Therapeutics
Review: Glucosamine (sulfate or hydrochloride) does not reduce pain in knee or hip osteoarthritis
Wu D, Huang Y, Gu Y, Fan W. Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013;67:585-94.
Clinical impact ratings: F ★★★★★★✩ R ★★★★★✩✩ Question
Conclusion
Does glucosamine sulfate (GS) or glucosamine hydrochloride (GH) reduce pain in knee or hip osteoarthritis (OA)?
Neither glucosamine sulfate nor glucosamine hydrochloride reduces pain compared with placebo in knee or hip osteoarthritis.
Review scope
Source of funding: Not stated.
Included studies compared GS or GH with placebo in patients with knee or hip OA. Primary outcome was pain reduction assessed using a visual analogue scale, the Western Ontario and McMaster Universities Osteoarthritis Index, or the Lequesne Index (LI]); analyses used a prespecified hierarchical scale preference. LI physical function was also reported.
For correspondence: Professor W. Fan, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. E-mail [email protected]. ■
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to Mar 2012); proceedings of annual conferences in the past 3 years (American College of Rheumatology, British Society for Rheumatology, and Osteoarthritis Research Society International); and reference lists were searched for double-blind, randomized, controlled trials (RCTs). 19 RCTs (n = 3159, duration range 4 to 156 wk) met the selection criteria: 15 RCTs (n = 1941) used GS, and 4 (n = 1218) used GH. 17 RCTs were done in patients with knee OA, 1 in those with hip OA, and 1 in both types of OA. 16 RCTs scored ≥ 4 out of 5 on the Jadad quality scale.
Main results Meta-analysis showed that neither GS nor GH reduced pain compared with placebo (Table). GS improved physical function compared with placebo (Table); in subgroup analysis, the effect was maintained in the 2 RCTs with duration > 24 weeks (n = 412, standardized mean difference [SMD] −0.36, 95% CI −0.56 to −0.17) but not in the 3 RCTs with duration < 24 weeks (n = 563, SMD −0.55, CI −1.22 to 0.11). No trials evaluated GH for improving physical function. Glucosamine vs placebo in knee or hip osteoarthritis* Treatments
Outcomes†
Number of trials (n)
Standardized mean difference (95% CI)‡
Pain
17 (2752)
−0.16 (−0.34 to 0.01)
Glucosamine sulfate
Pain
13 (1534)
−0.22 (−0.48 to 0.04)
Glucosamine hydrochloride
Pain
4 (1218)
−0.03 (−0.14 to 0.08)
Physical function
5 (975)
−0.47 (−0.82 to −0.12)
Glucosamine sulfate or glucosamine hydrochloride
Glucosamine sulfate *CI defined in Glossary.
†Pain was assessed using visual analogue scales, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Lequesne Index. Physical function was assessed using the Lequesne Index. ‡Negative values indicate benefit with glucosamine. Data were pooled using a random-effects model. Heterogeneity was high (I2 > 78%) for all analyses except glucosamine hydrochloride vs placebo for pain reduction (I2 = 0%).
JC8
© 2013 American College of Physicians
Commentary OA, a painful and disabling condition, is routinely treated with analgesics because we lack disease-modifying interventions. Several studies have suggested that GS/chondroitin sulfate (CS) may offer some benefits (1-3), not just for knee OA but also for hand OA. However, there is only 1 definitive conclusion: GH does not seem to do much. In their meta-analysis of GS and GH, Wu and colleagues conclude that GS does not improve pain but may improve function; GH is ineffective. Unfortunately, it is difficult to compare different trials with different preparations in different patient populations. In addition, the pain of OA is multifactorial. Most positive clinical trial results have been documented with 1 pharmaceutical product of glucosamine sulfate manufactured by Rotta Laboratories, a European preparation (4). Nutraceuticals are not strictly regulated by the US Food and Drug Administration, and it is hard to know exactly what these preparations contain. Using a combination of GS/CS continues to be controversial. Although this study pertains only to GS and GH preparations, as opposed to GS/CS combination products, hundreds of GS/CS products are available over the counter in the USA (5). So what do we tell patients? Given the minimal risk for side effects and that patients will probably use these medications anyway, my approach is to make them aware of available data and current controversies. Data on the efficacy of these products leave important questions; study results are not sufficiently strong or convincing to recommend either for or against GS/CS supplements for knee or hip osteoarthritis. Lack of good efficacy data does not necessarily imply lack of efficacy. Simply put, well-conducted RCTs are needed. Emilio B. Gonzalez, MD, FACP, FACR University of Texas Medical Branch (UTMB Health) Galveston, Texas, USA References 1. Clegg DO, Reda DJ, Harris CL, et al. N Engl J Med. 2006;354:795-808. 2. Sawitzke AD, Shi H, Finco MF, et al. Ann Rheum Dis. 2010;69:1459-64. 3. Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Arthritis Rheum. 2011;63:3383-91. 4. Pavelká K, Gatterová J, Olejarová M, et al. Arch Intern Med. 2002;162:2113-23. 5. Bruyere O, Reginster JY. Drugs Aging. 2007;24:573-80.
