Oral Chondroitin Sulfate Research Articles

Oral chondroitin sulfate functionalized natural polyphenol for targeted therapy of ulcerative colitis

Ulcerative colitis (UC) is an idiopathic, chronic, and progressive inflammatory set of conditions that affects the colonic mucosa. Natural polyphenols are well documented for their excellent antioxidant properties and have obvious advantages in the strategy of anti-oxidation treatment of UC. However, the poor water solubility, low bioavailability, and unstable nature have hindered their clinical application. Therefore, we efficiently encapsulated bioactive polyphenol epigallocatechin gallate (EGCG) with poly(N-vinylpyrrolidone) (PVP) via reliable intermolecular hydrogen-bonded interactions, and conjugated polysaccharide chondroitin sulfate (CS) with excellent gastrointestinal stability and CD44 active targeting capability onto the surface to achieve targeted delivery (EPC). The obtained EPC system showed an average diameter of 54 nm, monodisperse size distribution, and negatively charged surface. In vitro studies demonstrated the obvious reactive oxygen species (ROS)-scavenging and anti-inflammatory abilities of the EPC system. After oral administration, EPC system localized in the inflamed colon and effectively alleviated the symptoms in dextran sulfate sodium salt (DSS)-induced UC mice. Specifically, the EPC system down-regulated the expression of inflammatory cytokines, up-regulated the expression of tight junction-associated proteins to restore intestinal barrier, and modulated the gut microbiota. This oral drug delivery system with a simple self-assembling process may pave new strategy for polyphenol-based therapy in UC.

Effect of Oral Chondroitin Sulfate Supplementation on Acute Brain Injury in a Murine Necrotizing Enterocolitis Model.

Necrotizing enterocolitis (NEC) is a devastating condition where inflammatory changes and necrosis in the gut results in activation of brain microglia and subsequent neurodevelopmental impairment. Chondroitin sulfate (CS) is a glycosaminoglycan in human breast milk that is absent in conventional formulas. We hypothesized that oral formula supplementation with CS during a murine model of experimental NEC would not only attenuate intestinal injury, but also brain injury. NEC was induced in mouse pups on postnatal days (PNDs) 5 to 8. Three conditions were studied: (1) breastfed controls, (2) NEC, and (3) NEC+enteral CS (formula+200 mg/kg/d of CS). Pups were euthanized on PND 9 or reunited with dams by the evening of PND 8. Intestinal segments were H&E stained, and immunohistochemistry was performed on brain tissue for Iba-1 to assess for microglial morphology and cortical changes. Neurodevelopmental assays were performed on mice reunited with foster dams on PND 9. Single-cell RNA-sequencing analysis was performed on human intestinal epithelial cells exposed to (1) nothing, (2) hydrogen peroxide (H 2 O 2 ) alone, or (3) H 2 O 2 + CS to look at the differential gene expression between groups. Groups were compared with ANOVA or Kruskal-Wallis tests as appropriate with p < 0.05 considered significant. Compared with NEC, mice treated with oral CS showed improved clinical outcomes, decreased intestinal injury, and attenuated microglial activation and deleterious cortical change. Mice with CS performed better on early neurodevelopmental assays when compared with NEC alone. Single-cell analysis of HIEC-6 cells demonstrated that CS treatment down regulated several inflammatory pathways including nuclear factor κB-suggesting an explanation for the improved Th17 intestinal cytokine profile. Oral CS supplementation improved both physiological, clinical, and developmental outcomes. These data suggest that CS is a safe compound for formula supplementation for the prevention of NEC.

Effects of oral treatment with chondroitin sulfate and glucosamine in an experimental model of metacarpophalangeal osteoarthritis in horses

BackgroundCombined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound based on CS and GlcN to treat and/or modulate this disease. The study analyzed the metacarpophalangeal joint of the left thoracic limb of 16 horses divided into two groups, with eight horses treated with CS and GlcN in the treated group (GT) and eight untreated horses in the control group (GC). Chondral lesions were induced through arthroscopy, which was defined as time-point zero (T0). Physical, ultrasonographic, and radiographic examinations and synovial fluid biomarkers measurements were performed on days 0, 30, 60, 90, and 120. At the end of the experiment (T4), arthroscopy was performed again to macroscopically evaluate the joints and collect material for microscopic analysis.ResultsSignificant differences were observed between groups in some evaluated parameters, such as visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination. However, the GT still presented slightly improved results for joint flexion angle, analysis of lameness using sensors, and histopathological analysis of chondral repair tissue, however, without the statistical significance (p>0.05).ConclusionsThe treatment was considered effective in the clinical modulation of experimental osteoarthritis, with improvement of some parameters in the GT. However, this type of treatment may not be entirely effective to change the catabolic process in articular cartilage and the progressive induced chondral damage.

Comparative Analysis of the Bioactive Compounds in Chicken Cartilage: Protective Effects of Chondroitin Sulfate and Type II Collagen Peptides Against Osteoarthritis Involve Gut Microbiota.

This study was designed to explore osteoarthritis (OA) treatment from bioactive compounds of chicken cartilage food supplements. The OA rat model induced by sodium iodoacetate was used to evaluate the treatment effect in vivo. In this study, we used animal experiments to show that oral chondroitin sulfate (CS), cartilage powder, and type II collagen peptides could increase the athletic ability of rats and reduce inflammatory cytokine levels in serum or synovial fluid, including prostaglandin E2, tumor necrosis factor-α, interleukin (IL) 1β, IL-6, and IL-17. CS displayed the best treatment effect against OA. The morphological structure of articular cartilage indicated that CS could significantly improve cartilage tissue morphology and reduce OA score. Oral CS slowed down the development of OA by modulating gut microbiota. These results provided a useful scientific basis for the high-value utilization of chicken cartilage.

AB0885 EFFECTIVENESS AND SAFETY OF GLUCOSAMINE AND CHONDROITIN COMBINATION IN PATIENTS WITH KNEE AND HIP OSTEOARTHRITIS: INTERIM ANALYSIS RESULTS OF AN OBSERVATIONAL STUDY

Background:Combined treatment with oral glucosamine hydrochloride (GH) and chondroitin sulfate (CS) was shown to be efficient for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain [1,2].Objectives:To investigate demographic and clinical characteristics, changes in pain, functions of daily living, quality of life and treatment satisfaction of patients with knee osteoarthritis (KOA) or hip osteoarthritis (HOA) receiving long-term treatment with oral GH and CS combination in routine clinical practice.Methods:An open-label, multicenter, observational prospective study is being conducted in the Russian Federation. Patients of both sexes with KOA or HOA (Kellgren and Lawrence grades I-III) who receive GH 500 mg+CS 400 mg capsules three times a day for the first 3 weeks of treatment, then twice daily, are included in the study. The interim analysis has been conducted after the first 550 enrolled patients (50% of the total sample size) had completed the first follow-up visit (Week 16-24 after the start of treatment).Results:The study group included 406 (73.8%) patients with KOA and 144 (26.2%) patients with HOA enrolled in 43 centers in Russia. The mean age of the patients was 61.1 years; most patients were women (88.7%). The predominant risk factors for OA were non-genetic causes (excess weight, hormonal disorders, malformations of bones and joints, joint operations) (52.8% of patients), exogenous risk factors (professional activity, trauma, sports) and hereditary diseases of bones and joints were reported in 15.5% and 4.1% of patients, respectively.Interim analysis showed clinically significant improvement in each of the KOOS and HOOS subscales at 4-6 months after the start of treatment. In patients with KOA, the mean score increase was 15.7 for the Pain subscale, 14.6 for the Quality of Life subscale, 13.8 for the Physical function (KOOS-PS), and 11.7 for the Symptoms subscale. The percentage of patients who rated the pain frequency as ‘always’ or ‘daily’ decreased from 60% to 25%.In patients with HOA, the mean score increase was 16.0 for the Pain subscale, 14.3 for the Quality of Life subscale, 16.1 for the Physical function (HOOS-PS), and 10.3 for the Symptoms subscale. The percentage of patients who rated the pain frequency as ‘never’ or ‘monthly’ increased from 34% to 60%.Most patients (89.1%) were receiving the medicinal product for ≥3 months. Treatment-related AEs were reported in 16 (3.0%) patients and mainly included gastrointestinal tract disorders (in 12 (2.2%) patients).Conclusion:The results obtained at 4-6 months after the start of treatment demonstrate clinically significant reduction of frequency and intensity of pain and other OA symptoms, as well as improvement of functions in daily living and quality of life in patients with KOA or HOA after the first course of treatment with GH + CS capsules. The majority of patients (72.5%) were satisfied with the treatment. The incidence of drug-related AEs was low, and the nature of AEs was consistent with known safety profile of GH and CS combination.

