency between direct and indirect evidence in the network, although some comparisons were based on a small number of trials. Table 1 provides information regarding statistical heterogeneity in pairwise comparisons (I). For most comparisons 95% confidence intervals for statistical heterogeneity were wide and included values suggesting either no or large heterogeneity, which reflects the small number of studies available for most pairwise comparisons.
Figure 2 summarises the results of the network meta-analyses for the outcome measure of pain for all trials (regardless of the joint involved). Strengthening exercise only, strengthening plus flexibility, combined strengthening plus flexibility plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility were significantly more effective than no exercise control (see Appendix 6 for pairwise comparisons). The overall difference in pain intensity (v control) was −2.03 cm (95% credible interval −2.82 to −1.26 cm, large effect size) on a 10 cm visual analogue scale for strengthening only exercise, −1.26 cm (−2.12 to −0.40 cm, medium effect size) for flexibility plus strengthening exercise, −1.74 cm (−2.60 to −0.88 cm, medium effect size) for flexibility plus strengthening plus aerobic, −1.87 cm (−3.56 to −0.17, medium effect size) for aquatic strengthening, and −1.87 cm (−4.11 to −0.68 cm, large effect size) for aquatic flexibility plus strengthening exercise. In terms of the cumulative probability of being the overall best exercise intervention for pain in lower limb osteoarthritis, aquatic strengthening plus aerobic flexibility exercise (81%) was closely followed by strengthening exercise only (76%), and aquatic strengthening plus aerobic exercise (73%) (Figure 2).
(Enlarge Image)
Figure 2.
Forest plots for network meta-analysis for pain and physical function outcomes with no exercise as reference group. SMD=standardised mean difference, SUCRA=surface under cumulative ranking. SUCRA=1 when exercise intervention is certain to be best (that is, always ranks first) and 0 when exercise intervention is certain to be worst
When we limited the analysis to trials focusing on knee osteoarthritis, the cumulative rankings did not change much ( Table 2 ), but effect estimates tended to be larger compared with the overall analysis, which also included trials focusing on hip osteoarthritis and trials investigating osteoarthritis in any joint. The results of the meta-regression analyses did not show any significant association between exercise effects and either one of the three study level covariates considered ( Table 2 ). Comparative effect estimates (SMDs) and cumulative rankings of exercise interventions also did not change appreciably in meta-regression analyses when we adjusted for trial publication year, number of supervised sessions, or duration of follow-up ( Table 2 ).
For function outcomes there seemed to be no evidence of inconsistency between direct and indirect evidence in the network, although the number of trials for some comparisons was small. The combined intervention of strengthening plus flexibility plus aerobic exercise was significantly more effective than no exercise controls (Appendix 6). The overall difference in function (versus no control) was −1.32 units (95% credible interval −2.44 to −0.21 units, medium effect size) on a WOMAC disability scale ranging from 0 to 10 for the combination of strengthening, flexibility, and aerobic exercise. Figure 2 shows that this combination of three types of exercise (71%) and aquatic strengthening plus aerobic (71%) exercises had the highest probability of being the best overall treatment for function.
Similar to the analysis of pain, when we limited the network meta-analysis to knee osteoarthritis trials, the cumulative rankings showed little change, although effect estimates were generally slightly larger compared with the overall analysis ( Table 3 ). The meta-regression analyses did not detect any significant association between exercise treatment effects and the three study level covariates considered ( Table 3 ). After adjustment for possible differences in these study level factors, however, combined exercise programmes including flexibility, strengthening, and aerobic exercise were no longer significantly more effective than no exercise controls.
There were no significant differences for pairwise comparisons between the different types of exercise, with small to moderate effect sizes for both pain and function (Appendix 6). Figure 3 shows the scatterplot of cumulative probabilities of being the most effective exercise intervention for both pain and function, which indicates that it is likely that interventions consisting of a combination of strengthening exercises with aerobic and/or flexibility exercises are most effective.
(Enlarge Image)
Figure 3.
Scatter plot presenting ranking of exercise interventions for pain reduction and physical function based on cumulative probability of being most effective intervention
Results
Study Selection and Characteristics
The literature search yielded 3796 articles, from which we selected 177 full text articles for critical reading (Figure 1). Of the 177 articles, 115 did not meet the inclusion criteria and were excluded. Sixty randomised controlled trials (8218 patients) with usable outcome data met the inclusion criteria and were included. Appendix 2 details the characteristics of the included trials. The trials were published between 1989 and 2012. The maximum length of follow-up ranged from 4 weeks to 79 weeks (median 15 weeks). Most of the trials were from the US (n=17, 28%), followed by the UK (n=9, 15%) and Australia (n=8, 13%). Trials recruited participants mostly from local communities. Most of the trials recruited patients with knee osteoarthritis (n=44, 73%), two investigated hip osteoarthritis (4%), and 14 (23%) recruited a mix of patients with osteoarthritis of the hip, knee, or other joints.
(Enlarge Image)
Figure 1.
Study selection of trials examining exercise in treatment of lower limb osteoarthritis
Risk of Bias of Included Trials
We assessed risk of bias in all included trials (see Appendix 3 for summary and graph). The generation of the allocation sequence was adequate in most trials (n=42, 60%). Allocation concealment was adequate in almost half of the trials (n=25, 42%). Thirty one trials (52%) masked outcome assessors to treatment allocation. The potential risk of bias likely to be introduced by incomplete data was high in 10 trials (18%). The risk of selective reporting bias was low in most trials (n=53, 88%).
