Pharmacological Treatment Of Osteoarthritis Research Articles

Small molecule inhibitors of osteoarthritis: Current development and future perspective.

Osteoarthritis (OA) is one of the common degenerative joint diseases in clinic. It mainly damages articular cartilage, causing pain, swelling and stiffness around joints, and is the main cause of disability of the elderly. Due to the unclear pathogenesis of osteoarthritis and the poor self-healing ability of articular cartilage, the treatment options for this disease are limited. At present, NSAIDs, Glucocorticoid and Duloxetine are the most commonly used treatment choice for osteoarthritis. Although it is somewhat effective, the adverse reactions are frequent and serious. The development of safer and more effective anti-osteoarthritis drugs is essential and urgent. This review summarizes recent advances in the pharmacological treatment of OA, focusing on small molecule inhibitors targeting cartilage remodeling in osteoarthritis as well as the research idea of reducing adverse effects by optimizing the dosage form of traditional drugs for the treatment of osteoarthritis. It should provide a reference for exploration of new potential treatment options.

Effect of intra-articular dexmedetomidine on experimental osteoarthritis in rats.

Pharmacological treatment of osteoarthritis is still inadequate due to the low efficacy of the drugs used. Dexmedetomidine via the intra-articular (i.a.) route might be an option for the treatment of osteoarthritis-associated pain. The present study assessed the analgesic and anti-inflammatory effects of dexmedetomidine administered via the i.a. route in different doses in an experimental model of rat knee osteoarthritis induced with monosodium iodoacetate. Rats were allocated to four groups with 24 animals in each group. The OA (osteoarthritis), DEX-1 (dexmedetomidine in dose of 1μg/kg) and DEX-3 (dexmedetomidine in dose of 3μg/kg) groups were subjected to induction of osteoarthritis through injection of monosodium iodoacetate (MIA) via the i.a. route on the right knee; the control group was not subjected to osteoarthritis induction. Clinical assessment was performed on day 0 (before osteoarthritis induction) and then on days 5, 10, 14, 21 and 28 after induction. Treatment was performed on day 7 via the i.a. route, consisting of dexmedetomidine in doses of 1 and 3 μg/kg, while group OA received 0.9% normal saline. The animals were euthanized on days 7, 14, 21 and 28. Samples of the synovial membrane were collected for histopathological analysis, and the popliteal lymph nodes were collected for measurement of cytokines (interleukin [IL] IL-6, tumor necrosis factor alpha [TNF-α]). Dexmedetomidine (1 and 3 μg/kg) significantly reduced the animals' weight distribution deficit during the chronic-degenerative stage of osteoarthritis and improved the pain threshold throughout the entire experiment. Histological analysis showed that dexmedetomidine did not cause any additional damage to the synovial membrane. The TNF-α levels decreased significantly in the DEX-3 group on day 28 compared with the OA group. Dexmedetomidine reduced pain, as evidenced by clinical parameters of osteoarthritis in rats, but did not have an anti-inflammatory effect on histological evaluation.

Резолюция международного совещания экспертов "Возможности фармакологического лечения остеоартрита"

Резолюция международного совещания экспертов "Возможности фармакологического лечения остеоартрита"

Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug

ABSTRACT Introduction: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) is an investigational agent that has potential as a disease-modifying osteoarthritis drug (DMOAD). It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which are molecular regulators in Wnt signaling, chondrogenesis, and inflammation. Areas covered: This paper discusses the current pharmacologic guidelines for the treatment of knee OA and illuminates the potential of a new agent, Lorecivivint, as a disease-modifying osteoarthritis drug (DMOAD). Efficacy and safety and the challenges for this novel agent come under the spotlight. Expert opinion: LOR may be a potential DMOAD for the treatment of patients with knee OA. While the Phase 2A trial did not meet its primary endpoint, preplanned analyses did identify a target population for further evaluation of its potential as a DMOAD. Phase 3 trials are ongoing, but this intra-articular drug is currently considered safe and well tolerated, with no significant reported systemic side effects.

The role of chondroprotectors in the pharmacological treatment of osteoarthritis

The article is devoted to third-generation slow-modifying chondroprotective drug therapy including Alflutop. The evidence-based medicine showed and substantiated in vitro effect of the drug on the pathogenetic processes in the cartilage tissue, its promotion of the inflammation regression in the musculoskeletal system. The authors present a series of clinical studies of top osteoarthritis doctors, which showed that Alflutop had an anti-inflammatory, chondroprotective, analgesic effect, and that the administration of the drug allowed patients to reduce the doses of NSAIDs, and it could be used in patients with comorbid diseases.

Role of Interleukin-1 Inhibitors in Osteoarthritis

Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians' complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the above mentioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.

Kristallines Glucosaminsulfat in der Therapie der Arthrose

The pharmacological treatment of osteoarthritis is traditionally accomplished with nonspecific symptomatic agents, which are generally effective only for acute symptom relief. Compounds are under investigation that might exert specific effects on osteoarthritis pathogenesis and thus induce at least a similar short-term symptomatic effect, but also control disease progression in the long term. Glucosamine sulphate (CAS 29031-19-4) reverses the proinflammatory and joint-degenerating effects of interleukin-1 by inhibiting the cytokine intracellular pathway. Clinical trials with the crystalline glucosamine sulphate formulation (CGS; dona) approved as a medicinal drug, predominantly used at the oral dose of 1,500 mg once daily, demonstrated a specific symptom-modifying effect on knee osteoarthritis over short- and long-term treatment courses. Two 3-year trials suggested that the drug also has joint structure-modifying properties and, therefore, might be useful as a disease-modifying agent in osteoarthritis.

Glucosamine sulfate for knee osteoarthritis: science and evidence-based use

The pharmacological treatment of osteoarthritis is traditionally accomplished with nonspecific symptomatic agents that are generally effective only for acute symptom relief. Compounds are currently being searched for that might exert specific effects on osteoarthritis pathogenesis and thus induce at least a similar shortterm symptomatic effect, but also control the progression of the disease in the long-term. Glucosamine sulfate is, so far, the only drug that has demonstrated a combined symptom-modifying and potential structure-modifying effect in knee osteoarthritis when used as the prescription crystalline glucosamine sulfate formulation at the dose of 1500 mg once daily. These effects may be explained by reversal of the proinflammatory and joint-degenerating effects of IL-1 through the inhibition of the cytokine intracellular signaling pathway. However, efficacy data obtained with this prescription glucosamine sulfate formulation may not be applicable to all glucosamine products available as generics or dietary supplements, owing to pharmacodynamic and pharmacokinetic reasons.

Use of crystalline glucosamine sulfate in osteoarthritis

The pharmacological treatment of osteoarthritis is traditionally accomplished with nonspecific symptomatic agents, which are generally effective only for acute symptom relief. Compounds are under investigation that might exert specific effects on osteoarthritis pathogenesis and thus induce at least a similar short-term symptomatic effect, but also control disease progression in the long term. Glucosamine sulfate reverses the proinflammatory and joint-degenerating effects of interleukin-1 by inhibiting the cytokine intracellular signaling pathway. Clinical trials with the crystalline glucosamine sulfate formulation approved as a prescription drug, predominantly at the dose of 1500 mg once daily, demonstrated a specific symptom-modifying effect over short- and long-term treatment courses. Two 3-year trials suggested that the drug also has joint structure-modifying properties and, therefore, might be useful as a disease-modifying agent in osteoarthritis. However, efficacy data obtained with this prescription glucosamine sulfate formulation may not be applicable to all glucosamine products that are available as dietary supplements. Osteoarthritis is the most common form of arthritis and the most prevalent among rheumatic diseases. It is a degenerative joint disorder with minimal signs of inflammation, which may affect all diarthrodial joints and whose most appropriate definition combines a description of the pathology of the disease with pain that occurs with joint use [1]. Osteoarthritis is particularly frequent at the large, weight-bearing joints of the lower limbs. Radiographic osteoarthritic changes of the knee tibiofemoral compartment occur in 5–15% of the general population aged 35–74 years in the Western world [2]. Symptomatic knee disease occurs in approximately 6% of US adults over 30 years of age [3], with general incidence and prevalence increasing two- to tenfold from age 30 to 65 years [4]. The impact on disability attributable to knee osteoarthritis is similar to that due to cardiovascular disease and greater than that caused by any other medical condition in the elderly [5]. Treatment guidelines for knee and hip osteo

Advances in Chondroitin Sulfate Analysis: Application in Physiological and Pathological States of Connective Tissue and During Pharmacological Treatment of Osteoarthritis

Recent glycobiology studies have suggested fundamental biological functions for chondroitin sulfate (CS) and dermatan sulfate (DS), which are widely distributed as glycosaminoglycans (GAGs) sidechains of proteoglycans (PGs) in the extracellular matrix and at cellular level. Several biological functions are closely associated with the structure and in particular with the sulfation patterns of these polysaccharides. CS is also used as a structure-modifying osteoarthritis (OA) drug that reverses, retards, or stabilizes the pathology of OA, thereby providing symptomatic relief in the long-term treatment. Advances in analytical separational techniques, including agarose-gel electrophoresis, high-performance liquid chromatography (HPLC), capillary electrophoresis (HPCE), fluorophore-assisted carbohydrate electrophoresis (FACE) and electrospray ionization mass (ESI-MS) enable us to examine alterations of CS/DS with respect to their quantities and fine structural features in various pathological conditions, thus becoming applicable for diagnosis. Furthermore, sensitive analytical procedures enable us to follow the pharmacological application of CS in the treatment of OA and to monitor the progression of the disorder. In this review, the chromatographic and electromigration procedures developed to analyse and characterise CS/DS are presented. Moreover, a critical evaluation of the biological relevance of the results obtained by the developed methodology is discussed.

Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial

Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial