Glucosamin und Chondroitin als Nahrungsergänzungsmittel in der Knorpeltherapie

(C. Becher, G. Gkoudelis, HH Pässler)  
Aus: Atos News, Ausgabe 8 / Mai 2000

Knorpelschäden und Arthrose stellen die häufigste Problematik in Gelenken des Menschen mittleren und höheren Alters dar. Der lokale oder globale Verlust der Knorpelsubstanz, Veränderungen am Knochen und entzündliche Veränderungen an der Gelenkschleimhaut charakterisieren den Verlauf der Erkrankung. Schätzungsweise 1/3 der Menschen über 45 Jahre in der westlichen Welt klagen über Beschwerden welche auf Knorpelveränderungen zurückzuführen sind. Verschiedenste Arten von Nahrungsergänzungsmittel werden in der Laienpresse angepriesen um die Symptome zu lindern oder eine Heilung zu erzielen. Die Substanzen Glucosamin und Chondroitin sind in den letzten Jahren intensiv beforscht worden. Der Wirkungsansatz und wissenschaftliche Hintergrund wird folgend dargestellt.

Gelenkknorpel besteht aus Chondrozyten (Knorpelzellen), die in eine extrazelluläre Matrix eingebettet sind. Dabei stellen die Chondrozyten nur 1-4% des Gesamtvolumens dar. Die entscheidenden funktionellen Eigenschaften bestimmt die Extrazelluläre Matrix, welche zu 60-80% aus Gewebsflüssigkeit und 20-40% aus Strukturmakromolekülen gebildet wird. Der Anteil der Strukturmakromoleküle im Gelenkknorpel wird durch Kollagene, Proteoglycane und Nichtkollagene Proteine bestimmt, wobei Kollagene etwa 50%, Proteoglycane 30-35% und Nichtkollagene Proteine 15-20% des Trockengewichts ausmachen. Gebildet werden sie von den Chondrozyten.

Proteoglycane sind relativ große, komplizierte Makromoleküle, die in verschiedenen Formen die größten Strukturmakromoleküle der Knorpelgrundsubstanz darstellen. Die Proteoglycane sind für die Knorpelmatrix aufgrund ihres hohen Wasserbindungsvermögens für die Druckelastizität des Knorpels äußerst wichtig. Glucosamin ist ein Aminosaccharid und besteht aus Zucker (Glucose) und der Aminosäure Glutamin. Die Glucosamine dienen als Substrat bei der Synthese der Protheoglycane und anderen Makromolekülen der Knorpelmatrix durch die Chondrozyten.

Die Substanz wird aus Schalentieren (Krebse, Lobster etc.) gewonnen oder synthetisch hergestellt und in Form der Verbindungen Glucosaminsulfat, Glucosaminhydrochlorid oder N-Acetyl-Glucosamin von der pharmazeutischen Industrie angeboten.  Chondroitin ist ein Glycosaminoglycan, welches sich mit anderen Glycosminoglycanen und Proteinen verbindet und somit einen wichtigen Bestandteil des Proteoglycanaggregats darstellt. Chondroitin wird üblicherweise aus Knorpelbestandteilen von Rindern, Schweinen oder Haien hergestellt und meist in sulfatierter Form angeboten.

Unter physiologischen Bedingungen herrscht im Gelenk ein Gleichgewicht zwischen anabolen (aufbauenden) und katabolen (abbauenden) Stoffwechselprozessen. Bei degenerativen Gelenkserkrankungen ist dieses Verhältnis zugunsten der destruktiven Vorgänge verschoben. Die Ursachen hierfür sind sehr vielschichtig und liegt in einer noch nicht in allen Einzelheiten verstandenen Kombination aus metabolischen, biochemischen und biomechanischen Faktoren.

Proinflammatorische Zytokine (Entzündungsfördernde Proteine) wie beispielsweise IL-1 und TNF-a werden allerdings als Schlüsselfaktoren in der Knorpeldestruktion angesehen. Sie führen zu einer gesteigerten Produktion knorpelschädigender Substanzen (Metalloproteinasen-MMPs, Kollagenasen etc.), sowie zu einem Anstieg von Prostaglandinen (PGE2), Stickstoffmonoxidradikalen (NO) und weiteren katabolen Enzymen, welche das Gelenkgleichgewicht zerstören und somit zu den typischen Veränderungen der Arthrose führen.

Bisher gibt es keine kausale Behandlungsmöglichkeit der arthrotischen Veränderungen. Die Physio- und Pharmakotherapie bietet eine Möglichkeit die Schmerzsymptomatik und Funktion zu verbessern. Pharmazeutisch werden klassische schmerzlindernde und entzündungshemmende Substanzen (NSAID, Kortikosteroide) eingesetzt. Während für Phytopharmaka (z.B. Weidenrindenextrakt, Teufelskrallenwurzel, Vitamine, Spurenelemente etc.) keine oder zweifelhafte wissenschaftlichen Belege der Wirksamkeit erbracht werden konnten, gibt es Belege für den positiven Einfluss von beispielsweise Glucosamin, Chondroitin, Hyaluronsäure und Diacerhein. Glucosamin und Chondroitin werden hierbei zu den „slow acting drugs in osteoarhritis – SADOA“ gezählt. Sie werden charakterisiert durch eine langsam wirkende Verbesserung der Symptomatik durch eine antiinflammatorische (entündungshemmende) Wirkung, sowie Steigerung der Proteoglycansynthese und somit Verbesserung der Knorpelgrundsubstanz. Im Vergleich zu den klassischen NSAID´s wird nur ein geringes Risiko für Nebenwirkungen beschrieben. Die empfohlenen Tagesdosen variieren. Die Gabe von 1,5g Glucosaminsulfat und 0,8-1,2g Chondroitinsulfat pro Tag wird allerdings momentan als die effektivste Dosis angesehen. Inwieweit die oral eingenommenen Substanzen vom Körper aufgenommen und tatsächlich im Gelenk zur Verfügung stehen, wird momentan noch kontrovers diskutiert.

In einer Metaanalyse von McAlindon et al. aus dem Jahre 2000, welche im Journal of the American Medical Association veröffentlicht wurde, wird mit einer Ausnahme von ausschließlich positiven Ergebnissen durch die Einnahme von Glucosamin und Chondroitin berichtet. Die meisten dieser Studien wurden allerdings von der pharmazeutischen Industrie gesponsert. Towheed et al. veröffentlichten kürzlich einen systematischen Überblick über die vorhandenen Studien bezüglich der Einnahme von Glucosamin. Zusammengefasste Daten zeigten im Vergleich mit Placebo eine Verbesserung in Bezug auf den Lequesne-Index bei Schmerz von 28% und auf Funktion von 21%. Der WOMAC-Arthrose-Index zeigte allerdings keine signifikante Verbesserung in Bezug auf Schmerz, Funktion und Steifigkeit. Diese Heterogenität der Ergebnisse ist nicht eindeutig erklärbar. In einer aktuellen Studie von Michel et al. wird von einem signifikant geringeren radiologischem Fortschreiten der Arthrose (gemessen an der Gelenkspaltweite) nach Einnahme von 800mg Chondroitin berichtet. Allerdings gab es keinen Unterschied in Bezug auf die Symptome der Erkrankung.

Im Rahmen einer experimentellen Studie an Pferden konnte gezeigt werden, dass die besten Effekte erzielt werden, wenn beide Substanzen gemeinsam verabreicht werden. In einer weiteren tierexperimentellen Studie wurde eine geringere genetisch gesteuerte Produktion von NO und PGE2 beobachtet, was eine Erklärung für den antientzündlichen Effekt darstellen könnte. Eine weitere Arbeitsgruppe beschreibt, dass die metabolische Antwort von älteren Rindern auf Gelenkbelastung unter der Gabe von Glucosamin und Chondroitin größer ist als ohne Belastung oder bei jungen Rindern. Sie folgerten, dass Glucosamin und Chondroitin die Fähigkeit des Knorpel zur Reparatur und Regeneration erhöht.

Zusammengefasst lässt die Studienlage keine abschließende Beurteilung zu. Die bisherigen klinischen Mittel der Gelenkspaltveränderung mittels Röntgenbild und die uneinheitliche Standardisierung der Beschreibung des Ausmaßes der Arthrose müssen aber als unzureichend angesehen werden und dementsprechend eingeschränkt werden, dass der Evidenz-basierte Beweis einer Arthrose-Reduktion im klinischen Einsatz bisher nicht eindeutig erbracht worden ist.

Zusammenfassung
Mit Glucosamin und Chondroitin stehen oral verabreichbare Substanzen mit geringem Nebenwirkungspotential in der Behandlung von Knorpelschäden und der Arthrose zur Verfügung. Die klinische Wirksamkeit ist nicht eindeutig bewiesen, es gibt positive wie negative Beurteilungen. Der genaue Wirkungsmechanismus ist momentan Gegenstand der experimentellen Forschung und führt zu interessanten Ergebnissen. Aus unseren Erfahrungen und nach momentanem Stand der Forschung kann der Einsatz, insbesondere wegen des geringen Nebenwirkungspotentials, empfohlen werden. Der Effekt in Abhängigkeit der Pathologie kann allerdings nicht genau vorrausgesagt werden.

Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies.

Bruyere O, Pavelka K, Rovati LC, Deroisy R, Olejarova M, Gatterova J, Giacovelli G, Reginster JY. WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, Liege, Belgium.

OBJECTIVE: To investigate the effect of glucosamine sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). DESIGN: This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA. RESULTS: Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, glucosamine sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the postmenopausal women subset. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of -0.33 mm (95% CI, -0.44 to -0.22; P < 0.0001 between the two groups). Percent changes after 3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14.1% (95%, -22.2 to -5.9)] and a trend for worsening in the placebo group (5.4% (95% CI, -4.9 to 15.7) (P = 0.003 between the two groups). CONCLUSION: This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.

Osteoarthritis Cartilage. 2003 Jan;11(1):1-5. Related Articles, Links

Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate.

Bruyere O, Honore A, Ethgen O, Rovati LC, Giacovelli G, Henrotin YE, Seidel L, Reginster JY. WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, Liege, Belgium.

OBJECTIVE: To investigate the relationship between baseline radiographic severity of knee osteoarthritis (OA) and the importance of long-term joint space narrowing. DESIGN: Sub-analysis from a three-year randomized, placebo-controlled, prospective study, of 212 patients with knee OA, recruited in an osteoarthritic outpatient clinic and having been part of a study evaluating the effect of glucosamine sulfate on symptom and structure modification in knee OA. MATERIAL AND METHODS: Measurements of mean joint space width (JSW), assessed by a computer-assisted method, were performed at baseline and after 3 years, on weightbearing anteroposterior knee radiographs. RESULTS: In the placebo group, baseline JSW was significantly and negatively correlated with the joint space narrowing observed after 3 years (r=-0.34, P=0.003). In the lowest quartile of baseline mean JSW (<4.5mm), the JSW increased after 3 years by (mean (S.D.)) 3.8% (23.8) in the placebo group and 6.2% (17.5) in the glucosamine sulfate group. The difference between the two groups in these patients with the most severe OA at baseline was not statistically significant (P=0.70). In the highest quartile of baseline mean JSW (>6.2mm), a joint space narrowing of 14.9% (17.9) occurred in the placebo group after 3 years while patients from the glucosamine sulfate group only experienced a narrowing of 6.0% (15.1). Patients with the most severe OA at baseline had a RR of 0.42 (0.17-1.01) to experience a 0.5mm joint space narrowing over 3 years, compared to those with the less affected joint. In patients with mild OA, i.e. in the highest quartile of baseline mean JSW, glucosamine sulfate use was associated with a trend (P=0.10) towards a significant reduction in joint space narrowing. CONCLUSION: These results suggest that patients with the less severe radiographic knee OA will experience, over 3 years, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs. Copyright 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd.

Arch Intern Med. 2002 Oct 14;162(18):2113-23. Related Articles, Links

Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study.

Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Department of Medicine and Rheumatology, Charles University, Prague, Czech Republic.

BACKGROUND: Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomized, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested. METHODS: Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomized to receive oral glucosamine sulfate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities). RESULTS: Osteoarthritis was of mild to moderate severity at enrollment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups. CONCLUSION: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.

Cranio. 2001 Apr;19(2):130-9. Related Articles, Links

A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study.

Nguyen P, Mohamed SE, Gardiner D, Salinas T. Louisiana State University Health Sciences Center, New Orleans, USA.

