Dr. Nicholas DiNubile, MD02.05.15
As an orthopedic surgeon specializing in knee disorders, I see countless patients who suffer with knee osteoarthritis. As osteoarthritis is a chronic condition, with no cure, this patient population represents a major clinical challenge in terms of finding safe, effective long-term strategies for their disease management.
This past week, results from a landmark clinical study showed that joint supplements are indeed helpful for patients with knee osteoarthritis. In this published research, the combination of two dietary supplements, glucosamine hydrochloride and chondroitin sulfate (GH+CS), reduced pain, functional disability, joint stiffness, swelling and effusion in patients living with knee osteoarthritis (OA). As reported in the current online issue of Annals of Rheumatic Diseases, six months of GH+CS treatment provided efficacy and safety that were comparable to the non-steroidal anti-inflammatory drug (NSAID) celecoxib in patients with severe OA.1
This study, called MOVES (Multicentre Osteoarthritis InterVEntion trial with Sysadoa), is important because it supports the long-term use of GH+CS in OA disease management, an approach that I have taken for many years in my practice. Moreover, the results arguably represent a “tipping point” in the ongoing debate over whether there is sufficient clinical evidence supporting the safe and effective use of GH+CS to manage joint health.
The multicenter, randomized, parallel-group, double-blind, MOVES trial sponsored by Bioibérica, compared the efficacy and safety of GH+CS to celecoxib in 606 patients with primary knee OA and moderate to severe pain. The patients, who were recruited from 42 centers in Spain, Germany, France and Poland GH+CS, received daily doses of pharmaceutical-grade GH+CS (at 1500 mg and 1200 mg, respectively, a combination available in the U.S. as CosaminDS) or celecoxib (200 mg) for six months.
The combination of GH and CS produced clinically relevant reductions in each of the study’s endpoints. Specifically, the results showed improvements in the following parameters:
Overall, 51% (155/304) of patients in the GH+CS group experienced at least one treatment-emergent adverse event (AE), compared to 50.5% (151/299) of celecoxib-treated patients. Most AEs were of mild or moderate intensity, with only 17 deemed serious, seven (2.3%) in the GH+CS group and 10 (3.3%) in the celecoxib group. No deaths were reported in the study.
Although both GH+CS and celecoxib exhibited a good safety profile and tolerability in the study population, the investigators commented that celecoxib is associated with increased risk of cardiovascular thrombotic events, congestive heart failure and major gastrointestinal events, compared with placebo, and in the European Union is contraindicated in patients with known cardiovascular and peripheral vascular disease. They added that the GH+CS combination may “offer an alternative, especially for individuals with cardiovascular or gastrointestinal conditions who have contraindications for treatment with NSAIDs.”1 Also, in this study, patients with known gastrointestinal and cardiovascular issues were excluded. These are individuals who would have been more likely to experience medical complications with NSAID therapy and in my experience tolerate the combination of GH+CS.
In short, the MOVES study provides additional evidence to support the safe and effective use of glucosamine hydrochloride and chondroitin sulfate in managing joint health in a wide variety of patients with knee OA. The results are consistent with those reported by Clegg and colleagues in a study known as GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial). In that study, published in 2006 in the New England Journal of Medicine2, the combination of GH+CS was superior to placebo in patients with moderate to severe pain. In fact, it is my understanding that MOVES was developed as an extension of GAIT, to confirm the latter trial’s results. Also, MOVES focused on the subgroup of patients with moderate to severe pain associated with knee OA, and these are typically a more challenging patient subgroup to manage. Since GAIT compared the GH+CS combination to both, celecoxib and placebo, the MOVES trial was designed as a non-inferiority study comparing only the combination versus celecoxib.
Speaking as an orthopedic surgeon specializing in sports medicine for more than 20 years, the MOVES findings are important not only for use of the glucosamine chondroitin combination but to the nutraceutical product community as a whole. The findings underscore both the current value and potential of many supplements as complementary or even alternative therapy in managing a wide variety of conditions.
I am not surprised by these findings because cartilage cell-culture research has demonstrated that glucosamine and chondroitin sulfate work synergistically to stimulate the production of cartilage matrix components and to inhibit enzymes that break down cartilage.
Research has also shown that the combination of GH+CS inhibits expression of several markers involved in cartilage breakdown. In laboratory cell-culture studies of markers associated with both joint discomfort and cartilage breakdown, glucosamine and chondroitin sulfate reduced these markers more effectively when used in combination than when administered separately, again demonstrating a synergistic effect.
