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Arthritis pain? These supplements provide little relief
Tell patients with large joint arthritis that glucosamine and chondroitin have been found to be little better than placebo.1
Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ .2010;314:c4675.
STRENGTH OF RECOMMENDATION
A: Based on a good-quality meta-analysis.
ILLUSTRATIVE CASE
A 64-year-old woman with osteoarthritis (OA) of both knees reports that acetaminophen does not relieve the pain, and both ibuprofen and naproxen give her an upset stomach. She wonders if glucosamine and chondroitin would help relieve the pain. How should you respond?
Degenerative joint disease is a common and frustrating problem for patients and clinicians. Symptomatic knee OA has a prevalence of 16% among adults older than 45 years, and is one of the top 5 reasons for disability in noninstitutionalized adults.2 With no highly effective treatment for OA of the hip or knee other than joint replacement surgery, patients often turn to unproven over-the-counter remedies. Individuals with OA spend about $2600 per year out-of-pocket on disease-related expenses.2
Trials of these supplements have had mixed results
Glucosamine and chondroitin have been touted as beneficial, and sales have grown rapidly over the last decade, reaching nearly $900 million in the United States in 2008 alone.3 There have been many randomized trials of these supplements, with inconsistent results.
Larger and higher quality studies have found little or no effect, while smaller studies reported that glucosamine and chondroitin helped to relieve joint pain. A meta-analysis published in 2000 found 15 studies and reported moderate to large effect sizes, but the authors noted that quality issues and publication bias probably exaggerated the benefit.4 An updated Cochrane meta-analysis of 25 randomized controlled trials (RCTs), published in 2009, found little benefit from glucosamine. A subgroup analysis found that one company’s preparation appeared to be beneficial, but all 14 studies of that particular formulation had some connection with the manufacturer.5
STUDY SUMMARY: Effects of glucosamine and chondroitin, alone or together, were small
The meta-analysis we review in this PURL only included RCTs with an average of ≥100 patients with hip or knee OA in each group.1 This was based on the minimum sample size needed to detect a small or moderate difference between the 2 groups (roughly 1 cm on a 10-cm visual analogue scale [VAS]). The authors found 10 eligible RCTs with a total of 3803 patients; the average age of participants ranged from 58 to 66 years. Most of the trials studied knee arthritis, and most were sponsored by pharmaceutical firms.
Included studies had to compare glucosamine sulphate, glucosamine hydrochloride, chondroitin sulphate, or a combination, either with a placebo or head-to-head. Minimum daily doses were 800 mg chondroitin and 1500 mg glucosamine. The primary outcome was absolute pain intensity over the duration of the study. The authors summarized pain scores every 3 months for up to 2 years; they also analyzed changes in joint space narrowing in the studies reporting that measure.
The authors used a sophisticated framework that adjusted for comparisons over time and between studies, allowing them to increase the power, and likely the accuracy, of their comparisons. They reported outcomes as effect sizes, then translated the findings to a real-world outcome by converting results to a 10-cm VAS. Typically, an effect size of 0.2 standard deviation (SD) units is considered small, 0.5 SD units is a moderate difference, and 0.8 SD units is large. The authors set their threshold for a clinically important difference at 0.37 SD units, which translated to a 0.9 cm change on a 10-cm VAS—a generally accepted minimal clinically significant difference in pain.
They found that all 3 interventions (glucosamine alone, chondroitin alone, and a combination) were statistically better than placebo, with very little difference in outcomes over time. Compared with placebo, VAS improvements were 0.4 cm for glucosamine (95% confidence interval [CI], 0.1-0.7), 0.3 cm for chondroitin (95% CI, 0-0.7) and 0.5 cm for the combination (95% CI, 0-0.9). All of these improvements in pain were less than the authors’ defined minimum clinically significant improvement of 0.9 cm on a 10-cm scale.
Among the 6 trials that reported on joint space narrowing, the changes were minute and not statistically significant. There was a net difference between treatment and placebo groups of less than 0.2 mm (an effect size ≤0.16 SD units). There was no evidence of increased risk of adverse effects or increased dropout rates with any of the substances.
WHAT’S NEW: Study results leave little room for doubt
This meta-analysis used more sophisticated comparison techniques and used only larger (and probably better quality) studies than previous meta-analyses. However, inclusion and exclusion were not based on any study quality criteria.
