The effect of combined hydrolyzed type 2 collagen, methylsulfonylmethane, glucosamine sulfate and chondroitin sulfate supplementation on knee osteoarthritis symptoms.

Objectives: This study aimed to evaluate the effects of the combined hydrolyzed type 2 collagen, methylsulfonylmethane (MSM), glucosamine sulfate (GS), and chondroitin sulfate (CS) supplement on knee pain intensity in patients with knee osteoarthritis (OA). Patients and methods: This multicenter, observational, noninterventional study included 98 patients (78 females, 20 males; mean age: 52.8±6.5 years; range, 40 to 64 years) who had Grade 1-3 knee OA between May 2022 and November 2022. The patients were prescribed the combination of hydrolyzed type 2 collagen, MSM, GS, and CS as a supplement for knee OA. The sachet form of the combined supplement containing 1250 mg hydrolyzed type 2 collagen, 750 mg MSM, 750 mg GS, and 400 mg CS was used once daily for two consecutive months. Patients were evaluated according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS)-pain, and Health Assessment Questionnaire (HAQ). Patients were scheduled to visit for follow-up four weeks (Visit 2) and eight weeks (Visit 3) after Visit 1 (baseline; day 0 of the study). Results: For the VAS-pain, WOMAC, WOMAC-subscale, and HAQ scores, the differences in improvement between the three visits were significant (p<0.001 for all). The patient compliance with the supplement was a median of 96.77%, both for Visit 2 and Visit 3. Conclusion: The combination of hydrolyzed type 2 collagen, MSM, GS, and CS for eight weeks in knee OA was considered an effective and safe nutritional supplement.

Therapeutic effect of San Bi Tang combined with glucosamine sulfate capsules in cold-dampness-type knee osteoarthritis.

BACKGROUND: Cold-dampness-type knee osteoarthritis is a common middle-aged and elderly disease, but its pathogenesis is not fully understood, and its clinical treatment has limitations. Glucosamine sulfate capsules are commonly used for treating arthritis, and San Bi Tang is a classic formula of traditional Chinese medicine (TCM) that has the effects of warming yang, dispelling dampness, relaxing muscles, and activating collaterals. This research hypothesized that the combination of modified San Bi Tang and glucosamine sulfate capsules could enhance the clinical efficacy of treating cold-dampness-type knee osteoarthritis through complementary effects. AIM: To analyze the clinical efficacy of San Bi Tang combined with glucosamine sulfate capsules when treating cold-dampness-type knee osteoarthritis. METHODS: A total of 110 patients with cold-dampness-type knee osteoarthritis were selected as research subjects and randomly divided into a control group and an experimental group of 55 cases each. The control group received only treatment with glucosamine sulfate capsules, while the experimental group received additional treatment with modified San Bi Tang for a duration of 5 wk. The patients' knee joint functions, liver and kidney function indicators, adverse reactions, and vital signs were evaluated and analyzed using SPSS 26.0 software. RESULTS: Before treatment, the two groups' genders, ages, and scores were not significantly different, indicating comparability. Both groups' scores improved after treatment, which could indicate pain and knee joint function improvement, but the test group had better scores. The TCM-specific symptoms and the clinical efficacy of the treatment in the test group were higher. Before and after treatment, there were no abnormalities in the patients' liver and kidney function indicators. CONCLUSION: The combination of modified San Bi Tang and glucosamine sulfate capsules is superior to treatment with sulfated glucosamine alone and has high safety.

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.

The short-term effect of glucosamine-sulfate, nonanimal chondroitin-sulfate, and S-adenosylmethionine combination on ultrasonography findings, inflammation, pain, and functionality in patients with knee osteoarthritis: A pilot, double-blind, randomized, placebo-controlled clinical trial.

