Chondroprotectors Danilevskaya. Clinical efficacy of chondroprotectors in the complex therapy of knee osteoarthritis

For citation: Peshekhonova L.K., Peshekhonov D.V., Kuzovkina T.N. Clinical efficacy of chondroprotectors in the complex therapy of osteoarthritis of the knee joints // RMJ. 2009. No. 21. S. 1486

Currently, chondroprotectors are an obligatory component of the complex therapy of osteoarthritis (OA), since the pathogenetic basis of this disease is an imbalance in the processes of synthesis and resorption of articular tissues, mainly hyaline cartilage and subchondral bone. Cartilage destruction is more often caused by a person's professional activity, joint overload, sports injuries, metabolic disorders, rather than age-related wear of the joints. Thus, OA is a heterogeneous group of diseases of various etiologies with similar biological, morphological, clinical manifestations and outcomes, which are based on damage to all components of the joint, primarily cartilage, as well as subchondral bone, synovial membrane, ligaments, capsule, periarticular muscles.

OA has a significant prevalence, especially in older age groups, where the frequency of its occurrence exceeds 50%. According to epidemiological data, 20 million adults in the United States have OA diagnosed by doctors. The most significant in our time is gonarthrosis, the occurrence of which is 2 times more common than coxarthrosis. No less important is disability, both temporary and permanent: in terms of the number of days of disability, OA is comparable to cardiovascular pathology. A significant percentage of disability in knee OA is due to the growing frequency of arthroplasty.
According to modern concepts, OA is based on many endogenous and exogenous factors. The first respectively include age, gender, developmental defects, hereditary predisposition, and the second - injuries, professional activities, sports activity and overweight. Because many risk factors are not modifiable, OA tends to be progressive disease.
Currently, there are 2 main forms of OA: primary (localized or generalized) and secondary (post-traumatic, caused by congenital, metabolic, endocrine and a number of other diseases).
Thus, modern OA therapy is a complex complex task, including load correction, the use of additional support, weight loss, muscle strength increase, which in general is a physical rehabilitation program, and drug therapy aimed at reducing pain and increasing joint mobility. Of course, the methods of treating OA of the knee joints are more complex, which served as the basis for the formulation of international recommendations of the special Commission of the Standing Committee of the European Antirheumatic League (EULAR) on international clinical trials in 2003. In accordance with these recommendations, the presence of risk factors must be taken into account in the treatment of OA of the knee joints ( obesity, undesirable mechanical factors, increased physical activity), the presence of common risk factors (age, comorbidities, taking medications of various groups), the severity of pain and functional insufficiency of the joints, the presence of signs of inflammation, including synovitis, localization and degree of structural damage .
According to evidence-based medicine and the opinion of EULAR international experts, complex therapy for OA should include slow-acting drugs (glucosamine sulfate, chondroitin sulfate, avocado/soybean unsaponifiable compounds, diacerein and hyaluronic acid). The essence of this fundamentally new approach to the treatment of OA is due to the effect of this group of drugs on the metabolic processes of cartilage tissue and the regeneration of the reparative capabilities of chondrocytes. The use of chondroitin, glucosamine and hyaluronan (HL) has been carried out in clinical practice since the early 1980s. At present, a significant scientific base has been accumulated, represented by dozens of controlled studies with a high level of evidence 1A-1B, according to the American College of Rheumatology (ACR) 2000, 2005.
In the complex therapy of OA, as mentioned above, it is necessary to include non-pharmacological treatment with regular educational programs, physical exercises, supporting means (knee joint fixators, orthoses, sticks). Symptomatic drugs that can eliminate pain and reduce the degree of functional insufficiency include paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, topical applications using NSAIDs and capsaicin. With exacerbations of pain in the knee joint, especially in the presence of concomitant synovitis, intra-articular injections of long-acting corticosteroids are indicated.
In OA therapy, one of the leading tasks is a complex effect on degenerating cartilage that loses its cushioning properties (Fig. 1). The pathogenesis of OA determines a significant increase in the load on the subchondral bone with a violation of bone remodeling, the development of osteoid and the appearance of osteophytes.
Treatment with chondroitin sulfate (CS) has a significant impact on the metabolic processes of various structures of the joint, affecting almost all the main pathogenetic mechanisms for the development of OA. First of all, the hyperexpression of pro-inflammatory mediators decreases, which contribute to inflammatory-degenerative processes in the joint and apoptosis of chondrocytes, which replenish the synthesis of glycosaminoglycans. The ability of cholesterol to influence cartilage metabolism was demonstrated in a one-year placebo-controlled study in patients with knee OA, in which there was a significant decrease in cartilage degradation markers (keratan sulfate) and bone tissue destruction markers (pyridinoline and deoxypyridinoline) . No less significant is the symptom-modifying effect of cholesterol, registered as a decrease in pain compared with NSAID monotherapy and an improvement in the functional ability of the joints.
A special place among chondroprotectors is occupied by preparations of hyaluronic acid - hyaluronan (GL), since these preparations are injected into the affected joints. The high frequency of damage to the knee joints in OA determines the need for a differentiated approach to the appointment of chondroprotectors: in case of polyosteoarthrosis - systemic administration of chondroitin and glucosamine, and in local forms - GL.
Hyaluronan in combination with collagen is the main component of proteoglycan, i.e. the connective tissue biopolymer (Fig. 2).
Proteoglycan has the ability to form a solid environment of hyaline cartilage. GL has unique viscoelastic properties, being present on the surface of the articular cartilage and synovium, it acts as a lubricant and absorber of mechanical shocks (Fig. 2).
Hyaluronan, in addition to its lubricant and damping properties, is used by chondrocytes in the process of synthesis of hyaline cartilage proteoglycans. Thus, Figure 3 shows the functional and metabolic relationships of synovial fluid and articular cartilage, chondrocytes and cartilage matrix, where the leading role belongs to hyaluronan. In osteoarthritis, the concentration of GL decreases, the molecules of synovial hyaluronic acid are shortened, which reduces the viscosity of the synovial fluid (Fig. 3).
Thus, the indication for the introduction of hyaluronan preparations into the affected joint is obvious.
In our study, in patients with gonarthrosis, we studied the clinical efficacy and tolerability of complex therapy for OA of cholesterol (as a systemic chondroprotector) and the intraarticularly administered drug Synocrom (a hyaluronan preparation) for 6 months. 60 outpatients (15 men and 45 women) aged 42-68 years were included in an open clinical study after a pre-signed informed consent (Table 1). The patients were divided into 2 groups. Patients of the 1st group received cholesterol 500 mg 2 times / day. during the 1st month and 250 mg 2 times / day. over the next 5 months. Patients of the 2nd group, who took cholesterol according to the same scheme, were additionally injected intraarticularly three times with an interval of 1 week. According to the indications, patients of both groups took NSAIDs in individually selected dosages (diclofenac 100 mg/day in the absence of gastroenterological pathology, meloxicam 15 mg/day in the presence of an ulcer history).
OA was diagnosed in accordance with the ACR 1987 criteria. In both observation groups, 2 non-modifiable risk factors prevailed - a history of trauma and age factor, as well as overweight as a modifiable factor (Fig. 4).
In the examined patients, pain was assessed according to VAS (100 mm visual analogue scale) at rest and when walking, morning stiffness in minutes, functional insufficiency of the joints was determined (according to the WOMAC questionnaire), the therapeutic effect was assessed, according to the patient and the doctor, as well as adverse events during therapy. Clinical indicators were observed before the start of therapy, after 3 and 6 months.
As a result of the study, against the background of taking systemic chondroprotective therapy for cholesterol, there was a positive trend in assessing pain according to VAS both at rest and when walking. However, additional intra-articular administration of the drug Synocrom after 3 months. therapy showed a statistically significant difference from the results of the dynamics of pain in the 1st group. Over the next 3 months. the analgesic effect lasted longer and also statistically significantly differed from the result of patients in the first group (Fig. 5, 6).
The dynamics of the duration of morning stiffness observed by us in the examined patients in the observation groups did not differ statistically significantly (Table 2).
To assess the functional activity of patients, we studied the dynamics of the WOMAC index, which was positive in patients of the first observation group who received systemic cholesterol therapy. At the same time, in patients with OA of the 2nd group, stabilization of the state and expansion of functional capabilities were observed from the 3rd month of combination therapy, which was provided by a pronounced analgesic and anti-inflammatory effect of complex therapy, significantly and steadily optimizing functional activity (Fig. 7).
The overall assessment of the effectiveness of treatment by the patient and the doctor based on the results of 6 months. therapy is presented in table 3, the results of which reflect the improvement in the functional state of the knee joints against the background of pharmacotherapy with chondroprotectors, especially with the intra-articular administration of Synocrom, while there is no significant difference in the assessment of the effect by the patient and the doctor.
Assessing the tolerability of complex therapy in the observation groups, it should be noted that it was good and was canceled due to side effects in both observation groups. In 2 patients of the 1st group and in one patient of the 2nd group, dyspeptic symptoms were noted, which were stopped by diet correction, no medications were prescribed.
According to the results of the therapy, 6 patients (20%) of the 1st group and 10 patients (33.33%) of the 2nd group were able to completely abandon NSAIDs.
Thus, patients with OA should include chondroprotectors of the chondroitin sulfate group in complex therapy and, in case of localized lesions, additionally administer Synocrom, since these medications provide an effective effect on the critical links of pathogenesis, pain syndrome and the severity of functional deficiency.

Literature
1. Alekseeva L.I., Tsvetkova E.S. Osteoarthritis: from the past to the future // Scientific and Practical Rheumatology. No. 2. 2009, application. pp. 31-37.
2. Badokin V.V., Godzenko A.A., Korsakova Yu.L. Local therapy of osteoarthritis // The attending physician. No. 10. 2007. S. 2-4.
3. Belenky A.G. Hyaluronan preparations in the treatment of osteoarthritis of the knee and hip joints Textbook GOU DPO RMAPO Roszdrav of 23.04.2007.
4. Berglezov M.A., Andreeva T.M. Osteoarthritis (etiology, pathogenesis) // Bulletin of Traumatology and Orthopedics. N.N. Priorova.- 2006.- No. 4.- S. 79-86.
5. Vezikova N.N. Evaluation of the effectiveness of disease-modifying drugs and local therapies in osteoarthritis of the knee. Abstract diss. doc. honey. Sciences. Yaroslavl, 2005. 30 p.
6. Vertkin A.L., Alekseeva L.I., Naumov A.V. etc. Osteoarthritis in the practice of a general practitioner // RMJ. 2008. V.16. No. 7. pp. 478-480.
7. Goryachev D.V. The place of chondroitin sulfate preparations in the arsenal of drugs for the treatment of osteoarthritis // BC. T.16. No. 10, 2008. S. 3-7.
8. Clinical rheumatology. SPb., 2005. S. 386-388.
9. Clinical recommendations. Osteoarthritis. Diagnosis and management of patients with osteoarthritis of the knee and hip joints / Ed. O.M. Lesnyak.- M.: GEOTAR-Media, 2006. 176 p.
10. Nasonova V.A., Alekseeva L.I. Arkhangelskaya G.S. et al. Results of a multicenter clinical trial of Structum in Russia. New opportunities in the treatment of osteoarthritis and osteochondrosis. M., 2006. S. 5-7.
11. Nasonova V.A., Erdes Sh.F. About the World Decade of Osteoarticular Diseases 2000-2010 // Scientific and Practical Rheumatology. 2004. No. 4. pp. 14-16.
12. National leadership. Rheumato-logia / Ed. E.L. Nasonova, V.A. Nasonova.- M.: GEOTAR-Media, 2008. S. 573-588.
13. Pavlova V.N., Kapyeva T.N., Slutsky L.I., Pavlov G.G. Cartilage. Moscow: Medicine, 1998. 320 p.
14. Protsenko G.A. Chondroprotectors in the complex treatment of deforming arthrosis. Abstracts of the III Congress of Rheumatologists. Scientific and practical rheumatology, 2001. No. 3. P.98.
15. Rational pharmacotherapy of rheumatic diseases. M., 2003. V.3. pp. 143-149.
16. Guide for doctors. Health School. Osteoarthritis / Ed. O.M. Lesnyak.- M.: GEOTAR-Media, 2008.- P.81-89.
17. Salikhov I.G., Volkova E.R., Yakupova S.P. Periarticular use of chondroprotectors in patients with gonarthrosis with signs of damage to the tendon-ligamentous apparatus // Consislium medicum. 2006. V.8. No. 2. pp.59-61.
18. Conditions and requirements for intra-articular and periarticular administration of GCS preparations (method. instructions of the Ministry of Health of the Russian Federation No. 2001/25). M., 2001.
19. Tsurko V.V. Local treatment of articular syndrome in osteoarthritis: a rational choice of drug and dosage form // Handbook of a polyclinic doctor. No. 8. 2006. S. 3-8.
20. Tsurko V.V. Osteoarthritis: a geriatric problem // BC. T.13. No. 24. 2005. S. 1627-1631.
21. Chichasova N.V. The place of slow-acting drugs in the rational therapy of deforming osteoarthrosis // Consislium medicum. 2005. V.7. No. 8. pp. 634-638.
22. Chichasova N.V. Chondroitin sulfate (Structum) in the treatment of osteoarthritis: pathogenetic action and clinical efficacy // RMJ. T.17. No. 3. 2009. S. 3-7.

CHONDROPROTECTORS

UDC 615.276.4

© V. E. Novikov

GOU VPO Smolensk State Medical Academy of the Ministry of Health of the Russian Federation

Keywords:

chondroprotectors; chondroitin sulfate; glucosamine; osteoarthritis.

Summary:_______________________________________

The review article discusses the issues of pharmacodynamics and clinical use of drugs of a metabolic type of action that stimulate regeneration processes and have a protective effect on cartilage tissue in osteoarthritis. An analysis of the materials of experimental and clinical studies of the main representatives of the preparations of the chondroprotector group was carried out.

Novikov V.E. Chondroprotectors // Clinical Reviews. pharmacol. and lek. therapy. - 2010. - T. 8. - No. 4. - S. 41-47.

INTRODUCTION

One of the urgent problems of modern clinical medicine is diseases of the musculoskeletal system. The most commonly diagnosed osteoarthritis, which affects up to 20% of the population of our planet. In Russia, about 15 million people suffer from osteoarthritis. With age, the incidence of osteoarthritis increases, in people over 50 years old it is 27%, and in people over 60 years old it reaches 90%. Women get sick twice as often as men, which is presumably due to estrogen deficiency. Osteoarthritis significantly impairs the quality of life of patients and is one of the main causes of disability and disability.

Treatment of osteoarthritis of various localization is still mainly symptomatic with the use of analgesics and anti-inflammatory drugs. In recent years, drugs of the so-called chondroprotectors have been actively offered for the treatment of osteoarthritis, attributing to them sometimes unusual

pharmacological effects. Chondroprotectors enter the pharmaceutical market both in the form of drugs and in the form of biologically active food supplements (BAA). In the medical literature and especially in the media in relation to this group of drugs, sometimes mutually exclusive opinions are expressed, from sublimely enthusiastic to complete denial of the therapeutic effect. So what are cartilage tissue protectors, what are their pharmacodynamics and clinical efficacy?

PATHOGENETIC PREREQUISITES FOR THE USE OF CHONDROPROTECTORS

Cartilaginous tissue is positioned as the main target of chondroprotectors. To understand the pharmacodynamics of chondroprotectors and their role in the pharmacotherapy of osteoarthritis, it is necessary to remember what cartilage tissue is and what degenerative-destructive processes develop in it during osteoarthritis.

Cartilage tissue consists of chondrocyte cells, collagen structures and ground substance. The most important components of the main substance are hyaluronic acid and complex proteo-glycan complexes consisting of glycosaminoglycans (chondroitin sulfate, keratan sulfate, etc.) combined with proteins. Threads of hyaluronic acid permeate the entire space of cartilage tissue, the same hyaluronic acid provides "lubrication" of the cartilage surface.

In osteoarthritis, degradation of cartilage tissue occurs, which is manifested primarily by the destruction of proteoglycan complexes and subsequent dehydration of the cartilage. The metabolism in the cartilaginous tissue changes, the balance between anabolic and catabolic processes is disturbed in the direction of the predominance of the latter. The biosynthetic activity of chondrocytes decreases, resulting in a decrease in the synthesis of the main macromolecules - proteoglycans and type II collagen and an increase in

synthesis of collagen I, III, X types (short collagen) unusual for normal cartilage tissue. The cartilage matrix loses chondroitin sulfate and hyaluronic acid, which are synthesized by cartilage cells - chondrocytes. According to modern concepts, the development of osteoarthritis may be based on many endogenous and exogenous factors. At the same time, cartilage destruction and the development of osteoarthritis are associated primarily with professional human activity, joint injuries, metabolic disorders and overweight, and not with age-related wear of the joints.

Along with degenerative changes, inflammation plays a very important role in the development and progression of osteoarthritis. In the affected joint, the production of “pro-inflammatory” cytokines, cyclooxygenase, is increased, which initiates inflammatory reactions and aggravates damage to the cartilage tissue and surrounding structures of the joint. Interleukin-1b (IL-1b), which is expressed in osteoarthritis-affected cartilage and stimulates the production of metalloproteinases, is of key importance in the large cascade of pro-inflammatory mediators. In addition, IL-1 inhibits the expression of collagen and proteoglycans, stimulates the synthesis and release of eicosanoids - prostaglandins and leukotrienes. Increased production of nitric oxide triggers apoptosis of chondrocytes. Damaged chondrocytes produce collagen and proteoglycans (short collagen, low molecular weight small proteoglycans) that are different from normal cartilage tissue. Proteoglycan deficiency of the matrix develops, cartilage tissue loses glycosaminoglycans.

Cartilage degradation products have antigenic properties. Once in the synovial fluid, they provoke synovial inflammation, which leads to disruption of metabolic processes in synoviocytes and a decrease in the formation of endogenous hyaluronic acid and synovial fluid. The main clinical manifestations of osteoarthritis are joint pain, subsequent deformity of the joints and limitation of their mobility.

PHARMACODYNAMICS OF CHONDROPROTECTORS

Based on pathogenetic prerequisites, for effective pharmacotherapy of osteoarthritis, it is necessary to suppress the initiated inflammation reactions and normalize metabolic processes in cartilage tissue. From this point of view, medicinal

drugs used in the treatment of osteoarthritis are usually divided into 2 main groups: symptom-modifying and structural-modifying. As symptom-modifying drugs, analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are mainly used. Chondroprotectors are offered as structure-modifying (slow-acting) drugs.