The authors found that glucosamine and chondroitin, used alone or in combination, provide little benefit in terms of pain relief of OA of the knee or hip compared with placebo, and contend that we should recommend against patients buying them. This meta-analysis is consistent with the American Academy of Orthopedic Surgeons 2008 guideline for knee OA, which recommends not using glucosamine and/or chondroitin based on good evidence.6
CAVEATS: Rate of joint replacement was not considered
This meta-analysis did not study the effect of these supplements on joint replacement. In a 5-year follow-up study after completion of 2 of the RCTs included in this meta-analysis, the relative risk of total joint replacement was 0.43 (95% CI, 0.2-0.92) for those in the glucosamine group (who had taken 1500 mg glucosamine sulphate for 12-36 months) compared with placebo (NNT=12).7 However, the authors were only able to follow up with 81% of the original participants. In the meta-analysis reported here, the difference in joint space narrowing was unlikely to be clinically significant or to lead to a difference in joint replacement rates.
Among the studies included in the meta-analysis, commercially funded trials had a greater decrease in pain with glucosamine or chondroitin compared with independent trials. This did not change the overall outcome of the meta-analysis, thereby supporting the validity of the results.
CHALLENGES TO IMPLEMENTATION: These supplements are available OTC
There are few barriers to advising patients not to use these products. Since glucosamine and chondroitin are available over-the-counter, however, patients have ready access to them, even if their doctors don’t recommend them. Several meta-analyses have not found an increased risk of harm from these products (other than the expense).1,5
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
1. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.-
2. Centers for Disease Control and Prevention (CDC). Arthritis. Last updated June 25, 2010. Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed June 5, 2011.
3. Heller L. US glucosamine grows slow, lags global sales. Last updated March 2, 2009. Available at: http://www.nutraingredientsusa.com/Consumer-Trends/US-glucosamine-grows-slow-lags-global-sales. Accessed May 7, 2011.
4. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475.
5. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2009;(2):CD002946.-
6. National Guideline Clearinghouse (NGC). Guideline summary: American Academy of Orthopaedic Surgeons treatment of osteoarthritis of the knee (non-arthroplasty). Rockville, MD: Agency for Healthcare Research and Quality, 2008. Last updated December 6, 2008. Available at: http://www.guidelines.gov/content.aspx?id=14279. Accessed May 16, 2011.
7. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteo Cartilage. 2008;16:254-260.
Tell patients with large joint arthritis that glucosamine and chondroitin have been found to be little better than placebo.1
Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ .2010;314:c4675.
STRENGTH OF RECOMMENDATION
A: Based on a good-quality meta-analysis.
ILLUSTRATIVE CASE
A 64-year-old woman with osteoarthritis (OA) of both knees reports that acetaminophen does not relieve the pain, and both ibuprofen and naproxen give her an upset stomach. She wonders if glucosamine and chondroitin would help relieve the pain. How should you respond?
Degenerative joint disease is a common and frustrating problem for patients and clinicians. Symptomatic knee OA has a prevalence of 16% among adults older than 45 years, and is one of the top 5 reasons for disability in noninstitutionalized adults.2 With no highly effective treatment for OA of the hip or knee other than joint replacement surgery, patients often turn to unproven over-the-counter remedies. Individuals with OA spend about $2600 per year out-of-pocket on disease-related expenses.2
Trials of these supplements have had mixed results
Glucosamine and chondroitin have been touted as beneficial, and sales have grown rapidly over the last decade, reaching nearly $900 million in the United States in 2008 alone.3 There have been many randomized trials of these supplements, with inconsistent results.
Larger and higher quality studies have found little or no effect, while smaller studies reported that glucosamine and chondroitin helped to relieve joint pain. A meta-analysis published in 2000 found 15 studies and reported moderate to large effect sizes, but the authors noted that quality issues and publication bias probably exaggerated the benefit.4 An updated Cochrane meta-analysis of 25 randomized controlled trials (RCTs), published in 2009, found little benefit from glucosamine. A subgroup analysis found that one company’s preparation appeared to be beneficial, but all 14 studies of that particular formulation had some connection with the manufacturer.5
STUDY SUMMARY: Effects of glucosamine and chondroitin, alone or together, were small
The meta-analysis we review in this PURL only included RCTs with an average of ≥100 patients with hip or knee OA in each group.1 This was based on the minimum sample size needed to detect a small or moderate difference between the 2 groups (roughly 1 cm on a 10-cm visual analogue scale [VAS]). The authors found 10 eligible RCTs with a total of 3803 patients; the average age of participants ranged from 58 to 66 years. Most of the trials studied knee arthritis, and most were sponsored by pharmaceutical firms.