Objectives: This study aimed to investigate the efficacy of glucosamine-sulfate (GS), nonanimal chondroitin-sulfate (naCS), and S-adenosylmethionine (SAMe) combination on ultrasound findings, inflammation, pain, and functionality in knee osteoarthritis. Patients and methods: In the prospective, randomized, double-blind, placebo-controlled pilot study conducted between August 2019 and November 2019, 120 participants (28 males, 92 females; mean age: 66.4±7.9 years; range, 42.4 to 74.5 years) were randomized at a 1:1:1 ratio to the placebo group, the first experimental group (a combination of GS, naCS, and SAMe was administered to the experimental groups. The first experimental group received 375 mg of GS, 300 mg of naCS, and 100 mg of SAMe, whereas the second experimental group received 750 mg of GS, 600 mg of naCS, and 200 mg of SAMe). Laboratory (erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, interleukin [IL]-1ß, IL-6, IL-17), clinical (Visual Analog Scale [VAS], short form health survey [SF-36], the Western Ontario and McMaster Universities Arthritis Index [WOMAC], and the Tegner Lysholm Knee Scoring Scale [TLKS]), and musculoskeletal ultrasound (MSUS) assessments were performed at baseline and after three and six months. Results: A minor increase was observed in the second experimental group after six months using ultrasonography to evaluate articular cartilage thickness (p<0.05). The investigational product's superiority in reducing osteoarthritis ultrasonographic findings was not proven. A moderately negative association was found between cartilage thickness and VAS scores at baseline (ρ=-0.36, p<0.01), while the presence of massive osteophytes on MSUS showed a low to moderate association with all clinical outcomes. There was no difference in the delta changes between groups for the VAS, TLKS, WOMAC, and SF-36. The only serum inflammatory marker outside the reference range was IL-1ß, but no significant changes were observed after six months. Conclusion: According to the results of our investigation, treatment for knee osteoarthritis should be evaluated using more objective outcomes. The most important conclusion of our study is that IP may result in a slight increase in articular cartilage thickness, which was associated with a decrease in pain intensity at baseline. Clarification of the potential influence of this combination on radiographic progression and laboratory markers of inflammation requires further exploration.

MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1ß.

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1ß (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1ß. The transfection with miRNA specific inhibitors significantly counteracted the IL-1ß activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators.

Design and development of keratin/chitosan/glucosamine sulfate composite loaded MWCNT intended for osteoarthritis drug delivery.

Osteoarthritis (OA) is an inflammatory disease that affects the cartilage and tissues around the joints, which results in excessive pain and stiffness. One of the most critical challenges for improving the therapeutic effect in OA treatments is the current drug design utilizing functional polymers. Indeed, there is a need to design and develop novel therapeutic drugs for positive outcomes. In this view, glucosamine sulfate is a drug used to manage OA because of its potential therapeutic effects on cartilage and ability to inhibit disease progression. This research aims to develop a keratin/chitosan/glucosamine sulfate (KRT/CS/GLS) composite loaded functionalized multi-walled carbon nanotubes (MWCNTs) as a potential carrier for the treatment of OA. The nanocomposite was developed using various ratios of KRT/CS/GLS, and MWCNT. Molecular docking analysis has been performed with (D-glucosamine) and targeted proteins (Protein Data Bank ID: 1HJV, 1ALU) to determine the binding affinity and interactions. Field emission scanning electron microscopy study showed that the composite KRT/CS/GLS incorporated on the surface of functionalized MWCNTs effectively. Fourier transform infrared spectroscopy analysis confirmed the presence of KRT/CS/GLS in the nanocomposite and remained intact. X-ray diffraction analysis indicated that the nature of the composite in MWCNT transformed from a crystalline to an amorphous state. Thermo gravimetric analysis revealed that the nanocomposite has a high thermal decomposition temperature of 420 °C. The MTT assay results showed that 83% of cell viability has remained in RAW 264.7 cells at the maximum concentration (500 µg ml-1) of MWCNT-GLS/KRT/CS nanocomposite. Also, molecular docking results revealed the excellent binding affinity of D-glucosamine to each protein structure (PDB ID: 1HJV and 1ALU).

Delayed Skin Allergy to Glucosamine Chondroitin Supplement.

Glucosamine chondroitin is a popular dietary supplement used for joint health and osteoarthritis pain and is one of the dietary supplements commonly recommended by chiropractors. Herein, we present the case of a 36-year-old woman who developed a skin rash with delayed onset after taking glucosamine and chondroitin pills for lumbar degenerative joint disease. Within 3 hours of taking the supplement, she developed an itchy rash on her torso and legs. Over the next few hours, the rash spread over her entire body, and facial swelling developed. Given the timing of the symptoms after the administration of glucosamine chondroitin, an allergic reaction was suspected. The supplement was withdrawn and the allergic reactions were treated with antihistamines and steroids for several days. This case report demonstrates the need to recognize delayed allergic reactions as a potential side effect of widely used supplements, such as glucosamine chondroitin, which can produce hypersensitivity reactions in sensitive individuals.