Growing Dossier
For many years the ongoing debate about the efficacy of dietary supplements has cast doubt upon the value and utility of non-pharmaceutical approaches to disease management. Studies like MOVES add to a growing body of evidence of impressive outcomes produced by highly active, high-quality supplements administered at appropriate doses and concentration levels in a controlled clinical environment. The authors actually stressed the importance of selecting a high-quality brand of GH+CS to achieve the effectiveness demonstrated in their research. This is something I cannot emphasize enough to my patients when I recommend GH+CS. The latest results also provide reassurance that my approach to long-term disease management is in line with evidence-based research, especially in patients for whom certain pharmaceutical options present safety and potential tolerability issues.
The three main takeaways from this study are:
1) Use of a clinical supplement such as glucosamine/chondroitin sulfate is safe and effective in patients with OA of the knee, and can be a long-term approach to managing OA, especially in patient populations for whom NSAID use is not preferred.
2) The MOVES study is one of the largest of its kind and is an important piece of evidence that supports the use of dietary supplements for joint health.
3) Not all supplements are created equal. To reach optimal clinical effect, one must use supplements with the highest quality pharmaceutical-grade ingredients that were used in clinical studies.
I hope that the outcomes from MOVES and earlier studies like GAIT spur future research in this area, and that larger studies provide solid, indisputable evidence that dietary supplements can be an important part—perhaps even an essential part—of the treatment paradigm in OA. Until that time, the reported patient response rates provide sufficient evidence to warrant continued use of pharmaceutical-grade glucosamine and chondroitin sulfate, especially when combined in a supplement containing the highest quality and purest concentration of these ingredients. This is an approach I will continue to take with many of my patients.
Nicholas DiNubile, MD, is a best-selling author of the FrameWork series of health and fitness books, and an orthopedic surgeon specializing in sports medicine. He is in private practice in Havertown, PA and is a clinical associate in the Department of Orthopedic Surgery at the Hospital of the University of Pennsylvania. Dr. DiNubile has been profiled in “Best Doctors in America” as well as in the “Guide to America’s Top Surgeons.” For more information: www.drnick.com
1. Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2015;0:1-8. doi: 10.1136/annrheumdis-2014-206792.
2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
This past week, results from a landmark clinical study showed that joint supplements are indeed helpful for patients with knee osteoarthritis. In this published research, the combination of two dietary supplements, glucosamine hydrochloride and chondroitin sulfate (GH+CS), reduced pain, functional disability, joint stiffness, swelling and effusion in patients living with knee osteoarthritis (OA). As reported in the current online issue of Annals of Rheumatic Diseases, six months of GH+CS treatment provided efficacy and safety that were comparable to the non-steroidal anti-inflammatory drug (NSAID) celecoxib in patients with severe OA.1
This study, called MOVES (Multicentre Osteoarthritis InterVEntion trial with Sysadoa), is important because it supports the long-term use of GH+CS in OA disease management, an approach that I have taken for many years in my practice. Moreover, the results arguably represent a “tipping point” in the ongoing debate over whether there is sufficient clinical evidence supporting the safe and effective use of GH+CS to manage joint health.
The multicenter, randomized, parallel-group, double-blind, MOVES trial sponsored by Bioibérica, compared the efficacy and safety of GH+CS to celecoxib in 606 patients with primary knee OA and moderate to severe pain. The patients, who were recruited from 42 centers in Spain, Germany, France and Poland GH+CS, received daily doses of pharmaceutical-grade GH+CS (at 1500 mg and 1200 mg, respectively, a combination available in the U.S. as CosaminDS) or celecoxib (200 mg) for six months.
The combination of GH and CS produced clinically relevant reductions in each of the study’s endpoints. Specifically, the results showed improvements in the following parameters:
| Outcome | GH+CS | Celecoxib | p-value |
| Reduction in pain | 50.1% | 50.2% | 0.92 |
| Reduction in functional disability | 45.5% | 46.4% | 0.53 |
| Reduction in joint stiffness | 46.9% | 49.2% | 0.43 |
| Reduction in joint swelling | 52.8% | 67.9% | 0.54 |
| Reduction in joint effusion | 55.9% | 47.4% | 0.61 |
Overall, 51% (155/304) of patients in the GH+CS group experienced at least one treatment-emergent adverse event (AE), compared to 50.5% (151/299) of celecoxib-treated patients. Most AEs were of mild or moderate intensity, with only 17 deemed serious, seven (2.3%) in the GH+CS group and 10 (3.3%) in the celecoxib group. No deaths were reported in the study.