Included studies had to compare glucosamine sulphate, glucosamine hydrochloride, chondroitin sulphate, or a combination, either with a placebo or head-to-head. Minimum daily doses were 800 mg chondroitin and 1500 mg glucosamine. The primary outcome was absolute pain intensity over the duration of the study. The authors summarized pain scores every 3 months for up to 2 years; they also analyzed changes in joint space narrowing in the studies reporting that measure.
The authors used a sophisticated framework that adjusted for comparisons over time and between studies, allowing them to increase the power, and likely the accuracy, of their comparisons. They reported outcomes as effect sizes, then translated the findings to a real-world outcome by converting results to a 10-cm VAS. Typically, an effect size of 0.2 standard deviation (SD) units is considered small, 0.5 SD units is a moderate difference, and 0.8 SD units is large. The authors set their threshold for a clinically important difference at 0.37 SD units, which translated to a 0.9 cm change on a 10-cm VAS—a generally accepted minimal clinically significant difference in pain.
They found that all 3 interventions (glucosamine alone, chondroitin alone, and a combination) were statistically better than placebo, with very little difference in outcomes over time. Compared with placebo, VAS improvements were 0.4 cm for glucosamine (95% confidence interval [CI], 0.1-0.7), 0.3 cm for chondroitin (95% CI, 0-0.7) and 0.5 cm for the combination (95% CI, 0-0.9). All of these improvements in pain were less than the authors’ defined minimum clinically significant improvement of 0.9 cm on a 10-cm scale.
Among the 6 trials that reported on joint space narrowing, the changes were minute and not statistically significant. There was a net difference between treatment and placebo groups of less than 0.2 mm (an effect size ≤0.16 SD units). There was no evidence of increased risk of adverse effects or increased dropout rates with any of the substances.
WHAT’S NEW: Study results leave little room for doubt
This meta-analysis used more sophisticated comparison techniques and used only larger (and probably better quality) studies than previous meta-analyses. However, inclusion and exclusion were not based on any study quality criteria.
The authors found that glucosamine and chondroitin, used alone or in combination, provide little benefit in terms of pain relief of OA of the knee or hip compared with placebo, and contend that we should recommend against patients buying them. This meta-analysis is consistent with the American Academy of Orthopedic Surgeons 2008 guideline for knee OA, which recommends not using glucosamine and/or chondroitin based on good evidence.6
CAVEATS: Rate of joint replacement was not considered
This meta-analysis did not study the effect of these supplements on joint replacement. In a 5-year follow-up study after completion of 2 of the RCTs included in this meta-analysis, the relative risk of total joint replacement was 0.43 (95% CI, 0.2-0.92) for those in the glucosamine group (who had taken 1500 mg glucosamine sulphate for 12-36 months) compared with placebo (NNT=12).7 However, the authors were only able to follow up with 81% of the original participants. In the meta-analysis reported here, the difference in joint space narrowing was unlikely to be clinically significant or to lead to a difference in joint replacement rates.
Among the studies included in the meta-analysis, commercially funded trials had a greater decrease in pain with glucosamine or chondroitin compared with independent trials. This did not change the overall outcome of the meta-analysis, thereby supporting the validity of the results.
CHALLENGES TO IMPLEMENTATION: These supplements are available OTC
There are few barriers to advising patients not to use these products. Since glucosamine and chondroitin are available over-the-counter, however, patients have ready access to them, even if their doctors don’t recommend them. Several meta-analyses have not found an increased risk of harm from these products (other than the expense).1,5
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
Tell patients with large joint arthritis that glucosamine and chondroitin have been found to be little better than placebo.1
Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ .2010;314:c4675.
STRENGTH OF RECOMMENDATION
A: Based on a good-quality meta-analysis.
ILLUSTRATIVE CASE
A 64-year-old woman with osteoarthritis (OA) of both knees reports that acetaminophen does not relieve the pain, and both ibuprofen and naproxen give her an upset stomach. She wonders if glucosamine and chondroitin would help relieve the pain. How should you respond?
Degenerative joint disease is a common and frustrating problem for patients and clinicians. Symptomatic knee OA has a prevalence of 16% among adults older than 45 years, and is one of the top 5 reasons for disability in noninstitutionalized adults.2 With no highly effective treatment for OA of the hip or knee other than joint replacement surgery, patients often turn to unproven over-the-counter remedies. Individuals with OA spend about $2600 per year out-of-pocket on disease-related expenses.2
Trials of these supplements have had mixed results
Glucosamine and chondroitin have been touted as beneficial, and sales have grown rapidly over the last decade, reaching nearly $900 million in the United States in 2008 alone.3 There have been many randomized trials of these supplements, with inconsistent results.
Larger and higher quality studies have found little or no effect, while smaller studies reported that glucosamine and chondroitin helped to relieve joint pain. A meta-analysis published in 2000 found 15 studies and reported moderate to large effect sizes, but the authors noted that quality issues and publication bias probably exaggerated the benefit.4 An updated Cochrane meta-analysis of 25 randomized controlled trials (RCTs), published in 2009, found little benefit from glucosamine. A subgroup analysis found that one company’s preparation appeared to be beneficial, but all 14 studies of that particular formulation had some connection with the manufacturer.5
STUDY SUMMARY: Effects of glucosamine and chondroitin, alone or together, were small
The meta-analysis we review in this PURL only included RCTs with an average of ≥100 patients with hip or knee OA in each group.1 This was based on the minimum sample size needed to detect a small or moderate difference between the 2 groups (roughly 1 cm on a 10-cm visual analogue scale [VAS]). The authors found 10 eligible RCTs with a total of 3803 patients; the average age of participants ranged from 58 to 66 years. Most of the trials studied knee arthritis, and most were sponsored by pharmaceutical firms.
Included studies had to compare glucosamine sulphate, glucosamine hydrochloride, chondroitin sulphate, or a combination, either with a placebo or head-to-head. Minimum daily doses were 800 mg chondroitin and 1500 mg glucosamine. The primary outcome was absolute pain intensity over the duration of the study. The authors summarized pain scores every 3 months for up to 2 years; they also analyzed changes in joint space narrowing in the studies reporting that measure.
The authors used a sophisticated framework that adjusted for comparisons over time and between studies, allowing them to increase the power, and likely the accuracy, of their comparisons. They reported outcomes as effect sizes, then translated the findings to a real-world outcome by converting results to a 10-cm VAS. Typically, an effect size of 0.2 standard deviation (SD) units is considered small, 0.5 SD units is a moderate difference, and 0.8 SD units is large. The authors set their threshold for a clinically important difference at 0.37 SD units, which translated to a 0.9 cm change on a 10-cm VAS—a generally accepted minimal clinically significant difference in pain.
They found that all 3 interventions (glucosamine alone, chondroitin alone, and a combination) were statistically better than placebo, with very little difference in outcomes over time. Compared with placebo, VAS improvements were 0.4 cm for glucosamine (95% confidence interval [CI], 0.1-0.7), 0.3 cm for chondroitin (95% CI, 0-0.7) and 0.5 cm for the combination (95% CI, 0-0.9). All of these improvements in pain were less than the authors’ defined minimum clinically significant improvement of 0.9 cm on a 10-cm scale.
Among the 6 trials that reported on joint space narrowing, the changes were minute and not statistically significant. There was a net difference between treatment and placebo groups of less than 0.2 mm (an effect size ≤0.16 SD units). There was no evidence of increased risk of adverse effects or increased dropout rates with any of the substances.
WHAT’S NEW: Study results leave little room for doubt
This meta-analysis used more sophisticated comparison techniques and used only larger (and probably better quality) studies than previous meta-analyses. However, inclusion and exclusion were not based on any study quality criteria.
The authors found that glucosamine and chondroitin, used alone or in combination, provide little benefit in terms of pain relief of OA of the knee or hip compared with placebo, and contend that we should recommend against patients buying them. This meta-analysis is consistent with the American Academy of Orthopedic Surgeons 2008 guideline for knee OA, which recommends not using glucosamine and/or chondroitin based on good evidence.6
CAVEATS: Rate of joint replacement was not considered
This meta-analysis did not study the effect of these supplements on joint replacement. In a 5-year follow-up study after completion of 2 of the RCTs included in this meta-analysis, the relative risk of total joint replacement was 0.43 (95% CI, 0.2-0.92) for those in the glucosamine group (who had taken 1500 mg glucosamine sulphate for 12-36 months) compared with placebo (NNT=12).7 However, the authors were only able to follow up with 81% of the original participants. In the meta-analysis reported here, the difference in joint space narrowing was unlikely to be clinically significant or to lead to a difference in joint replacement rates.
Among the studies included in the meta-analysis, commercially funded trials had a greater decrease in pain with glucosamine or chondroitin compared with independent trials. This did not change the overall outcome of the meta-analysis, thereby supporting the validity of the results.
CHALLENGES TO IMPLEMENTATION: These supplements are available OTC
There are few barriers to advising patients not to use these products. Since glucosamine and chondroitin are available over-the-counter, however, patients have ready access to them, even if their doctors don’t recommend them. Several meta-analyses have not found an increased risk of harm from these products (other than the expense).1,5
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
1. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.-
2. Centers for Disease Control and Prevention (CDC). Arthritis. Last updated June 25, 2010. Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed June 5, 2011.
3. Heller L. US glucosamine grows slow, lags global sales. Last updated March 2, 2009. Available at: http://www.nutraingredientsusa.com/Consumer-Trends/US-glucosamine-grows-slow-lags-global-sales. Accessed May 7, 2011.
4. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475.
5. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2009;(2):CD002946.-
6. National Guideline Clearinghouse (NGC). Guideline summary: American Academy of Orthopaedic Surgeons treatment of osteoarthritis of the knee (non-arthroplasty). Rockville, MD: Agency for Healthcare Research and Quality, 2008. Last updated December 6, 2008. Available at: http://www.guidelines.gov/content.aspx?id=14279. Accessed May 16, 2011.
7. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteo Cartilage. 2008;16:254-260.
1. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675.-
2. Centers for Disease Control and Prevention (CDC). Arthritis. Last updated June 25, 2010. Available at: http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed June 5, 2011.
3. Heller L. US glucosamine grows slow, lags global sales. Last updated March 2, 2009. Available at: http://www.nutraingredientsusa.com/Consumer-Trends/US-glucosamine-grows-slow-lags-global-sales. Accessed May 7, 2011.
4. McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475.
5. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2009;(2):CD002946.-
6. National Guideline Clearinghouse (NGC). Guideline summary: American Academy of Orthopaedic Surgeons treatment of osteoarthritis of the knee (non-arthroplasty). Rockville, MD: Agency for Healthcare Research and Quality, 2008. Last updated December 6, 2008. Available at: http://www.guidelines.gov/content.aspx?id=14279. Accessed May 16, 2011.
7. Bruyere O, Pavelka K, Rovati LC, et al. Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteo Cartilage. 2008;16:254-260.
Copyright © 2011 The Family Physicians Inquiries Network.
All rights reserved.
An alternative to oral NSAIDs for acute musculoskeletal injuries
For patients with acute musculoskeletal injuries, topical NSAIDs are an effective alternative for pain relief.1
STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of 47 high-quality randomized clinical trials.
Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.
ILLUSTRATIVE CASE
A 47-year-old man limps into your office complaining of ankle pain. The patient is well known to you and has a long history of dyspepsia, which is aggravated when he takes any oral nonsteroidal anti-inflammatory drug (NSAID). He injured his ankle while playing basketball. You diagnose acute ankle sprain. Would a topical NSAID be a safe option for pain relief for this patient?
Patients with tendon and ligament injuries often see their family physician for care. Rest, ice, compression, elevation (RICE) therapy is first-line treatment for these injuries.2 Oral NSAIDs, such as diclofenac, piroxicam, and ibuprofen reduce swelling and lead to a more rapid return to activity than RICE alone in patients with ankle sprains,3 and relieve pain associated with muscle strains, too. Acetaminophen provides comparable pain relief and resumption of normal activities.4
Help for those who can’t take oral NSAIDs
Oral NSAIDs, however, are contraindicated for patients with a history of gastrointestinal bleeding and must be used cautiously in those with chronic kidney disease. Some patients can’t tolerate the adverse effects, which may include stomach upset, vomiting, and abdominal pain. Others may have medication interactions that prohibit use of oral NSAIDs.
Numerous high-quality, randomized, double-blinded placebo-controlled trials of topical NSAIDs have been conducted in recent years, involving diclofenac—the only topical NSAID available in the United States— as well as other topical agents on the market outside of this country. A recent Cochrane review, detailed below, assessed the efficacy of topical NSAIDs for patients with acute musculoskeletal injuries.
STUDY SUMMARY: Topical NSAIDs provided significant relief
This meta-analysis of 47 high-quality, randomized, double-blinded, placebo-controlled trials included 3455 patients with acute strain, sprain, sport, or overuse injuries.1 Four of the 47 trials, with a total of 746 participants, studied topical diclofenac.
There was significant heterogeneity in the studies included in the review, but each arm of every trial had at least 10 participants >16 years of age with a painful musculoskeletal injury sustained within the previous 48 hours. To be included in the Cochrane meta-analysis, participants had to have used a topical NSAID at least once a day for ≥3 days.
The primary outcome measure was a reduction in pain ≥50% from baseline. Post-treatment data were obtained approximately 7 days after the injury. Of the patients receiving any topical NSAID, 65% (1181/1822) had successful treatment, compared with 43% (695/1633) receiving a placebo. The number needed to treat (NNT) with a topical NSAID instead of placebo was 4.5 (95% confidence interval, 3.9-5.3) to reduce pain ≥50%.
For patients using topical diclofenac, 52% (166/319) had a 50% reduction in pain, vs 25% (77/307) using a topical placebo. The NNT for topical diclofenac was 3.7, about the same as for oral NSAIDs.5
Adverse events were rare in the topical NSAID group: 6.3% had a local adverse event such as a skin reaction vs 5.9% in the topical placebo group. There were no systemic adverse events with topical diclofenac. While all topical NSAIDs combined showed a few minor adverse events compared with placebo, no serious systemic events were reported.
WHAT’S NEW: Topical NSAIDs are a useful alternative
Patients now have another option when seeking treatment for acute musculoskeletal pain. In addition to those who are unable to take oral NSAIDs, some patients may prefer a topical preparation because of perceived or actual side effects and safety profiles.
CAVEATS: Dosing intervals were not established
This meta-analysis included studies that examined a variety of dosing strategies and conditions, so an optimal dosing interval is not clear. However, the studies generally found evidence of benefit regardless of the acute condition and the amount and type of topical NSAID used. Diclofenac had the best results compared with other topical NSAIDs. Benzydamine, which is not sold in the United States, was the only topical NSAID not found to be statistically beneficial compared with placebo, based on 3 studies.
Topical NSAIDs have a small amount of systemic absorption, with blood concentrations about 5% of those from oral NSAIDs. However, patients with a strict contraindication to oral NSAIDs (for example, severe allergy) may also have a contraindication to topical NSAIDs. Also, all patients should be cautioned to avoid oral NSAIDs while using a topical preparation.6
CHALLENGES TO IMPLEMENTATION: Topical NSAIDs are costly
In the United States, topical diclofenac is available only by prescription. This may create accessibility and cost differences between oral and topical NSAIDs. The average cost of a typical 10-day acute injury treatment of an adult with oral ibuprofen would be about $3 for plain tablets ($10 for extended release and enteric coated), vs about $65 for diclofenac gel, $113 for a diclofenac patch, and $66 for a diclofenac topical solution (www.drugstore.com, accessed December 2, 2010).
Physician inertia may also interfere with implementation. Physicians may not add a new medication to current prescribing options, although there appear to be no medical barriers to topical NSAIDs. This meta-analysis shows that topical NSAIDs are safe and effective for pain relief from acute injuries.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
1. Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.-
2. Ivins D. Acute ankle sprain. Am Fam Physician. 2006;74:1714-1720.
3. Slatyer M, Hensley M, Lopert R. A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med. 1997;25:544-553.
4. Dalton JD, Jr. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006;48:615-623.
5. Paolini J, Orchard J. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust. 2005;183:384-388.
6. Evans JMM, McMahon AD, McGilchrist MM, et al. Topical nonsteroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ. 1995;6996:22-26.
For patients with acute musculoskeletal injuries, topical NSAIDs are an effective alternative for pain relief.1
STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of 47 high-quality randomized clinical trials.
Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.
ILLUSTRATIVE CASE
A 47-year-old man limps into your office complaining of ankle pain. The patient is well known to you and has a long history of dyspepsia, which is aggravated when he takes any oral nonsteroidal anti-inflammatory drug (NSAID). He injured his ankle while playing basketball. You diagnose acute ankle sprain. Would a topical NSAID be a safe option for pain relief for this patient?
Patients with tendon and ligament injuries often see their family physician for care. Rest, ice, compression, elevation (RICE) therapy is first-line treatment for these injuries.2 Oral NSAIDs, such as diclofenac, piroxicam, and ibuprofen reduce swelling and lead to a more rapid return to activity than RICE alone in patients with ankle sprains,3 and relieve pain associated with muscle strains, too. Acetaminophen provides comparable pain relief and resumption of normal activities.4
Help for those who can’t take oral NSAIDs
Oral NSAIDs, however, are contraindicated for patients with a history of gastrointestinal bleeding and must be used cautiously in those with chronic kidney disease. Some patients can’t tolerate the adverse effects, which may include stomach upset, vomiting, and abdominal pain. Others may have medication interactions that prohibit use of oral NSAIDs.
Numerous high-quality, randomized, double-blinded placebo-controlled trials of topical NSAIDs have been conducted in recent years, involving diclofenac—the only topical NSAID available in the United States— as well as other topical agents on the market outside of this country. A recent Cochrane review, detailed below, assessed the efficacy of topical NSAIDs for patients with acute musculoskeletal injuries.
STUDY SUMMARY: Topical NSAIDs provided significant relief
This meta-analysis of 47 high-quality, randomized, double-blinded, placebo-controlled trials included 3455 patients with acute strain, sprain, sport, or overuse injuries.1 Four of the 47 trials, with a total of 746 participants, studied topical diclofenac.
There was significant heterogeneity in the studies included in the review, but each arm of every trial had at least 10 participants >16 years of age with a painful musculoskeletal injury sustained within the previous 48 hours. To be included in the Cochrane meta-analysis, participants had to have used a topical NSAID at least once a day for ≥3 days.
The primary outcome measure was a reduction in pain ≥50% from baseline. Post-treatment data were obtained approximately 7 days after the injury. Of the patients receiving any topical NSAID, 65% (1181/1822) had successful treatment, compared with 43% (695/1633) receiving a placebo. The number needed to treat (NNT) with a topical NSAID instead of placebo was 4.5 (95% confidence interval, 3.9-5.3) to reduce pain ≥50%.
For patients using topical diclofenac, 52% (166/319) had a 50% reduction in pain, vs 25% (77/307) using a topical placebo. The NNT for topical diclofenac was 3.7, about the same as for oral NSAIDs.5
Adverse events were rare in the topical NSAID group: 6.3% had a local adverse event such as a skin reaction vs 5.9% in the topical placebo group. There were no systemic adverse events with topical diclofenac. While all topical NSAIDs combined showed a few minor adverse events compared with placebo, no serious systemic events were reported.
WHAT’S NEW: Topical NSAIDs are a useful alternative
Patients now have another option when seeking treatment for acute musculoskeletal pain. In addition to those who are unable to take oral NSAIDs, some patients may prefer a topical preparation because of perceived or actual side effects and safety profiles.
CAVEATS: Dosing intervals were not established
This meta-analysis included studies that examined a variety of dosing strategies and conditions, so an optimal dosing interval is not clear. However, the studies generally found evidence of benefit regardless of the acute condition and the amount and type of topical NSAID used. Diclofenac had the best results compared with other topical NSAIDs. Benzydamine, which is not sold in the United States, was the only topical NSAID not found to be statistically beneficial compared with placebo, based on 3 studies.
Topical NSAIDs have a small amount of systemic absorption, with blood concentrations about 5% of those from oral NSAIDs. However, patients with a strict contraindication to oral NSAIDs (for example, severe allergy) may also have a contraindication to topical NSAIDs. Also, all patients should be cautioned to avoid oral NSAIDs while using a topical preparation.6
CHALLENGES TO IMPLEMENTATION: Topical NSAIDs are costly
In the United States, topical diclofenac is available only by prescription. This may create accessibility and cost differences between oral and topical NSAIDs. The average cost of a typical 10-day acute injury treatment of an adult with oral ibuprofen would be about $3 for plain tablets ($10 for extended release and enteric coated), vs about $65 for diclofenac gel, $113 for a diclofenac patch, and $66 for a diclofenac topical solution (www.drugstore.com, accessed December 2, 2010).
Physician inertia may also interfere with implementation. Physicians may not add a new medication to current prescribing options, although there appear to be no medical barriers to topical NSAIDs. This meta-analysis shows that topical NSAIDs are safe and effective for pain relief from acute injuries.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
For patients with acute musculoskeletal injuries, topical NSAIDs are an effective alternative for pain relief.1
STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of 47 high-quality randomized clinical trials.
Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.
ILLUSTRATIVE CASE
A 47-year-old man limps into your office complaining of ankle pain. The patient is well known to you and has a long history of dyspepsia, which is aggravated when he takes any oral nonsteroidal anti-inflammatory drug (NSAID). He injured his ankle while playing basketball. You diagnose acute ankle sprain. Would a topical NSAID be a safe option for pain relief for this patient?
Patients with tendon and ligament injuries often see their family physician for care. Rest, ice, compression, elevation (RICE) therapy is first-line treatment for these injuries.2 Oral NSAIDs, such as diclofenac, piroxicam, and ibuprofen reduce swelling and lead to a more rapid return to activity than RICE alone in patients with ankle sprains,3 and relieve pain associated with muscle strains, too. Acetaminophen provides comparable pain relief and resumption of normal activities.4
Help for those who can’t take oral NSAIDs
Oral NSAIDs, however, are contraindicated for patients with a history of gastrointestinal bleeding and must be used cautiously in those with chronic kidney disease. Some patients can’t tolerate the adverse effects, which may include stomach upset, vomiting, and abdominal pain. Others may have medication interactions that prohibit use of oral NSAIDs.
Numerous high-quality, randomized, double-blinded placebo-controlled trials of topical NSAIDs have been conducted in recent years, involving diclofenac—the only topical NSAID available in the United States— as well as other topical agents on the market outside of this country. A recent Cochrane review, detailed below, assessed the efficacy of topical NSAIDs for patients with acute musculoskeletal injuries.
STUDY SUMMARY: Topical NSAIDs provided significant relief
This meta-analysis of 47 high-quality, randomized, double-blinded, placebo-controlled trials included 3455 patients with acute strain, sprain, sport, or overuse injuries.1 Four of the 47 trials, with a total of 746 participants, studied topical diclofenac.
There was significant heterogeneity in the studies included in the review, but each arm of every trial had at least 10 participants >16 years of age with a painful musculoskeletal injury sustained within the previous 48 hours. To be included in the Cochrane meta-analysis, participants had to have used a topical NSAID at least once a day for ≥3 days.
The primary outcome measure was a reduction in pain ≥50% from baseline. Post-treatment data were obtained approximately 7 days after the injury. Of the patients receiving any topical NSAID, 65% (1181/1822) had successful treatment, compared with 43% (695/1633) receiving a placebo. The number needed to treat (NNT) with a topical NSAID instead of placebo was 4.5 (95% confidence interval, 3.9-5.3) to reduce pain ≥50%.
For patients using topical diclofenac, 52% (166/319) had a 50% reduction in pain, vs 25% (77/307) using a topical placebo. The NNT for topical diclofenac was 3.7, about the same as for oral NSAIDs.5
Adverse events were rare in the topical NSAID group: 6.3% had a local adverse event such as a skin reaction vs 5.9% in the topical placebo group. There were no systemic adverse events with topical diclofenac. While all topical NSAIDs combined showed a few minor adverse events compared with placebo, no serious systemic events were reported.
WHAT’S NEW: Topical NSAIDs are a useful alternative
Patients now have another option when seeking treatment for acute musculoskeletal pain. In addition to those who are unable to take oral NSAIDs, some patients may prefer a topical preparation because of perceived or actual side effects and safety profiles.
CAVEATS: Dosing intervals were not established
This meta-analysis included studies that examined a variety of dosing strategies and conditions, so an optimal dosing interval is not clear. However, the studies generally found evidence of benefit regardless of the acute condition and the amount and type of topical NSAID used. Diclofenac had the best results compared with other topical NSAIDs. Benzydamine, which is not sold in the United States, was the only topical NSAID not found to be statistically beneficial compared with placebo, based on 3 studies.
Topical NSAIDs have a small amount of systemic absorption, with blood concentrations about 5% of those from oral NSAIDs. However, patients with a strict contraindication to oral NSAIDs (for example, severe allergy) may also have a contraindication to topical NSAIDs. Also, all patients should be cautioned to avoid oral NSAIDs while using a topical preparation.6
CHALLENGES TO IMPLEMENTATION: Topical NSAIDs are costly
In the United States, topical diclofenac is available only by prescription. This may create accessibility and cost differences between oral and topical NSAIDs. The average cost of a typical 10-day acute injury treatment of an adult with oral ibuprofen would be about $3 for plain tablets ($10 for extended release and enteric coated), vs about $65 for diclofenac gel, $113 for a diclofenac patch, and $66 for a diclofenac topical solution (www.drugstore.com, accessed December 2, 2010).
Physician inertia may also interfere with implementation. Physicians may not add a new medication to current prescribing options, although there appear to be no medical barriers to topical NSAIDs. This meta-analysis shows that topical NSAIDs are safe and effective for pain relief from acute injuries.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Click here to view PURL METHODOLOGY
1. Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.-
2. Ivins D. Acute ankle sprain. Am Fam Physician. 2006;74:1714-1720.
3. Slatyer M, Hensley M, Lopert R. A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med. 1997;25:544-553.
4. Dalton JD, Jr. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006;48:615-623.
5. Paolini J, Orchard J. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust. 2005;183:384-388.
6. Evans JMM, McMahon AD, McGilchrist MM, et al. Topical nonsteroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ. 1995;6996:22-26.
1. Massey T, Derry S, Moore RA, et al. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.-
2. Ivins D. Acute ankle sprain. Am Fam Physician. 2006;74:1714-1720.
3. Slatyer M, Hensley M, Lopert R. A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med. 1997;25:544-553.
4. Dalton JD, Jr. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006;48:615-623.
5. Paolini J, Orchard J. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust. 2005;183:384-388.
6. Evans JMM, McMahon AD, McGilchrist MM, et al. Topical nonsteroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ. 1995;6996:22-26.
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