Evaluation of Local Application of Glucosamine Sulfate and Chondroitin Sulfate on Temporomandibular Joint Response and Alleviation of Pain and Tension During the Functional Treatment of Skeletal Class II Patients: A Randomized Control Clinical Trial.

OBJECTIVE:  This study was conducted to assess the effects of applying a gel of combined glucosamine sulfate and chondroitin sulfate on the temporomandibular joint (TMJ) area in patients with skeletal Class II malocclusion treated by removable functional appliances in terms of TMJ internal proportions, levels of pain, and tension. MATERIALS AND METHODS: The study included 36 patients aged 10-13 years with skeletal Class II malocclusion due to retrusion of the mandible characterized by: 4-8 degrees of the sagittal skeletal discrepancy (ANB) angle, 4-7 mm of overjet, 72-76 degrees of the sagittal mandibular positioning (SNB) angle, and a bone maturity stage located at pubertal growth spurt. Patients were distributed to the experimental group (Twin-Block appliance + Jointance® gel) or the control group (conventional treatment with the Twin-Block appliance). An allocation ratio of 1:1 was employed. Pre- and post-treatment digital lateral cephalometric radiograms were taken, and the TMJ joint spaces were measured using the Viewbox software (dHAL Software, Kifissia, Greece). The pain and discomfort levels were evaluated using a questionnaire with a four-point Likert scale at three assessment times. RESULTS:  The anterior and posterior glenoid and anterior condylar distances to the pterygoid vertical (PTV) reference plane significantly decreased after treatment (p<.001), and the anterior joint space decreased significantly (p<.001). In contrast, the superior distance of the condyle to the Frankfort horizontal reference plane increased significantly after treatment, and the same results were found for the posterior and superior joint spaces (p<.05). There were no significant differences between the two groups in the evaluated linear variables. No significant differences were found when comparing pain and tension levels between the two groups at each assessment time. A gradual decrease in pain and tension levels was observed between the three evaluation times in both groups. CONCLUSIONS:  A combination of glucosamine sulfate and chondroitin sulfate did not affect the temporomandibular joint spaces, pain, and tension levels in patients with skeletal Class II malocclusions treated by removable functional appliances.

Possible synergic action of non-steroidal anti-inflammatory drugs and glucosamine sulfate for the treatment of knee osteoarthritis: a scoping review.

BACKGROUND: Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of non-steroidal anti-inflammatory drugs (NSAIDs) in knee OA have also been investigated. However, limited literature has reported the combined effect of GS and NSAIDs. The aim of this scoping review is to describe the scope and volume of the literature investigating the potential benefits and synergistic effect of a combination of GS and NSAIDs in patients with knee OA. METHODS: PubMed and Embase were searched for studies published from inception through April 2022, evaluating the effects of the combination of GS and NSAIDs in OA patients, versus either treatment alone. Data are reported narratively. RESULTS: Five studies were included in this review; 4 were randomized control trials and one was a prospective observational study. The duration of combination treatment was 6 to 12 weeks. The combination was compared to celecoxib in 2 studies, meloxicam in 1, etoricoxib in 1, and a conventional NSAID in 1 (ibuprofen or piroxicam). All 5 studies reported that in patients with knee OA, the combination of GS plus NSAID yielded a significantly greater benefit than single-agent therapy, in terms of outcomes including pain reduction, function, joint stiffness, and markers of inflammatory activity and cartilage degradation. CONCLUSION: The 5 studies included in this scoping review all report a significantly greater clinical benefit with a combination of GS plus NSAID compared to either treatment alone. The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. However, further randomized trials with larger sample sizes are warranted to confirm these findings.

[Points of undenatured type II collagen application in musculoskeletal pain syndromes treatment]. / Tochki prilozheniya nedenaturirovannogo kollagena II tipa v terapii skeletno-myshechnykh bolevykh sindromov.

The dominant collagen of the cartilaginous matrix in adults is type II collagen. The amount of type II collagen in the intercellular matrix of cartilage is significantly reduced against the background of musculoskeletal system diseases. The basis of articular cartilage is hyaline cartilage tissue consisting of chondrocytes with tissue-specific antigens that induce the production of antibodies in patients with osteoarthritis (OA). Today, new approaches are being considered in the treatment of OA with the use of udenatured type II collagen (UC-II). Such molecular mechanisms of action of UC-II as the formation of a systemic response through oral tolerance are discussed, since the induction of tolerance is the immune pathway, by default, in the intestine. A number of experimental, preclinical (on volunteers) and clinical studies have shown the effectiveness and safety of the use of UC-II in OA. Standardized extracts of UC-II exhibit anti-inflammatory, immunoregulatory, chondroprotective effects, contributing to the reduction of pain symptoms of OA. Against the background of taking UC-II with induced OA, there is a statistically significant decrease in the level of proinflammatory cytokines, such as interleukin (IL-1ß, IL-6), tumor necrosis factor alpha (TNF), C-reactive protein (CRP) in serum and the level of max proteinases (MMP-3), nucleated factor «kappa-bi¼ (NF-κB) in the knee joint. UC-II significantly inhibits the production of prostaglandin E2 (by 20%) and the expression of genes encoding proinflammatory proteins. In experimental models and in OA patients, a decrease in the severity of pain syndrome, an increase in endurance, mobility and an improvement in the functional state of the joints were noted. Clinically, no changes in the structure of the muscle fiber were detected with increased physical exertion. With OA on the background of UC-II (10-40 mg/s), there was a statistically significant decrease in joint pain according to WOMAC. A promising direction of OA therapy is the combination of UC-II with chondroitin sulfate and glucosamine sulfate.

Prescription-grade crystalline glucosamine sulfate as an add-on therapy to conventional treatments in erosive osteoarthritis of the hand: results from a 6-month observational retrospective study.

OBJECTIVE: To evaluate the efficacy of prescription-grade Crystalline Glucosamine Sulfate (pCGS) as an add-on treatment to conventional therapy, compared to usual therapy alone, in patients with erosive osteoarthritis of the hand (EHOA). METHODS: This 6-month retrospective case-control study included patients with concomitant knee osteoarthritis and symptomatic EHOA. Participants were stratified into two groups based on whether or not pCGS (1500 mg/day) was added to the conventional therapy (education and training in ergonomic principles, exercise and use on-demand of symptomatic drugs) for hand osteoarthritis. Patients were evaluated at baseline, after 3 and 6 months. Primary outcomes were the change from baseline to month 6 in Visual Analogue Scale (VAS) hand pain and in Functional Index for Hand Osteoarthritis (FIHOA) score. A set of secondary parameters was also evaluated. RESULTS: 123 patients were included as follows: 67 treated with pCGS in addition to conventional therapy (pCGS Group) and 56 with conventional therapy alone (Control Group). After 6 months a significant difference in VAS and in FIHOA score (p < 0.01 and p < 0.001, respectively) was observed in favor of pCGS Group. Similar results were found for morning stiffness duration (p < 0.05), health assessment questionnaire (p < 0.01) and physical and mental component score of 36-item short form (p < 0.05 and p < 0.001, respectively). A significant reduction of symptomatic drug consumption at 3 and 6 months was reported in the pCGS Group (p < 0.001). No serious adverse event was recorded in both groups. CONCLUSIONS: Despite all the limitations inherent to an observational study, our results suggest the potential effectiveness of pCGS, when used in combination with conventional therapy in EHOA. Further randomized placebo-controlled trials are needed to confirm these positive findings. TRIAL REGISTRATION: ClinicalTrials.gov, http://www. CLINICALTRIALS: gov , date of registration: February 2, 2022, NCT05237596. The present trial was retrospectively registered.

Investigation of the mechanisms involved in anticancer effect of glucosamine sulfate on SH-SY5Y cell line.