Currently, the effectiveness of chondroprotectors has been studied and confirmed in many experimental and clinical studies. They are an essential component of the complex therapy of osteoarthritis, recommended for this purpose by the European Antirheumatic League. Some authors refer them to the basic means of treating osteoarthritis. Such a fundamentally new approach to the pharmacotherapy of osteoarthritis is due to the positive effect of chondroprotective drugs on the metabolic processes of cartilage tissue, stimulation of regeneration and reparative capabilities of chondrocytes. Their appointment is justified at any stage of osteoarthritis for a period of at least 6 months. The use of chondroprotectors slows down the progression of degenerative changes in the joints and spine, has a delayed anti-inflammatory and analgesic effect, and allows to achieve a long-term effect. The pharmaco-economic expediency of including chondroprotectors in the complex treatment of patients with osteoarthritis is shown.

The use of chondroprotectors in osteoarthritis reduces swelling and the amount of effusion in the joints. Their potential chondroprotective effect is manifested by an increase in the anabolic activity of chondrocytes and a simultaneous inhibition of the degenerative effects of cytokines on cartilage. By correcting impaired metabolism in hyaline cartilage, normalizing or stabilizing structural changes in it, they slow down the progression of osteoarthritis and prevent its development in the unaffected joint. These properties, in essence, constitute the content of the structure-modifying (chondroprotective) action of this group of drugs. Chondroprotectors increase the resistance of chondrocytes to the effects of pro-inflammatory cytokines, and the cartilage matrix to the negative effects of NSAIDs and glucocorticoids when they are used simultaneously as part of complex pharmacotherapy. They maintain the elasticity of cartilage.

The main advantages of using chondro-protectors in clinical practice can be expressed in the following terms:

They reduce the severity of symptoms of arthrosis (pain relief, improvement of joint function);

Combined with analgesics and NSAIDs;

Allow to reduce the dose of NSAIDs;

Their effect persists after the end of treatment;

They do not have serious side effects;

They slow the progression of the disease. The effect of chondroprotectors usually occurs

a few weeks after the start of use. Therefore, they are prescribed for a long time, usually in the form of repeated courses for many months and even years. At the same time, it should be noted the high safety of the use of chondroprotectors.

Of the chondroprotectors, chondroitin sulfate and glucosamine sulfate (hydrochloride), which are structural analogues of cartilage glycosaminoglycans, are the most studied and have shown clinical efficacy in multicenter studies. Diacerein, hyaluronan, piascledin are also recommended as effective drugs in European countries.

preparations of chondroprotectors

Let us dwell on the characteristics of the main preparations of chondroprotectors used today in official rheumatological practice.

chondroitin sulfate (c6H14No5)so4 x 2Nacl

Chondroitin sulfate, along with hyaluronic acid and glucosamine sulfate, belongs to the natural components of the intercellular substance of hyaline cartilage. The chondroitin sulfate molecule is highly charged and has polyanionic properties, due to which it is involved in the transport of water, amino acids and lipids. Pharmacokinetic studies have shown that the bioavailability of the drug when administered orally is about 13-15%, when applied externally it reaches 20-40%. The maximum concentration of chondroitin sulfate in the blood is detected 3-4 hours after ingestion, and in the synovial fluid - after 4-5 hours. It is excreted mainly by the kidneys during the day. Shows a high tropism for cartilaginous tissue, the therapeutic effect usually develops within 3-5 weeks from the start of administration. After discontinuation of the drug, the therapeutic effect continues for another 2-3 months. Against the background of the use of chondroitin sulfate, it is possible to increase the effect of indirect anticoagulants, antiplatelet agents, fibrinolytics.

Chondroitin sulfate is the main active ingredient in many chondroprotector preparations: chonsuride, chondrolon, rumalon, chondroxide, structum, etc. They are produced in various dosage forms for oral, intramuscular, and external administration. However, more often chondroitin sulfate preparations are used orally (systemic action) and externally (local action).

With external use of drugs, the decisive moment is the penetration of the active substance directly into the tissues of the joint (cartilaginous matrix, synovial membrane or joint fluid). Chondroitin sulfate is a large molecular compound known to be difficult to penetrate physiological barriers. The penetration of chondroitin sulfate into the joint tissue can be increased with the help of excipients, such as dimethyl sulfoxide. It has been shown that the latter acts as a conductor for chondroitin sulfate through cell membranes. For better penetration of the ointment or gel of chondroxide into the tissues of the joint, magnetophoresis and ultraphonophoresis are used.

The clinical efficacy of preparations containing chondroitin sulfate is associated with the ability of this substance to replace glycosaminoglycans and thereby restore proteoglycan complexes of the main substance of cartilage tissue. Such an effect of exogenous chondroitin sulfate seems to be very doubtful. A more plausible mechanism of action of chondroitin sulfate is the activation of the function of chondrocytes and, as a result, stimulation of their synthesis of proteoglycans with a normal polymeric structure (matrix). In addition, the drug inhibits the activity of metalloproteinase enzymes - stromelysin, collagenase, phosphalipase A2, involved in the destruction of cartilage, and reduces the synthesis of inflammatory mediators. Thus, it has been shown that chondroitin sulfate inhibits the synthesis of metalloproteinases (stromelysin) by chondrocytes by 28%, and also reduces the expression of metalloproteinase induced by lipopolysaccharides and IL-1b. Under its influence, the level of IL and other inflammatory mediators in serum decreases. The anti-inflammatory effect of the drug is associated with inhibition of the activity of lysosomal enzymes, superoxide radicals and the expression of pro-inflammatory cytokines. In favor of the latter is the possibility of reducing the dose of NSAIDs during treatment with chondroitin sulfate. The drug activates the synthesis of high molecular weight hyaluronic acid by synoviocytes, suppresses premature death (apoptosis) of chondrocytes. It has a significant impact

influence on the metabolic processes of various structures of the joint, affecting almost all the main pathogenetic mechanisms of the development of osteoarthritis. In other words, the mechanism of action of chondroitin sulfate is reduced to the suppression of catabolic and stimulation of anabolic processes, which indicates a chondromodifying (chondroprotective) effect of the drug.

The therapeutic activity of chondroitin sulfate has been proven in numerous clinical placebo-controlled studies. It is recommended by the European League Against Rheumatism (EULAR) as a delayed-acting symptom-modifying drug for the treatment of osteoarthritis. The effectiveness of the use of chondroitin sulfate preparations in the treatment of osteoarthritis and osteochondrosis has been shown. Its use, in particular, reduces pain both at rest and during movement, reduces the intensity and duration of morning stiffness, and improves joint function. At the same time, the drug is well tolerated by patients, adverse events were observed only in 2% of patients and were manifested by gastralgia, exacerbation of chronic cholecystitis, allergic reaction and swelling of the legs. EULAR has assessed chondroitin sulfate as the safest drug for the treatment of osteoarthritis, with a toxicity value of 6 on a 100-point scale. Clinical studies have not revealed any significant side effects and undesirable interactions with other drugs during its long-term use.

Glucosamine sulfate (hydrochloride)

Glucosamine is a monosaccharide that is the precursor of many glycosaminoglycans, such as chondroitin sulfate, kerotane sulfate, hyaluronan. It is used in the form of glucosamine sulfate and glucosamine hydrochloride. Pharmacodynamics of glucosamine preparations is close to that of chondroitin sulfate preparations. So, in the experiment it was found that glucosamine sulfate stimulates chondrocytes and increases their synthesis of proteoglycans (chondroprotective effect), suppresses the production of IL-β, tumor necrosis factor (TNF-a), and other markers of inflammation, and also reduces the production of superoxide anions by macrophages and inhibits the development collagen arthritis (anti-inflammatory effect) . The use of glucosamine hydrochloride is preferred over glucosamine sulfate due to greater bioavailability (81.3% and 47.8%, respectively) and greater chemical purity (99.1%

and 80%, respectively). In addition, glucosamine sulfate is unstable in humid environments.

The experiments revealed synergism in the action of chondroitin and glucosamine, which was manifested by a significant increase in the production of proteoglycans by chondrocytes with the combined use of these substances compared with monotherapy. So, with monotherapy with chondroitin sulfate and glucosamine hydrochloride, the production of glycosaminoglycans by chondrocytes increased by 32%, and with combination therapy - by 96.6%. This was the experimental rationale for the combined use of chondroitin sulfate and glucosamine sulfate or hydrochloride. Combined preparations containing both of these substances have appeared, for example, preparations of arthra, teraflex.

Hyaluronan

Among chondroprotectors, hyaluronic acid preparations occupy a special place, since they are injected directly into the affected joints (intra-articular injection). Hyaluronic acid preparations include hyaluronan, synocrom, synvisc, ostenil, fer-matron. Hyaluronic acid in combination with collagen is the main component of proteoglycan, which forms the solid environment of hyaline cartilage. Being present on the surface of articular cartilage and synovium, hyaluronic acid gives them unique viscoelastic properties. It is also used by chondrocytes during the synthesis of hyaline cartilage proteoglycans. With osteoarthritis, the concentration of hyaluronic acid decreases, its molecules shorten, which reduces the viscosity of the synovial fluid.

Intra-articular administration of hyaluronic acid preparations in complex therapy with systemic chondroprotectors has shown clinical efficacy in the treatment of patients with gonarthrosis. However, this approach is not unambiguous and requires further research.

Piascledin

In European countries, the herbal drug piascle-din is officially recommended for the treatment of osteoarthritis. In its composition, it contains active substances from avocado and soy, which are supposed to reduce the production of pro-inflammatory cytokines and have an anabolic effect (stimulate the regeneration of cartilage tissue).

Alflutop

The drug is a standardized sterile extract from 4 types of marine fish, contains sulfated glycosaminoglycans (chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, keratan sulfate), low molecular weight polypeptides, free amino acids and trace elements.

The mechanism of the chondroprotective action of alflutop is associated with the regulation of the metabolism of functioning chondrocytes. It stimulates the synthesis of cartilage tissue matrix macromolecules (proteoglycans, type II collagen), stimulates the synthesis of hyaluronic acid and prevents its destruction, as it inhibits hyaluronidase. A number of clinical studies have shown an increase in the concentration of hyaluronic acid in the synovial fluid with intramuscular and intraarticular administration of alflutop. The drug inhibits the biosynthesis of inflammatory mediators and has an anti-inflammatory effect. A two-year follow-up of patients with osteoarthritis who received two courses of treatment with alflutop annually showed a significant effectiveness of the drug in terms of maintaining the functional capabilities of patients in comparison with the control group. In 60% of patients treated with alflutop, a significant improvement was noted, in 35% - satisfactory, and only in 5% - a slight improvement. No effect or worsening was observed in any patient. Pharmacopuncture with alflutop had a positive effect on dorsalgia.

Clinical and instrumental research methods indicate that alflutop exhibits chondroprotective and anti-inflammatory effects, stimulates regeneration. The drug showed high efficiency and good tolerance in patients with osteoarthritis (coxarthrosis, gonarthrosis, arthrosis of small joints), osteochondrosis, with periarthritis.

conclusion

Thus, chondroprotectors are slow-acting structural-modifying drugs, the inclusion of which in the complex pharmacotherapy of osteoarthritis should be considered reasonable. Based on pharmacodynamics (stimulation of chondrocyte function, cartilage tissue regeneration processes, inhibition of the synthesis of inflammatory mediators), they should be prescribed at relatively early stages of the disease, when there is something to “test”. In the early stages of arthrosis

they are the most efficient. However, it is not necessary to exaggerate the therapeutic possibilities of chondroprotectors. With their help, it is impossible to completely restore cartilage tissue and even more so to grow a new one. Therefore, with deep degenerative changes in the cartilage, they are ineffective.

Chondroprotectors act very slowly. They are used for a long time. To obtain a real therapeutic effect, at least 4-6 months of treatment are required, and preferably 2-3 courses during the year. The choice of the drug is determined by the individual characteristics of the patient, the localization and characteristics of the course of the disease (the severity of the process, the severity of symptoms, the presence of inflammation, etc.), the properties of the drug and the evidence base for its clinical effectiveness. Numerous clinical data on the effectiveness of chondroprotectors refer mainly to chondroitin sulfate and glucosamine preparations. When they are used together, an additive effect is observed and the effectiveness of treatment increases.

Literature

1. Alekseeva L. I. Prospects for chondroprotective therapy of osteoarthritis // Scientific and Practical Rheumatology. - 2003. - No. 4. - S. 83-86.

2. Alekseeva L. I., Tsvetkova E. S. Osteoarthritis: from the past to the future // Nauch.-prakt. rheumatology. - 2009. - No. 2, app. - S. 31-37.

3. Alekseeva L. I., Chichasova N. V., Belevolenskaya L. I. et al. Prospects for combined chondroprotective therapy for osteoarthritis. Results of an open randomized study of Artra in patients with gonarthrosis // Nauch.-prakt. rheumatology. -

2004. - No. 4. - S. 77-79.

4. Alekseeva L. I., Chichasova N. V., Mendel O. I. Results of the use of Artra in gonarthrosis // Nauch.-prakt. rheumatology. - 2004. - No. 2. - S. 45-47.

5. Alekseeva L. I., Sharapova E. P. Chondroitin sulfate in the treatment of osteoarthritis // Ros. honey. magazine. - 2009. - T. 17, No. 21. - S. 1448-1453.

6. Annenfeld M. New data on glucosamine sulfate // Nauch.-prakt. rheumatology. - 2005. - No. 4. - S. 76-80.

7. Artamonov R. G. Medicine of evidence - two sides of the coin // Med. department. - 2005. - T. 16, No. 5. - S. 136-139.

8. Artemenko N. A., Chvamaniya M. A. Features of progression and treatment of osteoarthritis // Ros. honey. magazine. - 2005. - T. 13, No. 7. - S. 403-407.

9. Badokin VV Preparations of chondroitin sulfate in the treatment of osteoarthritis // Ros. honey. magazine. - 2009. - T. 17, No. 21. - S. 1461-1466.

10. Badokin VV The importance of inflammation in the development and course of osteoarthritis // Consilium medicum. - 2009. - T. 11, No. 9. - S. 91-95.

11. Badokin V. V., Godzenko A. A., Korsakova Yu. L. Local therapy of osteoarthritis // Lech. doctor. - 2007. - No. 10. - S. 2-4.

12. Barsukova N. A. The effectiveness of the treatment of patients 30.

osteoarthritis with reactive periarthritis by low-intensity laser radiation in combination with chondroprotectors: Abstract of the thesis. dia... cand. honey. Sciences. - Voronezh, 2008. - 22 p. 31.

13. Berglezov M. A., Andreeva T. M. Osteoarthritis (etiology, pathogenesis) // Bulletin of traumatol. and orthopedics

them. N. N. Priorova. - 2006. - No. 4. - S. 79-86. 32.

14. Bortkevich O.P. Osteoarthritis: disease control is achievable // Healthy Ukraine. - 2008. - No. 22. -

15. Vezikova N. N. Evaluation of the effectiveness of disease-modifying drugs and local methods of therapy 33. in osteoarthritis of the knee joints: Avto-ref. dis. ... Dr. med. Sciences. - Yaroslavl, 2005. - 30 p.

16. Vertkin A. L., Alekseeva L. I., Naumov A. V. et al. Osteoarthritis in the practice of a general practitioner // Ros. honey. magazine - 34. cash. - 2008. - T. 16, No. 7. - S. 476-480.

17. Goryachev D.V. The place of chondroitin sulfate preparations in the arsenal of drugs for the treatment of osteoarthritis // 35.

Ros. honey. magazine. - 2008. - T. 16, No. 10. - S. 478-480.

18. Drozdov V. N., Kolomiets E. V. The use of alflutop in

patients with osteoarthritis with NSAID-gastropathy // Farmateka. - 2005. - No. 20. - S. 125-128. 36.

19. Zborovsky A. B., Mozgovaya E. E. Alflutop: experience of many years of clinical use // Farmateka. -

2006. - No. 19. - S. 1-5.

20. Korshunov N. I. Chondroprotective therapy for pain 37.

nyh osteoarthritis // Farmateka. - 2008. - No. 12. -

21. Lila A. M., Mazurov V. I., Shidlovskaya O. V. et al.

Raflex in the complex therapy of osteoarthritis of the knee joints and osteochondrosis of the spine // Ros. honey. 38.

magazine. - 2005. - T. 13, No. 24. - S. 1618-1622.

22. G. V. Lukina, Ya. A. Sigidin, and L. N. Denisov, Multi-year

niy experience of using alflutop in clinical practice // Nauch.-prakt. rheumatology. - 2005. - No. 5. - 39.

23. Mayko O. Yu., Bagirova G. G. The use of the cost-utility method in pharmacoeconomic 40. analysis of the effectiveness of drug therapy for osteoarthritis in a polyclinic // Ural Med. magazine. - 2008. - No. 5. - S. 45-54.

with the use of chondroprotectors and NSAIDs on the quality of life of patients with osteoarthritis // Klin. honey. - 2009. -

No. 4. - S. 47-48.

25. Nasonova V. A., Alekseeva L. I., Arkhangelskaya G. S. et al. 42.

Results of a multicenter clinical trial of Structum in Russia // New opportunities in the treatment of osteoarthrosis and osteochondrosis. - M., 2006. - S. 5-7. 43.

26. Nasonova V. A., Nasonov E. L. Rational pharmacotherapy of rheumatic diseases. - M.: Litera,

27. Peshekhonova L. K., Peshekhonov D. V., Kuzovkina T. N. 44.

Clinical efficacy of chondroprotectors in the complex therapy of osteoarthritis of the knee joints //

Roa honey. magazine. - 2009. - T. 17, No. 21. - S. 14861490.

28. Salikhov I. G., Volkova E. R., Yakulova S. P. Periarty

cular application of chondroprotectors in patients 45.

gonarthrosis with signs of damage to the tendon-ligamentous apparatus // Consilium medicum. - 2006. -

No. 2. - S. 59-61.

29. Svetlova M. S. The use of drugs alflutop and 46

glucosamine hydrochloride in the treatment of patients with osteoarthritis: Abstract of the thesis. dis. ... cand. honey. Sciences. - Yaroslavl,

TereshinaL. G. New methods of drug phonophoresis in the treatment of patients with osteoarthritis working under physical stress // Med. labor and industrial ecology. - 2007. - No. 3. - S. 39-42.

Tikhaya O. A. Optimization of traditional technologies of restorative medicine: Abstract of the thesis. dis. ... cand. honey. Sciences. - M., 2007. - 20 p.

Fedotova M. V. Regulatory effects of polyenzymatic, chondroprotective and antihypoxic drugs in adjuvant arthritis in the experiment // Bulletin of the Saratov State Agrarian University. N. I. Vavilov. - 2008. - No. 8. - S. 32-35.

Khodyrev V. N., Znaisheva N. I., Lobanova G. M., Ridnyak L. M. Evaluation of the clinical efficacy of alflutop in osteoarthritis // Nauch.-prakt. rheumatology. -

2003. - No. 1. - S. 43-46.

Khodyrev VN, Golikova LG Clinical efficacy of alflutop in osteoarthritis of the spine // Nauch.-prakt. rheumatology. - 2005. - No. 2. - S. 33-36. Chichasova N.V. The place of slow-acting drugs in the rational therapy of deforming osteoarthritis // Consilium medicum. - 2005. - V. 7, No. 8. - S. 634-638.

Chichasova NV Chondroitin sulfate (Struktum) in the treatment of osteoarthritis: pathogenetic action and clinical efficacy // Ros. honey. magazine. - 2009. - V. 17, No. 3. - S. 3-7.

Chichasova N. V., Alekseeva L. I., Benevolenskaya L. I. et al. A new direction in the treatment of osteoarthritis - combined therapy with chondroitin sulfate and glucosamine hydrochloride // Ros. honey. magazine. -

2004. - T. 12, No. 23. - S. 1337-1341.

Caraglia M., Beninati S., Alessandro A. et al. Alternative therapy of earth elements increases the chondroprotec-tive effects of chondroitin sulfate in mice // Exp. Mol. Med. -

2005. - Vol. 37. - P. 476-481.

Bana G., Jamard B., Verrouil E., Mazieres B. Chondroitin sulfate in the management of hip and knee OA: an overview // Adv. Pharmacol. - 2006. - Vol. 53.-P. 507-522. Clegg D. O., Reda D. J., Harris C. L. et al. Glucosamine, Chondroitin sulfate, and two in combination for painful knee osteoarthritis // New Engl. J. Med. - 2006. - Vol. 354. - P. 795-808.

Chan P. S, Caron J. P., Orth M. W. Shot-term gene expression changes in cartilage explants stimulated with interleukin beta glusglucosamine and chondroitin sulfate // J. Rheumatol. - 2006. - Vol. 33. - P. 1329-1340.

Hathcock J. N., Shao A. Risk assessment for Glucosamine and Chondroitin sulfate // Regul. Toxicol. Pharmacol. -

2007. - Vol. 47. - P. 78-83.

Holzmann J., Brandl N., Zemann A. et al. Assorted effects of TGFbeta and chondroitin sulfate on p38 and ERK 16 activation levels in human articular chondrocytes stimulated with LPS // Osteoarthritis Cartilage. - 2006. - Vol. 14. - P. 519-525. Jordan K. M., Arden N. K., Doberty M. et al. EULAR Recommendations: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for international Clinical Studies including Therapeutic Trials // Ann. Rheum. Dis. - 2003. - Vol. 62. - P. 1145-1155.

Laurence D., Massicotte F., Pelletier J., Martel-Pelletier J. Subchondral bone sclerosis in osteoarthritis: not just an innocept bystander // Modern Rheumatol. - 2003. - Vol. 13. - P. 7-14.

Leeb B. F., Schweizer M., Montag K., Smolen J. A meta-analisis of chondroitin sulphate in treatment of osteoarthritis // J. Rheumatol. - 2006. - Vol. 27. - P. 205-211.

47. Lippielo L., Grande D. In vitro chondroprotection of clu-cosamine and chondroitin sulfate in a rabbit model of a OA and demonstration of metabolic synergy on chondrocyte in vitro, Ann. Rheum. Dis. - 2000. - Vol. 59, Suppl. 1. - P. 266.

48. Monfort J., Nacher M., Montell E. et al. Chondroitin sulfate and Hyaluronic acid inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes // Drugs Exp. Clin. Res. -

2005. - Vol. 31. - P. 71-76.

49. Monfort J., Pellietier J-P., Garcia-Giralt N., Martel-Pellietier J. Biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues // Ann. Rheum. Dis. - 2008. - Vol. 67. - P. 735-740.

50. Register J., Rovati L., Deroisy R. et al. Glucosamine sulfate slows - down ostearthritis progressin in postmenopausal women: pooled analysis of two large, independent, randomized double - blind placebo - controlled, prospective 3 - year trials // Ann. Rheum. Dis. - 2002. - Vol. 61, Suppl. 1. - THU 0196.

51. Richy F., Bruyere O., Ethgen O. et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis // Arch. Intern. Med. - 2003. - Vol. 163. - P. 1514-1522.

52. Rovetta G., Monteforte P., Molfetta G., Balestra G. A two-years study of chondroitin sulfate in erosive osteoarthritis of the hand: behavior of erosions, osteophytes, pain and hand dysfunction // Drug Exp. Clin. Res., 2004. - Vol. 30, No. 1. - P. 11-16.

53. Teitelbaum S. L. Bone resorption by osteoclasts // Science. - 2000. - Vol. 289. - P. 147-148.

54. Uebelhart D., Knols R., de Bruin E. D., Verbruggen G. Chondroitin sulfate as a structure-modifying agent // Adv. Pharmacol. - 2006. - Vol. 53. - P. 475-488.

55. Valenta C., Barbara G., AunerB. G. The use of polymers for dermal and transdermal delivery // Eur. J. Pharmaceutics and Biopharmaceutics. - 2004. - Vol. 58, No. 2. - P. 279-289.

56. Volpi N. Oral bioavailability of chondroitin sulfate (Chondrosulf) and its constituents in healthy male volunteers // Osteoarthritis Cartilage. - 2002. - Vol. 10, No. 10. - P. 768-777.

57. Volpi N. Chondroitin sulphate for the treatment of osteoarthritis, Curr. Med. Chem. - 2005. - Vol. 4, No. 3. - P. 221-234.

58. Zhang W., Moskowitz R., Nuki G. et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines // Osteoarthritis Cartilage. - 2008. - Vol. 16, No. 2. - P. 137-162.

chondroprotective agents

♦ Summary: The review considers pharmacodynamics and clinical applications of drugs with the metabolic type of action which stimulate regeneration and provide the protective action on articular cartilage in osteoarthritis. The review analyzes the data of the experimental and clinical trials of main chondroprotective agents.

♦ Key words: chondroprotective agents; chondroitin sulfate; glucosamine; osteoarthritis.

Novikov Vasily Egorovich - Doctor of Medical Sciences, Professor, Head of the Department of Pharmacology.

GOU VPO Smolensk State Medical Academy of the Ministry of Health and Social Development of the Russian Federation.

214019, Smolensk, st. Krupskaya, 28.

Email: [email protected]

Novikov Vasiliy Egorovich - Doctor of Medical Sciences, professor Head of the Department of Pharmacology.

Smolensk State Medical Academy.

Krupskoy st., 28, Smolensk, 214019.

Dear friends, hello!

After a short break, we return to the conversation about drugs, and today's conversation will be devoted to a group that causes a lot of controversy. We will talk about chondroprotectors.

Throughout the past week, I have been studying this issue and came to the conclusion that modern chondroprotective drugs are still a “dark horse”.

But one thing is clear: the whole people is divided in relation to this group into 2 camps. And they all share:

1. Doctors. Some consider chondroprotectors to be the main pathogenetic treatment for arthrosis. Others say that this is pure profanity. The latter, in particular, include your beloved Elena Malysheva, who from the big podium, or rather, directly from the TV, said that chondroprotectors are drugs with unproven effectiveness.
2. Pharmacy staff. Some, having read publications and clinical studies, think the same way as a TV star. Others argue that chondroprotectors really work. This, firstly, is said by grateful customers, secondly, “I took it myself, it became easier”, thirdly, “I gave it to my mother, there is an effect.”
3. Sufferers who know what it is, firsthand. Some write reviews like: “drank, it’s no use. Just wasted money." Others retort them: “But it helped me!”

After studying and comprehending the videos, clinical studies and the opinions of doctors, I formed my own opinion.

CHONDROPROTECTOR DRUGS WORK, unless…

Although no, we will not run ahead of the locomotive.

I feel now how happy the supporters of this group were, and how their opponents frowned, dreaming of throwing rotten tomatoes at me.

Do not order to execute, order to say a word!

Moreover, it is in your own interests to fall in love with this group of funds: otherwise, how are you going to sell them?

We will now consider the following questions:

• Why don't chondroprotectors always help?
• How do they share?
• Why do they have side effects?
• Which is better: a single drug or a combination drug?
• What are the features and "chips" of popular chondroprotectors?

But first, as usual, let's remember how the joint is arranged in our body, and due to what it works.

How is the joint arranged?

So, the joint is a connection of articular surfaces of bones, each of which is covered with cartilage.

The joint is enclosed in a joint bag, or capsule, which is attached to the articulating bones. It provides tightness of the joint and protects it from damage.

The cartilage of the joint is a kind of gasket necessary for the smooth sliding of the heads of the bones relative to each other and for absorbing the loads that the joint experiences during movement.

Between the heads of the bones is a slit-like space - the joint cavity.

The inner lining of the joint capsule is called synovial and produces synovial fluid into the joint cavity.

Synovial fluid is needed to lubricate the articular surfaces of the bones, so that the cartilage does not dry out, and for all the functions of the ship to work properly.

Cartilage resembles a sponge in its structure: when the joint cavity is loaded, synovial fluid is released from the cartilage, and as soon as the compression stops, the fluid returns back to the cartilage.

What is articular cartilage made of?

Cartilage is made up of collagen fibers that run in different directions to form a network. The mesh cells contain proteoglycan molecules that hold water in the joint. Therefore, cartilage is approximately 70-80% water.

Proteoglycans are made up of protein and glycosaminoglycans.

Glycosaminoglycans are carbohydrates, which include hyaluronic acid and chondroitin sulfate, among others. Look at the picture above: chondroitin is the brush hairs in proteoglycans.

Both require glucosamine to produce. It is formed by cartilage tissue cells, chondrocytes, from substances that enter the body with food.

In other words, glucosamine is the building block for chondroitin. And chondroitin is needed for the synthesis of hyaluronic acid.

What is synovial fluid?

It is a blood plasma filtrate, which contains hyaluronic acid, obsolete joint cells, electrolytes, proteolytic enzymes that destroy old proteins.

Hyaluronic acid binds and retains water in the joint cavity, due to which the synovial fluid moisturizes the articular surfaces of the bones, and they move relative to each other like clockwork.

And one more important point. The fluid in the joint cavity is not worth it, as in a swamp.

She circulates. Old cells die, new ones are born, the blood plasma filtrate is renewed, and for this process, like air, movement is necessary.

How is the joint fed?

The nutrition of the joint leaves much to be desired.

It has no independent blood supply.

Its "nurse" is the synovial fluid, from where the cartilage, through osmosis, that is, leakage, takes the nutrients it needs. And they enter the synovial fluid from the blood vessels passing near the joint.

But even here it is not so simple.

The cartilage absorbs the synovial fluid only during movement: the leg was bent, the synovial fluid came out of the cartilage into the joint cavity, straightened it went back into the cartilage, delivering the necessary “food” to it.

When moving, the muscles that attach to the elements of the joint contract, and due to this, blood is pumped through their vessels, delivering more nutrients to the cartilage.

More about chondrocytes

Chondrocytes are involved in the restoration and production of substances necessary for cartilage. But the whole problem lies in the fact that there are very few of them: only 5%, and everything else (95%) is cartilage matrix (collagen fibers).

In addition, among chondrocytes there are young, mature and aged cells. The parade is commanded, of course, by mature people. Others either STILL do not have enough strength to synthesize the substances necessary for cartilage, or ALREADY do not have enough.

But with adequate loads and normal nutrition of the joint, this is enough.

findings

Thus, for the normal operation of the joint, you need:

1. Mature chondrocytes receiving adequate nutrition.
2. Normal blood supply to the joint.
3. Adequate work of the muscles surrounding the joint.

Why does arthritis develop?

It most often develops as a result of one of four problems:

1. Or they overloaded the joint (excess weight or sports loads that exceed the ability of the cartilage to extinguish them).
2. Or they didn’t load it (physical inactivity, as a result of which the blood supply to the joint is disturbed, the cartilage does not receive adequate nutrition and begins to collapse).
3. Or all together (+ hypodynamia).
4. Or a serious injury in which the metabolism in the joint and its nutrition are disturbed.

What happens in the joint under the influence of these factors?

1. Chondrocytes do not have time (with OVERLOAD) or cannot (with UNDERload) form a sufficient amount of glucosamine.
2. If there is no glucosamine, chondroitin is not formed.
3. If chondroitin is not formed, hyaluronic acid is not formed.
4. If hyaluronic acid is not formed, fluid is not retained in the joint.
5. If there is little fluid in the joint, the articular heads of the bones are not moistened.

And then this is what happens:

Stages of arthrosis

Stage 1 arthrosis:

1. Cartilage loses water, i.e. dries up.
2. Collagen fibers are torn or completely destroyed.
3. The cartilage becomes dry, rough and cracks.
4. Instead of sliding freely, the cartilages of the articulating bones "cling" to each other.

Stage 2 arthrosis:

1. The pressure on the bone increases.
2. The heads of the bones begin to gradually flatten out.
3. The cartilage thins out.
4. The joint space is reduced.
5. The joint capsule and synovial membrane "wrinkle".
6. Bone outgrowths - osteophytes - appear along the edges of the bones.

Stage 3 arthrosis:

1. The cartilage disappears completely in places.
2. The bones begin to rub against each other.
3. The deformity of the joint increases.

Stage 4 arthrosis:

1. The cartilage is completely destroyed.
2. The joint gap is practically absent.
3. The articular surfaces are exposed.
4. The deformity of the joint reaches its maximum.
5. Movement is not possible.

As a result of these changes, inflammation develops in the joint. It becomes edematous, but intensifies.

Now let's move on to the drugs.

But first, a few basics.

When do chondroprotectors "work"?

First of all, let's clarify the following for ourselves:

1. Chondroitin and glucosamine are effective on 1-2 stages of arthrosis, when there is no cartilage destruction yet, and chondrocytes are alive.
2. Chondroitin sulfate is a large molecule, about 100 times larger than glucosamine, so its bioavailability is only 13%.
3. The bioavailability of glucosamine is greater, but also not much, only 25%. This means that 25% of the dose taken will reach the joint directly.
4. The optimal daily therapeutic dosages of chondroprotectors for oral administration, according to practitioners, are as follows:

1. To get real results, you need 2-3 courses of treatment with these drugs, which will take up to 1.5 years.
2. Practitioners advise taking chondroprotectors continuously for 3-5 months and repeating the course every six months.
3. Chondroprotectors should be taken regularly, in courses, and not on a case by case basis.
4. It is pointless to take chondroprotective drugs if you continue to mock the joint with excessive loads. To achieve the effect, you need to reduce weight, and athletes abandon conventional training.
5. You can take this group for a very long time and not see the result if you do not provide normal nutrition to the joint. This requires special (!) Exercises.
6. For the production of chondroitin and glucosamine, cartilage of cattle, extracts from marine fish are used. It is difficult to achieve 100% purification, therefore, when taking these drugs allergic reactions occur and problems from the gastrointestinal tract (abdominal pain, diarrhea, constipation, etc.).
7. Chondroitin sulfate reduces clotting blood, so it can not be used together with anticoagulants and with a tendency to bleeding.
contraindicated pregnant and lactating women, children.
8. Diabetics when taking these drugs need to carefully control their sugar levels. It can rise (carbohydrates after all).

How do chondroprotectors work?

What does glucosamine do?

• Stimulates the activity of chondrocytes.
• Necessary for the synthesis of chondroitin sulfate and hyaluronic acid.
• Prevents the destructive effect on the cartilage of NSAIDs and glucocorticosteroids.

What does chondroitin sulfate do?

• Necessary for the synthesis of hyaluronic acid.
• Normalizes the production of synovial fluid.
• Reduces the activity of enzymes that damage cartilage.
• It has an anti-inflammatory effect.

Types of chondroprotectors

Let's analyze how chondroprotectors are divided.

According to the way of taking exist:

• Preparations for oral administration (Struktum, Dona powders and tablets, Artra, etc.)
• Preparations for injections (Dona r / r, Alflutop, Rumalon, etc.)
• Preparations for external use (Chondroxide, Chondroitin, etc.).

With parenteral administration, the bioavailability of chondroprotectors is significantly higher, so they are prescribed when you need to quickly relieve an exacerbation, or when the patient prefers short courses of treatment, or when there are problems with the liver, so as not to burden it.

Preparations for external use are effective only in combination with other forms of release.

By composition, chondroprotectors are divided into:

• Monopreparations that contain only chondroitin sulfate (CS) or glucosamine (GA): Structum, Don.
• Combined products containing both one and the other component: Artra, Teraflex.
• Means that, in addition to cholesterol and GA, contain a non-steroidal (i.e., non-hormonal) anti-inflammatory agent: Teraflex Advance.

With the latter, everything is clear: if there are signs of inflammation (severe pain, swelling), at first we recommend a drug with NSAIDs. After 2-3 weeks, you can switch to a "clean" chondroprotector.

As for the first two, there is no unequivocal answer to the question “which is better”. Some doctors prefer single drugs, others combined, and still others prescribe both, depending on the situation.

But I noticed that glucosamine gives more side effects from the gastrointestinal tract.

Therefore, the combination of GA and CS seems to me the most optimal: it increases the bioavailability of the drug and reduces the frequency of adverse reactions.

Well, now let's go over the drugs.

I'll start with the "oldies":

RUMALON- solution for intramuscular injection.

Compound:

Glycosaminoglycan-peptide complex derived from cartilage and bone marrow of calves (powerful allergen due to animal proteins).

What is he doing:

It improves the synthesis of cholesterol, promotes the maturation of chondrocytes, stimulates the synthesis of collagen and proteoglycans. Moreover, the manufacturer writes that the drug is effective both in the early and late stages of arthrosis. The latter makes me doubt.

Application: administered according to the scheme for 5-6 weeks, 2 times a year.

Side effects: allergic reactions.

ALFLUTOP- injection.

Ingredients: bioactive concentrate from small marine fish.

Contains amino acids useful for cartilage, mucopolysaccharides, trace elements: sodium, magnesium, zinc, iron, etc.

What it does: It inhibits the activity of hyaluronidase, an enzyme that breaks down hyaluronic acid. So the latter becomes larger, and the condition of the cartilage improves.

Application:

There are 2 ways to use it:

1. Intramuscularly daily 1 ml for 20 days.
2. Intra-articular 1 or 2 ml per joint every 3-4 days. Only 5-6 injections.

The course is repeated after six months.

Sometimes doctors start with intra-articular injections, then move on to intramuscular injections. It depends on the doctor. How many doctors, so many methods.

Contraindications: Allergy to seafood (sometimes very strong).

CHONDROLONE- lyophilisate (i.e. the active substance is in a dried state) for the preparation of a solution

Composition: contains chondroitin sulfate 100 mg per ampoule.

Since the bioavailability is high with this administration, this dosage is sufficient.

It is obtained from the cartilage of the trachea of ​​cattle.

What it does: inhibits the activity of enzymes that cause cartilage destruction, stimulates the production of glycosaminoglycans by chondrocytes, normalizes the production of synovial fluid, and has an anti-inflammatory effect.

Application: in / m 1-2 ampoules every other day. Only 25-30 injections. The course is repeated after six months.

DONA- monopreparation.

Ingredients: contains glucosamine sulfate.

What it does: stimulates the synthesis of hyaluronic acid and other glycosaminoglycans, inhibits enzymes that cause cartilage destruction.

In one tablet 750 mg HA.

How to take: 1 t. 2 times a day with meals. Improvement occurs in 2-3 weeks. The minimum course is 4-6 weeks. Repeat the course after 2 months.

The powder contains 1500 mg of HA.

For whom is it optimal this form of release: powders are especially good for working citizens, who find it more convenient to take the drug only 1 time per day.

And also for those who have difficulty swallowing tablets.

Application: the powder is dissolved in a glass of water and taken 1 time per day (also better with meals). The course is 6 weeks, repeated after 2 months.

Solution for i / m administration: in 1 ampoule 400 mg of glucosamine. Bioavailability 95%. In addition to glucosamine, it contains lidocaine, therefore it has many contraindications: cardiovascular insufficiency, impaired liver and kidney function, epileptic seizures, etc. There are many side effects.

Medical prescription only!

Application: Enter 3 times a week for 4-6 weeks. And then as the doctor decides. Maybe he will switch to powders or tablets.

STRUKTUM- capsules.

Ingredients: contains chondroitin sulfate.

There are 250 mg and 500 mg. To be honest, I don’t know why the first form of release exists, since the manufacturer recommends taking 500 mg 2 times a day.

Judging by the presence in Moscow pharmacies, Structum 250 mg is leaving the shelves. Maybe I'm wrong.

What is he doing? Stimulates the synthesis of glycosaminoglycans, improves the metabolic process in the cartilage.

Application: take it 500 mg 2 times a day for 6 months.

The action after cancellation lasts 3-5 months, then you need to repeat the course.

- combined remedy.

Composition : contains very adequate dosages of chondroitin and glucosamine: 500 mg each

What it does: All the good things HA and CS do in the joint.

Application: take this drug 1 ton 2 times a day for the first 3 weeks, then 1 ton a day for a long time, but not less than 6 months.

TERAFLEX ADVANCE - another combination drug.

Composition: it contains: GA 250 mg, cholesterol 200 mg and ibuprofen 100 mg.

So, in addition to all the beneficial effects of the first two substances, it also has an anti-inflammatory and analgesic effect.

In addition to all the beneficial effects of the first two substances, it also has an anti-inflammatory and analgesic effect.

True, contraindications and side effects due to ibuprofen become several times larger.

Application: take it 2 capsules 3 times a day after meals for no more than 3 weeks. Then they switch to the usual Teraflex.

TERAFLEX

Composition: contains GA 500 mg, cholesterol 400 mg.

Application: take it for the first 3 weeks, 1 capsule 3 times a day, then 1 capsule 2 times a day for 3-6 months, preferably with meals. Then, as usual, the course is repeated.

External chondroprotectors

Here I will focus only on the most popular drug Chondroxide.

CHONDROXIDE

Composition: contains 1 g of 50 mg of chondroitin sulfate.

Release form: ointment and gel.

Application:

A large molecule of chondroitin cannot penetrate the skin on its own, therefore, in order to pass it through cell membranes, dimexide is added to the drug, which also has an anti-inflammatory and analgesic effect.

Do not apply to open wounds.

CHONDROXIDE FORTE – cream

Composition: contains cholesterol and the anti-inflammatory substance Meloxicam, that is, it reduces inflammation and pain.

Contraindications standard for NSAIDs.

Given this composition, it is better not to advise the elderly. For them, there is a gel for the period of exacerbation.

This is not just a cream, it is a transdermal glucosamine complex (glucosamine + triglycerides).

Compound . contains glucosamine, and not chondroitin, like the previous forms, and dimexide, so we recommend it when an allergic reaction to other external forms of chondroxide has been noted in the past.

And also when the buyer does not care about the high price. The main thing is that the effect is maximum.

The active substance is enclosed in a shell of lipids, which together form a micelle (nanoparticle), which delivers the active substance to the joint in a concentration comparable to an injection.

Application: apply it 2-3 times a day for 3-4 weeks. If necessary, the course is repeated.

I end with this.

You have a lot of chondroprotectors in your assortment: both drugs and dietary supplements.

But knowing the basic things that I talked about, you can now independently understand the composition of such a tool and its effectiveness.

I hope that now you can easily continue the phrase:

CHONDROPROTECTORS WORK, unless…

And as a homework, I suggest you think about:

What questions should a buyer ask when choosing a chondroprotector?

Having studied everything thoroughly, I understood why in some countries all chondroprotectors are considered additives: because their bioavailability is low (and manufacturers, by the way, do not hide this), and the therapeutic effect is greatly delayed in time.

And in conclusion, I will answer the most common question:

Why are there many bad results of using chondroprotectors?

1. Because, as usual, people are hoping for a magic pill without putting in the effort to lose weight and work muscles.
2. Because they want quick results, and not seeing them, they stop treatment.
3. Because they begin to "drink Borjomi when the kidneys have failed", i.e. take chondroprotectors at 3-4 stages of arthrosis.

That's all.

How did you like this article, friends?

What do you think about chondroprotectors YOU?

Add, comment, share your experience, click on the social buttons. networks.

See you on the blog for hard workers!

With love to you, Marina Kuznetsova

For citation: Lygina E.V., Miroshkin S.V., Yakushin S.S. Chondroprotectors in the treatment of degenerative-dystrophic diseases of the joints and spine // RMJ. 2014. No. 10. S. 762

Chondroprotectors are structural elements (glycosaminoglycans) of natural cartilage tissue necessary for the construction and renewal of articular cartilage. They belong to the group of symptomatic slow acting drugs (Symptomatic Slow Acting Drugs for OsteoArthritis - in the English nomenclature), have a moderate analgesic effect and improve the functional performance of the joints.

According to a number of prospective studies, chondroprotectors are able to have a modifying effect on the course of degenerative-dystrophic diseases of the joints and spine (osteoarthritis (OA), dorsopathy). Among this group of drugs, the largest evidence base is available for chondroitin sulfate (CS) and glucosamine (GA). These drugs are widely used in the practice of a rheumatologist and a neurologist.

CS is a glycosaminoglycan consisting of long polysaccharide chains of repeating compounds of the disaccharide N-acetylgalactosamine and glucuronic acid. According to the chemical structure, cholesterol is a sulfated glycosaminoglycan isolated from the cartilage of birds and cattle. It is a major component of the extracellular matrix of many tissues, including cartilage, bone, skin, arterial walls, ligaments, and tendons. In the body, it is formed from HA and consists of several fractions that differ in molecular weight. In the gastrointestinal tract, its low molecular weight fractions are almost completely absorbed. Pharmacokinetic studies have shown that the bioavailability of the drug when administered orally is about 13-15%. The maximum concentration of cholesterol in the blood is detected 3-4 hours after ingestion, and in the synovial fluid - after 4-5 hours. It is excreted mainly by the kidneys during the day. It exhibits a high affinity for cartilaginous tissue, however, a necessary condition for effectiveness is its accumulation in the tissues of the joint, so the therapeutic effect usually develops within 3-5 weeks. from the start of admission. After discontinuation of the drug, the therapeutic effect continues for another 2-3 months. The drug is well tolerated by patients, adverse events were observed only in 2% of patients and were manifested by gastralgia, exacerbation of chronic cholecystitis, allergic reactions and swelling of the legs. According to EULAR, cholesterol is the safest drug for the treatment of OA, its toxicity value is 6 on a 100-point scale. Clinical studies have not revealed any significant side effects and undesirable interactions with other drugs during its long-term use.

The mechanism of action of cholesterol is complex, multifaceted and covers almost all key aspects of the pathogenesis of OA. CS leads to the activation of chondrocytes and, as a result, there is an increase in their synthesis of proteoglycans with a normal polymer structure. By activating synoviocytes, it leads to an increase in their synthesis of high molecular weight hyaluronic acid. It causes suppression of the activity of cartilage-destroying enzymes - metalloproteinases (stromelysin, collagenase, etc.). Suppresses premature death (apoptosis) of chondrocytes, biosynthesis of IL-1β and other inflammatory mediators. Improves microcirculation in the subchondral bone and synovium. Masks secondary antigenic determinants and suppresses chemotaxis. Its anti-inflammatory effect is also associated with the inhibition of the activity of lysosomal enzymes, superoxide radicals and the expression of pro-inflammatory cytokines. The latter is supported by the possibility of reducing the dose of non-steroidal anti-inflammatory drugs (NSAIDs) during the treatment of cholesterol. CS reduces the processes of resorption in the subchondral bone, suppressing the expression of RANKL and activating the synthesis of osteoprotegerin. Thus, cholesterol causes suppression of catabolic and stimulation of anabolic processes, has an anti-inflammatory effect and changes the processes of subchondral bone remodeling, which substantiates the concept of the chondromodifying effect of the drug.

GA is an amino-monosaccharide derived from chitin isolated from the shell of crustaceans. Exists in the form of 3 salts: glucosamine hydrochloride, glucosamine sulfate and N-acetylglucosamine. GA, being a monosaccharide, is the precursor of many glycosaminoglycans such as heparan sulfate, keratan sulfate, and hyaluronan. HA is an essential component of the cell membrane and cell surface, and plays a role in the formation of cartilage, ligaments, tendons, synovial fluid, skin, bones, nails, heart valves, and blood vessels. Pharmacodynamics of GA is close to that of CS. GA stimulates chondrocytes and increases their synthesis of proteoglycans (chondroprotective action). Suppresses the production of IL-1β, TNF-α and other inflammatory mediators, reduces the production of NO, lysosomal enzymes (anti-inflammatory effect).

The action of GA and cholesterol has been studied in many clinical studies. At the moment, there is sufficient evidence of the symptom-modifying and structure-modifying effects of these drugs.

McAlindon et al. (2000) conducted a meta-analysis of 15 double-blind placebo-controlled trials (6 for GA, 9 for cholesterol), the results of which indicated the effectiveness of the drugs (standardized mean difference for GA was 0.44 (95% CI 0.24- 0.64) and for cholesterol - 0.78 (95% CI 0.60-0.95)) .

Almost at the same time, T.E. Towheed et al. published data from a systematic review of 16 randomized controlled trials comparing GA and placebo (13 studies), GA and NSAIDs (3 studies) . They highlighted the considerable heterogeneity of the studies in terms of the mode of administration of GA, the classification of OA, the groups of joints assessed, and the measurement of endpoints. Fifteen studies examined HA sulfate and one studied HA hydrochloride. The authors showed that GA treatment produced a reduction in pain and improvement in joint function similar to other symptomatic drugs (simple analgesics, NSAIDs), and the safety of the drug did not differ from placebo.

A meta-analysis of cholesterol by B.F. Leeb et al., who included 7 double-blind, placebo-controlled clinical trials (703 patients) lasting from 56 to 1095 days (most studies lasted from 90 to 180 days), determined the effectiveness of cholesterol for pain therapy equal to 0.9 (95% CI 0.80-1.0), and for joint function 0.74 (95% CI 0.65-0.85).

G. Bana et al. analyzed the results of 7 randomized clinical trials of the use of cholesterol in OA of the hip and knee joints. A significant decrease in the intensity of pain in the joints and the Lequesne index was noted.

The structure-modifying effect of cholesterol has been studied in several long-term, double-blind, placebo-controlled studies in patients with OA. In a study conducted by B. Michel et al., the structural endpoint (X-ray dynamics of changes in the width of the joint space) was used as the main criterion for assessing the action of cholesterol. It was shown that cholesterol therapy at a dose of 800 mg/day for 2 years had a statistically significant stabilizing effect on the width of the joint space in patients with gonarthrosis.

In 2006, at the session of the European Antirheumatic League (EULAR), A. Kahan et al. presented results from the STOPP study, consistent with previous work. Based on the analysis of the results of treatment of CS for 2 years in 622 patients with gonarthrosis, a slowdown in the progression of the disease in patients treated with CS was shown compared with placebo groups. In a recent meta-analysis by M. Hochberg et al. (2008) reached similar conclusions.

L.M. Wildi et al. used to assess the structural-modifying effect of cholesterol magnetic resonance imaging (MRI). A one-year pilot multicenter randomized clinical trial was conducted, which included 69 patients with gonarthrosis and signs of synovitis. Patients received cholesterol at a standard dose of 800 mg/day. After 6 months in the group taking cholesterol, there was a smaller loss of total cartilage volume (p=0.03), cartilage in the lateral sections (p=0.015) and in the tibia (p=0.002); these results persisted throughout the observation period. The authors also noted a lower degree of change in the subchondral bone in the main group compared to the control group. Differences reached statistical significance 1 year after the start of the study and were predominantly observed in the lateral parts of the joint.

The use of cholesterol for 3 years in OA of the joints of the hands had a protective effect in relation to the appearance of new erosions. These data were confirmed by the results of studies by G. Rovetta et al. based on the treatment of patients with cholesterol at a dose of 800 mg / day for 2 years.

The experiment revealed synergism in the action of cholesterol and GA, which was manifested by a significant increase in the production of proteoglycans by chondrocytes when these substances were used together compared with monotherapy with each of these drugs. So, with monotherapy with cholesterol and GA, the production of glycosaminoglycans by chondrocytes increased by 32%, and with combination therapy - by 96.6%. This served as an experimental justification for the combined use of cholesterol and HA, combined preparations containing both of these substances appeared, for example, Teraflex and others.

In the United States, to evaluate the symptom-modifying effect of these drugs, a multicenter, double-blind, placebo-controlled, parallel-group clinical trial was conducted to compare the effectiveness of cholesterol, GA hydrochloride, celecoxib, a combination of cholesterol and HA hydrochloride against placebo in patients with gonarthrosis (Glucosamine / Chondroitin Arthritis Intervention Trial - GAIT), performed under the auspices of the US National Institutes of Health. The study included 1583 patients (men and women over 40 years old) from 16 medical centers with Kellgren-Lawrence stage II-III gonarthrosis and pain syndrome lasting at least 6 months. The primary end points of the study were a 20% reduction in joint pain according to the WOMAC scale after six months of treatment, the structural-modifying effect was assessed after 24 months. The results of a study evaluating the effect of drugs on the symptoms of the disease indicate that the combination of cholesterol and HA was more effective in reducing pain in the subgroup of OA patients with moderate to severe pain in the knee joints compared with placebo (79.2 and 54.3 %, respectively; p=0.002). However, the authors failed to show the structure-modifying effect of all drugs compared to placebo, only in patients with the initial stages of OA (X-ray stage II) after 2 years of treatment, a slowdown in the narrowing of the joint space was noted, although not significant. Probably, these data require detailed interpretation, since they do not agree with the previously obtained results on the structure-modifying effect, for example, cholesterol. Thus, with the combined use of cholesterol and GA sulfate, an additive effect is observed and the effectiveness of treatment increases.

Another 6-month open multicenter clinical trial also evaluated the efficacy, tolerability and aftereffect of Teraflex in patients with symptomatic gonarthrosis. The patients were randomized into 2 groups: patients of the 1st group received Teraflex 1 tablet 2 times a day for the first month, then 1 tablet 1 time a day for another 2 months. in combination with diclofenac at a dose of 75 mg / day, patients of the second group - diclofenac at a daily dose of 75 mg. By the end of the 3rd month treatment, the intensity of pain in the knee joint significantly decreased, and it remained at this level until the end of the 6th month. treatment. In the control group, there was also a positive trend in this indicator, but to a much lesser extent compared to the main group. A similar trend was noted for the functional WOMAC index.

In a study by F. Richy et al. The symptom-modifying and structure-modifying effects of the combination of HA hydrochloride and cholesterol were evaluated. Positive dynamics of the WOMAC index, normalization of the functional ability of the joints and slowing down of the narrowing of the joint space were revealed.

The impact of long-term therapy with Teraflex on the rate of radiographic progression of gonarthrosis was assessed by M.S. Svetlova. Patients were divided into 2 groups, comparable in terms of the main parameters of the disease. Patients of the main group (104 patients) took Teraflex according to the generally accepted scheme for 6 months, then the drug was prescribed in repeated courses of 2 capsules per day for 2 months. with an interval of 1 month. The total duration of therapy was 3 years. Patients in the control group (140 patients) were prescribed diclofenac 100 mg/day in combination with various types of physiotherapy. All patients underwent radiography of the knee joints in frontal, lateral and axial projections in the position of maximum knee extension. The degree of narrowing of the joint space and the severity of osteophytosis were assessed by a semi-quantitative method. X-ray progression by the end of the 1st year of therapy was detected in 8.6% of cases in the main group and in 9.2% in the control group, after 2 years of therapy - in 15.4 and 18.3% of cases, respectively, and after 3 years - in 21.4 and 32.7%.

Also M.S. Svetlova, a study was conducted in which the symptom-modifying effect of long-term (within 1 year) therapy with Teraflex in patients with coxarthrosis (CA) was evaluated. The main group included 44 patients with CA. All patients of the main group were prescribed Teraflex traditionally for 6 months, and then repeated courses of 2 capsules per day for 2 months. with a break of 1 month, the total duration of the drug was 10 months. When joint pain increased, patients took NSAIDs. The control group consisted of 28 patients with CA. Patients in the control group were recommended to take NSAIDs in combination with various types of physiotherapy. When a positive effect was achieved, NSAIDs were prescribed only with increased pain in the joints. In patients of the main group after 6 months. continuous use of Teraflex significantly decreased the severity of pain when walking and at rest, stiffness, improved the function of the affected joints. A positive result persisted after a year of taking the drug with repeated courses and significantly differed from the initial values. Against the background of treatment with Teraflex after 6 months. observations, about half of the patients were able to completely stop taking NSAIDs or significantly reduce their daily dose. In the control group after 6 months. treatment, some positive dynamics of clinical indicators was also noted, however, after 1 year, their values ​​did not significantly differ from the initial ones.

According to EULAR 2003, the use of NSAIDs and chondroprotectors in the treatment of OA is the most effective (class IA evidence). A number of Russian and foreign scientists in the course of long-term prospective observational studies have proven that joint pain in OA is one of the independent predictors of disease progression. Pain reduction is the main goal of OA treatment. The highest prevalence of OA occurs in the group of elderly and senile patients, who often have comorbidities that require drug therapy. Taking NSAIDs aggravates the course of arterial hypertension (AH), reduces the effectiveness of antihypertensive therapy, and can aggravate congestive heart failure. The development of NSAID gastropathy, NSAID enteropathy, NSAID-associated dyspepsia is well known, the increase in the frequency of which is observed in the elderly. When using GA and CS, an extremely low frequency of adverse reactions is observed. Given that the metabolism of these drugs occurs without the participation of the cytochrome P450 system, the risk of negative interactions with other drugs is unlikely. Along with the symptom-modifying and structural-modifying effects of GA and CS, this partly determines their widespread use, especially in older age groups among patients with high comorbidity and age-related changes in the functions of internal organs. The use of cholesterol and GA in OA is supported by the Russian Association of Rheumatologists, foreign rheumatological associations, EULAR and OARSI recommendations.

In recent years, a number of researchers have recommended the use of cholesterol in the complex therapy of vertebrogenic diseases of the nervous system. According to ICD-10, dorsopathies are divided into deforming dorsopathies, spondylopathies, other dorsopathies (degeneration of the intervertebral discs, sympathetic syndromes). In most cases, vertebral neurological pathology is caused by degenerative-dystrophic changes in the spine (destruction of the intervertebral discs, spondylarthrosis, stenosis of the spinal canal and intervertebral foramina) and is represented by dorsopathy. The main manifestation of dorsopathy is back pain.

It should be noted that the evidence base for the effectiveness of the use of chondroprotectors in dorsopathies is poorer than in OA of large joints, however, there are a number of publications devoted to this problem.

For the first time, CS in vertebrogenic pathology was used by K.D. Christensen et al. in 1989; in their work, the researchers demonstrated the effectiveness of cholesterol in chronic pain in the lower back.

A.V. Chebykin evaluated the effectiveness of including chondroprotectors in the complex therapy of patients with nonspecific back pain. Patients of the main group (1430 people), along with standard treatment (NSAIDs, muscle relaxants, non-drug therapy) received a combination of cholesterol (500 mg) and GA (500 mg) orally for 6 months. Patients in the control group (118 people) received only standard therapy. In the main group, there was a persistent decrease in pain on the visual analogue scale (VAS), normalization of range of motion in the joints of the spine, a decrease in the need for NSAIDs, and in some cases, refusal to take these drugs, and an improvement in the quality of life. The effect of chondroprotectors was significantly manifested after 3-4 months. treatment, increased by the 6th month. and kept for at least 5 months. after the end of therapy. In patients of the control group, with the abolition of NSAIDs and muscle relaxants, a stepwise increase in pain was observed; the index of pain syndrome after 1 year was significantly higher than in the main group.

Similar results when using chondroprotectors in the treatment of patients with degenerative-dystrophic diseases of the spine were obtained by other researchers. T.V. Chernysheva et al. evaluated the anti-inflammatory, analgesic and chondroprotective effects of cholesterol during long-term course treatment of clinically significant osteochondrosis (OC) of the lumbar spine. The efficacy and tolerability of the drug was studied in an open controlled study; The patients were divided into 2 groups (main and control) of 40 people. Patients of the main group received 100 mg of cholesterol intramuscularly every other day, the course of treatment was 20 injections; subsequent courses were carried out with an interval of 6 months. within 2 years. Patients in both groups, if necessary, took NSAIDs. In patients of the control group, NSAIDs were the only treatment for exacerbations of spinal CO. In patients of the main group, in addition to reducing the pain syndrome and the need to take NSAIDs, improving mobility in the lumbar spine, reducing the frequency and duration of exacerbations of AC, there was a significant (p<0,05) уменьшение фрагментации фиброзного кольца верхних межпозвонковых дисков поясничного отдела (L1-2, L2-3, L3-4) по данным ультразвукового исследования. Случай регенерации межпозвонкового диска у пациента, страдающего болью в спине, ассоциированной с дегенеративной болезнью диска, на фоне 2-летнего приема хондропротекторов описан также W.J. van Blitterswijk и соавт. . Таким образом, доказано не только симптом-модифицирующее, но и структурно-модифицирующее действие ХС при дегенеративно-дистрофической патологии позвоночника.

The effectiveness and tolerability of cholesterol in patients with pain in the lower back caused by degenerative-dystrophic changes in the spine and concomitant pathology of the cardiovascular system (IHD and AH) was studied by V.I. Mazurov et al. . CS was prescribed for 6 months. (in the first 20 days, 1500 mg, then 1000 mg). By the end of the 1st month treatment was noted significant (p<0,05) уменьшение интенсивности боли по ВАШ как при движении (на 27%), так и в покое (на 22%). К 6-му мес. наблюдалось достоверное (р<0,01) увеличение подвижности позвоночника по данным функциональных позвоночных проб. При динамической оценке индекса хронической нетрудоспособности Вадделя выявлено значительное повышение переносимости бытовых, социальных и спортивных нагрузок. 27% больных отказались от приема НПВП из-за отсутствия боли через 1 мес. терапии, 32% - через 3 мес., 42% - через 6 мес. Через 3 мес. после отмены ХС сохранялся его достоверный (р<0,01) клинический эффект; через 6 мес. эффект последействия препарата снизился, но показатели болевого синдрома были ниже, чем до лечения. Подавляющее большинство пациентов отметили хорошую переносимость ХС; побочные эффекты (гастралгия, крапивница) наблюдались в единичных случаях. При оценке клинического течения ИБС не было отмечено достоверных различий по частоте возникновения ангинозных болей, аритмий, выраженности хронической сердечной недостаточности с исходными данными в ходе 6-месячной терапии ХС. Через 1 мес. от начала приема ХС на фоне постепенного уменьшения потребности в НПВП констатировано снижение АД у пациентов с АГ, что позволило уменьшить среднесуточную дозу антигипертензивных препаратов. Исследователи полагают, что уменьшение потребности в НПВП при терапии ХС приводит к повышению синтеза вазодилатирующих простагландинов и простациклина, что стабилизирует течение ИБС и АГ.

Given the synergism in the action of GA and CS, a number of researchers recommend prescribing a combination of these drugs for dorsopathy. The optimal synergistic effect is achieved when using HA and cholesterol in a ratio of 5:4; it is in this proportion that these substances are contained in Teraflex. According to the prognostic model, the maximum effect of Teraflex should be expected at the initial stages of degenerative-dystrophic lesions of the spine; clinically, this means the use of the drug after the 1st recurrence of non-specific back pain, especially in the presence of symptoms of spondyloarthrosis. In this case, the course treatment has a preventive effect in relation to chronic pain. However, the drug can also be useful for a detailed picture of spondyloarthrosis; in this case, we can expect stabilization of the state and slowing down the progression of the process.

When prescribing chondroprotective therapy for dorsopathy during a painful episode, Teraflex Advance is preferred, since this drug also contains NSAIDs. After stopping the pain syndrome, it is rational to switch to taking Teraflex. In the vast majority of patients, when using Teraflex, there is a positive trend in the form of pain reduction and a decrease in neurological symptoms.

The presented data indicate that cholesterol and GA have not only symptom-modifying, but also structural-modifying properties, and they can be considered as a means of pathogenetic therapy for degenerative-dystrophic diseases of the joints and spine.

Literature

1. Jordan K.M. et al. EULAR Recommendation 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for international Clinical Studies including Therapeutic Trials (ESCISIT) // Ann. Rheum. Dis. 2003. No. 62. S. 1145-1155.
2. Leeb B.F., Schweitzer H., Montag K., Smolen J.S. A meta-analysis of chondroitin-sulfate in the treatment of osteoarthritis // J. Rheum. 2000. No. 27. S. 205-211.
3. Nasonova V.A., Nasonov E.L. Rational pharmacotherapy of rheumatic diseases. M.: Litera, 2003. 507 p.
4. Volpi N. Oral bioavailability of chondroitin sulfate (Chondrosulf) and its constituents in healthy male volunteers // Osteoarthritis Cartilage. 2002 Vol. 10, No. 10. P. 768-777.
5. Hathcoock J.N., Shao A. Risk assessment for Glucosamine and Chondroitin sulfate // Regul. Toxicol. Pharmacol. 2007 Vol. 47, No. 1. P. 78-83.
6. Alekseeva L.I., Sharapova E.P. Chondroitin sulfate in the treatment of osteoarthritis // Ros. honey. magazine. 2009. V.17, No. 21. S. 1448-1453.
7. Monfort J. et al. Chondroitin sulfate and Hyaluronic acid inhibit stromelysin-1 synthesis in human osteoarthritis chondrocytes // Drugs Exp. Clin. Res. 2005 Vol. 31. P. 71-76.
8. Caraglia M. et al. Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice // Exp. Mol. Med. 2005. Vol.37. P. 476-481.
9. Chan P.S., Caron J.P., Orth M.W. Short-term gene expression changes in cartilage explants stimulated with interleukin beta glucosamine and chondroitin sulfate // J. Rheumatol. 2006 Vol. 33. P. 1329-1340.
10. Holzmann J. et al. Assorted effects of TGF-beta and chondroitin sulfate on p38and ERK ½ activation levels in human articular chondrocytes stimulated with LPS // Osteoarthritis Cartilage. 2006. Vol.14. P. 519-525.
11. Monfort J., Pellietier J.-P., Garcia-Giralt N., Martel-Pellietier J. Biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues // Ann. Rheum. Dis. 2008 Vol. 67. P. 735-740.
12. Chichasova N.V., Mendel O.I., Nasonov E.L. Osteoarthritis as a general therapeutic problem // RMJ. 2010. V.18, No. 11. pp. 729-734.
13. Novikov V.E. Chondroprotectors // Clinical Reviews. farm. and medicines. therapy. 2010. V. 8, No. 2. S. 41-47.
14. Kwan Tat S. et al. The differential expression of osteoprotegerin (OPG) and receptor of nuclear factor kB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cell // Clin. Exp. Rheum. 2008 Vol. 26. P. 295-304.
15. Alekseeva L.I. Symptomatic slow-acting drugs in the treatment of osteoarthritis // Consilium Medicum. 2009. V.11, No. 9. S. 100-104.
16. Annefeld M. New data on glucosamine sulfate // Scientific and Practical Rheumatology. 2005. No. 4. S. 76-80.
17. Register J. et al. Glucosamine sulfate slows - down osteoarthritis progressin in postmenopausal women: pooled analysis of two large, independent, randomized double-blind placebo-controlled, prospective 3-year trials // Ann. Rheum. Dis. 2002 Vol. 61 (Suppl. 1). THU 0196.
18. McAlindon T.E., LaValley M.P., Gulin J.P., Felson D.T. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis // JAMA. 2000 Vol. 283. R. 1469-1475.
19. Towbeed T.E., Maxwell L., Anastassiades T.P. et al. Glucosamine therapy for treating osteoarthritis // Cochrane Database Syst. Rev. 2005 Vol. 2.
20. Leeb B.F., Schweitzer H., Montag K., Smolen J.S. A meta-analysis of chondroitinsulfate in the treatment of osteoarthritis // Osteoarthritis Cartilage. 1999. Vol.7 (Suppl A). Abstr. 130.
21. Bana G., Jamard B., Verrouil E., Mazieres B. Chondroitin sulfate in the management of hip and knee OA: an overview // Adv. Pharmacol. 2006 Vol. 53. R. 507-522.
22. Michel B.A. et al. Chondroitin 4 and 6 sulfatein osteoarthritis of the knee: A randomized, controlled trial // Arthritis Rheum. 2005 Vol. 52. P. 779-786.
23. Wildi L.M. et al. Chondroitin sulfate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI // Ann. Rheum. Dis. 2011 Vol. 70(6). R. 982-989.
24. Verbuggen G., Goemaere S., Veys E.M. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA // Osteoarthritis Cartilage. 1998 Vol. 6 (Suppl. A.). P. 37-38.
25. Rovetta G., Monteforte P., Molfetta G., Balestra G. A two-years study of chondroitin sulfatein erosive osteoarthritis of the band: behavior of erosions, osteophytes, pain and hand dysfunction // Drug. Exp. Clin. Res. 2004 Vol. 30(1). P.11-16.
26. Lippielo L., Grande D. In vitro chondroprotection of glucosamine and chondroitin sulfate in a rabbit model of a OA and demonstration of metabolic synergy on chondrocyte in vitro // Ann. Rheum. Dis. 2000 Vol. 59 (Suppl. 1). P. 266.
27. Lila A.M. Teraflex in the complex therapy of osteoarthritis of the knee joints and osteochondrosis of the spine // Ros.med. magazine. 2005. V.13, No. 24. S.1618-1622.
28. Clegg D.O. et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis // N. Engl. J. Med. 2006 Vol. 354. P. 795-808.
29. Richy F. et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: A comprehensive meta-analysis // Arch. Intern. Med. 2003. Vol.163. P. 1514-1522.
30. Svetlova M.S. Diagnosis and structure-modifying therapy of osteoarthritis of the knee joint // Modern rheumatology. 2012. No. 1. S. 38-44.
31. Svetlova M.S. Osteoarthritis of the hip joint: clinic, diagnosis, approaches to treatment // Modern rheumatology. 2013. No. 1. S. 46-50.
32. Rachin A.P. Evidence-based pharmacoanalytics of osteoarthritis therapy // Farmateka. 2007. No. 19. S. 81-86.
33. Kashevarova N.G., Zaitseva E.M., Smirnov A.V., Alekseeva L.I. Pain as one of the risk factors for the progression of osteoarthritis of the knee joints // Scientific and Practical Rheumatology. 2013. No. 4. S. 387-390.
34. Dieppe P., Cushnaghan J., Young P., Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy // Ann. Rheum. Dis. 1993 Vol. 52. R. 557-563.
35. Cooper C. et al. Risk factors for the incidence and progression of radiographic knee osteoarthritis // Arthritis. Rheum. 2000 Vol. 43. P. 995-1000.
36. Conaghan P.G. et al. Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study // Ann. Rheum. Dis. 2010 Vol. 69. R. 644-647.
37. Savenkov M.P., Brodskaya S.A., Ivanov S.N., Sudakova N.I. Influence of non-steroidal drugs on the antihypertensive effect of ACE inhibitors // BC. 2003. No. 19. S. 1056-1059.
38. Heerdink E.R. et al. NSAIDs associated with increase risk of congestive heart in elderly patients taking diuretics // Arch. Int. Med. 1998 Vol. 158. P. 1108-1112.
39. Page J., Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients // Arch. Int. Med. 2000. Vol.160. P. 777-784.
40. Warksman J.C. Nonselective nonsteroidal anti-inflammatory drugs and cardiovascular risk: are they safe? // Ann. Rharmacother. 2007 Vol. 41. R.1163-1173.
41. Rheumatology. Clinical guidelines / Ed. E.L. Nasonov. M.: GEOTAR-Media, 2010. 752 p.
42. Clinical guidelines. Osteoarthritis. Diagnosis and management of patients with osteoarthritis of the knee and hip joints / Ed. O.M. Lesnyak. M.: GEOTAR-Media, 2006. 176 p.
43. Tugwell P. Philadelphia panel evidence-based clinical practice guidelines on selected rehabilitation interventions for knee pain // Phys. Ther. 2001 Vol. 81. P.1675-1700.
44. Conaghan P.G., Dickson J., Grant R.L. Care and management of osteoarthritis in adults: summary of NICE guidance // BMJ. 2008. Vol.336. R. 502-503.
45. National Collaborating Center for Chronic Conditions. Osteoarthritis: national clinical guideline for care and management in adults. London: Royal College of Physicians, 2008. 316 p.
46. Zhang W. et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) // Ann. Rheum. Dis. 2005 Vol. 64. P. 669-681.
47. Zhang W. et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) // Ann. Rheum. Dis. 2007 Vol. 66. R. 377-388.
48. Zhang W. et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines // Osteoarthritis Cartilage. 2008. Vol.16. P. 137-162.
49. Zhang W. et al. OARSI for the management of hip and knee osteoarthritis: part III recommendations: Changes in evidence following systematic cumulative update of research published through January 2009 // Osteoarthritis Cartilage. 2010. Vol.18. P. 476-499.
50. Alekseev V.V. Chondroprotectors in neurology: grounds for use // Consilium Medicum. Neurology. Rheumatology. 2012. No. 9. P.110-115.
51. Alekseev V.V., Alekseev A.V., Goldzon G.D. Nonspecific pain in the lower back: from symptomatic to pathogenetic treatment // Zhurn. neurology and psychiatry. S.S. Korsakov. 2014. No. 2. S. 51-55.
52. Badokin V.V. Arthra is a model of combined symptom-modifying therapy for osteoarthritis and intervertebral osteochondrosis. Neurology, neuropsychiatry, psychosomatics. 2012. No. 2. S. 91-95.
53. Chebykin A.V. Experience in the use of chondroprotector artra in patients with back pain // Neurology, neuropsychiatry, psychosomatics. 2012. No. 3. S. 69-71.
54. Christensen K.D., Bucci L.R. Comparison of nutritional supplement effects on functional assessments of lower back patients measured by an objective computer-assisted tester // Second Symposium on Nutrition and Chiropractic. Davenport: Palmer College of Chiropractic, 1989, pp. 19-22.
55. Shostak N.A. Pain in the lower back with osteochondrosis of the spine: experience with the use of a chondroprotective drug // Ter. archive. 2003. No. 8. S. 67-69.
56. Cox J.M. Low back pain: mechanism, diagnosis and treatment. Baltimore: Williams & Wilkins, 1999. 735 p.
57. Gorislavets V.A. Structural-modifying therapy for neurological manifestations of spinal osteochondrosis // Consilium Medicum. 2010. No. 9. S. 62-67.
58. ON THE. Shostak et al. Dorsopathies - approaches to diagnosis and treatment // Difficult patient. 2010. No. 11. S. 22-25.
59. Chernysheva T.V., Bagirova G.G. Two years of experience with the use of chondrolon in osteochondrosis of the spine // Kazan Med. magazine 2009. No. 3. S. 347-354.
60. Van Blitterswijk W.J., van de Nes J.C., Wuisman P.I. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: biochemical rationale and case report // BMC Complement Altern Med. 2003 Vol. 3. URL: http://www.biomedcentral.com/1472-6882/3/2 (date of access: 03/11/2014).
61. Mazurov V.I., Belyaeva I.B. The use of structum in the complex treatment of pain syndrome in the lower back // Ter. archive. 2004. No. 8. S. 68-71.
62. Manvelov L.S., Tyurnikov V.M. Lumbar pain (etiology, clinic, diagnosis and treatment) // Ros. honey. magazine Neurology. Psychiatry. 2009. No. 20. P.1290-1294.
63. Vorobieva O.V. The role of the articular apparatus of the spine in the formation of chronic pain syndrome. Issues of therapy and prevention // Ros. honey. magazine 2010. No. 16. S. 1008-1013.

