Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma.

PRCIS: Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted. BACKGROUND: The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP. METHODS: In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP. RESULTS: In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP ( P =0.002, 2-tailed t test). This was also true in subjects without glaucoma ( P =0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant ( P <0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95). CONCLUSION: Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.

Inverse association of glucosamine use and risk of new-onset kidney stones in UK adults with less sedentary time.

OBJECTIVE: To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic risk of kidney stones on this association. METHODS: 473,225 participants free of kidney stones at baseline from the UK Biobank were included. Total sedentary time was calculated as the sum of the duration of TV-watching, driving, and non-occupational computer using. The primary outcome was new-onset kidney stones. RESULTS: During a median follow-up of 12.0 years, 5528 cases of kidney stones were documented. All major sedentary behaviors and total sedentary time were significantly positively related to the risk of kidney stones (All P for trend<0.05). Participants with total sedentary time ≥ 3.5 h/day had a significantly higher risk of new-onset kidney stones (vs. <3.5 h/day [tertile 1]; HR, 1.18; 95%CI,1.10-1.27). Compared with non-users, participants who regularly used glucosamine had a significantly lower risk of new-onset kidney stones in those with total sedentary time < 3.5 h/day (HR, 0.72; 95%CI,0.59-0.86), but not in those with total sedentary time ≥ 3.5 h/day (HR, 0.99; 95%CI,0.91-1.08; P-interaction = 0.001). Among participants with total sedentary time < 3.5 h/day, there was a dose-response relationship of glucosamine use with new-onset kidney stones (P for trend<0.001). Genetic risks of kidney stones did not significantly modify the association. CONCLUSIONS: TV-watching, driving and non-occupational computer using were all positively associated with the risk of new-onset kidney stones. Glucosamine use was associated with a lower risk of new-onset kidney stones in participants with total sedentary time < 3.5 h/day, following a dose-response relationship.

Palmitoyl-glucosamine co-micronized with curcumin for maintenance of meloxicam-induced pain relief in dogs with osteoarthritis pain.

BACKGROUND: Osteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments-i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)-while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales. RESULTS: A total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18-39). Based on owner's assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001). CONCLUSION: The findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.

Transforming growth factor-ß receptor 1: An intervention target for genetic poor cartilage quality induced by prenatal dexamethasone exposure.

INTRODUCTION: Fetal-originated osteoarthritis is relative to poor cartilage quality and may exhibit transgenerational genetic effects. Previous findings revealed prenatal dexamethasone exposure (PDE) induced poor cartilage quality in offspring. OBJECTIVES: This study focused on further exploring molecular mechanism, heritability, and early intervention of fetal-originated osteoarthritis. METHODS: Pregnant rats (F0) were segregated into control and PDE groups depending upon whether dexamethasone was administered on gestational days (GDs) 9-20. Some female offspring were bred with healthy males during postnatal week (PW) 8 to attain the F2 and F3 generations. The F3-generation rats were administrated with glucosamine intragastrically at PW12 for 6 weeks. The knee cartilages of male and female rats at different time points were harvested to assay their morphologies and functions. Furthermore, primary chondrocytes from the F3-generation rats were isolated to confirm the mechanism and intervention target of glucosamine. RESULTS: Compared with the control, female and male rats in each generation of PDE group showed thinner cartilage thicknesses; shallower and uneven staining; fewer chondrocytes; higher Osteoarthritis Research Society International scores; and lower mRNA and protein expression of SP1, TGFßR1, Smad2, SOX9, ACAN and COL2A1. After F3-generation rats were treated with glucosamine, all of the above changes could be reversed. In primary chondrocytes isolated from the F3-generation rats of PDE group, glucosamine promoted SP1 expression and binding to TGFßR1 promoter to increase the expression of TGFßR1, p-Smad2, SOX9, ACAN and COL2A1, but these were prevented by SB431542 (a potent and selective inhibitor of TGFßR1). CONCLUSIONS: PDE induced chondrodysplasia in offspring and stably inherited in F3-generation rats, which was related to decreased expression of SP1/TGFßR1/Smad2/SOX9 pathway to reduce the cartilage matrix synthesis, without major sex-based variations. Glucosamine could alleviate the poor genetic cartilage quality in offspring induced by PDE by up-regulating SP1/TGFßR1 signaling, which was prevented by a TGFßR1 inhibitor. This study elucidated the molecular mechanism and therapeutic target (TGFßR1) of genetic chondrodysplasia caused by PDE, which provides a research basis for precisely treating fetal-originated osteoarthritis.