AIM: Glucosamine derivatives have been found to have anticancer effects in many cancer cell lines in previous investigations. The effect of glucosamine sulfate on neuroblastoma, however, is uncertain. The potential cytotoxic effects of glucosamine sulfate on the SH-SY5Y cell line were investigated in this study. The underlying mechanisms of this cytotoxicity have also been studied. MATERIAL AND METHODS: In this study, the SH-SY5Y cell lines were used. The cells were treated with various concentrations of glucosamine sulfate (0.3125, 0.625, 1.25 and 2.5 µg/mL) and the viability of the cells was determined using the XTT assay after 24 hours. The quantities of cleaved PARP, BCL-2, 8-Hydroxy-desoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant in the cells were determined by ELISA kits. RESULTS: At doses of 0.3125, 0.625, 1.25 and 2.5 µg/mL, glucosamine sulfate dramatically reduced cell viability in SH-SY5Y cells (p<0.001). ELISA tests demonstrated that 1.25 µg/mL glucosamine sulfate considerably increased the amounts of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP and total oxidant. However, 1.25 µg/mL glucosamine sulfate treatment did not change the quantity of BCL-2 protein. CONCLUSIONS: Altogether, glucosamine sulfate produced considerable cytotoxicity in SH-SY5Y cells by triggering oxidative stress, inducing DNA damage, and finally causing apoptosis. In addition, more research is needed to determine the efficacy of glucosamine sulfate as an anticancer drug in the treatment of neuroblastoma (Fig. 5, Ref. 39).

[SYSADOA place in degenerative-dystrophic joints diseases treatment of neurological practice from the standpoint of evidence-based medicine]. / Mesto preparatov SYSADOA v lechenii degenerativno-distroficheskikh zabolevanii sustavov v nevrologicheskoi praktike s pozitsii dokazatel'noi meditsiny.

Neurologists in their practice often face pain syndrome against the background of degenerative-dystrophic changes in the spine, in the therapy of which drugs of delayed-action symptomatic therapy of osteoarthritis (OA) (Symptomatic Slow Acting Drugs for OsteoArthritis, SYSADOA) are used. SYSADOA includes medicinal drugs (MD) containing chondroitin sulfate (CS), glucosamine, avocado/soy unsaponifiables (ASU), diacerein, intra-articular hyaluronic acid, which can give symptomatic benefit with low toxicity, and with prolonged (up to 6 months) the course of treatment. In Russia, they are guided by the clinical recommendations of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), in which the algorithm for managing patients with knee joint OA with the appointment of CS and glucosamine sulfate (GS) form the basic part of the treatment of OA (Step 1). In order to achieve the expected clinical effects in patients with OA medical drugs (MD) of the SYSADOA class must meet the following criteria: 1) be of pharmaceutical quality and standardization with studied pharmacokinetics; 2) meet the criteria of evidence-based medicine (to have randomized clinical trials (RCTs), to have confirmed the effectiveness of meta-analyses of studies and /or systematic reviews, to have confirmed the safety of use in comorbid patients, to have the conclusions of fundamental and clinical studies of recent years justifying the need for its use); 3) be approved by the regulator - the Ministry of Health of the Russian Federation (be present in the current Clinical Recommendations of the Ministry of Health of the Russian Federation and standards for the treatment of diseases of the musculoskeletal system); 4) be approved and recommended by international and Russian professional communities, associations, experts; 5) have clinical and economic advantages in terms of the outcomes of therapy and the lowest cost-effectiveness coefficient per patient. After analyzing the research materials, it was concluded that the pharmacologically standardized CS (Chondroguard®) satisfies all the above criteria for the reasonable choice of a SYSADOA class MD for the treatment of patients with OA of various localization.

¿Conlleva la desprescripción de condroprotectores en pacientes con artrosis un incremento del consumo de analgésicos? Estudio observacional retrospectivo / Does the deprescription of chondroprotectors in patients with osteoarthritis lead to an increase in the consumption of analgesics? Observational retrospective study

Objetivo: El objetivo del estudio es evaluar si la desprescripción de medicamentos considerados de bajo valor intrínseco como los condroprotectores o SYSADOA, conlleva un empeoramiento sintomáti-co de la artrosis, incrementándose el consumo de analgésicos.Material y métodos: Siguiendo la práctica clínica habitual se retiró el tratamiento con SYSADOA a pa-cientes de un Centro de Atención Primaria (pobla-ción asignada: 34.382 habitantes, 17% mayores de 65 años) en base a la evidencia científica publicada y a la recomendación de la administración sanitaria de reducir los tratamientos con medicamentos de bajo valor intrínseco. Mediante un estudio obser-vacional post-intervención se analizaron diferen-cias de consumo de analgésicos y AINEs entre un periodo anterior a la retirada y el mismo periodo post-retirada.Resultados: Se analizaron 354 pacientes (68,4% mujeres, media de edad 66,2 años). No se encon-traron diferencias estadísticamente significativas en el consumo de analgesia total en el periodo de 6 meses post-retirada (media de 3,97 envases) com-parado con el periodo de 6 meses previo (media de 4,04 envases). Al estratificar por código ATC, edad y género, únicamente se encontraron diferencias en el consumo de otros analgésicos y antipiréticos teniendo en cuenta el sexo.Conclusión: Se concluye que, considerar con el paciente la desprescripción de SYSADOA a criterio del médico, es seguro y no conlleva un aumento del consumo de analgésicos (otros analgésicos y anti-piréticos, AINE, opioides menores, opioides mayo-res) sugiriendo que no implica un empeoramiento de la enfermedad artrósica. La desprescripción de SYSADOA, además, puede contribuir a reducir la po-limedicación sin alterar la situación clínica y evitar posibles riesgos de efectos adversos o interaccio-nes potenciales (AU)

Objective: The objective of this study is to assess if the deprescription of medications that are consid-ered low intrinsic value medications such as the chondroprotectors or SYSADOA entails a symptom-atic worsening of the arthrosis and consequently an increase of the consumption of analgesics.Material and Methods: Following the usual clinical practise, the SYSADOA treatment was withdrawn to the patients from a Primary Health Care Centre (assigned population: 34,382 inhabitants, 17% up to 65 years old) according to the published scientific proof and the recommendation of the health ad-ministration consisting of reducing the treatments with low intrinsic value medications. Differences in consumption of analgesics and AINEs between a previous period before the withdrawn and the same period post-withdrawn were studied through an observational post-intervention study.Results: 354 patients were analysed (68,4% wom-en, average age 66,2 years). There were not found significant differences from a statistical point of view in the total consumption of analgesia in the 6 months period post-withdrawn (average of 3,97 packagings) compared to the previous period of 6 months (average of 4,04 packagings). When stratifying by ATC code, age and gender, there were only found differences in the consumption of other analgesics and antipyretics taking into account the sex.Conclusion: It is concluded that considering togeth-er with the patient the deprescription of SYSADOA according to doctor’s criteria is safe and does not involve an increase of analgesics consumption (other analgesics, antipyretics, AINEs, major and minor opiods) suggesting that it does not suppose a worsening of the arthrosis disease. Besides, the deprescription of SYSADOA may contribute to re-duce polymedication without disrupting the clinical situation and avoid possible risks of adverse effects or potential interactions

Literature Analysis Regarding the Combination of Substances: Glucosamine + Chondroitin in the Treatment of Osteoarthritis.

An essential component of joint quality is cartilage. Therefore, the protection of this is a prerequisite for maintaining the condition of each joint. The assessment of the presence of articular cartilage is shown by X-ray of both joints in the standing position. Cartilage protection is possible for 1, 2 and 3 degree of cartilage damage according to the Kellgren and Lawrence scale.The challenge for the physician is to identify the cause of OA in accordance with the principles of Evidence Based Orthopedics/Traumatology, and not merely treat symptomatically, which is usually ineffective.In order to objectively present treatment methods, indications and the period of their implementation, it is biologically reasonable to refer to the needs of cartilage tissue resulting from the analysis of the causes of its damage and indications for justified methods of its protection.Biomechanical and biological elements are important in the process of implementing articular cartilage protection.The biomechanical elements are: limb axis disorders, differences in length, distortions at the level of the support quadrilateral, pelvic triangle and shoulder triangle, as well as balance disorders resulting from disturbances in the segmental proportion of the Fi number according to Leonardo da Vinci.There are many biological elements of the discussed disorder and they concern: the state of articular cartilage structure, matrix structure, matrix biophysical elements, molecular sponge mechanism, chondrocytes, cartilage nutrition and the severity of osteoarthritis (OA).The improvement of the conditions of the biological elements of damaged articular cartilage is considered fundamental and concerns the positive impact on numerous cartilage matrix proteins by chondroprotection. This element of treatment consists in the use of chondroitin sulphate and glucosamine as a drug, administered together in the appropriate dose and for a long time depending on the degree of degradation of the articular cartilage, usually from several to several months. The combination of chondroitin sulfate with glucosamine causes the activation of a much larger number of matrix proteins than each of the preparations separately.The pharmacokinetics of chondroitin sulfate and glucosamine are positive and favor their chondroprotective effect.The pharmacoproteomics of chondroitin sulfate and glucosamine administered together result from the activation of as many joint cartilage matrix proteins as possible. The development of proteomic techniques creates completely new therapeutic possibilities and is used to study the action of individual molecules.A clinically significant fact is that both chondroitin and glucosamine are natural, endogenous components of bone tissue and articular cartilage, so the use of both drugs is biologically compatible and results in numerous elements of cartilage protection.