Previous studies have shown chondroitin sulfate and glucosamine hydrochloride have beneficial effects on symptoms of osteoarthritis of the knee. Our aim was to study the effect of a daily dose of 1500 mg of glucosamine hydrochloride (GH) and 1200 mg of chondroitin sulfate (CS) taken for twelve weeks on subjects diagnosed with capsulitis, disk displacement, disk dislocation, or painful osteoarthritis of the temporomandibular joint (TMJ). Forty-five subjects were enrolled in the study and were randomly assigned to either an active medication group or a placebo group. Eleven subjects were lost from the study for various reasons, resulting in fourteen subjects remaining in the active medication group and twenty subjects remaining in the placebo group. Subjects taking CS-GH had improvements in their pain as measured by one index of the McGill Pain Questionnaire, in TMJ tenderness, in TMJ sounds, and in the number of daily over-the-counter medications needed. Subjects taking the placebo medication had improvements in their pains as measured by the visual analog scale and by four indices of the McGill Pain Questionnaire. Additional studies are required to evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism by which CS-GH affects the articular cartilage of synovial joints.

Osteoarthritis Cartilage. 2000 Sep;8(5):343-50. Related Articles, Links

Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis.

Das A Jr, Hammad TA.
Hendersonville Orthopedics Associates, Hendersonville, North Carolina 28739, USA.

OBJECTIVES: The objective of this study was to evaluate the oral combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate for the treatment of osteoarthritis (OA) of the knee. DESIGN: A randomized placebo-controlled study design was implemented. We recruited 93 patients with OA of the knee from a single center. The intervention group received 1000 mg FCHG49 glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate and 152 mg manganese ascorbate twice daily (Cosamin DS). Patients were evaluated initially and then every 2 months for 6 months. The primary outcome was the Lesquene Index of severity of osteoarthritis of the knee (ISK). RESULTS: Patients with radiographically mild or moderate OA (N=72) in the intervention group showed significant improvement in the ISK at 4 and 6 months (P=0.003 and P=0.04, respectively). The response rate to the medication was 52% vs a 28% response rate to placebo. Patients with radiographically severe osteoarthritis (N=21) did not show significant improvements in the ISK. There was a 17% incidence of adverse events in the intervention group and 19% in the placebo group. CONCLUSIONS: The studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate was found to be effective for the treatment of radiographically mild to moderate OA of the knee as measured by the ISK. This is the first U.S. study of these agents. Copyright 2000 OsteoArthritis Research Society International.
Publication Types: * Clinical Trial

Harefuah. 2000 Mar 15;138(6):451-3, 518. Related Articles, Links

GAG for osteoarthritis of the knee–a prospective study

(Article in Hebrew) Debi R, Robinson D, Agar G, Halperin N. Orthopedic Dept., Assaf Harofeh Medical Center, Zrifin.

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans due to imbalance between synthesis and degradation. The availability of glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate-limiting for proteoglycan production in cartilage tissue culture. 57 patients suffering from osteoarthritis of the knee were randomized into a group treated for 4 weeks with daily i.v. glucosamine sulfate (GS) together with 800 mg chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on palpation, as well as range of knee motion were then recorded. In the GS group, there was significant reduction of clinical symptoms (p < 0.01), but no significant reduction in the placebo group. Physicians‘ assessment of tenderness and range of motion were significantly in favor of the GS group ( p < 0.01). In those treated with glycosamine there were no adverse reactions and no changes in laboratory blood tests. We conclude that GS can be considered the drug of choice for prolonged treatment of osteoarthritis.
Publication Types: * Clinical Trial, * Randomized Controlled Trial

Equine Vet J. 2005 May;37(3):227-31. Related Articles, Links             

Effects of glucosamine hydrochloride and chondroitin sulphate, alone and in combination, on normal and interleukin-1 conditioned equine articular cartilage explant metabolism.

Dechant JE, Baxter GM, Frisbie DD, Trotter GW, McIlwraith CW. Equine Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.

REASONS FOR PERFORMING STUDY: Clinical trials in human and veterinary literature have documented the benefits of oral nutraceutical joint supplements containing glucosamine (GU) and chondroitin sulphate (CS) to treat mild to moderate osteoarthritis, but the effects of these components have not yet been conclusively determined. OBJECTIVES: To assess varying dosages of GU and CS on normal and interleukin-1alpha (IL-1) conditioned equine cartilage explants and rationalise the use of these products. HYPOTHESIS: Treatment would not be detrimental to cartilage metabolism and higher dosages and the combination of GU and CS would be more beneficial than lower dosages and. GU or CS alone. METHODS: Articular cartilage explants collected from the femoral trochlea and condyles were cultured in normal and IL-1 conditioned media. Treatment groups included 0, 12.5, 25,125 and 250 microg/ml concentrations of GU alone, CS alone, or GU+CS in combination. Glycosaminoglycan (GAG) synthesis and total GAG content in the explants and media were analysed. RESULTS: There were no detrimental effects of GU, CS or GU+CS on cartilage metabolism. High dosages of GU+CS reduced total GAG release into the media (degradation). CONCLUSIONS: Our results suggests that GU+CS may prevent cartilage GAG degradation. POTENTIAL RELEVANCE: The combination of GU and CS may be more effective in preventing or treating osteoarthritis in horses than either product alone.

Exp Biol Med (Maywood). 2005 Apr;230(4):255-62. Related Articles, Links

Effects of chondroitin and glucosamine sulfate in a dietary bar formulation on inflammation, interleukin-1beta, matrix metalloprotease-9, and cartilage damage in arthritis.

Chou MM, Vergnolle N, McDougall JJ, Wallace JL, Marty S, Teskey V, Buret AG. Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada, T2N 1N4.

This study examined the effects of chondroitin sulfate (CS) alone and CS plus glucosamine sulfate (GS) in a dietary bar formulation on inflammatory parameters of adjuvant-induced arthritis and on the synthesis of interleukin-1beta (IL-1beta) and matrix metalloprotease-9 (MMP-9). Following 25 days pretreatment with dietary bars containing either CS alone, CS plus GS, or neither CS nor GS, rats were either sham injected or injected with Freund’s complete adjuvant into the tail vein. Rats were fed their respective bars for another 17 days after inoculation. Parameters of disease examined included clinical score (combination of joint temperature, edema, hyperalgesia, and standing and walking limb function), incidence of disease, levels of IL-1beta in the serum and paw joints, levels of MMP-9 in the paw joints, paw joint histology, and joint cartilage thickness. Treatment with CS plus GS, but not CS alone, significantly reduced clinical scores, incidences of disease, joint temperatures, and joint and serum IL-1beta levels. Treatment with CS alone and CS plus GS inhibited the production of edema and prevented raised levels of joint MMP-9 associated with arthritis. Similarly, CS alone and CS plus GS treatment also prevented the development of cartilage damage associated with arthritis. Combination CS plus GS treatment in a dietary bar formulation ameliorates clinical, inflammatory, and histologic parameters of adjuvant-induced arthritis. The benefits of CS and GS in combination are more pronounced than those of CS alone. The reduction of arthritic disease by CS plus GS is associated with a reduction of IL-1beta and MMP-9 synthesis.

Arthritis Rheum. 2005 Mar;52(3):779-86. Related Articles, Links

Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial.

Michel BA, Stucki G, Frey D, De Vathaire F, Vignon E, Bruehlmann P, Uebelhart D. University Hospital Zurich, Zurich, Switzerland.

OBJECTIVE: To determine whether chondroitin sulfate (CS) is effective in inhibiting cartilage loss in knee osteoarthritis (OA). METHODS: In this randomized, double-blind, placebo-controlled trial, 300 patients with knee OA were recruited from an outpatient clinic, from private practices, and through advertisements. Study patients were randomly assigned to receive either 800 mg CS or placebo once daily for 2 years. The primary outcome was joint space loss over 2 years as assessed by a posteroanterior radiograph of the knee in flexion; secondary outcomes included pain and function. RESULTS: Of 341 patients screened, 300 entered the study and were included in the intent-to-treat analysis. The 150 patients receiving placebo had progressive joint space narrowing, with a mean +/- SD joint space loss of 0.14 +/- 0.61 mm after 2 years (P = 0.001 compared with baseline). In contrast, there was no change in mean joint space width for the 150 patients receiving CS (0.00 +/- 0.53 mm; P not significant compared with baseline). Similar results were found for minimum joint space narrowing. The differences in loss of joint space between the two groups were significant for mean joint space width (0.14 +/- 0.57 mm; P = 0.04) and for minimum joint space width (0.12 +/- 0.52 mm; P = 0.05). CS was well tolerated, with no significant differences in rates of adverse events between the two groups. CONCLUSION: While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial

J Knee Surg. 2004 Oct;17(4):185-93. Related Articles, Links

Recent advances in glucosamine and chondroitin supplementation.

Owens S, Wagner P, Vangsness CT Jr. Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, Calif, USA.

Glucosamine and chondroitin are alternative solutions to previous pharmaceutical options for the treatment of osteoarthritis. This article describes the mechanisms of action, pharmacokinetics, recent findings, and upcoming studies of these two natural remedies. The majority of studies on the mechanisms behind glucosamine and chondroitin have been performed in vitro or on animal models; however, the results have shown favorable effects on the balance between cartilage matrix synthesis and degradation. The pharmacokinetics of the three main forms of glucosamine were compared, and glucosamine hydrochloride displayed the greatest compound purity, despite the compounds having equal oral absorption rates of 90%. Chondroitin sulfate has been the principal clinical formulation with a slightly lower oral absorption of 70%. Clinical trials were evaluated based on two categories-radiographic changes and symptom improvement of pain and function. Although adverse effects of these two remedies were minor, the quality and labeled quantity of these relatively unregulated products must be considered. More randomized controlled studies on humans in vivo need to evaluate the efficacy, long-term effects, and quality of these compounds.

Curr Drug Targets Immune Endocr Metabol Disord. 2004 Jun;4(2):119-27. Related Articles, Links

A two-year study of chondroitin sulfate in erosive osteoarthritis of the hands: behavior of erosions, osteophytes, pain and hand dysfunction.

Rovetta G, Monteforte P, Molfetta G, Balestra V. Department of Rheumatology, University Medical School, Genoa, Italy.

The aim of this study was to evaluate the effect of 800 mg/die of chondroitin sulfate (CHS) per os plus naproxen versus naproxen over 2 years in patients with erosive osteoarthritis (EOA) of the hands. Joint count for erosions, Heberden and Bouchard nodes, Dreiser’s algofunctional index and physicians‘ and patients‘ global assessment of disease activity were studied. A total of 24 consecutive patients (22 women and 2 men, mean age 53.0 +/- 6) suffering from symptomatic OA with radiographic characteristics of EOA were evaluated. The patients were divided into two groups of 12 patients each. The first group took naproxen 500 mg only. The second group was treated with CHS 800 mg orally plus naproxen 500 mg. Joint counts, radiological hand examinations and assessment of disease activity were performed at baseline, at 12 months and at 24 months. In the second year the treated group showed significant worsening in erosion, Heberden, Bouchard and Dreiser scores was recorded. Physician and patient global assessments of disease activity showed no significant difference from baseline scores. The untreated group showed significant worsening in erosion, Heberden and Bouchard nodes, Dreiser index and physician and patient global assessment scores. This study confirms the partial efficacy of oral CHS in improving some aspects of EOA.

Osteoarthritis Cartilage. 2004 Apr;12(4):269-76. Related Articles, Links

Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo.

Uebelhart D, Malaise M, Marcolongo R, DeVathaire F, Piperno M, Mailleux E, Fioravanti A, Matoso L, Vignon E. Department of Rheumatology, Institute of Physical Medicine, University Hospital Zurich, Switzerland.

OBJECTIVE: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. DESIGN: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne’s algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. RESULTS: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. CONCLUSION: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.
Publication Types:
* Clinical Trial
* Multicenter Study
* Randomized Controlled Trial

PMID: 15023378 [PubMed – indexed for MEDLINE]

Biol Pharm Bull. 2004 Jan;27(1):47-51. Related Articles, Links  

Effects of low molecular weight chondroitin sulfate on type II collagen-induced arthritis in DBA/1J mice.

Cho SY, Sim JS, Jeong CS, Chang SY, Choi DW, Toida T, Kim YS. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, Korea.

In order to evaluate the improvement in the treatment of chronic arthritis, we investigated chondroitin sulfate depolymerization product (low molecular weight chondroitin sulfate, LMWCS) and intact chondroitin sulfate (CS) in vitro and in vivo. LMWCS was prepared by a chemical depolymerization process induced by hydrogen peroxide in the presence of copper salts. LMWCS (300 mg/kg) and CS (1200 mg/kg) were orally administered to DBA/1J mice once daily for 14 d prior to initial immunization with type II collagen. Their elastase activities and the production of cytokines in sera were examined on type II collagen-induced arthritis in DBA/1J mice. We also compared the paracellular transport of LMWCS and CS across Caco-2 cell monolayers and examined the inhibitory effects on elastase activities. LMWCS inhibited elastase activity slightly, but CS did not show inhibition. Hind paw edema was significantly decreased by LMWCS treatment. Levels of anti-type II collagen antibody and tumor necrosis factor-alpha (TNF-alpha) in sera were also reduced by LMWCS treatment but not in case of CS, although no significant difference was observed between LMWCS and CS on interleukin-6 (IL-6) induction. The LMWCS preparation showed preventive effects on the type II collagen-induced arthritis in DBA/1J mice and better permeability through Caco-2 cells.

Arch Intern Med. 2003 Jul 14;163(13):1514-22. Related Articles, Links

Comment in:
* Arch Intern Med. 2004 Feb 9;164(3):338-9; author reply 339.
* J Fam Pract. 2003 Dec;52(12):919-20.    

Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis.

Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Faculty of Medicine, Department of Public Health, Public Health and Epidemiology, University of Liege, Liege, Belgium.  

                         OBJECTIVE: To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. METHODS: An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. RESULTS: Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. CONCLUSIONS: Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.

J Arthroplasty. 2003 Apr;18(3 Suppl 1):5-9. Related Articles, Links    

Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis.

Hungerford DS, Jones LC.
Division of Arthritis Surgery, Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, G-1 Good Samaritan Professional Building, 5601 Loch Raven Boulevard, Baltimore, MD 21239, USA.

The use of glucosamine and chondroitin sulfate for the symptomatic treatment of osteoarthritis has been a subject of controversy for several reasons. First, the medical community in general took offense at the title of Theodosakis‘ book, The Arthritis Cure. Second, the medical community is becoming divided into „traditional“ and „alternative“ camps with deep skepticism between them. Third, the whole nutraceutical industry is essentially unregulated, with manufacturers making outrageous claims on products that have never been tested at all, are often of poor quality, and occasionally lacking in any active ingredient. However, for the nutriceuticals evaluated here, there is abundant in vitro, in vivo, animal clinical, and human clinical evidence of both their efficacy and safety. They deserve a prominent place in the armamentarium of nonsurgical treatment of osteoarthritis. Copyright 2003 Elsevier Inc. All rights reserved.

Presse Med. 2002 Sep 14;31(29):1386-90. Related Articles, Links

Radiological progression of internal femoro-tibial osteoarthritis in gonarthrosis. Chondro-protective effect of chondroitin sulfates ACS4-ACS6

(Article in French)
Mathieu P.
Service de rhumatologie du Pr Vignon, CH Lyon Sud, 165, chemin du Grand Revoyet, 69495 Pierre-Benite.

OBJECTIVE: To confirm the structure-modulating properties of ACS4-ACS6 in gonathrosis by measuring the modifications in minimum joint space width, the mean thickness and the mean surface of the cartilage in internal femorotibial function. METHOD: This was a double blind prospective study versus placebo including 300 symptomatic patients with internal femorotibial gonathrosis. The measurements were made with a semi-automatic method validated from digitalized radiological images taken at two years in each patient. RESULTS: There was an equal number of dropouts in the 2 groups (40 in the ACS4-ACS6 group and 41 in the placebo group). After 2 years, there was a significant difference, with worsening of the affection in the placebo group. In the group treated with ACS4-ACS6, there was no significant variation in all the radiological parameters, which remained remarkably stable. When comparing the 2 groups, the statistical analysis revealed a significant difference in the ACS4-ACS6 group with maintenance of the cartilage analyzed, not only in the intent-to-treat patients but also in the per protocol population. CONCLUSION: ACS4-ACS6 is superior to the placebo with regard to the stabilization of minimum joint space width of the internal femorotibial articular space, the mean thickness and the surface.