17 December 2013 | ACP Journal Club | Volume 159 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/929454/ by a University of California San Diego User on 05/18/2017
Review: Glucosamine (sulfate or hydrochloride) does not reduce pain in knee or hip osteoarthritis
Wu D, Huang Y, Gu Y, Fan W. Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013;67:585-94.
Clinical impact ratings: F ★★★★★★✩ R ★★★★★✩✩ Question
Conclusion
Does glucosamine sulfate (GS) or glucosamine hydrochloride (GH) reduce pain in knee or hip osteoarthritis (OA)?
Neither glucosamine sulfate nor glucosamine hydrochloride reduces pain compared with placebo in knee or hip osteoarthritis.
Review scope
Source of funding: Not stated.
Included studies compared GS or GH with placebo in patients with knee or hip OA. Primary outcome was pain reduction assessed using a visual analogue scale, the Western Ontario and McMaster Universities Osteoarthritis Index, or the Lequesne Index (LI]); analyses used a prespecified hierarchical scale preference. LI physical function was also reported.
For correspondence: Professor W. Fan, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. E-mail [email protected]. ■
Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to Mar 2012); proceedings of annual conferences in the past 3 years (American College of Rheumatology, British Society for Rheumatology, and Osteoarthritis Research Society International); and reference lists were searched for double-blind, randomized, controlled trials (RCTs). 19 RCTs (n = 3159, duration range 4 to 156 wk) met the selection criteria: 15 RCTs (n = 1941) used GS, and 4 (n = 1218) used GH. 17 RCTs were done in patients with knee OA, 1 in those with hip OA, and 1 in both types of OA. 16 RCTs scored ≥ 4 out of 5 on the Jadad quality scale.
Main results Meta-analysis showed that neither GS nor GH reduced pain compared with placebo (Table). GS improved physical function compared with placebo (Table); in subgroup analysis, the effect was maintained in the 2 RCTs with duration > 24 weeks (n = 412, standardized mean difference [SMD] −0.36, 95% CI −0.56 to −0.17) but not in the 3 RCTs with duration < 24 weeks (n = 563, SMD −0.55, CI −1.22 to 0.11). No trials evaluated GH for improving physical function. Glucosamine vs placebo in knee or hip osteoarthritis* Treatments
Outcomes†
Number of trials (n)
Standardized mean difference (95% CI)‡
Pain
17 (2752)
−0.16 (−0.34 to 0.01)
Glucosamine sulfate
Pain
13 (1534)
−0.22 (−0.48 to 0.04)
Glucosamine hydrochloride
Pain
4 (1218)
−0.03 (−0.14 to 0.08)
Physical function
5 (975)
−0.47 (−0.82 to −0.12)
Glucosamine sulfate or glucosamine hydrochloride
Glucosamine sulfate *CI defined in Glossary.
†Pain was assessed using visual analogue scales, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Lequesne Index. Physical function was assessed using the Lequesne Index. ‡Negative values indicate benefit with glucosamine. Data were pooled using a random-effects model. Heterogeneity was high (I2 > 78%) for all analyses except glucosamine hydrochloride vs placebo for pain reduction (I2 = 0%).
JC8
© 2013 American College of Physicians
Commentary OA, a painful and disabling condition, is routinely treated with analgesics because we lack disease-modifying interventions. Several studies have suggested that GS/chondroitin sulfate (CS) may offer some benefits (1-3), not just for knee OA but also for hand OA. However, there is only 1 definitive conclusion: GH does not seem to do much. In their meta-analysis of GS and GH, Wu and colleagues conclude that GS does not improve pain but may improve function; GH is ineffective. Unfortunately, it is difficult to compare different trials with different preparations in different patient populations. In addition, the pain of OA is multifactorial. Most positive clinical trial results have been documented with 1 pharmaceutical product of glucosamine sulfate manufactured by Rotta Laboratories, a European preparation (4). Nutraceuticals are not strictly regulated by the US Food and Drug Administration, and it is hard to know exactly what these preparations contain. Using a combination of GS/CS continues to be controversial. Although this study pertains only to GS and GH preparations, as opposed to GS/CS combination products, hundreds of GS/CS products are available over the counter in the USA (5). So what do we tell patients? Given the minimal risk for side effects and that patients will probably use these medications anyway, my approach is to make them aware of available data and current controversies. Data on the efficacy of these products leave important questions; study results are not sufficiently strong or convincing to recommend either for or against GS/CS supplements for knee or hip osteoarthritis. Lack of good efficacy data does not necessarily imply lack of efficacy. Simply put, well-conducted RCTs are needed. Emilio B. Gonzalez, MD, FACP, FACR University of Texas Medical Branch (UTMB Health) Galveston, Texas, USA References 1. Clegg DO, Reda DJ, Harris CL, et al. N Engl J Med. 2006;354:795-808. 2. Sawitzke AD, Shi H, Finco MF, et al. Ann Rheum Dis. 2010;69:1459-64. 3. Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Arthritis Rheum. 2011;63:3383-91. 4. Pavelká K, Gatterová J, Olejarová M, et al. Arch Intern Med. 2002;162:2113-23. 5. Bruyere O, Reginster JY. Drugs Aging. 2007;24:573-80.
17 December 2013 | ACP Journal Club | Volume 159 • Number 12
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/929454/ by a University of California San Diego User on 05/18/2017