Although both GH+CS and celecoxib exhibited a good safety profile and tolerability in the study population, the investigators commented that celecoxib is associated with increased risk of cardiovascular thrombotic events, congestive heart failure and major gastrointestinal events, compared with placebo, and in the European Union is contraindicated in patients with known cardiovascular and peripheral vascular disease. They added that the GH+CS combination may “offer an alternative, especially for individuals with cardiovascular or gastrointestinal conditions who have contraindications for treatment with NSAIDs.”1 Also, in this study, patients with known gastrointestinal and cardiovascular issues were excluded. These are individuals who would have been more likely to experience medical complications with NSAID therapy and in my experience tolerate the combination of GH+CS.
In short, the MOVES study provides additional evidence to support the safe and effective use of glucosamine hydrochloride and chondroitin sulfate in managing joint health in a wide variety of patients with knee OA. The results are consistent with those reported by Clegg and colleagues in a study known as GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial). In that study, published in 2006 in the New England Journal of Medicine2, the combination of GH+CS was superior to placebo in patients with moderate to severe pain. In fact, it is my understanding that MOVES was developed as an extension of GAIT, to confirm the latter trial’s results. Also, MOVES focused on the subgroup of patients with moderate to severe pain associated with knee OA, and these are typically a more challenging patient subgroup to manage. Since GAIT compared the GH+CS combination to both, celecoxib and placebo, the MOVES trial was designed as a non-inferiority study comparing only the combination versus celecoxib.
Speaking as an orthopedic surgeon specializing in sports medicine for more than 20 years, the MOVES findings are important not only for use of the glucosamine chondroitin combination but to the nutraceutical product community as a whole. The findings underscore both the current value and potential of many supplements as complementary or even alternative therapy in managing a wide variety of conditions.
I am not surprised by these findings because cartilage cell-culture research has demonstrated that glucosamine and chondroitin sulfate work synergistically to stimulate the production of cartilage matrix components and to inhibit enzymes that break down cartilage.
Research has also shown that the combination of GH+CS inhibits expression of several markers involved in cartilage breakdown. In laboratory cell-culture studies of markers associated with both joint discomfort and cartilage breakdown, glucosamine and chondroitin sulfate reduced these markers more effectively when used in combination than when administered separately, again demonstrating a synergistic effect.
Growing Dossier
For many years the ongoing debate about the efficacy of dietary supplements has cast doubt upon the value and utility of non-pharmaceutical approaches to disease management. Studies like MOVES add to a growing body of evidence of impressive outcomes produced by highly active, high-quality supplements administered at appropriate doses and concentration levels in a controlled clinical environment. The authors actually stressed the importance of selecting a high-quality brand of GH+CS to achieve the effectiveness demonstrated in their research. This is something I cannot emphasize enough to my patients when I recommend GH+CS. The latest results also provide reassurance that my approach to long-term disease management is in line with evidence-based research, especially in patients for whom certain pharmaceutical options present safety and potential tolerability issues.
1) Use of a clinical supplement such as glucosamine/chondroitin sulfate is safe and effective in patients with OA of the knee, and can be a long-term approach to managing OA, especially in patient populations for whom NSAID use is not preferred.
2) The MOVES study is one of the largest of its kind and is an important piece of evidence that supports the use of dietary supplements for joint health.
3) Not all supplements are created equal. To reach optimal clinical effect, one must use supplements with the highest quality pharmaceutical-grade ingredients that were used in clinical studies.
I hope that the outcomes from MOVES and earlier studies like GAIT spur future research in this area, and that larger studies provide solid, indisputable evidence that dietary supplements can be an important part—perhaps even an essential part—of the treatment paradigm in OA. Until that time, the reported patient response rates provide sufficient evidence to warrant continued use of pharmaceutical-grade glucosamine and chondroitin sulfate, especially when combined in a supplement containing the highest quality and purest concentration of these ingredients. This is an approach I will continue to take with many of my patients.
Nicholas DiNubile, MD, is a best-selling author of the FrameWork series of health and fitness books, and an orthopedic surgeon specializing in sports medicine. He is in private practice in Havertown, PA and is a clinical associate in the Department of Orthopedic Surgery at the Hospital of the University of Pennsylvania. Dr. DiNubile has been profiled in “Best Doctors in America” as well as in the “Guide to America’s Top Surgeons.” For more information: www.drnick.com
1. Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2015;0:1-8. doi: 10.1136/annrheumdis-2014-206792.
2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
