Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis.

AIM: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. CONCLUSION: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA.

[Chondroitin sulfate in therapy osteoarthritis chronic pain patients according to actual clinical recommendations].

Of undoubted interest is the search for new drugs comparable in effectiveness to nonsteroidal anti-inflammatory drugs (NSAIDs), but with a safer application profile. NSAIDs are characterized by a good analgesic effect due to the modulation of prostaglandin metabolism by inhibition of cyclooxygenase-2. One of the promising directions of pharmacotherapy of degenerative-dystrophic joint lesions is the use of symptom-modifying drugs of delayed action, which include chondroitin sulfate (CS). CS has antiresorptive activity, anti-inflammatory and anti-inflamaging effects. In addition to the direct effect on pain syndrome severity, he also have a modulating level effect of systemic inflammation of cartilage tissue. According to experts of international and Russian societies, pharmaceutical prescription-quality CS is a basic part of the treatment of osteoarthritis. One of the advantages of CS over NSAIDs is the preservation of the effect for 24 months after the treatment. Against the background of the use of CS, it is possible to reduce the dose or completely cancel NSAIDs, which helps to reduce the frequency of adverse events associated with their intake. CS has a favorable safety profile, which is important for elderly patients and those with comorbid diseases (cardioprotective effects). CS drugs can be administered per orally, intramuscularly, intra-articularly and in combination with different administration methods. Several clinical trials of CS (Chondrogard), including randomized, were conducted in Russia. The Russia Health Ministry approved the appointment of parenteral CS in clinical guidelines: Chronic pain in elderly and senile patients (2020), Falls in elderly and senile patients(2020), "Knee osteoarthritis" (2021), "Hip osteoarthritis" (2021).

Comparison of Danaparoid Sodium and Synthetic Protease Inhibitors for the Treatment of Disseminated Intravascular Coagulation Associated with Hematological Malignancies: A Retrospective Analysis.

BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

(Semi)-Synthetic Fucosylated Chondroitin Sulfate Oligo- and Polysaccharides.

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan (GAG) polysaccharide with a unique structure, displaying a backbone composed of alternating N-acetyl-d-galactosamine (GalNAc) and d-glucuronic acid (GlcA) units on which l-fucose (Fuc) branches are installed. fCS shows several potential biomedical applications, with the anticoagulant activity standing as the most promising and widely investigated one. Natural fCS polysaccharides extracted from marine organisms (Echinoidea, Holothuroidea) present some advantages over a largely employed antithrombotic drug such as heparin, but some adverse effects as well as a frequently found structural heterogeneity hamper its development as a new drug. To circumvent these drawbacks, several efforts have been made in the last decade to obtain synthetic and semi-synthetic fCS oligosaccharides and low molecular weight polysaccharides. In this Review we have for the first time collected these reports together, dividing them in two topics: (i) total syntheses of fCS oligosaccharides and (ii) semi-synthetic approaches to fCS oligosaccharides and low molecular weight polysaccharides as well as glycoclusters displaying multiple copies of fCS species.

Danaparoid is effective and safe for patients with obstetric antiphospholipid syndrome.

Objectives: The objective is to evaluate whether danaparoid is effective in improving the live birth rate in patients with obstetric antiphospholipid syndrome (oAPS).Methods: This prospective study included 91 pregnancies of 60 patients with oAPS diagnosed according to criteria of the International Congress on APS. Live birth rates, adverse pregnancies and perinatal outcomes were compared among patients treated with danaparoid and low dose aspirin (danaparoid group, LDA), unfractionated heparin (UFH) and LDA (UFH group) and LDA and/or prednisolone (LDA group).Results: After excluding 11 miscarriages with abnormal embryonic chromosomes, one chemical pregnancy and one ectopic pregnancy, live birth rates were 87.5% (14/16) for the danaparoid group, 90.0% (36/40) for the UFH group and 63.6% (14/22) for the LDA group, respectively. The live birth rates of patients treated with danaparoid and UFH were similar and tended to be higher than that of patients treated with LDA, respectively (OR 4.0, 95% confidence interval 0.72-22.22 and 5.15, 1.33-20.00). No patient given danaparoid and one patient with UFH developed heparin-induced thrombocytopenia which resulted in a stillbirth. Another patient with UFH suffered a lumbar compression fracture.Conclusion: Danaparoid is effective for improving the live birth rate and is safe for patients with oAPS.

Microbial Co-Occurrence Patterns and Keystone Species in the Gut Microbial Community of Mice in Response to Stress and Chondroitin Sulfate Disaccharide.

Detecting microbial interactions is essential to the understanding of the structure and function of the gut microbiome. In this study, microbial co-occurrence patterns were inferred using a random matrix theory based approach in the gut microbiome of mice in response to chondroitin sulfate disaccharide (CSD) under healthy and stressed conditions. The exercise stress disrupted the network composition and microbial co-occurrence patterns. Thirty-four Operational Taxonomic Units (OTU) were identified as module hubs and connectors, likely acting as generalists in the microbial community. Mucispirillum schaedleri acted as a connector in the stressed network in response to CSD supplement and may play a key role in bridging intimate interactions between the host and its microbiome. Several modules correlated with physiological parameters were detected. For example, Modules M02 (under stress) and S05 (stress + CSD) were strongly correlated with blood urea nitrogen levels (r = 0.90 and -0.75, respectively). A positive correlation between node connectivity of the OTUs assigned to Proteobacteria with superoxide dismutase activities under stress (r = 0.57, p < 0.05) provided further evidence that Proteobacteria can be developed as a potential pathological marker. Our findings provided novel insights into gut microbial interactions and may facilitate future endeavor in microbial community engineering.

Chondroitin Sulfate Safety and Quality.

The industrial production of chondroitin sulfate (CS) uses animal tissue sources as raw material derived from different terrestrial or marine species of animals. CS possesses a heterogeneous structure and physical-chemical profile in different species and tissues, responsible for the various and more specialized functions of these macromolecules. Moreover, mixes of different animal tissues and sources are possible, producing a CS final product having varied characteristics and not well identified profile, influencing oral absorption and activity. Finally, different extraction and purification processes may introduce further modifications of the CS structural characteristics and properties and may lead to extracts having a variable grade of purity, limited biological effects, presence of contaminants causing problems of safety and reproducibility along with not surely identified origin. These aspects pose a serious problem for the final consumers of the pharmaceutical or nutraceutical products mainly related to the traceability of CS and to the declaration of the real origin of the active ingredient and its content. In this review, specific, sensitive and validated analytical quality controls such as electrophoresis, eHPLC (enzymatic HPLC) and HPSEC (high-performance size-exclusion chromatography) able to assure CS quality and origin are illustrated and discussed.

Clinical comparison of intravesical hyaluronic acid and chondroitin sulfate therapies in the treatment of bladder pain syndrome/interstitial cystitis.

INTRODUCTION: Intravesical glucosaminoglycan (GAG) replacement therapies are commonly used in the treatment of bladder pain syndrome (BPS)/interstitial cystitis (IC). Different intravesical glucosaminoglycan products are currently available. In this prospective study, clinical efficacy of chondroitin sulfate and hyaluronic acid are compared in patients with BPS/IC. METHODS: Patients were randomized to CS and HA groups. All patients were evaluated for visual analogue pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, and mean urine volume per void at the beginning of the therapy and after 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. RESULTS: There were 21 patients in both groups. Mean age of patients in CS and HA groups were 47.10 and 48.90, respectively(P > 0.05). Before treatment, Parson's test was positive in 64.3% of patients (27/42) with no difference between groups. VAS of pain, ICSI, ICPI, frequency at 24 h and nocturia results have improved significantly at both treatment arms. Intravesical CS was also found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI (P < 0.05). No severe adverse effects were reported. CONCLUSIONS: Data comparing clinical efficiencies of different GAG therapies are very limited. In this study, intravesical CS was found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI in patients with BPS/IC in short term follow-up. To provide a definitive conclusion on superiority of one GAG therapy to others, further evaluation with long term follow up is required.

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.

Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib.

OBJECTIVES: To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. METHODS: Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. RESULTS: The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. CONCLUSIONS: CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile. TRIAL REGISTRATION NUMBER: NCT01425853.

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial.

BACKGROUND: Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, ß-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS: Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS: The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI.

Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog.

A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis.

Syndrome de défaillance multiviscérale secondaire à un surdosage d'un supplément pour articulation chez un chien. Une chienne Bouvier bernois stérilisée âgée de 5 ans présentée avec une plainte principale de vomissements et de mélæna avait ingéré environ 200 comprimés de suppléments nutritionnels pour les articulations. Malgré une thérapie agressive, la patiente a développé une coagulopathie, une pancréatite, une péritonite et une blessure aiguë aux reins et a été euthanasiée. L'autopsie a révélé une nécrose du myocarde, une pneumonie, une hémorragie centrilobulaire et une nécrose du foie, une vasculite et une nécrose tubulaire.(Traduit par Isabelle Vallières).

Specific anti-IIa activity is a key indicator of safety and efficacy in validation of biosimilarity of unfractioned heparin preparations.

We compared anti-IIa activity of a heparin analogue and a reference product was carried out to confirm their biosimilarity. The experiment was based on the method of estimation of anti-IIa activity of a commercial sodium heparin preparation according to United States Pharmacopoeia. High similarity of the two medicinal heparin preparations by this parameter is shown. The method is recommended for the use in comparability studies.

Fucosylated chondroitin sulfate inhibits Plasmodium falciparum cytoadhesion and merozoite invasion.

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.

Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate.

INTRODUCTION: Herbal and dietary supplements are widely used as measures to improve and preserve health and well-being. Among the bestselling preparations are dietary supplement containing glucosamine and chondroitine sulfate taken to improve symptoms of osteoarthritis. METHODS AND RESULTS: We here present a case of a male patient with biopsy-proven acute and severe autoimmune hepatitis subsequent to intake of a preparation containing glucosamine and chondroitine sulfate. Response to steroids was favorable and resulted in complete remission of the patient. Diagnostic work-up of the case revealed no other possible cause of liver injury, and causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) resulted in a possible causal relationship between intake of glucosamine and chondroitine sulfate and the adverse hepatic reaction. CONCLUSION: The present case recalls that products containing glucosamine and chondroitine sulfate can occasionally cause acute liver injury mimicking autoimmune hepatitis, and reminds of the potential dangers of compounds with poor efficacy and ill-defined safety records.

Comparison of the ability of chondroitin sulfate derived from bovine, fish and pigs to suppress human osteoclast activity in vitro.

Chondroitin sulfate (CS) compounds are commonly used to manage OA symptoms. Recent literature has indicated that abnormal subchondral bone metabolism may have a role in the pathogenesis of OA. The aim of this study was to access the effects of chondroitin sulfate obtained from bovine, fish and porcine sources on human osteoclast formation and activity in vitro. Human osteoclasts were generated from blood mononuclear cells. Cells were cultured over 17 days with the addition of macrophage colony stimulating factor (M-CSF) and then stimulated with receptor activator of nuclear factor kappa B ligand from day 7. Cells were treated with the CS commencing from day 7 onwards. To assess effects on osteoclasts, tartrate resistant acid phosphatate (TRAP) expression and resorption of whale dentine assays were used. Bovine-derived CS consistently suppressed osteoclast activity at concentrations as low as 1 µg/ml. Fish and porcine CS was less consistent in their effects varying with different donor cells. All CS compounds had little effect on TRAP activity. mRNA analysis using real-time PCR of bovine CS treated cells indicated that the inhibition of activity was not due to inhibition of the late stage NFATc1 transcription factor (p > 0.05). These results are consistent with CS inhibition of mature osteoclast activity rather than the formation of mature osteoclasts. It would appear that there are differences in activity of the different CS compounds with bovine-derived CS being the most consistently effective inhibitor of osteoclast resorption, but the results need to be confirmed.

[Allergy of calcium phosphate cement material following skull reconstruction: a case report].

The paste form of calcium phosphate cement is often used in skull reconstruction because of the biocompatibility and early handling of these cements. Although it had rarely been shown to produce a foreign body reaction, we encountered a patient who experienced an allergic reaction to calcium phosphate cements(Biopex®. A patch test was performed and a positive reaction to magnesium phosphate was obtained. Biopex® contains magnesium phosphate, so we diagnosed this case as allergic reaction. Pathological analysis revealed infiltration of plasmacytes in the bone flap around the calcium phosphate cement. The postoperative course was uneventful 3 years after surgery. Allergy to calcium phosphate cements is rare, but must be considered in differential diagnosis of its side effects.

Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients. METHODS: We undertook a cluster-randomized, placebo-controlled trial in 251 patients with KBD. Participants were randomly allocated to comparing (1) chondroitin sulfate, (2) glucosamine hydrochloride, (3) a combination of chondroitin sulfate and glucosamine hydrochloride, or (4) placebo, for 6 months duration. The primary outcome measures of interest were 20% and 50% reductions in pain from baseline, measured by pain subscale in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Secondary outcome measures included parameters in the WOMAC Index such as pain, stiffness, and physical function, as well as patients' quality of life by the 12-item Short-Form General Health Survey. The trial registration number is ChiCTR-TRC-11001480 (http://www.chictr.org/). RESULTS: A combination therapy of chondroitin sulfate and glucosamine hydrochloride was effective in reducing WOMAC pain by 20% (differences of 23.4%, P=0.006) and 50% (differences of 15.7%, P=0.016), WOMAC pain (P=0.032), WOMAC stiffness (P=0.043), and WOMAC total score (P=0.035). Chondroitin sulfate used alone was also found to be effective in reducing WOMAC total score and stiffness score (P=0.038 and P=0.023, respectively). No significant positive effects in improving WOMAC Index scores were observed with glucosamine hydrochloride alone. CONCLUSION: The findings of this study indicate that a combination of chondroitin sulfate and glucosamine hydrochloride was more effective than placebo in treating KBD.

Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care. RESULTS: A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up. CONCLUSION: GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.