A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1β (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1β significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1β. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1β than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.

Evidence, Efficasy and Safety of the Chondroprotective Parapharmaceuticals in Treatment of the Early Stages of Osteoarthritis

Osteoarthritis (OA) is the most common joint disease that significantly affects the patients’ quality of life and requires significant medical and social investments for treatment and rehabilitation. There are no therapeutic agents which would be able to regenerate lost or damaged hyaline cartilage. The objective: to assess the efficacy and safety of the chondroprotective parapharmaceutical agent Flexogial in the complex treatment of patients with initial stages of the knee ОА. Materials and methods. 12-weeks study was conducted with the participation of 60 patients with knee OA aged 53,7±2,9 years, women – 36 (60%), men – 24 (40%) with the initial stages of the disease (I–II radiological stage). The main clinical group consisted of 30 patients who took the chondroprotective complex agent Flexogial 15 ml once a day; the comparison group included 30 patients who were administered glucosamine sulfate 1500 mg in a monopreparation taken once a day. Efficacy of the treatment was evaluated using the VAS scale, Tegner’s scale, Lisholm scale at the beginning of treatment, after 6 and 12 weeks in dynamics with subsequent statistical processing of the results. Results. The study demonstrated better indicators of functional activity and less pain intensity in the affected joints in patients of the main group who took the parapharmaceutical agent Flexogial compared to the group of patients who took glucosamine monopreparation with the same number of registered adverse events in both groups of patients (5%). Conclusions. The results of the presented clinical study proved the advantage of use of the combined chondroprotective drinking complex Flexogial in comparison with the monopharmaceutical preparation glucosamine sulfate in the treatment of patients with early stages knee OA in terms of the effect on the intensity of pain and improvement in the parameters of the functional activity of patients after 6 and 12 weeks with the same frequency of registered adverse events.

Therapeutic effects of combined meloxicam and glucosamine sulfate treatment on patients with osteoarthritis, and its effect on serum CTX-Ⅰ, CTX-Ⅱ, COMP and MMP-3

Purpose: To study the therapeutic influence of meloxicam-glucosamine sulfate combination in patients with osteoarthritis and their effect on serum CTX-I, CTX-II, COMP and MMP-3. Methods: A total of 88 patients with osteoarthritis were assigned to control (n = 44) and treatment groups (n = 44), using the random number table method. Control group was given 7.5 mg of meloxicam, while treatment group received 0.5 g of glucosamine sulfate capsule in addition to meloxicam. Both groups were treated continuously for 8 weeks. Serum levels of C-terminal telopeptide of type I collagen (CTX-I), C-terminal telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3) were compared for the two groups after treatment. Results: Lysholm score significantly increased in the two groups after treatment. Serum CTX-I, CTX-II, COMP and MMP-3 in the two groups were significantly lower than before treatment, but the reductions were more pronounced in the treatment group (p < 0.05). During treatment, mild vomiting and pruritus of the skin appeared in both groups, but these were relieved after symptomatic treatment without any serious adverse reactions. Conclusion: Treatment with a combination of meloxicam and glucosamine sulfate produces significant beneficial effects in patients with osteoarthritis by reduction of clinical symptoms, pain relief and reduction of serum CTX-I, CTX-II, MMP-3 and COMP.

Nanostructured glucosamine sulfate: properties and uses in the production of functional foods extending life

The paper presents the properties of nanostructured glucosamine sulfate and its application for the production of functional food products that extend life on the example of fermented milk products (yoghurts, kefir, fermented baked milk, sour cream, cottage cheese), marmalade, ice cream and bakery products. Data on the self-organization and size of nanostructured glucosamine sulfate using the NTA method are presented.

Treatment of knee osteoarthritis with a new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin: a multicenter, randomized, single-blind, non-inferiority clinical trial

Objectives To compare the efficacy and safety of a new formulation of a fixed dose combination of glucosamine sulfate (GS; 1500 mg) and bovine chondroitin sulfate (CS; 1200 mg) versus the reference product (RP) in patients with knee osteoarthritis (OA). Methods In this multicenter, randomized, single-blind trial, 627 patients with knee osteoarthritis (OA)—Kellgren-Lawrence grades 2 or 3 and mean score ≥ 40 mm in the WOMAC pain subscale—were randomized to receive GS/CS or the RP for 24 weeks. The primary efficacy endpoint was the absolute change in WOMAC pain subscale score. The secondary endpoints included the following: WOMAC total and subscale scores, overall assessment of the disease by the patient and the investigator, SF-12 score, OMERACT-OARSI response rate to the treatment, and rescue medication use. Results Mean reductions of WOMAC pain score were − 35.1 (sd = 23.2) mm in the GS/CS group and − 36.5 (sd = 24.9) mm in the RP group. The difference between the adjusted means of both treatments confirmed the non-inferiority of GS/CS versus the RP. Improvement was observed in pain, stiffness, physical function and total WOMAC score, as well as in overall OA assessment by the patient and the investigator for both groups. No improvement was observed in SF-12. The rate of OMERACT-OARSI responders was 89.4% in GS/CS group and 87.9% in the RP group. Headache and changes in glucose tolerance were the most frequent treatment-related adverse events. Conclusions The new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin sulfate was non-inferior to the RP in symptomatic treatment of knee OA, with a high responder rate and good tolerability profile. Trial registration ClinicalTrials.gov; Registration number NCT02830919; Date of registration: July 13, 2016; First randomization date: December 05, 2016).

Comparative analysis of the arthroscopy efficacy and complex therapy in the treatment of degenerative meniscal tears in patients with knee osteoarthritis

Aim: to evaluate the efficacy of conservative treatment in patients with degenerative meniscal tear (DMT) in the setting of knee osteoarthritis (OA) as an alternative to combined treatment. Patients and Methods: a prospective comparative study included 236 patients aged 45–65 years with DMT in the setting of stage I–III OA according to the Kellgren-Lawrence classification (70 of them — men). Group 1 consisted of 122 patients (86 of them — women) who underwent combined treatment: arthroscopy for DMT of the knee joint and complex therapy in the postoperative period: NSAIDs (celecoxib), a combined drug from the group of symptom-modifying slow-acting drugs SYSADOA (chondroitin sulfate + glucosamine sulfate), exercise therapy, physiotherapy. Group 2 (n=114) received only complex therapy. Control tests (pain assessment on the visual analog scale (VAS), WOMAC scale, life quality assessment on the EQ-5D scale, treatment satisfaction) were performed 10 and 20 weeks after the therapy initiation. Results: there was a statistically significant (p<0.05) improvement in VAS and WOMAC indicators, which continued to decline by week 20 after 10 weeks of both combined and conservative treatment. Also, it did not depend on gender, age, concomitant pathology, but on the body mass index and OA stage according to the Kellgren-Lawrence classification, which was confirmed by the results of the correlation analysis. Patients’ treatment satisfaction and improvement in their life quality were noted in 50% of patients in both groups. Conclusion: arthroscopic meniscectomy should not be indicated as the first treatment stage in patients with DMT during OA. Complex therapy, including the use of drugs from the NSAID and SYSADOA groups at the recommended doses, has demonstrated high treatment efficacy and safety of patients with DMT during OA. KEYWORDS: knee arthritis, degenerative meniscus tear, arthroscopy, celecoxib, chondroitin sulfate, glucosamine sulfate, life quality. FOR CITATION: Bessarab M.S., Krasnov G.O., Charchyan A.M., Khoroshkov S.N. et al. Comparative analysis of the arthroscopy efficacy and complex therapy in the treatment of degenerative meniscal tears in patients with knee osteoarthritis. Russian Medical Inquiry. 2021;5(2):71–77. DOI: 10.32364/2587-6821-2021-5-2-71-77.