Abstract: We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms). The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.

Plain-language summary: This summary of a Cochrane review of 22 studies with 8275 participants (search update: 15 August 2012) presents what we know from research about the effect of opioids on osteoarthritis (OA). We searched scientific databases for clinical trials looking at pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. The review shows that in people with osteoarthritis: - Opioids have a small effect on pain or physical function. - Opioids probably cause side effects. However, we do not have precise information about rare but serious side effects. What is osteoarthritis and what are opioids? OA is a disease of the joints, such as your knee or hip. When the joint loses cartilage, the bone grows to try to repair the damage. Instead of making things better, however, the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and unstable. This can affect your physical function or ability to use your knee. Opioids are generally conceived as powerful pain-relieving substances that are used for the pain of cancer or osteoarthritis. Some examples of opioids are codeine-containing Tylenol® (1, 2, 3, and 4), hydromorphone (Dilaudid), oxycodone (Percocet, Percodan), morphine, and others. They can be taken in a pill form, as an injection, or as a patch placed on the painful area. Best estimate of what happens to people with osteoarthritis who take opioids Pain - People who took opioids rated improvement in their pain to be about 3 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. - People who took a placebo rated improvement in their pain to be about 2 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. Another way of saying this is: - 41 people out of 100 who used opioids responded to treatment (41%). - 31 people out of 100 who used placebo responded to treatment (31%). - 10 more people responded to treatment with opioids than with placebo (difference of 10%). (High-quality evidence) Physical function - People who took opioids rated improvement in their physical function to be about 2 points on a scale of 0 (no disability) to 10 (extreme disability) after one month. - People who took a placebo rated improvement in their physical function to be about 1 point on a scale of 0 (no disability) to 10 (extreme disability) after one month. Another way of saying this is: - 34 people out of 100 who used opioids responded to treatment (34%). - 26 people out of 100 who used placebo responded to treatment (26%). - 8 more people responded to treatment with opioids than with placebo (difference of 8%). (High-quality evidence) Side effects - 22 people out of 100 who used opioids experienced side effects (22%). - 15 people out of 100 who used a placebo experienced side effects (15%). - 7 more people experienced side effects with opioids than with placebo (difference of 7%). (Moderate-quality evidence) Drop-outs because of side effects - 64 people out of 1000 who used opioids dropped out because of side effects (6.4%). - 17 people out of 1000 who used a placebo dropped out because of side effects (1.7%). - 47 more people dropped out because of side effects with opioids than with placebo (difference of 4.7%). (High-quality evidence) Side effects resulting in hospitalisation, persistent disability, or death - 13 people out of 1000 who used opioids experienced side effects resulting in hospitalisation, persistent disability, or death (1.3%). - 4 people out of 1000 who used a placebo experienced side effects resulting in hospitalisation, persistent disability, or deaths (0.4%). - 9 more people experienced side effects resulting in hospitalisation, persistent disability, or death with opioids than with placebo (difference of 0.9%). (Low-quality evidence) Withdrawal symptoms - 24 people out of 1000 who used opioids experienced withdrawal symptoms (2.4%). - 9 people out of 1000 who used a placebo experienced withdrawal symptoms (0.9%). - 15 more people experienced withdrawal symptoms with opioids than with placebo (difference of 1.5%). (Moderate-quality evidence)