Pre-clinical investigation of protective effect of nutraceutical D-glucosamine on TNBS-induced colitis.

OBJECTIVE: The level of precursors involved in the biosynthesis of glycosaminoglycan (GAG), glucosamine synthase, and N-acetyl glucosamine (NAG), are significantly reduced in inflammatory bowel disease (IBD). This results in deficient GAG content in mucosa, which eventually disrupt the gut wall integrity, provoking abnormal immunological responses. This is characterized by colossal liberation of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukins (ILs), and reactive oxygen species (ROS) provoking colonic inflammation. D-glucosamine (D-GLU) is reported to suppress oxidative stress, and pro-inflammatory cytokines and acts as a starting material for biosynthesis of NAG. The potential of D-GLU and its combination with mesalamine (5-ASA) was investigated in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-instigated IBD in Wistar rats. MATERIALS AND METHODS: Standard and test drugs were given orally for 5 d to separate groups of rats. Colonic inflammation was evaluated by disease activity score rate (DASR), colon/body weight ratio, colon length, diameter, colon pH, histological injury, and score. Inflammatory biomarkers IL-1ß, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. RESULTS: Combination of D-GLU + 5-ASA significantly ameliorated severity of colonic inflammation by lowering DASR (p < 0.001) and colon/body weight ratio (p < 0.001), restored the colonic architecture and suppressed the histopathological score (p < 0.001), along with the absence of major adverse reactions. The combination suppressed the levels of inflammatory markers (p < 0.001) and MDA (p < 0.001) while enhancing GSH level (p < 0.001). CONCLUSION: In comparison to individual 5-ASA and D-GLU, combination of drugs significantly diminished colitis severity through their combined anti-inflammatory and antioxidant effects by acting on multiple targets simultaneously. The combination holds remarkable potential in the management of IBD.

Glucosamine Use Is Associated with a Higher Risk of Cardiovascular Diseases in Patients with Osteoarthritis: Results from a Large Study in 685,778 Subjects.

Glucosamine is widely used around the world and as a popular dietary supplement and treatment in patients with osteoarthritis in China; however, the real-world cardiovascular risk of glucosamine in long-term use is still unclear. A retrospective, population-based cohort study was performed, based on the Beijing Medical Claim Data for Employees from 1 January 2010 to 31 December 2017. Patients newly diagnosed with osteoarthritis were selected and divided into glucosamine users and non- glucosamine users. The glucosamine users group was further divided into adherent, partially adherent, and non-adherent groups according to the medication adherence. New-onset cardiovascular diseases (CVD) events, coronary heart diseases (CHD), and stroke, were identified during the observational period. COX proportional regression models were used to estimate the risks. Of the 685,778 patients newly diagnosed with osteoarthritis including 240,419 glucosamine users and 445,359 non-users, the mean age was 56.49 (SD: 14.45) years and 59.35% were females. During a median follow-up of 6.13 years, 64,600 new-onset CVD, 26,530 CHD, and 17,832 stroke events occurred. Glucosamine usage was significantly associated with CVD (HR: 1.10; 95% CI: 1.08−1.11) and CHD (HR: 1.12; 95% CI: 1.09−1.15), but not with stroke (HR: 1.03; 95% CI: 0.99−1.06). The highest CVD risk was shown in the adherent group (HR: 1.68; 95% CI: 1.59−1.78), followed by the partially adherent group (HR: 1.26, 95% CI: 1.22−1.30), and the non-adherent group (HR: 1.03; 95% CI: 1.02−1.05), with a significant dose−response relationship (p-trend < 0.001). In this longitudinal study, adherent usage of glucosamine was significantly associated with a higher risk for cardiovascular diseases in patients with osteoarthritis.

Clinical Efficacy and Safety of Chondroitin Combined with Glucosamine in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Objective: This analysis was aimed at providing evidence-based medicine basis for systematic evaluation of chondroitin combined with glucosamine in the treatment of knee osteoarthritis. Methods: The randomized controlled trials (RCTs) of chondroitin combined with glucosamine in the treatment of knee osteoarthritis (KOA) were searched in PubMed, EMBASE, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database. The retrieval time ranges from the database creation to the present. Two investigators gathered the information individually. The risk of bias was assessed using the criteria of the Cochrane back review group. RevMan5.4 statistical software analyzed the selected data. Results: A total of 6 RCT articles were obtained. Overall, 764 samples were evaluated by meta-analysis. The clinical efficacy of chondroitin combined with glucosamine was significantly better than that of routine treatment by meta-analysis. The confidence interval of 95% was (4.86, 17.08) (Z = 6.89, P < 0.00001). The scores of joint pain, tenderness, swelling, and dysfunction in patients with knee osteoarthritis treated with chondroitin combined with glucosamine were significantly lower than those treated with routine treatment. There was no significant difference in the incidence of adverse reactions between chondroitin combined with glucosamine and single treatment of KOA. Due to the small number of documents included in the analysis, it is not suitable to make a funnel chart, but there may be some publication deviation in the analysis. Conclusion: Chondroitin combined with glucosamine is more effective than chondroitin or glucosamine alone in the treatment of KOA and deserves clinical promotion. However, this conclusion still needs to be supported by multicenter, high-quality, double-blind, large-sample randomized controlled clinical trials due to the limitations of the six trials included.

Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study.

BACKGROUND: Research on glucosamine shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study. METHODS: Participants were enrolled between 2006 and 2010 and followed-up to 2020. The Cox proportional hazards model was used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. RESULTS: 439 393 participants (mean age 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. 82 603 (18.80%) participants reported regular use of glucosamine at baseline. During follow-up, 1971 (0.45%) lung cancer events were documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio (HR) 0.84, 95% CI 0.75-0.92; p<0.001) and lung cancer mortality (HR 0.88, 95% CI 0.81-0.96; p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history. CONCLUSION: Regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

Glucosamine promotes seizure activity via activation of the PI3K/Akt pathway in epileptic rats.

CONTEXT: Glucosamine is an amino monosaccharide with a small molecular weight and has a protective effect against various neurological diseases including multiple sclerosis and encephalomyelitis. Interestingly, low-dose glucosamine has exhibited anti-epilepsy activity. Recent studies have shown that the activation of the protein kinase B (Akt) signaling pathway may promote epilepsy. Glucosamine can increase the level of Akt phosphorylation in the brain tissue, which may aggravate epilepsy. Hence, we speculate that a higher dose of glucosamine may aggravate epilepsy via AKT signaling. OBJECTIVE: To investigate the effect of glucosamine on the behavior and electrophysiology of epileptic rats through PI3K/Akt pathway. METHODS: Glucose (2.0 g/kg) and glucosamine (0, 0.5, 1.0, and 2.0 g/kg) were added to 2 mL of drinking water, respectively. An acute seizure rat model of lithium-pilocarpine and PTZ-kindling were constructed to observe the effects of different doses of glucosamine on epileptic behavior and hippocampal electrical activity. Meanwhile, the changes in Akt were detected by western blot. RESULTS: Epileptic seizures were induced by a single dose of pilocarpine or PTZ and 2.0 g/kg of glucosamine significantly prolonged the duration and severity of epileptic seizures, enhanced hippocampal electrical activity energy density, and increased phosphorylated AKT levels. A glucosamine dose of 2.0 g/kg also significantly increased the total onset energy density. Furthermore, 2.0 g/kg glucosamine facilitated the development of the chronic PTZ-kindling process. CONCLUSIONS: Glucosamine may exacerbate acute and chronic epileptic seizures via activation of the PI3K/Akt pathway in rats with experimental epilepsy.

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).

The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin for joint pain.

Background Arthritis is a common chronic joint disease. It progressively causes joint pain, stiffness, and disability. Glucosamine sulfate has been shown to be an effective symptom-relieving biological agent. Pharmaceutical care, including patient counseling, is very important to overcome inconsistencies in compliance and adherence. Objective The aim of this study is to evaluate the impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin (TGC-Plus cream) in the management of chronic joint pain. Settings A rheumatology outpatient clinic, Jordan University Hospital, Amman, Jordan. Methods A cross sectional study with a single treatment group was conducted. One hundred (100) patients diagnosed with either osteoarthritis, rheumatoid arthritis or chronic joint pains were recruited. Patients started on TGC-Plus cream applied twice daily for duration of 12 weeks. Patients received pharmaceutical care services during the study duration. Main outcome measure Efficacy and safety of TGC-Plus cream in pain relief and joint function improvement (alleviating joint stiffness) the need of alternative analgesics and number of doctor's visits. Results There was a significant reduction of numerical pain score (7 ± 1.40 vs. 3.53 ± 2.13, p < 0.05), with significant reduction in the limitation of joint movement (6.18 ± 2.14 vs. 3.47 ± 2.23, p < 0.05) after 12 weeks. In addition, the need for analgesics and the number of doctor's visits were significantly reduced (1.99 ± 2.77 vs. 0.71 ± 1.90, p < 0.05), (1.11 ± 1.28 vs. 0.06 ± 0.293, p < 0.05) respectively. Conclusion Pharmacist supervised treatment with the TGC-Plus cream significantly reduces pain and enhances locomotor function in patients with chronic pain who failed to achieve adequate prior pain relief.

Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp.

BACKGROUND: Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS: Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS: Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS: Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT: Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.

Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011.

PURPOSE OF THE STUDY: This study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions. STUDY DESIGN: Case reports of ADR to glucosamine and chondroitin sent to the Therapeutic Goods Administration between 2000 and 2011 were obtained and analysed. The demographic information and severity of the ADR were recorded for individual ADR cases. These reactions were classified according to the Brown et al grading system for generalised hypersensitivity reactions. This included mild hypersensitivity reactions (generalised erythema, urticaria and angioedema) through to moderate hypersensitivity reactions (wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness and abdominal pain), and more severe reactions (hypotension, confusion and collapse). RESULTS: In this study of 366 ADRs to glucosamine and chondroitin preparations, 71.85% of cases (n=263) were found to have hypersensitivity reactions. Of these 263 cases, 92 cases were classified as mild (eg, pruritus, urticaria and lip oedema), 128 cases classified as moderate (such as dyspnoea, nausea and abdominal pain), and 43 cases classified as severe (including amnesia, gait disturbance, somnolence and hypotension). It is not clear whether the patients involved had a known shellfish allergy or underlying atopy. CONCLUSION: Results of this investigation support the need for clear labelling on glucosamine and chondroitin preparations to raise awareness of possible adverse events for those predisposed to allergy or atopy in response to shellfish.

Differentiation of patented crystalline glucosamine sulfate from other glucosamine preparations will optimize osteoarthritis treatment.

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.

Clinical efficacy of glucosamine hydrochloride tablets in the treatment of cervical spondylosis.

The aim of the stuy was to observe and analyze the effect of glucosamine hydrochloride tablets on patients with cervical spondylosis. This study was conducted on 130 patients diagnosed with cervical spondylosis who were treated in our hospital. The time period was from June 2015 to December 2017. The subjects were randomly divided into a reference group treated with cervical vertebra exercises and cervical occipital belt traction therapy and the study group was further treated with glucosamine hydrochloride tablets. The treatment efficacy of both groups was observed. Comparison of the overall treatment efficiency of patients showed that compared with the reference group, the study group has more significant advantages, P<0.05; comparison of the overall patient satisfaction rate showed that the study group was also superior to the reference group, P<0.05; In addition, statistical analysis of adverse reactions showed no statistically significant difference, P<0.05. The treatment of glucosamine hydrochloride tablets in patients with cervical spondylosis can achieve ideal results, improve the overall treatment efficiency, and thus, has important application significance.

Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.

OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis. METHODS: We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions. RESULTS: We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences. CONCLUSIONS: Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.

Multicenter, randomized, double-blind clinical trial to evaluate efficacy and safety of combined glucosamine sulfate and chondroitin sulfate capsules for treating knee osteoarthritis.

OBJECTIVES: To compare the efficacy and safety of a new fixed dose combination of glucosamine sulfate and chondroitin sulfate capsules (GS/CS) versus the fixed dose combination of glucosamine hydrochloride and chondroitin sulfate (Cosamin DS®) in capsules in patients with osteoarthritis (OA) of the knee. METHODS: Multicenter, randomized, double-blind study. Participants with knee OA Kellgren-Lawrence grades 1 to 3 and VAS of symptoms ≥4 cm were randomized to receive GS/CS or Cosamin DS® over 12 weeks. The primary efficacy endpoint was the evaluation of the analgesic efficacy by the investigator. Secondary efficacy endpoints included: joint pain and swelling, investigator efficacy of the medication, and the use of rescue medication. Adverse events and drug tolerability were analyzed. RESULTS: One hundred patients were randomized, and 50 patients were allocated to each group. The analgesic efficacy evaluated by the investigator in the GS/CS group was 88.9, 95%CI: 75.2, 95.8% and in the Cosamin DS® group was 85.4%; 95%CI: 70.1, 93.4%. The mean reduction in the pain intensity was significant in both groups (p < 0.001), with no difference between them. The primary efficacy analysis demonstrated the non-inferiority of the GS/CS group compared with the Cosamin DS® group; the lower limit of the 90% confidence interval (CI) between the two groups (- 8.39%) was higher than the established margin of non-inferiority of - 10.00%. Improvement in other efficacy outcomes was observed, again without differences between groups. Adverse events were similar between groups and both presented good tolerability. CONCLUSIONS: The new fixed-dose formulation of GS/CS is effective in treating knee OA, presenting a good safety and tolerability profile. TRIAL REGISTRATION: ( https://clinicaltrials.gov/ct2/show/NCT00955552?term=NCT00955552&rank=1 ; ClinicalTrials.gov ; register number NCT00955552; First randomized patient: 08/17/2010).

Comparison of the efficacy and tolerability of chondroitin plus glucosamine and D-002 (beeswax alcohols) in subjects with osteoarthritis symptoms.

BACKGROUND/AIMS: Osteoarthritis (OA), the commonest joint disorder, is a leading cause of disability. Symptomatic slow-acting drugs for OA (SYSADOA), particularly glucosamine plus chondroitin sulphate (GS/CS), are effective for symptom relief, protect joint cartilage and delay OA progression, with a good safety profile. D-002, a mixture of beeswax alcohols that inhibits both cyclooxygenase and 5-lipoxygenase activities, has been effective in experimental and clinical OA studies, showing also a chondroprotective effect. OBJECTIVES: To compare the effects of D-002 and GS/SC administered for 12 weeks on OA symptoms. METHODS: Participants were randomized to GS/CS (375/300 mg) or 50 mg D-002 once daily for 12 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the Visual Analogy Scale (VAS) scores. The primary outcome was the reduction of the total WOMAC score. Secondary outcomes included WOMAC pain, stiffness and function scores, VAS score and rescue medication consumption. RESULTS: Of 60 randomized patients, 59 completed the study. D-002 and GS/SC reduced significantly total WOMAC score (72.1% and 78.5%, respectively), and pain, joint stiffness and physical function scores versus baseline. VAS scores decreased significantly with D-002 (76.6%) and GS/SC (76.8%). The reductions, significant from the second week, were enhanced over the trial. Rescue medications were consumed by 3/30 D-002 and 4/30 GS/SC patients. No differences between groups were found. Treatments were well tolerated. CONCLUSIONS: D-002 (50 mg/day) administered for 12 weeks was safe and comparable to GS/SC for alleviating OA symptoms (pain, stiffness, and functional limitation) (RPCEC00000180).