chondroitin-sulfates and diacerein

Non-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages.

Topics: Adrenal Cortex Hormones; Analgesics; Anthraquinones; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Early Medical Intervention; Exercise Therapy; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Physical Therapy Modalities; Viscosupplementation; Viscosupplements

According to the European League of Associations of Rheumatology (EULAR) and the American College of Rheumatology (ACR), acetaminophen should be used as a first-line therapy in patients with osteoarthritis, because of its safety and effectiveness. NSAID should be considered in patients unresponsive to acetaminophen, and should be prescribed at the lowest effective dose and for the shortest duration. The use of stronger analgesics, such as weak opioids and narcotic analgesics, is only indicated when other drugs, such as NSAID, have been ineffective or are contraindicated. Symptomatic slow acting drugs (avocado soybean unsaponifiable, chondroitin sulphate, diacerein, glucosamine sulphate) have mild symptomatic effects and may reduce the consumption of NSAID.

Topics: Administration, Oral; Analgesics; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Doxycycline; Humans; Osteoarthritis; Treatment Outcome

There is an increasing incidence in osteoarthritis, particularly following the 5th life-decade. However, also young people may suffer from severe osteoarthritis, which is estimated to be the most common cause of disability in adults resulting in substantial economic burden. To this end, effective therapies are needed. Therapeutic options are very comprehensive, which are presented in this review as non-pharmacological, pharmacological and surgical treatment modalities. Treatment efficacy will be discussed with regard to alleviation of symptoms and potential prevention of disease progression according to the given evidence.

Topics: Administration, Oral; Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Combined Modality Therapy; Complementary Therapies; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Joint Prosthesis; Osteoarthritis; Treatment Outcome

Symptomatic slow-acting drugs (SYSADOA) have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA).. The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations.. Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed.. In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

Topics: Anthraquinones; Antirheumatic Agents; Calcitonin; Chondroitin Sulfates; Clinical Trials as Topic; Etidronic Acid; Glucosamine; Humans; Hyaluronic Acid; Organometallic Compounds; Osteoarthritis; Outcome Assessment, Health Care; Plant Extracts; Risedronic Acid; Thiophenes

Topics: Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Glucosamine; Hyaluronic Acid; Joints; Osteoarthritis; Treatment Outcome

Topics: Administration, Oral; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Evidence-Based Medicine; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Meta-Analysis as Topic; Osteoarthritis

The use of drugs for the treatment of osteoarthritis, with a view to obtain a long-term symptomatic as well as structural benefit, is still in a preliminary state. Nowadays, matricial precursors, such as glucosamine sulfate, are an interesting approach in this indication. They have demonstrated a symptomatic efficacy comparable to that of N.S.A.I.D., with significantly reduced side-effects. Glucosamine sulfate also appears to positively interfere with the structural evolution of osteoarthritis by preventing joint space narrowing which characterizes the evolution of the disease. Encouraging results have also been obtained with chondroitin sulfate and diacerein. As for other molecules, new studies should be undertaken to confirm the results already obtained.

Topics: Anthraquinones; Chondrocytes; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Plant Extracts

Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis (OA). The most compelling evidence of a potential for inhibiting the structural progression of OA has been obtained with glucosamine sulfate, while some preliminary results also suggest that other compounds could be used in the same indication. At any rate, several medications have clearly demonstrated a symptomatic action, mainly in OA of the lower limbs, including pain relief and improvement of functional disability. An important issue is that all conclusive studies with such chemical entities resulted from the use of prescription medicines and not over-the-counter or nutriceutical supplements.

Topics: Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Glucosamine; Humans; Nonprescription Drugs; Osteoarthritis; Plant Oils

Topics: Analgesics; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Chondroitin Sulfates; Delayed-Action Preparations; Drug Combinations; Glucosamine; Humans; Phytosterols; Plant Extracts; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors; Vitamin E

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hi

Topics: Acetaminophen; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Glucosamine; Humans; Meta-Analysis as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee

Assess the importance of the mid-term placebo effect of symptomatic slow acting drugs given for osteoarthritis.. We analyzed six controlled trials available in the literature. Trial duration ranged from 2 to 6 months. The trials had been conducted to assess the symptomatic effect of diacerhein, avocado/soya unsaponifiable chondrontin sulfate and oxaceprolin given for osteoarthritis of the hip or knee. The main clinical outcomes assessed were functional impairment using the Lequesnes index and a visual analog scale.. Globally, the trials showed decreased function impairment with a 2 to 3 points decrease in the Lequesnes index (15 to 20%) and a 10 to 16 mm fall in the visual analog scale (-20 to -30%) in the placebo groups.. Our findings confirms the importance of the mid-term placebo effect in the clinical course of osteoarthritis in patients given slow-acting drugs. This placebo effect, observed under these circumstances, is an expression of what clinicians will look for in future drugs and should be helpful for calculating the number of patients required in future trials.

Topics: Activities of Daily Living; Aged; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Time Factors; Treatment Outcome

Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans and its treatment is a major orthopaedic challenge because there is no ideal drug treatment to preserve joint structure and function, as well as to ameliorate the symptomatology of the disease. The aim of the present study was to assess, using histology, histomorphometry and micro-CT, the effects of the treatment with several drugs of the SYSADOA group and a bisphosphonate in a model of early osteoarthritis, comparing all the results obtained.. Osteoarthritis was surgically induced by anterior cruciate ligament transection and partial meniscectomy on one knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8 weeks; at the end of this period, the animals were sacrificed. Animals were divided into seven groups (8 animals each), one for each regimen of treatment (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein, risedronate and a combination of risedronate and glucosamine) and one for the control (placebo-treated) group. Following sacrifice, femoral osteochondral cylinders and synovial membrane samples were obtained for their evaluation by qualitative and quantitative histology and micro-CT.. The model induced osteoarthritic changes in the knee joints and none of the treatments showed a significantly better efficacy over the others. Regarding cartilage thickness and volume, all the treatments achieved scores halfway between control groups, without statistical differences. Regarding the synovial membrane, diacerein and risedronate showed the best anti-inflammatory profile, whereas glucosamine and chondroitin did not present any effect standing the hyaluronic acid results between the others. Regarding the subchondral bone, there were no differences in thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to have considerably modified the orientation of the trabecular lattice.. Out of the different drugs evaluated in the study for OA treatment, diacerein and risedronate showed, in all the parameters measured, a better profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and promoted bone formation, but with a poor synovial effect; and finally, chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way to the others, but had no effect on cartilage surface, synovial membrane or subchondral bone.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Arthrography; Bone Density Conservation Agents; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Drug Therapy, Combination; Female; Femur; Glucosamine; Hyaluronic Acid; Joints; Osteoarthritis; Rabbits; Risedronic Acid; Synovial Membrane; Tomography, X-Ray Computed

Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396±2.7nm, showed extended release up to 16h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8±1.23μg/ml) than that of drug dispersion (2.9±0.45μg/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA.. This study demonstrates the feasibility of targeted delivery of diacerein to articular tissue using soluble polysaccharide chondroitin sulfate as the targeting vector. This approach has the potential to significantly increase anti-arthritic drug concentration in joints without leading to systemic toxicity.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Drug Carriers; Female; Lipids; Male; Nanoparticles; Osteoarthritis; Rats

In order to assess agent with modulating properties of the course of the arthrosic condition, the so-called SYSADOA (Symptomatic Slow Acting Drugs for Osteoarthritis) and "structure modifiers" have been defined. Glucosamine sulfate, chrondroitin sulfate and diacerein have been considered among these agents. Based on the published data and according to the evidence available, the SYSADOA have symptomatic effects and can modify the structure. However, although there is scientific evidence for the use of these drugs in arthrosis treatment, the limited intensity of their action over the placebo makes it necessary to evaluate the clinical relevance of their application before recommending their generalized use.

Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

To investigate the effect of diacetyl rhein (DAR) on the synthesis, turnover and composition of cartilage in an experimental model of osteoarthritis in beagle bitches.. Osteoarthritis was induced in mature beagle bitches by the transection of the cranial cruciate ligament. Six animals received DAR 20 mg/kg daily for 11 weeks. A matched group received empty capsules daily for the same period. At 11 weeks, articular cartilage was examined for the ratio of the 6:4-sulfated disaccharides of chondroitin and the tissue concentration of hydroxyproline and glycosaminoglycan. In addition, labeling studies were performed to estimate the effect of DAR on proteoglycan synthesis and turnover.. DAR had no effect on body weight or food consumption but induced a mild diarrhea and slightly increased the incidence of vomiting. DAR tended to reduce proteoglycan synthesis, however, DAR did reduce proteoglycan turnover in the femoral cartilage. DAR produced changes in the composition of the osteoarthritic cartilage that could only partly be accounted for by changes in hydration and/or swelling. In addition, it was noted that induction of osteoarthritis increased the ratio of chondroitin 6-sulfated to chondroitin 4-sulfated disaccharides; DAR reduced the ratio in tibial plateau cartilage from osteoarthritic joints compared with untreated tissue from osteoarthritic joints. DAR showed moderate reduction on the biosynthesis of proteoglycans. DAR also produced a reduction in proteoglycan turnover from all anatomical areas compared with non-treated controls in both the lateral and medial femoral condyles.. DAR was well tolerated by the experimental animals, but did not produce significant changes in the synthesis or turnover of proteoglycans. The slight reduction in proteoglycan synthesis may prove to be biologically significant after chronic dosing. DAR's effects on the hydroxyproline and glycosaminoglycan content suggest, however, that it must influence the swelling of cartilage and loss of glycosaminoglycan. This indicates that small changes can translate, to significant differences in cartilage composition over an 11-week time period.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cartilage, Articular; Cells, Cultured; Chondroitin Sulfates; Disease Models, Animal; Dogs; Epitopes; Glycosaminoglycans; Hydroxyproline; Osteoarthritis; Proteoglycans