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Jeanyves Reginster - One of the best experts on this subject based on the ideXlab platform.

  • a combination of celecoxib and Glucosamine Sulfate has anti inflammatory and chondroprotective effects results from an in vitro study on human osteoarthritic chondrocytes
    International Journal of Molecular Sciences, 2021
    Co-Authors: Sara Cheleschi, Jeanyves Reginster, Sara Tenti, S Giannotti, Nicola Veronese, Antonella Fioravanti
    Abstract:

    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.

  • different Glucosamine Sulfate products generate different outcomes on osteoarthritis symptoms
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Jeanyves Reginster, Olivier Bruyere, C Cooper
    Abstract:

    Runhaar and colleagues1 produced an elegant meta-analysis of various Glucosamine-containing products in knee and hip osteoarthritis (OA), based on individual patient data (IPD). Although they were able to access and analyse only 5 out 21 eligible studies, their results are in agreement with most Glucosamine meta-analyses in OA: Glucosamine products other than prescription crystalline Glucosamine Sulfate are not effective in hip or knee OA pain and function. Such results, as acknowledged by the Authors, had already been demonstrated in several previous and more comprehensive meta-analyses, including a dedicated Cochrane Review2 and a recent effort by Eriksen et al 3 specifically investigating possible differences in efficacy among Glucosamine products. Indeed, Glucosamine exists in different forms for pharmaceutical use, as extensively reviewed by Altman.4 Among these, Glucosamine hydrochloride (used in three out of …

  • A review of Glucosamine for knee osteoarthritis: why patented crystalline Glucosamine Sulfate should be differentiated from other Glucosamines to maximize clinical outcomes
    Current medical research and opinion, 2016
    Co-Authors: Eugene J. Kucharz, Olivier Bruyere, Volodymyr Kovalenko, Sándor Szántó, Cyrus Cooper, Jeanyves Reginster
    Abstract:

    The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for knee osteoarthritis (OA) recommends symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) first line for the medium to long term management of OA, due to their ability to control pain, improve function, and delay joint structural changes. Among SYSADOAs, Glucosamine is probably the most widely used intervention. In the present review of Glucosamine for knee OA, we have investigated whether the evidence is greater for the patented crystalline Glucosamine Sulfate (pCGS) preparation (Rottapharm/Meda) than for other Glucosamine formulations. Glucosamine is actually widely available in many forms, as the prescription-grade pCGS preparation, generic and over-the-counter formulations of Glucosamine Sulfate (GS) and food supplements containing Glucosamine hydrochloride (GH), which vary substantially in molecular form, pharmaceutical formulation and dose regimens. Only pCGS is given as a highly bioavailable once daily dose (1500 mg) with a proven pharmacological effect. pCGS consistently reaches the plasma levels of around 10 μM required to inhibit interleukin-1 induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction, compared with sub-therapeutic levels achieved with GH. It is evident, from careful consideration of the evidence base, that only the pCGS formulation of Glucosamine reliably provides an effect size on pain that is higher than that of paracetamol and equivalent to that provided by non-steroidal anti-inflammatory drugs. In comparison, the effect size on pain of non-crystalline GS preparations and GH from randomized controlled trials is repeatedly demonstrated to be zero. In addition, there is evidence that chronic administration of pCGS has disease-modifying effects, with a reduction in the need for total joint replacement surgery lasting for at least 5 years after treatment cessation. Consequently, the pCGS preparation (Rottapharm/Meda) is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression.

  • efficacy and safety of Glucosamine Sulfate in the management of osteoarthritis evidence from real life setting trials and surveys
    Seminars in Arthritis and Rheumatism, 2016
    Co-Authors: Olivier Bruyere, Roy D Altman, Jeanyves Reginster
    Abstract:

    The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) including Glucosamine Sulfate (GS) and chondroitin Sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and Glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other Glucosamine preparations. Long-term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression.

  • Glucosamine and chondroitin Sulfate as therapeutic agents for knee and hip osteoarthritis
    Drugs & Aging, 2007
    Co-Authors: Olivier Bruyere, Jeanyves Reginster
    Abstract:

    problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of OA. This review evaluates published studies of the effect of Glucosamine salts and chondroitin Sulfate preparations on the progression of knee or hip OA. Despite multiple double-blind, controlled clinical trials of the use of Glucosamine and chondroitin Sulfate in OA, controversy regarding the efficacy of these agents with respect to symptomatic improvement remains. Several potential confounders, including placebo response, use of prescription medicines versus over-the-counter pills or food supplements, or use of Glucosamine Sulfate versus Glucosamine hydrochloride, may have relevance when attempting to interpret the seemingly contradictory results of different clinical trials. The National Institutes of Health-sponsored GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) compared placebo, Glucosamine hydrochloride, chondroitin Sulfate, a combination of Glucosamine and chondroitin Sulfate and celecoxib in a parallel, blinded 6-month multicentre study of patients with knee OA. This trial showed that Glucosamine hydrochloride and chondroitin Sulfate alone or in combination did not reduce pain effectively in the overall group of patients with OA of the knee. However, exploratory analyses suggest that the combination of Glucosamine hydrochloride and chondroitin Sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.

Olivier Bruyere - One of the best experts on this subject based on the ideXlab platform.

  • different Glucosamine Sulfate products generate different outcomes on osteoarthritis symptoms
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Jeanyves Reginster, Olivier Bruyere, C Cooper
    Abstract:

    Runhaar and colleagues1 produced an elegant meta-analysis of various Glucosamine-containing products in knee and hip osteoarthritis (OA), based on individual patient data (IPD). Although they were able to access and analyse only 5 out 21 eligible studies, their results are in agreement with most Glucosamine meta-analyses in OA: Glucosamine products other than prescription crystalline Glucosamine Sulfate are not effective in hip or knee OA pain and function. Such results, as acknowledged by the Authors, had already been demonstrated in several previous and more comprehensive meta-analyses, including a dedicated Cochrane Review2 and a recent effort by Eriksen et al 3 specifically investigating possible differences in efficacy among Glucosamine products. Indeed, Glucosamine exists in different forms for pharmaceutical use, as extensively reviewed by Altman.4 Among these, Glucosamine hydrochloride (used in three out of …

  • differentiation of patented crystalline Glucosamine Sulfate from other Glucosamine preparations will optimize osteoarthritis treatment
    International Journal of Rheumatic Diseases, 2017
    Co-Authors: Sukit Saengnipanthkul, Olivier Bruyere, C Cooper, Saranatra Waikakul, Sattaya Rojanasthien, Kitti Totemchokchyakarn, Attarit Srinkapaibulaya, Tai Cheh Chin, Nguyen Mai Hong
    Abstract:

    Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are recommended for the medium- to long-term management of knee osteoarthritis (OA) due to their abilities to control pain, improve function and delay joint structural changes. Among SYSADOAs, evidence is greatest for the patented crystalline Glucosamine Sulfate (pCGS) formulation (Mylan). Glucosamine is widely available as Glucosamine Sulfate (GS) and Glucosamine hydrochloride (GH) preparations that vary substantially in molecular form, pharmaceutical formulation and dose regimen. Only pCGS is given as a highly bioavailable once-daily dose (1500 mg), which consistently delivers the plasma levels of around 10 μmol/L required to inhibit interleukin-1-induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction. Careful consideration of the evidence base reveals that only pCGS reliably provides a moderate effect size on pain that is higher than paracetamol and equivalent to non-steroidal anti-inflammatory drugs (NSAIDs), while non-crystalline GS and GH fail to reach statistical significance for pain reduction. Chronic administration of pCGS has disease-modifying effects, with a reduction in need for total joint replacement lasting for 5 years after treatment cessation. Pharmacoeconomic studies of pCGS demonstrate long-term reduction in additional pain analgesia and NSAIDs, with a 50% reduction in costs of other OA medication and healthcare consultations. Consequently, pCGS is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression. Physician and patient education on the differentiation of pCGS from other Glucosamine formulations will help to improve treatment selection, increase treatment adherence, and optimize clinical benefit in OA.

  • A review of Glucosamine for knee osteoarthritis: why patented crystalline Glucosamine Sulfate should be differentiated from other Glucosamines to maximize clinical outcomes
    Current medical research and opinion, 2016
    Co-Authors: Eugene J. Kucharz, Olivier Bruyere, Volodymyr Kovalenko, Sándor Szántó, Cyrus Cooper, Jeanyves Reginster
    Abstract:

    The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for knee osteoarthritis (OA) recommends symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) first line for the medium to long term management of OA, due to their ability to control pain, improve function, and delay joint structural changes. Among SYSADOAs, Glucosamine is probably the most widely used intervention. In the present review of Glucosamine for knee OA, we have investigated whether the evidence is greater for the patented crystalline Glucosamine Sulfate (pCGS) preparation (Rottapharm/Meda) than for other Glucosamine formulations. Glucosamine is actually widely available in many forms, as the prescription-grade pCGS preparation, generic and over-the-counter formulations of Glucosamine Sulfate (GS) and food supplements containing Glucosamine hydrochloride (GH), which vary substantially in molecular form, pharmaceutical formulation and dose regimens. Only pCGS is given as a highly bioavailable once daily dose (1500 mg) with a proven pharmacological effect. pCGS consistently reaches the plasma levels of around 10 μM required to inhibit interleukin-1 induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction, compared with sub-therapeutic levels achieved with GH. It is evident, from careful consideration of the evidence base, that only the pCGS formulation of Glucosamine reliably provides an effect size on pain that is higher than that of paracetamol and equivalent to that provided by non-steroidal anti-inflammatory drugs. In comparison, the effect size on pain of non-crystalline GS preparations and GH from randomized controlled trials is repeatedly demonstrated to be zero. In addition, there is evidence that chronic administration of pCGS has disease-modifying effects, with a reduction in the need for total joint replacement surgery lasting for at least 5 years after treatment cessation. Consequently, the pCGS preparation (Rottapharm/Meda) is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression.

  • the role of diet and exercise and of Glucosamine Sulfate in the prevention of knee osteoarthritis further results from the prevention of knee osteoarthritis in overweight females proof study
    Seminars in Arthritis and Rheumatism, 2016
    Co-Authors: J Runhaar, Olivier Bruyere, Giampaolo Giacovelli, Rita Deroisy, Marienke Van Middelkoop, Francesco Barretta, Beatrice Barbetta, Edwin H G Oei, Dammis Vroegindeweij, Lucio C. Rovati
    Abstract:

    Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral Glucosamine Sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) Glucosamine Sulfate + no DEP (GS, N = 102), and (4) DEP + Glucosamine Sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline Glucosamine Sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with Glucosamine Sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving Glucosamine Sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine Sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine Sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss.

  • efficacy and safety of Glucosamine Sulfate in the management of osteoarthritis evidence from real life setting trials and surveys
    Seminars in Arthritis and Rheumatism, 2016
    Co-Authors: Olivier Bruyere, Roy D Altman, Jeanyves Reginster
    Abstract:

    The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) including Glucosamine Sulfate (GS) and chondroitin Sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and Glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other Glucosamine preparations. Long-term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression.

Lucio C. Rovati - One of the best experts on this subject based on the ideXlab platform.

  • the role of diet and exercise and of Glucosamine Sulfate in the prevention of knee osteoarthritis further results from the prevention of knee osteoarthritis in overweight females proof study
    Seminars in Arthritis and Rheumatism, 2016
    Co-Authors: J Runhaar, Olivier Bruyere, Giampaolo Giacovelli, Rita Deroisy, Marienke Van Middelkoop, Francesco Barretta, Beatrice Barbetta, Edwin H G Oei, Dammis Vroegindeweij, Lucio C. Rovati
    Abstract:

    Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral Glucosamine Sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) Glucosamine Sulfate + no DEP (GS, N = 102), and (4) DEP + Glucosamine Sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline Glucosamine Sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with Glucosamine Sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving Glucosamine Sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine Sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine Sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss.

  • absorption distribution metabolism and excretion of Glucosamine Sulfate a review
    Drug Research, 2011
    Co-Authors: Ivo Setnikar, Lucio C. Rovati
    Abstract:

    This article reviews the literature related to the absorption, distribution, metabolism and excretion (ADME) of Glucosamine (Gl) in man and in animals after administration of crystalline Glucosamine Sulfate (CGS). Intravenous administration of CGS In man, after single bolus intravenous (i.v.) injection of 1005 mg CGS (628 mg Gl), the parent Gl disappears from plasma with an apparent half life of 1.11 h. Investigations with uniformly 14 C labeled Gl ( 14 C-Gl) administered with 502 mg CGS indicate that the disappearance of Gl is due to an incorporation into the plasma globulins that occurs with a lag time of 0.45 h and a rate of 0.26 h −1 . The radioactivity reaches a peak after 10 h and is eliminated with a t 1/2 of 95 h. After single i.v. doses of 502 mg CGS traced with 14 C-G1, the urinary excretion in 120 h accounted for 29 % of the administered dose. Consistent results are obtained in rat and dogs, in which radioactivity rapidly appears in liver, kidneys and other tissues, including the articular cartilage. In man, after i.V. bolus injection of 1005 mg CGS, the urinary excretion in 24 h of Gl determined with ion exchange chromatography was 38 % of the administered dose, mostly in the first 8 h after administration. Similar results were obtained tracing CGS with 14 C-Gl. Consistent results of urinary excretion were obtained in rats and dogs tracing CGS with 14 C-Gl. The excretion of radioactivity in feces was small. The elimination of radioactivity with the expired air as 14 CO 2 measured in rats amounted to 49 % of the administered dose in the 144 h following the administration, 16 % of which occured in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with 14 C-G1, gave results similar to those after i.v. administration. Oral administration of CGS In man, after a single dose of 7.5 g CGS, Gl in plasma was below the limit of quantitation (3 μg/ml) of the ion exchange chromatography method. After a single dose of 314 mg CGS traced with 14 C-Gl, radioactivity appeared incorporated in plasma globulins with a lag time of 1.5 h and increasing with a rate of 0.24 h −1 . The peak was reached at the 9th h after administration. The radioactivity then was eliminated with a t 1/2 of 58 h. The absolute oral bioavailability evaluated on the AUCs of the globulin-incorporated radioactivity was 44 %. The fecal excretion in 120 h was 11.3 % of the administered dose showing that at least 88.7 % of the administered dose was absorbed through the gastrointestinal tract. The difference of 45 % is probably due to a hepatic first-pass effect. Investigated in the rat with doses from 126 to 3768 mg CGS traced with 14 C-G1, a linear relationship was found with the AUCs as well as between doses and the C max of radioactivity in total and in deproteinized plasma. The urinary elimination in man of the parent Gl in 24 h determined with ion exchange chromatography after a single dose of 7.5 g of CGS was 1.19 % of the administered dose, occuring mostly in the first 8 h after administration. After administration of 1884 mg repeated for 7 days the daily urinary excretion of Gl increased from 1.60 % of the daily dose during the first 24 h to 2.22 % of the daily dose in the last 24 h. The steady state was reached after the second day. The urinary excretion at steady state during repeated administration allowed to conclude that daily 1884 CGS administered either t.i.d. in sugar coated tablets or once a day in oral solution were bio-equivalent. The elimination of radioactivity with the expired as 14 CO 2 measured in rats was 82 % of the administered dose in the 144 h following the administration, 61 % of which occur in the first 6 h. Interaction of Gl with the ADME of glucose The ADME of glucose was investigated in the rat administering i.v. or orally 14 C uniformly labeled glucose. The kinetic in plasma and the tissue distribution of glucose differed totally from those of Gl, pointing out that exogenous glucose provides the energy for biochemical processes, whereas exogenous Gl acts mainly as substrate for the biosynthesis of mucopolysaccharides and of biopolymers of the articulations and bones. There was no evidence of interaction by Gl orally administered with the ADME of glucose.

  • crystalline Glucosamine Sulfate in the treatment of osteoarthritis evidence of long term cardiovascular safety from clinical trials
    The Open Rheumatology Journal, 2011
    Co-Authors: R P Reis, Federica Girolami, Giampaolo Giacovelli, Rui Andre, Albino Bonazzi, Lucio C. Rovati
    Abstract:

    Background and Objective: Glucosamine is a safe and common treatment for osteoarthritis. Even so, literature data on the cardiovascular safety of Glucosamine are limited. The objective of this paper is to investigate the long-term effects of crystalline Glucosamine Sulfate (CGS) on key measures of cardiovascular risk in patients with osteoarthritis.

  • Experimental Pharmacology of Glucosamine Sulfate
    International journal of rheumatology, 2011
    Co-Authors: R. Chiusaroli, Tiziana Piepoli, Tiziano Zanelli, Paola Ballanti, Marco Lanza, Lucio C. Rovati, Gianfranco Caselli
    Abstract:

    Several clinical studies demonstrated that Glucosamine Sulfate (GS) is effective in controlling osteoarthritis (OA), showing a structure-modifying action. However, little is known about the molecular mechanism(s) by which GS exerts such action and about the effects of GS at a tissue level on osteoarthritic cartilage and other joint structures. Here we provide mechanistic evidence suggesting that in vitro GS attenuates NF-κB activation at concentrations in the range of those observed after GS administration to volunteers and patients, thus strengthening previous findings. Furthermore, we describe the effects of GS at a tissue level on the progression of the disease in a relevant model of spontaneous OA, the STR/ort mouse. In this model, the administration of GS at human corresponding doses was associated with a significant decrease of OA scores. Histomorphometry showed that the lesion surface was also significantly decreased, while the number of viable chondrocytes within the matrix was significantly increased. GS improved the course of OA in the STR/Ort mouse, by delaying cartilage breakdown as assessed histologically and histomorphometrically.

  • Glucosamine Sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis evidence from two 3 year studies
    Menopause, 2004
    Co-Authors: Olivier Bruyere, Giampaolo Giacovelli, Lucio C. Rovati, K Pavelka, J Gatterova, M Olejarova, Rita Deroisy, Jeanyves Reginster
    Abstract:

    Objective: To investigate the effect of Glucosamine Sulfate on long-term symptoms and structure progression in postmenopausal women with knee osteoarthritis (OA). Design: This study consisted of a preplanned combination of two three-year, randomized, placebo-controlled, prospective, independent studies evaluating the effect of Glucosamine Sulfate on symptoms and structure modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were scored by the algofunctional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA. Results: Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, Glucosamine Sulfate and placebo groups were comparable for demographic and disease characteristics, both in the general population and in the postmenopausal women subset. After 3 years, postmenopausal participants in the Glucosamine Sulfate group showed no joint space narrowing [joint space change of +0.003 mm (95% CI, �0.09 to 0.11)], whereas participants in the placebo group experienced a narrowing of �0.33 mm (95% CI, �0.44 to �0.22; P < 0.0001 between the two groups). Percent changes after 3 years in the WOMAC index showed an improvement in the Glucosamine Sulfate group [�14.1% (95%, �22.2 to �5.9)] and a trend for worsening in the placebo group (5.4% (95% CI, �4.9 to 15.7) (P = 0.003 between the two groups). Conclusion: This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.

C Cooper - One of the best experts on this subject based on the ideXlab platform.

  • different Glucosamine Sulfate products generate different outcomes on osteoarthritis symptoms
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Jeanyves Reginster, Olivier Bruyere, C Cooper
    Abstract:

    Runhaar and colleagues1 produced an elegant meta-analysis of various Glucosamine-containing products in knee and hip osteoarthritis (OA), based on individual patient data (IPD). Although they were able to access and analyse only 5 out 21 eligible studies, their results are in agreement with most Glucosamine meta-analyses in OA: Glucosamine products other than prescription crystalline Glucosamine Sulfate are not effective in hip or knee OA pain and function. Such results, as acknowledged by the Authors, had already been demonstrated in several previous and more comprehensive meta-analyses, including a dedicated Cochrane Review2 and a recent effort by Eriksen et al 3 specifically investigating possible differences in efficacy among Glucosamine products. Indeed, Glucosamine exists in different forms for pharmaceutical use, as extensively reviewed by Altman.4 Among these, Glucosamine hydrochloride (used in three out of …

  • differentiation of patented crystalline Glucosamine Sulfate from other Glucosamine preparations will optimize osteoarthritis treatment
    International Journal of Rheumatic Diseases, 2017
    Co-Authors: Sukit Saengnipanthkul, Olivier Bruyere, C Cooper, Saranatra Waikakul, Sattaya Rojanasthien, Kitti Totemchokchyakarn, Attarit Srinkapaibulaya, Tai Cheh Chin, Nguyen Mai Hong
    Abstract:

    Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are recommended for the medium- to long-term management of knee osteoarthritis (OA) due to their abilities to control pain, improve function and delay joint structural changes. Among SYSADOAs, evidence is greatest for the patented crystalline Glucosamine Sulfate (pCGS) formulation (Mylan). Glucosamine is widely available as Glucosamine Sulfate (GS) and Glucosamine hydrochloride (GH) preparations that vary substantially in molecular form, pharmaceutical formulation and dose regimen. Only pCGS is given as a highly bioavailable once-daily dose (1500 mg), which consistently delivers the plasma levels of around 10 μmol/L required to inhibit interleukin-1-induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction. Careful consideration of the evidence base reveals that only pCGS reliably provides a moderate effect size on pain that is higher than paracetamol and equivalent to non-steroidal anti-inflammatory drugs (NSAIDs), while non-crystalline GS and GH fail to reach statistical significance for pain reduction. Chronic administration of pCGS has disease-modifying effects, with a reduction in need for total joint replacement lasting for 5 years after treatment cessation. Pharmacoeconomic studies of pCGS demonstrate long-term reduction in additional pain analgesia and NSAIDs, with a 50% reduction in costs of other OA medication and healthcare consultations. Consequently, pCGS is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression. Physician and patient education on the differentiation of pCGS from other Glucosamine formulations will help to improve treatment selection, increase treatment adherence, and optimize clinical benefit in OA.

  • a consensus statement on the european society for clinical and economic aspects of osteoporosis and osteoarthritis esceo algorithm for the management of knee osteoarthritis from evidence based medicine to the real life setting
    Seminars in Arthritis and Rheumatism, 2016
    Co-Authors: Olivier Bruyere, C Cooper, Jean-pierre Pelletier, Jaime Branco, Maria Luisa Brandi, John A Kanis, E Maheu, Francois Rannou, Roy D Altman
    Abstract:

    The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians' individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline Glucosamine Sulfate and chondroitin Sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.

  • an algorithm recommendation for the management of knee osteoarthritis in europe and internationally a report from a task force of the european society for clinical and economic aspects of osteoporosis and osteoarthritis esceo
    Seminars in Arthritis and Rheumatism, 2014
    Co-Authors: Olivier Bruyere, C Cooper, Jean-pierre Pelletier, Jaime Branco, Maria Luisa Brandi, F Guillemin, Marc C Hochberg, John A Kanis, Tore K Kvien
    Abstract:

    Objectives: Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint. Methods: ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shaped to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus. Results: Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight, and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for realignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) or pharmacological. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (e.g., prescription Glucosamine Sulfate and/or chondroitin Sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 Contents lists available at ScienceDirect

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  • combined treatment with chondroitin Sulfate and Glucosamine Sulfate shows no superiority over placebo for reduction of joint pain and functional impairment in patients with knee osteoarthritis a six month multicenter randomized double blind placebo controlled clinical trial
    Arthritis & Rheumatism, 2017
    Co-Authors: Jorge A Romanblas, O Sanchezpernaute, R Largo, Santos Castaneda, G Herrerobeaumont
    Abstract:

    Objective To assess the efficacy and safety of combination therapy with chondroitin Sulfate (CS) and Glucosamine Sulfate (GS) compared to placebo in patients with symptomatic knee osteoarthritis (OA). Methods A multicenter, randomized, double-blind, placebo-controlled study was performed in 164 patients with Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and moderate-to-severe knee pain (mean ± SD global pain score 62.1 ± 11.3 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to receive either combined treatment with CS (1,200 mg) plus GS (1,500 mg) or placebo in a single oral daily dose for 6 months. The mean change from baseline in the VAS global pain score was set as the primary end point. Secondary outcomes included the mean change in the investigator's global assessment of disease activity, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), pain and function subscale scores on the WOMAC, responder rates based on the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) 2004 response criteria, and rescue medication use. Adverse events were also recorded. A Data and Safety Monitoring Board was instituted to ensure patient safety and data accuracy. Results Intriguingly, in the modified intent-to-treat (mITT) population, CS/GS combination therapy was inferior to placebo in the reduction of joint pain (mean ± SD change in VAS global pain score over 6 months −11.8 ± 2.4 mm [19% reduction] in patients receiving CS plus GS versus −20.5 ± 2.4 mm [33% reduction] in patients receiving placebo; peak between-group difference in global pain score at 6 months 8.7 mm [14.2%], P < 0.03), but no between-group differences were seen in the per-protocol completers. Both placebo treatment and CS/GS combination treatment improved to a similar extent the total WOMAC score as well as the pain and function WOMAC subscale scores, both in the mITT population and in the per-protocol completers. Neither the OMERACT–OARSI responder rate nor the frequency of rescue medication use differed between the treatment groups. Severe adverse events were uncommon and equally distributed. Conclusion The results of this trial demonstrate a lack of superiority of CS/GS combination therapy over placebo in terms of reducing joint pain and functional impairment in patients with symptomatic knee OA over 6 months. Further research might fully elucidate the suitability of CS/GS combination therapy in patients with OA.

  • effect of a high dose of Glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis
    American Journal of Physiology-heart and Circulatory Physiology, 2009
    Co-Authors: R Largo, M J Martinezcalatrava, O Sanchezpernaute, Esther M Marcos, Juan Morenorubio, Cesar Aparicio, Jesus Egido, G Herrerobeaumont
    Abstract:

    Glucosamine Sulfate (GS) is a glycosaminoglycan with anti-inflammatory and immunoregulatory properties. Here we set out to explore the effect of GS administration on markers of systemic and local i...

  • Glucosamine Sulfate in the treatment of knee osteoarthritis symptoms a randomized double blind placebo controlled study using acetaminophen as a side comparator
    Arthritis & Rheumatism, 2007
    Co-Authors: G Herrerobeaumont, Jose Andres Roman Ivorra, Maria Del Carmen Trabado, Francisco J Blanco, Pere Benito, E Martinmola, Javier Paulino, Jose Luis Marenco, Armando Porto, Armando Laffon
    Abstract:

    Objective To assess the effects of the prescription formulation of Glucosamine Sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course. Methods Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral Glucosamine Sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis. Results At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index ∼11 points). Glucosamine Sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between Glucosamine Sulfate and placebo −1.2 [95% confidence interval −2.3, −0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference −0.8 [95% confidence interval −1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to Glucosamine Sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups. Conclusion The findings of this study indicate that Glucosamine Sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes.

  • Glucosamine inhibits il 1β induced nfκb activation in human osteoarthritic chondrocytes
    Osteoarthritis and Cartilage, 2003
    Co-Authors: R Largo, Jesus Egido, M A Alvarezsoria, I Diezortego, Emilio Calvo, Olga Sanchezpernaute, G Herrerobeaumont
    Abstract:

    Objective Glucosamine Sulfate (GS) is a commonly used drug for the treatment of osteoarthritis. The mechanism of the action of this drug does, however, remain to be elucidated. In human osteoarthritic chondrocytes (HOC) stimulated with a proinflammatory cytokine, we studied whether GS could modify the NFkappaB activity and the expression of COX-2, a NFkappaB-dependent gene. Methods Using HOC in culture stimulated with interleukin-1 beta (IL-1beta), the effects of GS on NFkappaB activation, nuclear translocation of NFkappaB/Rel family members, COX-1 and COX-2 expressions and syntheses and prostaglandin E2 (PGE2) concentration were studied. Results GS significantly inhibited NFkappaB activity in a dose-dependent manner, as well as the nuclear translocation of p50 and p65 proteins. Furthermore, GS-preincubated IL-1beta-stimulated HOC showed an increase in IkappaBalpha in the cell cytoplasm in comparison with HOC incubated with IL-1beta alone. GS also inhibited the gene expression and the protein synthesis of COX-2 induced by IL-1beta, while no effect on COX-1 synthesis was seen. GS also inhibited the release of PGE2 to conditioned media of HOC stimulated with IL-1beta. Conclusions GS inhibits the synthesis of proinflammatory mediators in HOC stimulated with IL-1beta through a NFkappaB-dependent mechanism. Our study further supports the role of GS as a symptom- and structure-modifying drug in the treatment of OA.