Trial Sequential Analysis
Trial sequential analysis showed that as of 2002 enough evidence had been accrued to show significant benefit of exercise intervention over no exercise control for both pain and functional improvement (see Appendix 4). The cumulative z curve for pain and function crossed the trial sequential monitoring boundaries, implying that there is firm evidence for a beneficial effect of exercise interventions over no exercise in people with lower limb osteoarthritis.
Network Meta-analysis of Exercise Interventions: Pain Outcome
There were 13 comparisons (12 exercise interventions plus no exercise controls) in the network of eligible exercise intervention comparisons for pain (see Appendix 5). Most trials included a no exercise control group (n=54, 90%). The commonest comparison was no exercise control versus strengthening exercise (n=12, 20%), followed by no exercise control versus combined exercise (flexibility plus strengthening plus aerobic exercise) (n=10, 17%). No comparison had undue influence or contribution to the effect estimates in the entire network. The weighted percentage contributions of each comparison were fairly equally distributed in the entire network of evidence. Analysis based on direct versus indirect comparisons showed no evidence of inconsistency between direct and indirect evidence in the network, although some comparisons were based on a small number of trials. Table 1 provides information regarding statistical heterogeneity in pairwise comparisons (I). For most comparisons 95% confidence intervals for statistical heterogeneity were wide and included values suggesting either no or large heterogeneity, which reflects the small number of studies available for most pairwise comparisons.
Figure 2 summarises the results of the network meta-analyses for the outcome measure of pain for all trials (regardless of the joint involved). Strengthening exercise only, strengthening plus flexibility, combined strengthening plus flexibility plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility were significantly more effective than no exercise control (see Appendix 6 for pairwise comparisons). The overall difference in pain intensity (v control) was −2.03 cm (95% credible interval −2.82 to −1.26 cm, large effect size) on a 10 cm visual analogue scale for strengthening only exercise, −1.26 cm (−2.12 to −0.40 cm, medium effect size) for flexibility plus strengthening exercise, −1.74 cm (−2.60 to −0.88 cm, medium effect size) for flexibility plus strengthening plus aerobic, −1.87 cm (−3.56 to −0.17, medium effect size) for aquatic strengthening, and −1.87 cm (−4.11 to −0.68 cm, large effect size) for aquatic flexibility plus strengthening exercise. In terms of the cumulative probability of being the overall best exercise intervention for pain in lower limb osteoarthritis, aquatic strengthening plus aerobic flexibility exercise (81%) was closely followed by strengthening exercise only (76%), and aquatic strengthening plus aerobic exercise (73%) (Figure 2).
(Enlarge Image)
Figure 2.
Forest plots for network meta-analysis for pain and physical function outcomes with no exercise as reference group. SMD=standardised mean difference, SUCRA=surface under cumulative ranking. SUCRA=1 when exercise intervention is certain to be best (that is, always ranks first) and 0 when exercise intervention is certain to be worst
When we limited the analysis to trials focusing on knee osteoarthritis, the cumulative rankings did not change much ( Table 2 ), but effect estimates tended to be larger compared with the overall analysis, which also included trials focusing on hip osteoarthritis and trials investigating osteoarthritis in any joint. The results of the meta-regression analyses did not show any significant association between exercise effects and either one of the three study level covariates considered ( Table 2 ). Comparative effect estimates (SMDs) and cumulative rankings of exercise interventions also did not change appreciably in meta-regression analyses when we adjusted for trial publication year, number of supervised sessions, or duration of follow-up ( Table 2 ).
Network Meta-analysis of Exercise Interventions: Function Outcomes
For function outcomes there seemed to be no evidence of inconsistency between direct and indirect evidence in the network, although the number of trials for some comparisons was small. The combined intervention of strengthening plus flexibility plus aerobic exercise was significantly more effective than no exercise controls (Appendix 6). The overall difference in function (versus no control) was −1.32 units (95% credible interval −2.44 to −0.21 units, medium effect size) on a WOMAC disability scale ranging from 0 to 10 for the combination of strengthening, flexibility, and aerobic exercise. Figure 2 shows that this combination of three types of exercise (71%) and aquatic strengthening plus aerobic (71%) exercises had the highest probability of being the best overall treatment for function.
Similar to the analysis of pain, when we limited the network meta-analysis to knee osteoarthritis trials, the cumulative rankings showed little change, although effect estimates were generally slightly larger compared with the overall analysis ( Table 3 ). The meta-regression analyses did not detect any significant association between exercise treatment effects and the three study level covariates considered ( Table 3 ). After adjustment for possible differences in these study level factors, however, combined exercise programmes including flexibility, strengthening, and aerobic exercise were no longer significantly more effective than no exercise controls.
There were no significant differences for pairwise comparisons between the different types of exercise, with small to moderate effect sizes for both pain and function (Appendix 6). Figure 3 shows the scatterplot of cumulative probabilities of being the most effective exercise intervention for both pain and function, which indicates that it is likely that interventions consisting of a combination of strengthening exercises with aerobic and/or flexibility exercises are most effective.
(Enlarge Image)
Figure 3.
Scatter plot presenting ranking of exercise interventions for pain reduction and physical function based on cumulative probability of being most effective intervention