Therapeutic effect of sodium hyaluronate combined with glucosamine sulfate on patients with knee osteoarthritis / 中华地方病学杂志

Objective:To explore the therapeutic effect of sodium hyaluronate combined with glucosamine sulfate in the treatment of knee osteoarthritis.Methods:A total of 90 outpatients and inpatients with knee osteoarthritis who visited the Department of Orthopedics and Traumatology, Daishan County Hospital of Traditional Chinese Medicine from January to June 2020 were selected, and they were divided into sodium hyaluronate group (control group) and sodium hyaluronate combined with glucosamine sulfate group (observation group) by random number table method, with 45 patients in each group. Visual analog scale (VAS) score was used to evaluate the changes of pain in the two groups before treatment, 5 weeks and 6 months after treatment, respectively; at the same time, the total effective rate of 5 weeks and 6 months after treatment was compared between the two groups.Results:Before treatment, there was no significant difference in VAS scores [(7.4 ± 1.5) vs (7.3 ± 1.7) points] between the two groups ( t = 0.24, P = 0.812); at 5 weeks [(5.3 ± 1.1) vs (4.1 ± 1.2) points] and 6 months after treatment [(4.0 ± 0.8) vs (3.2 ± 0.9) points], the VAS scores of the observation group were significantly lower than those of the control group, and the differences were statistically significant ( t = 5.54, 5.32, P < 0.001). Compared with the same group before treatment, VAS scores were lower in the two groups at 5 weeks and 6 months after treatment, and the differences were statistically significant ( P < 0.05). At 5 weeks after treatment, there was no significant difference in the total effective rates [44.4% (20/45) vs 48.9% (22/45)] between the two groups (χ 2 = 0.18, P = 0.672); at 6 months after treatment, the total effective rate of the observation group (91.1%, 41/45) was significantly higher than that of the control group (66.7%, 30/45), and the difference was statistically significant (χ 2 = 8.07, P = 0.004). Conclusion:Sodium hyaluronate combined with glucosamine sulfate can significantly reduce the pain in patients with knee osteoarthritis, the total effective rate is higher, and is better than the effect of sodium hyaluronate alone.

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-1ß (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-1ß significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1ß. 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-1ß 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.

2021 revised algorithm for the management of knee osteoarthritis-the Chinese viewpoint.

AIM: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice. METHODS: A WG was held between members of the international ESCEO task force and a group of Chinese experts. RESULTS: Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used. Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China. CONCLUSION: This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China.

2019 revised algorithm for the management of knee osteoarthritis: the Southeast Asian viewpoint.

BACKGROUND: Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide. AIM: Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice. METHODS: A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts. RESULTS: Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm. CONCLUSION: This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

The inhibiting effect of glucosamine sulfate combined with loxoprofen sodium on chondrocyte apoptosis in rats with knee osteoarthritis.

OBJECTIVES: To explore the efficacy of glucosamine sulfate (GS) combined with loxoprofen sodium (LS) in rats with knee osteoarthritis (KOA) and its effect on chondrocytes. METHODS: We randomly assigned 40 SPF SD rats to normal group (NG), control group (CG), treatment group (TG), and model group (MG). CG and TG were processed with continuous irrigation of LS and GS. NG and MG were given normal saline. We collected 3 mL of venous blood from the rat's lower limb for the detection of serum IL-1ß, IL-6, IL-8, and TNF-α by ELISA. Four weeks after irrigation, 5 rats in each group were randomly selected for anesthesia. The water content was detected, and the chondrocytes were collected. MTT assay was used to detect apoptosis, and Western blot (WB) to measure concentrations of Bax, Bcl-2, Caspase3, Caspase9, TLR4, and NF-kB. RESULTS: The levels of IL-1 ß, IL-6, IL-8, and TNF-α decreased in CG and TG, but increased in MG (P<0.05). After treatment, the expression of inflammatory factors was highest in MG (P<0.05). CONCLUSIONS: GS combined with LS showed good efficacy in rats with knee osteoarthritis, which may be achieved by inhibiting the expression of inflammatory factors and knee chondrocyte apoptosis via the TLR4-NF-kB pathway.