Сравнительный анализ эффективности лечения синдрома болезненного мочевого пузыря/интерстициального цистита внутрипузырными инстилляциями гиалуроната натрия изолированно и в сочетании с пероральным приемом хондроитин сульфата

It is established that intravesical sodium hyaluronate and chondroitin sulfate has high efficacy in patients with bladder pain syndrome/interstitial cystitis (BPS/IC). Currently, an oral form of chondroitin sulfate is also available. The aim of study was to compare the efficacy of intravesical hyaluronic acid monotherapy and long-term oral chondroitin sulfate in combination with intravesical therapy in patients with BPS/IC. A total of 59 patients with BPS/IC were randomized in two groups. In Group 1, 30 women (mean age 57.1 years) received viscoelastic solution of sodium hyaluronate 50 ml 1 time per week for 12 weeks as intravesical monotherapy. In Group 2 (n=29), patients were prescribed to complex therapy, which included the similar intravesical therapy combined with chondroitin sulfate in a dose 0.39 g, 2 capsules 3 times a day, also for 12 weeks. All patients completed visual analogue scale (VAS), interstitial cystitis symptom index (ISCI), interstitial cystitis problems index (ICPI) and voiding diary before and 1 week after the start of therapy. In all cases a cystoscopy and urodynamic study were performed in order to exclude other bladder pathologies. At baseline, a mean VAS score in both groups was 7 points, a mean ISCI score was 17 points in Group 1 and 18 points in Group 2 (p>0.1). The mean ICPI score in both groups was 15 points. A frequency of urination in Group 1 and 2 was 11.4 and 11.6 per day, respectively (p>0,1). A mean volume of urination was 138+/-24.6 and 131+/-18.6 , respectively. After 12 weeks of therapy there was significant improvement of VAS, ICSI and ICPI scores in both groups, as well as frequency and volume of urination, but in Group 2 an improvement in almost all parameters studied, except for the volume of urination, was more pronounced. The combined therapy of BPS/IC with intravesical hyaluronic acid and oral chondroitin sulfate provides significantly better results in comparison with intravesical hyaluronic acid as monotherapy.

Safety of oral chondroitin sulfate in the management of knee osteoarthritis: results of a new meta-analysis of randomlzed. Placebo-controlled trials

Safety of oral chondroitin sulfate in the management of knee osteoarthritis: results of a new meta-analysis of randomlzed. Placebo-controlled trials

The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies.

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

Daily Oral Chondroitin Sulfate Oligosaccharides for Knee Joint Pain in Healthy Subjects: A Randomized, Blinded, Placebo-Controlled Study

Background: The increased rate of population aging in Japan has led to an increase in the incidence of osteoarthritis (OA). Chondroitin sulfate has been reported to reduce the pain and swelling associated with OA and to improve knee function. Objective: We evaluated the safety and effects of oral chondroitin sulfate oligosaccharides on knee function in a randomized, double-blinded, placebo-controlled parallel group comparison study of healthy Japanese subjects with knee joint pain. Methods: Subjects were randomly divided into test and placebo groups and given either active-test capsules containing 100 mg of chondroitin sulfate oligosaccharides or placebo capsules daily for 8 weeks. The Japanese Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS), blood and physical examinations, and medical interviews were performed at weeks 0, 4, and 8, and the locomotive syndrome risk test was performed at weeks 0 and 8 during the test intake period. Results: The JKOM scores did not significantly differ between the test groups. However, among subjects with worse VAS scores, those in the active test group had significantly lower JKOM scores at 8 weeks, compared to those in the placebo group. Moreover, chondroitin sulfate oligosaccharide treatment tended to improve the subjects' scores on the stand-up test, which evaluates the risk of locomotive syndrome. Furthermore, no abnormal changes or severe adverse events were observed during physical or blood examinations or medical interviews. Conclusion: Our results suggest that chondroitin sulfate oligosaccharides improve knee pain and are safe for 8-week intake.

Comparison of efficacy of intravesical hyaluronic acid alone and in combination with oral chondroitin sulfate in patients with bladder pain syndrome

Comparison of efficacy of intravesical hyaluronic acid alone and in combination with oral chondroitin sulfate in patients with bladder pain syndrome

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial.

BackgroundCanine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress.ResultsTwenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group.ConclusionsThe combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI.

Poly-ion Complex of Chondroitin Sulfate and Spermine and Its Effect on Oral Chondroitin Sulfate Bioavailability

Chondroitin sulfate (CS) has been accepted as an ingredient in health foods for the treatment of symptoms related to arthritis and cartilage repair. However, CS is poorly absorbed through the gastrointestinal tract because of its high negative electric charges and molecular weight (MW). In this study, poly-ion complex (PIC) formation was found in aqueous solutions through electrostatic interaction between CS and polyamines-organic molecules having two or more primary amino groups ubiquitously distributed in natural products at high concentrations. Characteristic properties of various PICs generated by mixing CS and natural polyamines, including unusual polyamines, were studied based on the turbidity for PIC formation, the dynamic light scattering for the size of PIC particles, and ζ-potential measurements for the surface charges of PIC particles. The efficiency of PIC formation between CS and spermine increased in a CS MW-dependent manner, with 15 kDa CS being critical for the formation of PIC (particle size: 3.41 µm) having nearly neutral surface charge (ζ-potential: -0.80 mV). Comparatively, mixing tetrakis(3-aminopropyl)ammonium and 15 kDa of CS afforded significant levels of PIC (particle size: 0.42±0.16 µm) despite a strongly negative surface charge (-34.67±1.15 mV). Interestingly, the oral absorption efficiency of CS was greatly improved only when PIC possessing neutral surface charges was administered to mice. High formation efficiency and electrically neutral surface charge of PIC particles are important factors for oral CS bioavailability.

Effect of chondroitin sulfate on turpentine-induced down-regulation of CYP1A2 and CYP3A6

This study aimed to assess whether chronic administration of chondroitin sulfate (CS) affects baseline expression of cytochrome P450 isoforms and impedes the decrease in expression and activity of CYP1A2 and CYP3A6 in rabbits with a turpentine-induced inflammatory reaction (TIIR). Seven groups of 5 rabbits, 3 control groups and 4 receiving 20mg/kg/day of CS for 20 and 30days, were used. The rabbits of 1 control group and 2 groups receiving CS had a TIIR; finally, the rabbits of one of the control groups remained in the animal facilities for 30days to assess the effect of time and environment on cytochrome P450. In control rabbits, intake of CS for 20 and 30days did not affect CYP3A6, CYP1A2 and NADPH cytochrome P450 reductase (CPR) mRNA, protein expression and activity. Compared with control rabbits, the TIIR not only reduced mRNA, protein expression and activity of CYP3A6 and CYP1A2 but also that of CPR. In rabbits with TIIR, CS prevented the decrease of CYP3A6 expression but not the reduction in activity. CS did not impede TIIR-induced down-regulation of CYP1A2. Hepatic NO concentrations and NF-κB nuclear translocation were increased by the TIIR, effect reversed by CS. In vitro, in hepatocytes, CS did not alter the expression and activity of CYP3A6, CYP1A2, and CPR. In conclusion, oral CS elicits a systemic effect but does not affect CYP1A2, CYP3A6, and CPR in control rabbits, although in rabbits with TIIR, CS prevents CYP3A6 protein down-regulation but not that of CYP1A2.

Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.

Clinical review of chondroitin sulfate in osteoarthritis

Symptomatic slow-acting drugs for the treatment of osteoarthritis (SYSADOA; OA) are compounds which are prescribed as drugs in European countries since many years, whereas they are sold as nutraceuticals in USA. In Europe, the publication of the EULAR Recommendations for the Treatment of Knee OA in 2003 has listed oral chondroitin sulfate (CS) as evidence 1A and strength of recommendation A which represents the highest level for a therapeutic strategy. Symptomatic slow-acting drugs are intended to be used as ground therapy for OA; these compounds are not rapidly acting agents such as Non Steroidal Anti-Inflammatory Drugs (NSAIDs), and their clinical efficacy on algo-functional symptoms can only be demonstrated after a couple of weeks of regular intake. Interestingly, once the administration is stopped, they do show carry-over effects of various durations, from about 3 months with the oral formulations to 6-9 months with intra-articular formulations. The main rationale behind the use of the SYSADOA therapeutic class is the reduction of NSAIDs in the overall drug management of OA disease and therefore consequently to limit the very significant risks of upper Gastro-intestinal (GI) tract erosions, ulcers with bleeding and/or deleterious renal effects in elderly patients. The evidence for clinical efficacy of oral CS as a drug able to significantly improve the algo-functional symptoms of OA disease does come from a set of randomized clinical studies published a couple of years ago. Indeed, it was demonstrated that the drug was effective in knee and finger OA, whereas previous data suggested that hip OA patients could also benefit from it. In addition, oral CS supported the comparison with NSAIDs such as diclofenac sodium in a medium/long-term clinical study in patients with knee OA. A dose-finding study in patients with knee OA did provide strong data supporting the administration of 800 mg of CS orally which had nearly the same effects as 1200 mg/day, whereas the use of a sequential 3 months administration mode, twice a year was also shown to provide the same results as a continuous treatment. The good tolerability and safety aspects of oral CS were largely documented in these CTs. Taking these important points into account, we definitively have enough clinical data available supporting the view that oral CS is a valuable and safe symptomatic treatment for OA disease. More recent data based on a couple of previous trials and two pivotal studies do provide further evidence that oral CS does also have structure-modifying effects in knee OA patients. A couple of other compounds such as hyaluronan, diacerein, avocado and soya unsaponifiables, doxycycline have also been tested with respect to their potential disease-modifying effects. Additional compounds including receptor activator of NF-kappaB (RANK) ligand inhibitors, cathepsin K inhibitors, bisphosphonates are further assessed regarding their potential structure-modifying effect.

Effect of a glucosamine derivative on impact-induced chondrocyte apoptosis in vitro. A preliminary report

Here, we report that a lipophilic derivative of glucosamine, Glu5, is able to prevent impact-induced chondrocyte death by the putative mechanism of reducing mitochondrial depolarisation following a single impact load in vitro.

Patients With Knee Osteoarthritis Have Lower Total Hip Bone Mineral Density in the Symptomatic Leg Than in the Contralateral Hip

Osteoarthritis (OA) of the knee is common in the aging population. In patients with OA, bone mineral density (BMD) is usually increased, but the fracture rate does not appear to be systematically lower than in age-matched healthy controls. The aim of our study was to describe hip BMD in patients presenting with unilateral symptomatic knee OA. Patients with painful knee OA were prospectively included in a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the structure-modifying efficacy of an oral chondroitin sulfate treatment on the knee joint. The majority of these patients underwent additional measurements of BMD of their lumbar spine and both hips using dual-energy X-ray absorptiometry (DXA). The hip BMD values of the leg with symptomatic knee OA were compared with the contralateral hip. One-hundred and sixty-one patients (81 men and 80 women; aged 62.6 +/- 9.2 yr, range 40-82 yr) underwent DXA. The median total hip BMD was higher than in age-matched controls, but patients had a relatively lower hip BMD in the knee OA-affected leg (p = 0.001). Our knee OA patients rarely presented with concomitant osteoporosis, but usually had a relatively lower hip BMD on the affected leg. Therefore, we suggest that the hip of the leg with symptomatic knee OA should be measured if DXA is acquired only at one hip. Future studies have to assess whether the relative decrease of BMD at the hip of the leg with knee OA might influence fracture incidence.

Clinical and histopathological improvement of psoriasis with oral chondroitin sulfate: A serendipitous finding

We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.

Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo

Objective: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. Design: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800 mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne’s algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. Results: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. Conclusion: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800 mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.

Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis

High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides – including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate – stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers – apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a ‘placenta’ for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy.