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.

UNASSIGNED: This analysis was aimed at providing evidence-based medicine basis for systematic evaluation of chondroitin combined with glucosamine in the treatment of knee osteoarthritis.
UNASSIGNED: 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.
UNASSIGNED: 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) (Z = 6.89, P < 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.
UNASSIGNED: 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.

OBJECTIVE: Though glucosamine and chondroitin have become common practices for treating knee osteoarthritis, the clinical value of these two drugs in combination are still questionable. To evaluate the efficacy and safety of the combination of glucosamine (GS) and chondroitin (CS) in knee osteoarthritis (KOA) treatment.
METHODS: We searched electronic databases, including PubMed, Embase, Web of Science, SCOPUS, The Cochrane Central Register of Controlled Trials (CENTRAL), OVID, Chinese Clinical Trial Registry (ChiCTR), CBM, CNKI, WanFang and VIP from their inception to August 20, 2020, for literature concerning the combination of glucosamine and chondroitin in knee osteoarthritis treatment. The Cochrane Collaboration\'s tool for assessing risk of bias and Jadad scale were used to evaluate the risk of bias and quality of literature. The meta-analysis was performed using Review Manager 5.3 software.
RESULTS: Eight randomized controlled trials (RCTs) were included, including 7 studies in English and 1 study in Chinese. While the number of included papers was quite limited, the number of participants was decent, and quality appraisal result is acceptable. The total number of patients was 3793, with 1067 patients receiving a combination of glucosamine and chondroitin and 2726 patients receiving other treatments. The meta-analysis results revealed the following: (1) Regarding the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, compared with the placebo group, the combination group showed a statistically significant advantage [MD = - 12.04 (- 22.33 ~ - 1.75); P = 0.02], while the other groups showed no significance. (2) Regarding the VAS score, none of the comparisons showed significance. (3) In the secondary outcomes, except the comparison of JSN between the combination and placebo groups (MD = - 0.09 (- 0.18 ~ - 0.00); P = 0.04) and the comparison of the WOMAC stiffness score between the combination and CS groups [MD = - 4.70 (- 8.57 ~ - 0.83); P = 0.02], none of the comparisons showed a significant difference. (4)Safety analysis results show that none of the comparisons have significant differences.
CONCLUSIONS: Our study confirmed that the combination of glucosamine and chondroitin is effective and superior to other treatments in knee osteoarthritis to a certain extent. It is worthwhile to popularize and apply the combination in KOA treatment considering the point of effect, tolerability and economic costs. Additionally, regarding the limited number of studies and uneven trial quality, more high-quality trials are required to investigate the accurate clinical advantages of the combination.
UNASSIGNED: CRD42020202093.

Osteoarthritis (OA) is common and burdensome for patients and health care systems. Our study purpose was to evaluate the long-term efficacy and safety of DMOADs in adults with knee and hip osteoarthritis.
We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Knowledge without language, publication, or date restrictions from inception through November 2018 for randomized controlled trials assessing 12 classes of DMOADs with at least 12 months of follow-up. Therapeutic effects were evaluated with pairwise and network meta-analysis. Outcomes included pain, function, minimum joint space width or cartilage volume, radiographic progression, and total joint replacement. Analyses were also performed for drug safety.
Twenty-eight randomized controlled trials with 11,890 patients were included. Glucosamine and chondroitin minimally improved both structure (minimum joint width or cartilage volume: network results: glucosamine: SMD 0.16; 95% CI [0.04, 0.28], chondroitin: SMD 0.21 [0.10, 0.32]) and symptoms (glucosamine: pain: - 0.15 [- 0.25, - 0.05]; function: - 0.17 [- 0.28, - 0.07], chondroitin: pain: - 0.06 [- 0.15, 0.03], and function: - 0.15 [- 0.26, - 0.03]). Strontium demonstrated improvement in structure (minimum joint width or cartilage volume: 0.20 [0.02, 0.38]), and vitamin D on symptoms (pain: - 0.15 [- 0.27, -0.03]; function: - 0.18 [- 0.31, - 0.06]). Although doxycycline also demonstrated a favorable efficacy ranking, its safety profile was poor (withdrawal: network relative risk 1.69 [1.03, 2.75]). The therapeutic effects of other medications were not ranked as highly.
Glucosamine and chondroitin yielded statistically significant but clinically questionable long-term benefit on structure and symptoms, though both had favorable safety profiles. Strontium improved structure, and vitamin D improved symptoms. Although doxycycline had a favorable efficacy ranking, its safety profile was poor. None of the 12 classes of drugs appears to have long-term clinically significant benefit.

OBJECTIVE: This study aims to evaluate the efficacy of treatments for Kashin-Beck disease (KBD).
METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, SinoMed, Chinese National Knowledge Infrastructure, reference lists and published systematic reviews and registries of ongoing trials through May 2015 for randomised controlled trials (RCTs) of treatments for KBD. Outcomes of interest were pain, function, stiffness, overall clinical improvement, radiographic improvement (X-ray) and adverse events. Frequentist network meta-analyses were conducted using random-effects consistency model to assess the efficacy of treatments for KBD.
RESULTS: Forty-four RCTs with 9815 participants were included in the review. In children or adolescents, selenium (risk ratio 1.88, 95% confidence interval (CI) 1.51-2.33), vitamin C (2.03, 1.40-2.95) and aspirin (2.14, 1.12-4.08) were effective for radiographic structure improvement. In adults, chondroitin plus glucosamine was the best for pain (standardised mean difference 1.46, 95% CI 1.07-1.85), followed by intra-articular injection of hyaluronic acid (IAH) (1.09, 0.70-1.48), chondroitin (0.84, 0.47-1.21), diclofenac (0.63, 1.18-1.08), naproxen (0.55, 0.12-0.98), meloxicam (0.52, 0.03-1.01) and glucosamine (0.40, 0.13-0.67) compared to placebo, with similar results for other clinical outcomes in adults. However, the strength of most evidence was limited by the small number of trials with low to moderate quality.
CONCLUSIONS: Selenium supplement has demonstrated some benefits for structural improvement of the disease in children. Chondroitin, glucosamine, IAH and nonsteroid anti-inflammatory drugs are effective for symptom improvements of KBD in adults. Evidence of surgical and complementary treatments for symptoms and aspirin and vitamin C for structure has yet to be established.Key Points• There were 23 nutraceuticals, pharmaceuticals and surgical and complementary treatments assessed for Kashin-Beck disease (KBD) in randomised trials.• Among the 23 treatments, chondroitin, glucosamine, IAH and non-steroid anti-inflammatory drugs are more effective than placebo to relieve symptoms for adults with KBD.• Selenium supplement is more effective than placebo for radiographic improvement in children or adolescents.• The efficacy of surgeries, aspirin, vitamin C and complementary treatments for KBD has not been established yet.

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

Osteoarthritis is a slowly progressive and debilitating disease that affects canines of all breeds. Pain and decreased mobility resulting from osteoarthritis often have a negative impact on the affected canine\'s quality of life, level of comfort, daily functioning, activity, behaviour, and client-pet companionship. Despite limited and conflicting evidence, the natural products glucosamine hydrochloride (HCl) and chondroitin sulfate are commonly recommended by veterinarians for treating osteoarthritis in dogs. There is a paucity of well-designed clinical veterinary studies investigating the true treatment effect of glucosamine and chondroitin. The purposes of this review article are to provide a brief background on glucosamine and chondroitin use in canine osteoarthritis and to critically review the available literature on the role of these products for improving clinical outcomes. Based on critical review, recommendations for practice are suggested and a future study design is proposed.

BACKGROUND: Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP).
OBJECTIVE: To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis.
METHODS: Systematic review; Level of evidence, 2.
METHODS: A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using \"treatment,\" \"osteoarthritis,\" and \"knee\" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures.
RESULTS: A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP.
CONCLUSIONS: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection.

OBJECTIVE: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Collagen derivatives are candidates for disease-modifying OA drugs. This group of derivatives can be divided into undenatured collagen (UC), gelatine and collagen hydrolysate (CH). Collagen derivatives are marketed as having direct chondroprotective action and reducing complaints of OA. This review summarizes the evidence for the effectiveness of symptomatic and chondroprotective treatment with collagen derivatives in patients with OA.
METHODS: Eligible randomised controlled trials (RCTs) and quasi-RCTs were identified by searching PubMed, Embase and the Cochrane Central Register of Controlled Trials until November 2011. Methodological quality was assessed using methods of the Cochrane Back Review Group.
RESULTS: Eight studies were identified: six on CH, two on gelatine, and one on UC. The pooled mean difference based on three studies for pain reduction measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index comparing CH with placebo was -0.49 (95% CI -1.10-0.12). However, some studies report significant between-group differences in pain when measured with a visual analogical scale (VAS) or other instruments, or when CH is compared with glucosamine sulphate. For disability no significant between-group mean differences were found when comparing CH with placebo. Gelatine compared with placebo and with alternative therapies was superior for the outcome pain. UC compared with glucosamine+chondroitin showed no significant between-group differences for pain and disability. The most reported adverse events of collagen derivatives were mild to moderate gastro-intestinal complaints. The overall quality of evidence was moderate to very low.
CONCLUSIONS: There is insufficient evidence to recommend the generalized use of CHs in daily practice for the treatment of patients with OA. More independent high-quality studies are needed to confirm the therapeutic effects of collagen derivatives on OA complaints.

BACKGROUND: Nutritional supplements are commonly used for a variety of musculoskeletal conditions, including knee and hip degenerative joint disease. Although these supplements are occasionally recommended for patients with degenerative disc disease and spinal degenerative joint disease, the evidence supporting this use is unknown.
OBJECTIVE: To systematically search and assess the quality of the literature on the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane for the treatment of spinal osteoarthritis / degenerative joint disease, and degenerative disc disease.
METHODS: The Index of Chiropractic Literature, AMED, Medline, and CINAHL were searched for randomized controlled trials in English from 1984 to July 2009.
METHODS: Data from studies meeting the inclusion criteria was extracted and reviewed by three reviewers. The Jadad scale was used to assess study quality. No attempts were made at meta-analysis due to variation in study design.
RESULTS: Two articles met the inclusion criteria. One study was found to have good quality but reported negative results for the supplemented group compared with placebo, the other study had low quality but reported significant positive results for the supplemented group when compared with a no intervention control group.
CONCLUSIONS: There was little literature found to support the use of common nutritional supplements for spinal degeneration, making it difficult to determine whether clinicians should recommend them.