Meta-Analysis Review

Authors: Xiaoyue Zhu, Lingli Sang, Dandong Wu...

OBJECTIVE

To assess the symptomatic effectiveness and safety of oral symptomatic slow-acting drugs (SYSADOAs) on the treatment of knee and/or hip osteoarthritis, such as chondroitin, glucosamine, and combination treatment with chondroitin plus glucosamine.

METHODS

We searched electronic database including PubMed, Embase, Cochrane Library, and the reference lists of relevant articles published from inception to May 22, 2018. An updated meta-analysis was performed to assess the effectiveness of these slow-acting drugs for osteoarthritis.

RESULTS

Twenty-six articles describing 30 trials met our inclusion criteria and were included in the meta-analysis. The estimates between chondroitin and placebo showed that chondroitin could alleviate pain symptoms and improve function. Compared with placebo, glucosamine proved significant effect only on stiffness improvement. However, the combination therapy did not have enough evidence to be superior to placebo. Additionally, there was no significant difference in the incidence of AEs and discontinuations of AEs when compared with placebo.

CONCLUSIONS

Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function. Glucosamine showed effect on stiffness outcome. Regarding on the limited number of combination therapy, further studies need to investigate the accurate effectiveness. This information accompanied with the tolerability and economic costs of included treatments would be conducive to making decisions for clinicians.

Topics: Chondroitin; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Treatment Outcome

PubMed: 29980200
DOI: 10.1186/s13018-018-0871-5

Meta-Analysis Review

Authors: Maude Barbeau-Grégoire, Colombe Otis, Antoine Cournoyer...

With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.

Topics: Animals; Biological Products; Cannabidiol; Cat Diseases; Cats; Chondroitin; Collagen; Dietary Supplements; Dog Diseases; Dogs; Glucosamine; Osteoarthritis

PubMed: 36142319
DOI: 10.3390/ijms231810384

Review

Authors: Nicola Volpi

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.

Topics: Animals; Chondroitin Sulfates; Dietary Supplements; Humans; Osteoarthritis

PubMed: 31013685
DOI: 10.3390/molecules24081447

Randomized Controlled Trial

Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study.

Authors: Shyu-Jye Wang, Ya-Hui Wang, Liang-Chen Huang...

BACKGROUND

Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4-6 points).

METHODS

This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population.

RESULTS

Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups.

CONCLUSIONS

This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.

Topics: Administration, Oral; Aged; Chondroitin; Dietary Supplements; Double-Blind Method; Drug Combinations; Female; Glucosamine; Humans; Hyaluronic Acid; Male; Middle Aged; Osteoarthritis, Knee; Pain Management

PubMed: 34622845
DOI: 10.1097/MD.0000000000027405

Meta-Analysis

Authors: Zhiyao Wang, Rongtian Wang, Hui Yao...

OBJECTIVE

This analysis was aimed at providing evidence-based medicine basis for systematic evaluation of chondroitin combined with glucosamine in the treatment of knee osteoarthritis.

METHODS

The randomized controlled trials (RCTs) of chondroitin combined with glucosamine in the treatment of knee osteoarthritis (KOA) were searched in PubMed, EMBASE, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database. The retrieval time ranges from the database creation to the present. Two investigators gathered the information individually. The risk of bias was assessed using the criteria of the Cochrane back review group. RevMan5.4 statistical software analyzed the selected data.

RESULTS

A total of 6 RCT articles were obtained. Overall, 764 samples were evaluated by meta-analysis. The clinical efficacy of chondroitin combined with glucosamine was significantly better than that of routine treatment by meta-analysis. The confidence interval of 95% was (4.86, 17.08) ( = 6.89, < 0.00001). The scores of joint pain, tenderness, swelling, and dysfunction in patients with knee osteoarthritis treated with chondroitin combined with glucosamine were significantly lower than those treated with routine treatment. There was no significant difference in the incidence of adverse reactions between chondroitin combined with glucosamine and single treatment of KOA. Due to the small number of documents included in the analysis, it is not suitable to make a funnel chart, but there may be some publication deviation in the analysis.

CONCLUSION

Chondroitin combined with glucosamine is more effective than chondroitin or glucosamine alone in the treatment of KOA and deserves clinical promotion. However, this conclusion still needs to be supported by multicenter, high-quality, double-blind, large-sample randomized controlled clinical trials due to the limitations of the six trials included.

Topics: China; Chondroitin; Glucosamine; Humans; Multicenter Studies as Topic; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Treatment Outcome

PubMed: 35924114
DOI: 10.1155/2022/5285244

Authors: Markel Lafuente-Merchan, Sandra Ruiz-Alonso, Alaitz Zabala...

Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures. This study is focused on the development of nanocellulose-alginate (NC-Alg) based bioinks for 3D bioprinting for cartilage regeneration to which it is added chondroitin sulfate (CS) and dermatan sulfate (DS). First, rheological properties are evaluated. Then, sterilization effect, biocompatibility, and printability on developed NC-Alg-CS and NC-Alg-DS inks are evaluated. Subsequently, printed scaffolds are characterized. Finally, NC-Alg-CS and NC-Alg-DS inks are loaded with murine D1-MSCs-EPO and cell viability and functionality, as well as the chondrogenic differentiation ability are assessed. Results show that the addition of both CS and DS to the NC-Alg ink improves its characteristics in terms of rheology and cell viability and functionality. Moreover, differentiation to cartilage is promoted on NC-Alg-CS and NC-Alg-DS scaffolds. Therefore, the utilization of MSCs containing NC-Alg-CS and NC-Alg-DS scaffolds may become a feasible tissue engineering approach for cartilage regeneration.

Topics: Alginates; Animals; Bioprinting; Cartilage; Chondroitin; Dermatan Sulfate; Mice; Printing, Three-Dimensional; Regeneration; Tissue Engineering; Tissue Scaffolds

PubMed: 35029035
DOI: 10.1002/mabi.202100435

Authors: Jenna Bhimani, Kelli O'Connell, Deborah Kuk...

Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.

Topics: Humans; Adult; United States; Glucosamine; Chondroitin; Nutrition Surveys; Prospective Studies; Neoplasms

PubMed: 36971848
DOI: 10.1089/jicm.2022.0783

Review

Authors: E C Huskisson

Osteoarthritis (OA) is a common, chronic disease that most frequently affects the knees and is a major cause of disability in the elderly. It is characterized by progressive cartilage loss, accompanied by secondary changes such as osteophyte formation and calcium deposition. Inflammatory processes are also involved, leading to stiffness and pain, for which patients seek treatment. Conventional treatment includes analgesics or non-steroidal anti-inflammatory drugs, however life-style changes should also be recommended, such as weight reduction and specific exercises. Glucosamine and chondroitin, classed as over-the-counter supplements or nutraceuticals, are regularly self-administered by patients with OA. Both agents are produced endogenously in the human body and are essential components of cartilage. This review discusses the evidence that supports the use of these agents either alone or in combination for pain relief and as disease-modifying agents in OA.

Topics: Antirheumatic Agents; Cartilage; Chondroitin; Dietary Supplements; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Osteoarthritis; Treatment Outcome

PubMed: 19094424
DOI: 10.1177/147323000803600602

Review

Authors: Giulia Vessella, Serena Traboni, Antonio Laezza...

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan (GAG) polysaccharide with a unique structure, displaying a backbone composed of alternating -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 (, ) 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.

Topics: Animals; Chondroitin Sulfates; Fibrinolytic Agents; Sea Cucumbers

PubMed: 32492857
DOI: 10.3390/md18060293

Review

Authors: Vitor H Pomin

Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein.

Topics: Animals; Carbohydrate Sequence; Chondroitin Sulfates; Glycosaminoglycans; Humans; In Vitro Techniques; Molecular Sequence Data; Partial Thromboplastin Time; Sea Cucumbers

PubMed: 24413804
DOI: 10.3390/md12010232