ObjectivesTo compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.MethodsDouble-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.ResultsThe 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.ConclusionsCS+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.

Osteoarthritis is primarily characterized by areas of destruction of articular cartilage and by synovitis. Articular damage and synovitis are secondary to local increase of pro-inflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha), enzymes with proteolytic activity (matrix metalloproteinases), and enzymes with pro-inflammatory activity (cyclooxygenase-2 and nitric oxide synthase-2). Enhanced expression of these proteins in chondrocytes and in synovial membrane appears associated to the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB). Chondroitin sulfate (CS) prevents joint space narrowing and reduces joint swelling and effusion. To produce these effects, CS elicits an anti-inflammatory effect at the chondral and synovial levels. CS and its disaccharides reduce NF-kappaB nuclear translocation, probably by diminishing extracellular signal-regulated kinase1/2, p38mitogen-activated protein kinase and c-Jun N-terminal kinase activation. This review discusses the evidence supporting that CS pleiotropic effects in chondrocytes and synoviocytes are primarily due to a common mechanism, e.g., the inhibition of NF-kappaB nuclear translocation.

BackgroundKnee osteoarthritis (KOA) is a prevalent form of chronic joint disease associated with functional restrictions and pain. Activity limitations negatively impact social connectedness and psychological well-being, reducing the quality of life (QoL) of patients. The purpose of this review is to summarize the existing information on QoL in KOA patients and share the reported individual factors, which may influence it.MethodsWe conducted a systematic review examining the literature up to JAN/2017 available at MEDLINE, EMBASE, Cochrane, and PsycINFO using KOA and QOL related keywords. Inclusion criteria were QOL compared to at least one demographic factor (e.g., age, gender), lifestyle factor (e.g., functional independence), or comorbidity factor (e.g., diabetes, obesity) and a control group. Analytical methods were not considered as part of the original design.ResultsA total of 610 articles were reviewed, of which 62 met inclusion criteria. Instruments used to measure QoL included: SF-36, EQ-5D, KOOS, WHOQOL, HAS, AIMS, NHP and JKOM. All studies reported worse QoL in KOA patients when compared to a control group. When females were compared to males, females reported worse QOL. Obesity as well as lower level of physical activity were reported with lower QoL scores. Knee self-management programs delivered by healthcare professionals improved QoL in patients with KOA. Educational level and higher total mindfulness were reported to improve QoL whereas poverty, psychological distress, depression and lacking familial relationships reduce it. Surgical KOA interventions resulted in good to excellent outcomes generally; although, results varied by age, weight, and depression.ConclusionKOA has a substantial impact on QoL. In KOA patients, QoL is also influenced by specific individual factors including gender, body weight, physical activity, mental health, and education. Importantly, education and management programs designed to support KOA patients report improved QoL. QoL data is a valuable tool providing health care professionals with a better comprehension of KOA disease to aid implementation of the most effective management plan.

Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1–3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-κB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases.

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