06.01.2007, 09:20

Sorry to bring up an old thread, but I have a couple of questions:
1. Are chondroprotectors effective in relatively late stages of OA (with NFS...3-4)?
2. Still, chondroprotectors by the nature of their action are biostimulants, and the elderly (who most often suffer from OA) are at risk for oncopathology, is there any data on this problem?
3. Is it worth it to use domestic chondroprotectors, which are similar in composition to foreign ones, but unlike the latter, they have not passed normal clinical trials (EBM).

06.01.2007, 13:32

1) In the late stages of OA with severe functional insufficiency, the effectiveness of chondroprotectors is very low, here it is necessary to discuss arthroplasty.
2) There seems to be no evidence that CP increases the risk of malignant neoplasms.
3) What kind of domestic HP are we talking about? By the way, what do you mean by CP - tablet glucosamine and chondroilin or i / s hyaluronic acid?

06.01.2007, 22:46

Thanks for the quick response.

06.01.2007, 22:56

I don’t think anything .. neither about the first nor about the second. I just do not know. Who dreams of injections - that hyaluronate in / s.
Whoever has nowhere to inject hyaluronate due to the absence of a joint space, let him dream of prosthetics.

06.01.2007, 23:31

Thanks for the quick response.
I meant both those and those, and plus Alflutop, unknown in composition ...
For example, what do you think about the drug Hondrolon? It is in powders for injections - and many patients simply dream of injections ... And structum and don - only in capsules

Dona is also available in ampoules. In one ampoule 2 ml of solution - 400 mg. Enter 3 times a week, one injection for 4 to 6 weeks. It is effective to combine injections with oral administration of the drug daily 1 sachet once a day.

18.01.2007, 22:28

Thanks for the quick response.
I meant both those and those, and plus Alflutop, unknown in composition ...
For example, what do you think about the drug Hondrolon? It is in powders for injections - and many patients simply dream of injections ... And structum and don - only in capsules

"Alflutop is a natural original Romanian preparation, the active principle of which is a standardized, purified (fat-free and deproteinized) extract from 4 types of marine fish.
A complex chemical analysis of the drug, performed by electrophoresis, gas chromatography and spectrophotometry, made it possible to identify the following substances that cause the anti-hyaluronidase and chondroprotective effects of Alflutop: glycosaminoglycans (chondroitin-6-sulfate) with a molecular weight of about 40,000 DA, polypeptides with a molecular weight not exceeding 50,000 DA, free amino acids, as well as trace elements-ions Na, K, Fe, Cu, Zn were identified. Alflutop has anti-hyaluronidase, anti-inflammatory, regenerative, trophic and dermoregenerative activity."
According to personal observations. effective for 1-2 degrees of osteoarthritis, especially in relation to pain. It is produced in injectable form, there are administration schemes, depending on the clinic: in case of osteoarthritis involving many joints, intramuscular administration is recommended: one ampoule (1.0 ml) daily for throughout 20 days. The course is repeated after 3 months or as directed by a doctor; in case of involvement of large joints in the process, it is recommended to / with the introduction, continued in / m, according to the following scheme:
2 ampoules (2.0 ml) intramuscularly into each affected joint - once every 3 days, for 18 days (6 injections), followed by intramuscular injection of 1 ampoule (1.0 ml) per day for 20 days.
With OA 3, the expected effect was not achieved.

18.01.2007, 22:36

At the same time, we note that the PubMed system (the button on the right at the very bottom is the field-e-znaya ...) knows only 3 articles about ALFLUTOP (2 from Russia, 1 from Ukraine) and all of them ... well, let's say, are not impressive.

23.01.2007, 04:59

Thanks for the info colleague.
Just the other day, patients asked (by email) - maybe you should take Don and Structum at the same time (in a way, like chondroitin and glucosamine together are more effective).
What do you think about this?
It is logical to turn to Teraflex, but unlike Dona and Structum, there is little information on it

23.01.2007, 08:52

maybe you should take dona and structum at the same time (in a way like chondroitin and glucosamine together are more effective). Not forbidden. Look at the information about the drug called Artra.

23.01.2007, 15:51

1. Several clinical studies have evaluated the efficacy of the combination of glucosamine with chondroitin in relation to placebo. Comparisons of these combinations with each other, as well as with monotherapy, have not been conducted, so it is impossible to draw a conclusion about the advantages of this approach.
2. A study of glucosamine hydrochloride and chondroitin sulfate (Artra) in two centers was published in Russia. The study included 90 women with gonarthrosis. But female sex is known to be a risk factor for osteoarthritis, so the results cannot be extrapolated to the entire population of patients with osteoarthritis. This study is billed as an open, randomized study. It is known that methodologically imperfect studies distort the results: in trials where the blind control method was inadequate, the treatment effect was 41% greater. In general, we can say that in relation to combined drugs, a symptom-modifying effect has been proven, but a structure-modifying effect needs to be confirmed in long-term RCTs.

23.01.2007, 17:15

PS: The topic of chondroprotector extracts has been discussed more than once. The summary should sound in the tone that these products are medicines in form (in some places still sometimes :)), but dietary supplements in content.

What do you understand by "hoods-chondroprotectors"? What drugs? :rolleyes:

29.01.2007, 02:37

Concerning "extracts from cartilages" the theme sounded repeatedly; it is enough, for example, to look in the search for "rumalon" (this drug, like all its analogues, was very popular about twenty years ago, however, it disappeared as unnecessary everywhere, except for the post-Soviet space). However, in the rest of the world, such drugs are still commercially available, of course, in the form of supplements, not medicines.

29.01.2007, 16:03

If we turn to the Russian classification, we can find the following groups of "type of drugs":

Regenerants and reparants ([Only registered and activated users can see links]) and Correctors of bone and cartilage metabolism ([Only registered and activated users can see links])

From there:

Chondroprotectors are drugs that have a beneficial effect on cartilage, thereby preventing the development of osteoarthritis, and at the same time reduce inflammation in the joint. These include the drug Dona (glucosamine sulfate).

The active substance of Dona is a natural component of articular cartilage, physiologically present in the body

I believe that the level of evidence for the effectiveness of these drugs can not be discussed. :)

I think we can discuss

However, in the rest of the world, such drugs are still commercially available, of course, in the form of dietary supplements, not medicines.

Is it? In which country?

Such are the things

30.01.2007, 03:53

In return, I can give an illustration of who and why actually sell chondroitins and glucosamines in various forms:
[Only registered and activated users can see links] ([Only registered and activated users can see links])[Only registered and activated users can see links] - dietary supplements by mail:) ([Only registered and activated users can see links])

And the list of references under the article ([Only registered and activated users can see links]) will give an idea of ​​what kind of research material on clinical studies of "natural cartilage components" belongs to (at least after 1999).

PS: However, one study has actually been done:
Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis. ([Only registered and activated users can see links])
However, when discussing the merits of the case, one should pay attention to the fact that the positive results obtained in it, again, do not relate to drugs based on cartilage components, but to dietary supplements containing them.

30.01.2007, 08:02

Dear colleagues! Unfortunately, I could not find the specific discussion indicated in your post ... I would appreciate a link that helps clarify who exactly took part in the discussion. :)

In return, I can give an illustration of who and why actually sell chondroitins and glucosamines in various forms.

It's better to quote from respected guides instead;)

P.S. As for who and what contains, the following law is taught in Russian schools:

The law of the constancy of the composition of substances - every chemically pure substance, molecular structure, regardless of location and method of preparation, has the same constant composition.

30.01.2007, 09:32

Thank you very much for the information that books are sold on Amazon - I would never have guessed it myself. :cool:
It would be even more pleasant to receive an answer from you to the question, where did you meet a different attitude towards the products under discussion, rather than recognizing them as dietary supplements?
I don't know what made you deem disrespectful the research cited in NEJM, by the way, which was originally designed to support your point of view (didn't you like the conclusions in this trail and the reviews in articles on the topic at the bottom of the text?).
Message from Dr.
P.S. As for who and what contains, the following law is taught in Russian schools:
The law of the constancy of the composition of substances - every chemically pure substance, molecular structure, regardless of location and method of preparation, has the same constant composition.
Does this also apply to cartilage extracts? :)

In general, the situation can be described as follows: Oral glucosamine is commonly used for the treatment of osteoarthritis. Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine may help to rebuild cartilage and treat arthritis. Its use as a therapy for osteoarthritis appears safe, but there is conflicting evidence as to its effectiveness (Laverty et al., 2005; Biggee et al., 2005).From a clinical perspective, the administration of glucosamine did not prevent fibrillation and/ or erosions of the articular cartilage in all of the treated animals, and no effects were detected in the medial joint compartments. (This is a statement from the first author working on animal models).
With an intensification of research in this field come new clinical and basic science data, sometimes with surprising results. These confirm the considerable potential for a role of nutritional interventions for osteoarthritis, but they emphasize the need for systematic scientific evaluation of the claims made for such products. (From a speech by a second author studying the effects of nutritional supplements on humans.)

30.01.2007, 10:30

Dear colleagues,

Perhaps the most recent (November 2006) on the topic from here:

Comparative Effectiveness and Safety of Analgesics for Osteoarthritis: Executive Summary From AHRQ

Agency for Healthcare Quality and Research (AHRQ)

Glucosamine and chondroitin

In one large, good-quality trial the combination of pharmaceutical-grade glucosamine hydrochloride plus chondroitin (not currently available in the United States) was not superior to placebo among all patients studied. Neither glucosamine nor chondroitin alone was superior to placebo. In an analysis of a small subgroup of patients with at least moderate baseline pain, there was a modest benefit for pain relief, but this did not appear to be a preplanned analysis.

Systematic reviews of older trials found glucosamine modestly superior to oral NSAIDs and placebo in most trials, but there was some inconsistency between trials, most trials had some flaws and results may not be directly applicable to the United States because the positive trials primarily evaluated pharmaceutical- grade glucosamine available in Europe.

Only 2 of 20 placebo-controlled trials assessed effects of glucosamine on radiological disease progression. One fair- and one good-quality trial found pharmaceutical-grade glucosamine superior to placebo for progression of knee joint space narrowing over 3 years.

Glucosamine and chondroitin were generally well tolerated and no serious adverse events were reported in clinical trials.

30.01.2007, 16:42

It would be even more pleasant to receive an answer from you to the question, where did you meet a different attitude towards the products under discussion, rather than recognizing them as dietary supplements?

Now let's see who we have on the list of famous dietary supplements dealers

Harrison's Principles of Internal Medicine 16th Edition

Several studies have shown glucosamine to be superior to placebo and comparable to NSAIDs37 with respect to efficacy in patients with knee OA, and to have a better safety profile than NSAIDs. However, the efficacy of neither glucosamine nor chondroitin sulfate has been examined in large, well-designed placebo-controlled trials. In a meta-analysis of randomized, double-blind, placebo-controlled studies of glucosamine and chondroitin sulfate, moderate symptomatic benefit was demonstrated for both agents, relative to placebo. In studies of chondroitin sulfate, symptomatic improvement was apparent as long as 12 months after the onset of treatment. However, when only high-quality or large-size trials were considered, the effect sizes for glucosamine and chondroitin sulfate were diminished, i.e., the better the study design, the smaller the therapeutic benefit. In three recent randomized, double-blind trials in which the manufacturer did not have access to the raw data and was not involved in data analysis, glucosamine was no more effective than placebo.

The question arises whether glucosamine is "chondroprotective." Results of two recent randomized clinical trials have led to the suggestion that glucosamine not only improves joint pain in patients with knee OA1, but protects against articular cartilage damage, based upon analyzes of changes in joint space width in the standing anteroposterior (AP) knee radiograph . However, concern has been expressed about the interpretation of the results of these studies because of the limitations of the radiographic methods employed. A multicenter study supported by the National Institutes of Health, the Glucosamine Chondroitin Arthritis Intervention Trial (GAIT), is in progress which is comparing glucosamine, chondroitin sulfate, the combination, and celecoxib with placebo in patients with knee OA. Although the primary outcome measure is joint pain after 6 months of treatment, approximately 50% of the subjects will be maintained on treatment for 2 years and radiographs obtained at baseline will be compared with those obtained after 1 year and 2 years of treatment.

Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition (quoted above)

Diagnosis and treatment of adult degenerative joint disease (DJD) of the knee.

GUIDELINE STATUS
This is the current release of the guideline.

The nutraceutical agents glucosamine (1500 mg qD) and chondroitin sulfate (1200 mg qD) are widely available and tried by patients. A systematic quality assessment and meta-analysis of double-blind, placebo-controlled trials that tested glucosamine or chondroitin for hip or knee osteoarthritis concluded that some degree of efficacy appears probable for these preparations. It is reasonable to recommend a 60-day trial of the combination of glucosamine and chondroitin sulfate, leaving the decision for ongoing (continuing) therapy to patients on an individual basis.

This is where I want to make a small summary - dietary supplements, as you know, do not have the right to treat and prevent anything, therefore, considering them as a TREATMENT (one cannot speak of great efficiency, but also completely equate with placebo too) these substances do not make dietary supplements. Registered as medicines in many countries

I gave the exact quote of what seemed disrespectful to me, it was a link to the forum. I know the study, I respect it :)

PS: Unfortunately, in a different aspect, these substances have not been considered by anyone for seven years (unless, of course, one refers to Romanian sources).

Seven years? What a shame! We should write to these people:

Copyright © 2007 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher

They don't know :(

31.01.2007, 03:27

They are not in the know: (Meanwhile, the text you cited indicates that they are still in the know:
The nutraceutical agents glucosamine (1500 mg qD) and chondroitin sulfate (1200 mg qD) are widely available and tried by patients. Please note - it says so here: "nutraceutical agents", which means "food additives", i.e. "dietary supplements". ;)

01.02.2007, 16:19

Meanwhile, the text you cited indicates that they are still in the know:
Please note - it says so here: "nutraceutical agents", which means "food additives", i.e. "dietary supplements". ;)

The texts cited by me (and you) testify to therapeutic effectiveness. And dietary supplements, by definition, cannot have it:(. Therefore, these substances are considered in various manuals exclusively in the "treatment" section, and not in "make up for the cartilage deficiency in yourself if you eat little jelly";)

02.02.2007, 07:05

And since no effectiveness in the action of glucosamines, chondroitins and related substances has been proven, all these substances, regardless of whether they are called chondroprotectors or simply bio-active amino sugars, are made from cow cartilage or shrimp chitins, sold for consumption by patients with arthritis or just "for all diseases", are "dietary supplements", "nutraceutical agents", "Alternative Medicine pills" and similar empty shells, always meaning dietary supplements, only dietary supplements and nothing but dietary supplements (out of touch with what is reprinted in Harrison from editions for decades). :rolleyes:
Perhaps the review posted by S. Barrett on his anti-charlatan site ([Only registered and activated users can see links]) will be more convincing.

Glucosamine / Chondroitin Sulfate ([Only registered and activated users can see links])

GLUCOSAMINE: Review of its effectiveness in treating
knee osteoarthritis ([Only registered and activated users can see links])

03.02.2007, 14:15

Quite the opposite - indicating a lack of evidence of effectiveness - is the usual testing of supplements with the ephemeral hope of pushing them into the drug section.

Yes? Have a design complaint? To the magazines that published them? To the American manuals on OA?

And since no effectiveness in the action of glucosamines, chondroitins and related substances has been proven

Strictly speaking, this is not entirely true (c) Alon. More specifically, a deliberate lie.

Who am I quoting for?

See Related Guideline from CURRENT Practice Guidelines in Primary Care 2006

Analgesic and Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) (see Table 5–5) are more effective (and more toxic) than acetaminophen for osteoarthritis of the knee or hip. Their superiority is most convincing in those with severe disease. Patients with mild disease should start with acetaminophen (2.6–4 g/d). Glucosamine and chondroitin sulfate are also effective and safe for knee osteoarthritis; glucosamine may even reduce the progression of knee osteoarthritis. NSAIDs should be considered for patients who do not respond to acetaminophen, chondroitin sulfate, and glucosamine. (See discussion of NSAID toxicity in the section on treatment of rheumatoid arthritis.) High doses of NSAIDs, as used in more inflammatory arthritides, are unnecessary.

True, chondroprotectors, apparently, like all other drugs;) do not slow down the progression of OA. Nevertheless, in patients with OA, who have a rather meager choice - paracetamol, COX2 inhibitors or tramal + / paracetamol, chondroprotectors quite honestly occupied their therapeutic niche. After all, what is important for a practical doctor? Using the data of modern and qualitative research, treat a specific patient, achieving a minimum of side effects. Therefore, NOBODY, either in the USA or in Russia, WILL JUDGE me or anyone else for prescribing artra or structum.

Produced from cow cartilage or shrimp chitin, sold for consumption by patients with arthritis or simply "for all diseases", are

And warfarin is generally rat poison, and cutlets are balls from the corpses of dead animals:eek:

(out of touch with what has been reprinted in Harrison from edition to edition for decades)

Well, it’s in vain that you judge the respected leadership in such a way. However, especially for you, I quoted studies and guidelines from 2006 and 2007 (and some of you yourself)

(See "background"; from history

Thanks, I'd better look at the manual in which they write background: D

In some places in Europe, they still remain a type of medicine ...)

Yes, somewhere in most of the world in the most civilized countries. I wonder how you can inflate an argument out of nothing :D

03.02.2007, 22:32

Have a design complaint? To the magazines that published them? To the American manuals on OA? No complaints. There is only one question: name the specific chondroprotector listed in the guideline you found or in the same Harrison, which would be determined by its publishers as a medicine, and not as a dietary supplement.

PS: NOBODY, neither in the US nor in Russia, WILL JUDGE me or anyone else for prescribing artra or structum. It is not customary to condemn a doctor for prescribing bioadditives. The only thing is that in Russia you can call it "prescribing drugs", and in the USA you will have to specify that you recommend "buying a supplement (dietary supplement in our opinion)". :)

04.02.2007, 14:12

No complaints.

Excellent, no complaints, evidence - yes, clinical recommendations - are present (if you forgot which ones - I will quote the guide) - for me, as a practical doctor who adheres to the principles of medicine based on proven evidence, this is quite enough

There is only one question: name the specific chondroprotector listed in the guideline you found or in the same Harrison, which would be determined by its publishers as a medicine, and not as a dietary supplement.

I will answer it right after you find me any brand name of any other drug in the same guideline :). Let me remind you that brand names are not usually indicated in decent manuals. Specific substances are indicated - glucosamine and chondroitin. Where can I get medicine?

Molecule(s) Chondroitine sulfate

Classe therapeutique Antiarthrosique

Laboratoire(s) Pierre Fabre

Indications STRUCTUM est utilisé dans le traitement des manifestations de l "arthrose.

Informations pratiques Delivere sans ordonnance.

Mode d "action Cette molécule inhibe l"élastase, enzyme responsable de la dégradation du cartilage, et favorise la synthése de cartilage.

Effets secondaires Des manifestations cutanées allergiques, des nausées ou des vomissements ont été observés avec STRUCTUM.

Contra-indications /
Précautions d "emploi STRUCTUM est contre-indiqué en cas d" allergie à l "un des constituants et chez l" enfant de moins de 16 ans.

En cas de grossesse ou d "allaitement, ne prenez STRUCTUM que sur avis medical.

Interactions
medicamenteuses Pas d "interaction repertoriee.

Surdosage En cas de doute, contactez rapidement votre médecin traitant ou le center antipoison le plus proche.

PS: It is not customary to condemn a doctor for prescribing bioadditives. The only thing is that in Russia you can call it "prescribing drugs", and in the USA you will have to specify that you recommend "buying a supplement (dietary supplement in our opinion)". :)

But I don’t live in the USA and the FDA’s fantasies are not a decree for me :). My job is to treat specific people, professing the principles of EBM. In Russia and Europe there are medicines containing glucosamine +/- chondroitin and my conscience is clear

05.02.2007, 02:47

Who am I quoting for?

See Related Guideline from CURRENT Practice Guidelines in Primary Care 2006 Indeed, for those who

FDA fantasies are not a decree for me The position is not new and occurs periodically on the forum (everyone knows what among the adherents).

In Russia and Europe there are medicines containing glucosamine +/- chondroitin and my conscience is clear No one encroaches on your conscience - this is your own business. It will not be affected if you find a lot more like "drugs in Russia and Europe", for example, nootropics and vitamins.

Excellent, no complaints, evidence - yes, clinical recommendations - are present (if you forgot which ones, I will quote the guide)
Why quote something that is not a decree for you? ;) It is better to re-read the articles to which we have "no complaints". It clearly states that the results of the studies revealed insufficient reliability of data on possible effectiveness and require additional research ([Only registered and activated users can see links]).

This is the level of research that allows the production of relevant drugs in the form of dietary supplements and does not allow them to be considered drugs (unless, of course, they are produced in Russia and a number of European countries with rudimentary evidence-based legislation in the pharmaceutical sector).

05.02.2007, 17:57

Why quote something that is not a decree for you? It is better to re-read the articles to which we have "no complaints". It clearly states that the results of the studies revealed insufficient reliability of data on possible effectiveness and require additional research ([Only registered and activated users can see links]).

Well, what does the FDA have to do with it, my business is evidence. Please note that it's me, a wild Russian, quoting you modern guides, manuals, etc., and you offer me to master "anti-charlatan" articles whose authors cannot write the word background correctly :) (I don’t have an article in nejm in view)

And a number of European countries with rudimentary evidence-based legislation in the pharmaceutical sector).

Is this about France? Hard:). And how did you like this quote from the current guide (): "It is reasonable to recommend a 60-day trial of the combination of glucosamine and chondroitin sulfate"? "This is not a delivery for you, this is the United States of America (c)" :)

Still, it turns out that these substances are an example of dietary supplements that have proven their therapeutic effect. Unfortunately, you were mistaken when you wrote that you had already lost interest in them for 7 years;), as well as you were mistaken that they are called medicines "somewhere else" :).

06.02.2007, 04:21

Still, it turns out that these substances are an example of dietary supplements that have proven their therapeutic effect. That is, do you still agree that these substances are officially considered dietary supplements? Otherwise, it somehow turns out illogical: you refer to books - you quote, but about the official situation in the territory where the books were printed, i.e. about conclusions and results - forget to mention.
You were mistaken when you wrote that you have already lost interest in them for 7 years;) I didn’t say that everyone lost interest - BAD dealers are very interested. :)

Is this about France? Hard
Nothing, France with its powerful homeopathy, vitamin therapy and nootropic treatment does not read like that.
Evidence is my business. If you are talking about the French version of Evidence, then you can add Tanakan, Magne-B6, and much more, "proven in France" and loved in the post-Soviet space, to the chondroprotectors.

06.02.2007, 18:31

That is, do you still agree that these substances are officially considered dietary supplements? Otherwise, it somehow turns out illogical: you refer to books - you quote, but about the official situation in the territory where the books were printed, i.e. about conclusions and results - forget to mention.

And now let me remind you how the topic began;). The topic began with the fact that I criticized this judgment: “PS: The topic of chondroprotector extracts has already been discussed more than once. content".

I gave the necessary evidence to make it clear that they are still considered dietary supplements somewhere and sometimes (I'm not such a great fan of the USA to consider them most of the world;)), and in the rest of the world they are medicines. Which does NOT EXCLUDE the need for post-marketing research.

Indeed, I took the evidence that plays into the hands of chondroprotectors from American manuals because they are more convincing, and their authors are traditionally the most careful in their conclusions and judgments, which I like. If necessary, I can give publications from other countries: D

Of course, it is surprising that, despite the numerous references in various manuals in the "TREATMENT" section, they have not yet been classified as medicines, but what to do - time will tell.

You are talking about the French version of evidence, then you can add tanakan, and magne-B6 to chondroprotectors, and much more, "proven in France" and loved in the post-Soviet space.

This is not a variant of evidence at all, this is an annotation for a drug produced by Pierre Fabre: D Just to show the medicinal origin

11.02.2007, 22:00

I carefully read the discussion ... That's how long, ugly and painfully the truth is born! :)

17.02.2007, 19:26

sorry I don’t speak Latin, I probably missed a lot

01.04.2007, 23:01

02.04.2007, 07:00

So, Malysheva was right about chondroprotectors in the program "Health", in vain, it turns out, I paid 3 thousand :(. It's a shame. A sick person has money to spend besides dietary supplements.

I don’t know what Malysheva said there, but did you definitely read everything well? :rolleyes:

02.04.2007, 08:34

The question of the possibility of using glucosamines and chondroitin sulfates was considered during the development of these clinical guidelines, however, no grounds were found for their inclusion in the list of therapeutic measures (see section "Treatment", paragraph 12). :rolleyes:

DISEASE/CONDITION(S)

Osteoarthritis of the knee

GUIDELINE CATEGORY

Diagnosis
Evaluation
management
treatment

CLINICAL SPECIALTY

Family practice
internal medicine
Orthopedic Surgery
Physical Medicine and Rehabilitation
Rheumatology

INTENDED USERS

GUIDELINE OBJECTIVE(S)

To guide qualified physicians through a series of diagnostic and treatment decisions in an effort to improve the quality and efficiency of care in patients with osteoarthritis of the knee

TARGET POPULATION

Adults (skeletal mature individuals) with confirmed osteoarthritis of the knee
Note: The guideline does not address the treatment of children or the skeletally immature.

INTERVENTIONS AND PRACTICES CONSIDERED

Differential diagnosis of osteoarthritis of the knee based on patient history and physical findings

Treatment/Management

Analgesics (e.g., acetaminophen) or nonsteroidal anti-inflammatory medications (NSAIDs), including cyclooxygenase-II (COX-II) inhibitors
Activity modification
Ongoing monitoring of complete blood count, renal and liver function tests, and stool guaiac
Ongoing assessment of response to treatment, with medication change as needed
Radiography, including standing anteroposterior (AP) view, lateral view, tangential view of the patella-femoral joint ("sunrise" view), and standing posteroanterior (PA) view
Patient education (counseling about weight loss, avoidance of aggravating activities, and support groups)
Use of durable medical equipment (e.g., assistive devices, modified footwear, bracing)
Physical therapy including general conditioning, muscle strengthening, and range of motion
Aspiration of synovial fluid to assess for infection
Arthrocentesis with intraarticular steroid injection
Viscosupplementation
Glucosamine and chondroitin sulfate treatment (considered but no recommendation given) ;)
Referral to musculoskeletal specialist
MAJOR OUTCOMES CONSIDERED

Patient satisfaction with treatment and progress
Symptomatic relief (control of pain)
range of motion
physical functioning
Complications associated with treatment

02.04.2007, 09:13

I don’t know what Malysheva said there, but did you definitely read everything well? :rolleyes:
Yes, I read it very carefully. What was not clear - re-read. True, I don’t know foreign languages, but it’s written in Russian enough to understand that cartilage is not formed - drink, don’t drink.

Very interesting and persuasive conversation of course... :D
as if messages from outer space came - 2 studies ...

Here you can see the table of the same study (just clearer). 44 page

In the first subgroup, the result for ghx is higher than in the group taking celecoxib by 10 points, and than in placebo by 25 (!) points.
So, to put it mildly, they twitched a little. (In the program)

15.04.2007, 01:06

No, uv. April, the slide data is fully consistent with the conclusion made in the program:
only anecdotal inconsistent results in pain reduction in individual studies speak inconclusively about some possibly present analgesic effects (generally much less noticeable than with standard treatment) - and nothing more. :D
Read carefully!

15.04.2007, 08:14

No, uv. April, the slide data is fully consistent with the conclusion made in the program

I am a terribly attentive reader and listener :)

In fact, there are no conclusions in the transmission, there is an error on the error and the style of the store on the couch, visibility and everything else. I will not list everything.

Well, for example - "it is proved that there will be no analgesic effect."
No matter how vague the conclusion of such evidence is, this particular study does not provide. It would be fair to say that rx again showed an analgesic effect comparable to standard therapy, and in some subgroups more pronounced compared to standard therapy and placebo. (So the numbers are simple, nothing personal) And therefore, to add that standard therapy did not show itself very well.

And what kind of spenders are these Americans, spending money on research of obviously large molecules ...: D

15.04.2007, 20:51

15.04.2007, 20:59

Scared to death. Made the earth eat

Lies! They said that stabbing a Russian seafood cocktail in the asses of patients, which has no evidence base, is not evidence-based medicine and therefore it has no place on RMS: D

And so, as you can see, I also believe that: "It is reasonable to recommend a 60-day trial of the combination of glucosamine and chondroitin sulfate".

P.S. You are a cardiologist, why should you treat "acute chondrosis"? :)

15.04.2007, 21:07

15.04.2007, 21:47

FROM THE HOLE: as it turned out, treatment-resistant hypertension ceases to be resistant after 20 injections of alflutop .... holy ... holy ... holy ... \ climbed even deeper

No, you just inject into bioactive points :)

By the way, I also occasionally prescribe "combination of glucosamine and chondroitin sulfate". But I am very skeptical about the Romanian ear:cool:

15.04.2007, 22:51

With the complex therapy of alflutop, condras ... excuse me, chondroitin and glucosamine, I achieve restoration of patency in the vertebral arteries in 3-4 months, which solves the problem of refractory hypertension. Everyone is having fun now!

15.04.2007, 22:56

Well, you confirm the "restoration of patency" with a blind doppler ...;) That's the whole point.

15.04.2007, 23:07

Dear colleagues! I am very surprised by the situation that has arisen in this topic. By now, we are trying to argue about things that are simply obvious and have long been decided. Let's turn to the study, which was actually discussed in the TV show.
Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) Study Results ([Only registered and activated users can see links])

The study was organized due to the fact that the previous ones gave mixed results about the possibility of an analgesic effect (the only one that was still discussed at that time!).

Based on the results, it was concluded:
Overall, there were no significant differences between the other treatments tested and placebo.

There is no significant difference between these drugs and placebo.

This is the reason why no one includes chondroprotectors in any guidelines (see the previous post about how the Association of Surgeons found them useless) ...

What else can be discussed here? :confused:

15.04.2007, 23:35

This is the reason why no one includes chondroprotectors in any guidelines.

Dear Semen Nikolaevich,

Literally the following:

The American Pain Society recommends that adults with osteoarthritis be encouraged to take 1,500 mg of glucosamine daily as a dietary supplement but does not specifically recommend it as pharmacological management for pain.

Patients should be advised to take 1,500 mg of glucosamine daily, either once daily or in divided doses three times daily, and to continue therapy for at least four to eight weeks to allow for onset of benefit.

15.04.2007, 23:50

So this is exactly what, dear Vadim Valerievich, what I write about here all the time: chondroprotectors are dietary supplements, and recommendations for their use are given in the same way as in relation to any dietary supplements, not considering this drug therapy! :)

Results: A total of 212 patients were enrolled in the study (106 assigned to each group). The baseline characteristics were similar for the 2 groups. The mean age of the patients was 66 years, and about 80% were women. Only 71 patients (67%) in the glucosamine group and 68 (64%) in the placebo group completed the 3 years of follow-up. Intention-to-treat analysis revealed that the mean joint-space narrowing was –0.06 mm in the glucosamine group and –0.31 mm in the placebo group, for a difference of 0.24 mm (95% confidence interval 0.01 to 0.48, p = 0.043) . The minimum joint-space narrowing was –0.07 mm with glucosamine, as compared with –0.40 mm with placebo, for a similar difference of 0.33 mm (95% CI 0.12 to 0.54, p = 0.003). A preservation of about 0.3 mm in joint-space width over 3 years may not seem clinically significant, but the authors cite a rate of natural joint-space narrowing of –0.1 mm per year in other studies. The change in overall symptom score using visual analogue scales was –11.7% with glucosamine and 9.8% with placebo, for a difference of –21.6% (p = 0.02). Glucosamine was well tolerated.

Commentary: Although this was described as a double-blind study, there were no data on the success of allocation concealment, a criticism of earlier studies of glucosamine.2 If patients knew their treatment assignment, then the subjective perception of symptom relief with glucosamine may have been exaggerated. The measurements of joint-space narrowing, however, were objective and raise the possibility of a disease-modifying effect.

16.04.2007, 12:52

16.04.2007, 19:48

EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis ([Only registered and activated users can see links])
SYSADOA (glucosamine sulphate, chondroitin sulphate, ASU, diacerein, and hyaluronic acid) have symptomatic effects and may modify structure
SYSADOA is a generic term used for symptomatic slow acting drugs for OA, and includes glucosamine sulphate and related compounds, chondroitin sulphate, and diacerein. There is wide variability throughout Europe in the use of these drugs and how they are classified. In the United Kingdom, for instance, they are classified as a health food supplement rather than a prescribable drug, are available only over the counter, and are very widely self administered. Those SYSADOA (for example, glycosaminoglycan polysulphates) that are no longer in use throughout Europe have not been included in this analysis. The other products have been assessed individually.

Both chondroitin sulphate and glucosamine sulphate have been the focus of a meta-analysis, including all studies up to 1999.61 This report concluded that trials of chondroitin and glucosamine compounds demonstrated moderate to large effects on pain and disability in OA compared with placebo; however, these effects may have been exaggerated by publication bias. These products are also safe and associated with few side effects.

In summary, there is evidence to support the efficacy of HA in the management of knee OA both for pain reduction (1B) and functional improvement (1B). However, although pain relief may be obtained for several months, rather than for several weeks as with steroid, this benefit may be offset by its slower onset of action and by the requirement of a course of 3–5 weekly injections with the logistical and cost issues that that entails. There is minimal evidence for a role in disease modification. The term SYSADOA covers a range of agents. There is growing evidence to support the use of two of these agents for their symptomatic effects—namely, glucosamine sulphate (1A) and chondroitin sulphate (1A), but for the others the evidence is weak or absent. Chondroprotectors, at least with glucose and chondoitin, are drugs (drugs), which in some countries are available only as dietary supplements, are present in the above-cited European guide with an indication of the level of evidence.

16.04.2007, 20:00

There is data on the effect of chondroprotectors on the structure of the affected joints. With varying degrees of persuasiveness, studies have shown a slowdown in the progression of osteoarthritis.
Here is the latest review on glucosamine - Current role of glucosamine in the treatment of osteoarthritis ([Only registered and activated users can see links]) Jean-Yves Reginster, Olivier Bruyere and Audrey Neuprez. Rheumatology (Oxford). 2007 Mar 31 Results. Despite multiple controlled clinical trials of the use of glucosamine in OA (mainly of the knee), controversy on efficacy related to symptomatic improvement continues. Differences in results originate from the differences in products, study design and study populations. Symptomatic efficacy described in multiple studies performed with glucosamine sulphate (GS) support continued consideration in the OA therapeutic armamentarium. The most compelling evidence of a potential for inhibiting the progression of OA is also obtain with GS. Conclusions. GS has shown positive effects on symptomatic and structural outcomes of knee OA. These results should not be extrapolated to other glucosamine salts in which no warranty exists about content, pharmacokinetics and pharmacodynamics of the tablets. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis ([Only registered and activated users can see links] ) - a study, of course, with a mighty (c) design, and it must be admitted that its result is generally negative. However, here are a few quotes from the full text - Exploratory analyzes suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain Although the results for glucosamine did not reach significance, the possibility of a positive effect in the subgroup of patients with moderate-to-severe pain cannot be excluded, since the difference from placebo in the OMERACT–OARSI response rate approached significance in this group. Treatment with chondroitin sulfate was associated with a significant decrease in the incidence of joint swelling, effusion, or both. In Russian, there is a positive result in a subgroup of patients with severe pain who took the combination of glucosamine + chondroitin. Treatment with chondroitin was accompanied by a significant reduction in the incidence of joint swelling.

This study has a number of limitations -
1. Astronomically high placebo effect - 60%. Not every effective drug can overcome this barrier.
2. In this study, glucosamine hydrochloride was used, which is very strange, because. the strongest evidence base is for glucosamine sulfate.
3. Most patients (78%) had mild pain syndrome. Analysis of the primary outcome in the subgroup of patients with mild pain showed even smaller treatment effects, with the rate of response ranging from 8.6 percentage points higher in the celecoxib group to 1.9 percentage points higher in the glucosamine group than in the placebo group. None of the differences were significant. Results for the primary outcome in this stratum, which included 22 percent of the patients in the trial, indicated that combined treatment was significantly more effective than placebo (24.9 percentage points higher, P=0.002). That is, if all patients in the study had a pronounced pain syndrome, the result of the study could be positive.

17.04.2007, 03:35

The fact that all researchers come to the conclusion "There seems to be an effect, only some kind of subtle one" and "We need to continue research - then, you see, we will soon prove effectiveness" - this is a standard situation in all studies devoted to dietary supplements.
By the way, I don’t see much difference between the phrases “Chondroprotectors, at least glucosamine and chondroitin are drugs (drugs), which in some countries are available only as dietary supplements” and “Chondroprotectors are dietary supplements considered medicines in some countries.”
I believe that taking any dietary supplement at random, we can always find on the globe a country in which this drug is considered a medicine (drug). :)
By the way, in the Belgian study, for some reason, I did not find a comparison group (probably, I read it inattentively ...). That is, there are still claims to the design ...
As for the recommendations of the European Antirheumatic League (in fact, this is just a litho-review on knee arthrosis), they simply collect everything that has ever been used in the treatment of OA. By the way, EULAR draws the only conclusion - each country can choose from the above list of treatment methods what it likes (to whom chondroprotectors, to whom - laser therapy :)). By the way, the working group for the preparation of this document met in the UK - the result in the country of publication is already known to everyone. Thus, these "recommendations" cannot be considered an official document, on the basis of which doctors should choose treatment tactics.

17.04.2007, 06:13

Well, what can be found in the listed articles that is new?
The fact that all researchers come to the conclusion "The effect, it seems, is there, only some kind of elusive"

It's just that there are specific figures behind these speech turns. Let's say, behind the words "generally much less noticeable than with standard therapy", only 3.4 points of the difference are hidden.
The Belgian study was taken at random and it seems not a full text, there are a lot of studies of these .. and there will be more. There they simply did not know that the topic was already closed and the first stage was over. Or maybe they decided to entertain the patients, not everyone should drink placebo. .. :)

And, by the way, also according to this study, which we rambled on here, about 1358 people. There is a completely normal subsample, correctly divided into 5 groups of 70 heavier people, that is, this can be deduced as a study. In this group, the jump in gh to 79 %. The sample is 354 people. And for placebo there is 54%. (That is, on heavier placebos, apparently it did not work)

17.04.2007, 06:38

You correctly noticed this. After reviewing the slide #44 you mentioned, there are no more questions left. First of all, you should look at the overall result in the All patients group (N=1538): NSAIDs give a very weak effect, and chondroprotectors - these do not differ at all from placebo. :)

17.04.2007, 06:41

Thus, these "recommendations" cannot be considered an official document, on the basis of which doctors should choose treatment tactics. For me, only the recommendations of the local Ministry of Health can be an official document. So, what does the Ministry of Health of Ukraine recommend to treat osteoarthritis with?

MINISTRY OF HEALTHY "I OF UKRAINE" Order dated 05.05.2003 No. 191 On the approval of temporary state social standards for the provision of medical care in the specialty general practice-family medicine. "

Treatment:
1. Modification of the way of life
mode
3. Diet No. 5-15
4. Medication:
-NPZP (systemic and mystic forms) -GCS
-Basic therapy
a) chondroprotectors b) homotoxicological
-antioxidants
- reduction of microcirculation
- enzyme therapy
5.-exercise
6. physiotherapeutic procedures

Recommended drugs:
meloxicam (movalis), 7.5 mg
-nimesulide (mesulide), 100mg
- diclofenac 50; 100 mg
- local treatment with creams and gels - fastum-gel, long-term cream, felden-gel
Dimexide
- Kenalog 40 - 10-40 mg
- arteparone 50 mg IM
50 mg i.v.
-glucosamino sulfate 1500 mg
- Structum 250 mg
-Zell T 2.2ml
-traumeel C - (table)
vitamin E
(pentoxifyline (trental, agapurine) 100mg
vobenzym
diacerin (ART-50), 50 mg

There is an evidence base for hodroprotectors, albeit a weak one. There is evidence of both a symptomatic effect and an effect on the progression of the disease (especially for glucosamine sulfate). The safety is well proven. In the recommendations of the American and British, in "Harrison" they are mentioned as means acceptable for use. The range of methods for treating osteoarthritis is extremely narrow in my practice (I am a simple local therapist). I do not do intra-articular injections, joint prosthetics are not available to my patients, I will not prescribe drugs to such patients (tramadol is on our list of drugs). What remains? How to treat osteoarthritis? Only NSAIDs? I used, I use, and I will use chondroprotectors (glucosamine, chondroitin). I see good reasons for this.

Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip ([Only registered and activated users can see links]) No robust evidence supports the use of chondroitin in today's Annals of internal medicine osteoarthritis. Large-scale, methodologically sound trials indicate that the symptomatic benefit is minimal to nonexistent. The effect of chondroitin on joint space narrowing was assessed in only a few trials. This effect is likely to be small, and its clinical significance is uncertain. In patients with low-grade osteoarthritis, the use of chondroitin should be restricted to randomized, controlled trials. For patients with advanced osteoarthritis, a clinically relevant benefit is unlikely and the use of chondroitin should be discouraged.
This meta-analysis does not negate the positive meta-analysis on glucosamine published last month (Current role of glucosamine in the treatment of osteoarthritis ([Only registered and activated users can see links])), nor does it negate the positive effects of the combination of chondroitin with glucosamine proven in some studies. This meta-analysis suggests that further research is needed in this area.

17.04.2007, 06:47

You correctly noticed this. After reviewing the slide #44 you mentioned, there are no more questions left. First of all, you should look at the overall result in the All patients group (N=1538)

Have you looked at all? :)
And just like that, you have to watch it right? Well, I'll try ....: D:)

17.04.2007, 10:28

Still, what is more humane, to relieve pain with a substance of unknown action, which has practically no side effects, or to have an anti-inflammatory effect, risking serious complications, which have already been mentioned. I agree, provided that the effectiveness and safety of this substance is proven! I treat patients with refractory hypertension who have already been abandoned by other physicians. And pressure control at the recommended level is achieved by me. In fact, I get the result recommended by the official guides. How I get this result is practically irrelevant (which is also stated in the guides). Reducing pressure is not an end in itself. The goal is to reduce the risks associated with high blood pressure. And in practice, antihypertensive drugs should be used that have been proven to reduce not only blood pressure, but also these risks. It is possible to effectively lower the pressure with nifedipine and get an increased risk of heart attack. Such therapy for hypertension is unacceptable.

17.04.2007, 20:19

Dear Alexander Yurievich! The most important risk of hypertension is hypertension itself. And lowering blood pressure below 140/90 (130/80) is the first and main task. And then do you really think that I'm only a substance flying. Hypertension is refractory. CCB + thiazides + ACE inhibitors + BB. Zero effect (i.e. the main task has not been solved). We add substance - there is an effect. What am I doing wrong with this?

17.04.2007, 20:25

Make a separate topic and let's look at this outstanding case in all its details: rolleyes: In our hospital, it is also not customary to refuse patients, resistant hypertension happens, but we slowly manage without shamanism. In the world somehow too :confused:

17.04.2007, 20:40

17.04.2007, 20:48

I'll try to guess how you, Dear Alexander, manage in the hospital without shamanism. 5-10 droppers with Cavinton, 5-10 droppers with Pentyline ... and more magnesia, mildronate, piracetam. Give me an evidence base for these drugs, or is this not shamanism?

I don’t prescribe:(. And what helps with resistant hypertension? :D I suggest you digress from, to be honest, terrible messages like: “but I cure resistant hypertension with a domestic chondroprotector” (on RMS (at least in this section) NO PLACE FOR LOCAL WOMANSHIP, "but I like it and it helps everyone, by the way", etc.) and publish a specific clinical case in a separate topic (this one is about chondroprotectors;)). What kind of patient, what was treated, how secondary hypertension was excluded, what drugs were used, etc.

17.04.2007, 20:58

Sorry! We just use it everywhere. I have more than 500 cases. I see no reason to cite even one. The purpose of my statements is to illustrate the benefits of using HP. I see no point in convincing someone or sharing experience. I think that shamans (even local ones) have no place on RMS.

17.04.2007, 21:16

I have more than 500 cases. I see no reason to cite even one. The purpose of my statements is to illustrate the benefits of using HP. I see no point in convincing someone or sharing experience

Well, nothing, I will comment on what is.

Hypertension is refractory. CCB + thiazides + ACE inhibitors + BB. Zero effect What am I doing wrong?

For example, instead of an aldosterone antagonist, treat people with a drug (okay, I'll call it a MEDICINE) that isn't even close to hypertension. "Stop experimenting on people already" (c) Alon

[Only registered and activated users can see links]]These results demonstrate that an aldosterone antagonist can be effective in treating hypertension resistant to multidrug regimens that include a diuretic and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Additional blood pressure reduction was also achieved in subjects without hyperaldosteronism. Benefit in such subjects may have been secondary to additional diuretic effects of the aldosterone antagonist or, as we hypothesize, reflects a broad role of aldosterone in causing resistant hypertension even in the absence of demonstrable hyperaldosteronism.

This is offhand.

17.04.2007, 21:32

18.04.2007, 02:54

Molecular pathology of osteoarthritis as a basis for creating
pathogenetically substantiated structural-modifying
therapy. G. Golubev, O. Krigshtein ([Only registered and activated users can see links])
(You can isolate a literature review on HP, even more specifically - the attitude to the value of the results on them).

Have you looked at all? :)
And just like that, you have to watch it right? Well, I'll try ....: D:) Uv. April, you can personally look at what is more convenient for you, and choose from all the results that small subgroup in which you managed to notice "something like an effect" in the form of a 5 percent difference from placebo.
I hope this will help you stay confident when you prescribe miracle drugs with a 5% bioavailability. :p

18.04.2007, 06:35

Dear Alexander Yurievich! The most important risk of hypertension is hypertension itself. And lowering blood pressure below 140/90 (130/80) is the first and main task. And then do you really think that I'm only a substance flying. Hypertension is refractory. CCB + thiazides + ACE inhibitors + BB. Zero effect (i.e. the main task has not been solved). We add substance - there is an effect. What am I violating with this? A hypertensive person dies or becomes disabled not from high blood pressure figures, but from a heart attack, stroke, heart failure, and therapy should be aimed at reducing these risks.

Doxasosin was withdrawn from the ALLHAT study because, by lowering blood pressure, it increased the risk of heart failure, stroke, and cardiovascular events. Reducing pressure at such a price is unacceptable and contrary to the spirit of the guides.

Actually, I allow situations where a forced departure from the principles of evidence-based medicine is possible. This is possible, for example, when conducting "despair therapy" when nothing helps. However, in the treatment of arterial hypertension, in my opinion, there are enough funds with proven effectiveness. If hypertension is resistant against the background of maximum doses and optimal combinations, alternative approaches are acceptable, but they should be within the framework of common sense, agents with known effectiveness should be added, but not urine therapy or kerosene therapy.

18.04.2007, 07:01

The Moscow Representative Office of Rottapharm, the famous manufacturer of the Dona drug, in Russia and the CIS countries announced grants for 2007 within the framework of the project “Russian research on dietary supplements used in musculoskeletal diseases”. ([Only registered and activated users can see links])

Involve the most active and advanced scientists, doctors in the collection and analysis of scientific materials on dietary supplements;
prepare a scientific review that would analyze studies on the use of dietary supplements by adult patients as a means for the treatment and prevention of musculoskeletal diseases.
With which I congratulate all the doctors who treat patients with chondroprotectors - now their effectiveness will certainly be proven. :rolleyes:

18.04.2007, 08:49

I think for some it will be very surprising to hear that the cause of hypertension, including refractory, may be vertebrobasilar insufficiency due to cervical osteochondropathy. Here it is, the last one, and I am treating HP. See you on other sites!

First of all, don't leave, please :) The forum engine here is much more convenient for chams on the Solway, but you are not on other sites.

Secondly, you must agree, it is not at all a fact that you are treating hypertension, which arose precisely as a result of VBB against the background of o / x SHOP, since you confirm this by a method with low information content, especially for PA. It would be more correct to say that you treat with alflutop injections (by the way, do you inject it into the buttock or neck muscles?) and get the result in the form of a decrease in blood pressure. And why blood pressure is decreasing is another question that colleagues want to discuss.

18.04.2007, 10:02

SW. April, you can personally look at what is more convenient for you, and choose from all the results that small subgroup in which you managed to notice "something like an effect" ..

You notice it as soon as you read the full text (for the first time) and open the tables. :p
A subgroup of 354 people. (not small) The effect reaches a statistically significant result in it. :)
And Malysheva would be nice to call about large molecules ..: D

79-54=25. :) it's not a phone

18.04.2007, 10:59

18.04.2007, 11:31

The evening has ceased to be languid ..

Well, it was necessary to dodge it in order to consistently weed out most of the observation groups: first, seriously ill patients - then light ones, first write that they are observing the effect of the drug on functions - then forget about it so much that you don’t even think of removing empty words from the title; evaluate the most subjective test options - and even add analgesics-on-demand to an already practically insensitive observation. Quite naturally, what is amorphous in design..

Are you talking about a slide? Do you know why it happened? Different pages do not correspond to each other, just as the illustrations at the end of the book are not interconnected. They refer to different parts of it.
And here is the full link [Only registered and activated users can see links] You brought it yourself.

18.04.2007, 11:37

Are you talking about a slide? This is about a study and its results. Well, very unconvincing!

18.04.2007, 11:39

What kind of study is SW.Hard. There is a set of pictures for different studies.
[Only registered and activated users can see links]
Do you have design concerns here?

On page 44 there is a table from there

I propose to finalize the discussion in 1538. Let me find something new for you. :)

18.04.2007, 11:54

It is the most - GAIT. Which was held under the roof of NIH, but in fact was given to the alternatives from NCCAM in full control.

18.04.2007, 19:26

Dear Mikhail Vladimirovich! I poke at me. But what about a noticeable anti-inflammatory effect - pain in the neck and joints disappears, the range of motion increases, dizziness, claustrophobia disappear, sleep normalizes, etc. But what about LBF in the vertebral artery from 85 before injections to 30 after (you know the way to make sure that this is exactly the vertebral artery). And then I'm a private practice doctor: the hell with two, I would earn a living if there was no effect. And I use veroshpiron when necessary, don't make me a kerosene monster!

18.04.2007, 20:44

And one more nuance I use Romanian illicit alflutop (alflutop acting from Russia of effect does not give)

23.04.2007, 19:06

Tell me, if all these drugs are extracts from bones and cartilage, then maybe jelly as such has medicinal properties in relation to the treatment of diseases of the joints? :) And tasty and nice...

23.04.2007, 19:11

Wee, you will laugh ... (c)
92 publications. Only not in PubMed, but in Yandex. Like...
... You need to take beef articular bones, preferably from young calves, and cook them at a low boil for 4-5 hours, like jelly. The resulting broth is warm, along with fat, drink 3-4 times a day for 200-300 g. In addition, you need ...
At the beginning of treatment, exacerbations are possible, but then everything returns to normal, the pain goes away and the joints become mobile.
Quackery has no limits.

24.04.2007, 04:42

"Medicines" invented on the basis of the idea of ​​organ affinity have been present in the medical theories of all civilizations. The history of their origin is lost in the prehistoric wilds of our planet. In that dark period of the first steps of human society on the planet, the main engine of intellect was mystical thinking, which was not yet able to separate the objects encountered and the observed phenomena.
It was then that an idea was formed about the possibility of direct influence on the observed world through the things responsible for it and the reverse effect, the essence of which is spells.
In the context of the issue of drugs, we are interested in just the direct mechanism, i.e. the ability of a substance to exert a purposeful effect on phenomena subordinate to it.
In ancient philosophical and medical treatises, we find echoes of this magical knowledge in the form of recipes for the preparation of organ-like mixtures and elixirs. One of the most popular drugs of this kind is a decoction of the cranial bones of a mountain yak, which, according to the ideas of Tibetan applied cosmology, is capable of producing a healing effect on lesions of the central nervous system, mainly brain injuries.
It is not known whether this magical brew would have remained in the undivided property of the servants of the monasteries lost in the distant skies, but fate decreed otherwise. In the very center of European civilization, such an interest arose in the mystical secrets of the universe that the wheel of history almost jumped off into the abyss of obscurantism. Through the efforts of the new Nazi barbarians, by the middle of the 20th century, humanity was "beneficial" with a number of medicines created using the technologies of "secret knowledge" by the heirs of the "initiated highlanders of the east."
To this day, thanks to those same experts, we can easily find in the lists of drugs a wide range of offspring of technomagic, for example, cerebrolysin, familiar to everyone since childhood, is a descendant of a decoction of yak skulls.
It should be noted that the homeopathic theory of similarity does not fully reflect the main idea of ​​the ancient mystical theory, since it very freely interprets the main canon of magic - material affinity. This situation even caused a split in the camp of medical occultists, dividing them into true adherents of the figurative perception of similarity and revisionists, who elevated the thesis of related similarity into a dogma and introduced organ preparations to perpetuate it.
Against the backdrop of such a flourishing flowering of primitive thinking, half-brothers of cerebrolysin naturally grew up, occupying similar niches in most sections of private pharmacology. At present, the degree of closeness of a medicinal substance to an organ is not always a decisive factor in assessing the magical effectiveness of a drug. The main active principle is now assigned to the chemical proximity of the constituents of the drug and the diseased part of the body, as is, for example, the case with the liver healer Essentiale and articular polysaccharides. Although, of course, there should be exceptions that support the permanent path - this is what the last objects of the classical organomagic cult serve - chondroprotectors of cartilage extract.

07.08.2008, 21:45

Although the topic has died down for a long time, maybe someone will tell you: SYNOCROM (1% solution of sodium hyaluronate) Austria, for intra-articular injection - what is it? chondroprotector, dietary supplement or still a medicine? The rheumatologist prescribed 5 injections, but each one costs 3,100 rubles. Involuntarily, you will wonder what to pay money for ...

07.08.2008, 22:11

So, with deforming osteoarthritis of the knee joint 2 tbsp. pierce its meaning should be?

07.08.2008, 22:15

The meaning may be. Feel the difference with "should be".

07.08.2008, 22:35

11.08.2008, 03:14

Thank you, Sereda Andrey, for prompt response! I'll try to feel the meaning between "can" and "should". The problem is that I already had one injection, but they didn’t hit the joint (in May). Not fatal, but the knee was well swollen, it hurt for a long time and 3 thousand "down the drain" - it was a pity, although they apologized ... the remaining 4 ampoules - the syringes are lying, I'm sitting, looking at them, wondering which doctor to go to now - the injection was done by an orthopedic doctor, with a good reputation ...
1. The likelihood of an adverse reaction to repeated administration of hyaluronate if an adverse reaction occurred during the first administration is considered to be increased. According to your description, it can be assumed that the components of the drug are intolerant, but I do not have the details to confirm this assumption.

2. You have not provided any information about your medical condition. If there is currently no pain syndrome, the expediency of introducing hyaluronate "just in case" and "treat the joint" is doubtful. There are no studies proving the preventive properties of hyaluronates.

24.01.2009, 22:48

Current Concepts
A Review of Evidence-Based Medicine for Glucosamine and Chondroitin Sulfate Use in Knee Osteoarthritis
C. Thomas Vangsness Jr. M.D. , a, William Spiker M.D.a and Juliana Erickson B.A.a
aDepartment of Orthopedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A.

24.01.2009, 22:49

Abstract
The investigation of disease-modifying treatment options for osteoarthritis (OA) has become an important aspect of orthopaedic care. The purpose of this review is to critically evaluate the evidence for the use of glucosamine and chondroitin sulfate for knee OA with the goal of elucidating their indications for clinical use. The published clinical studies of glucosamine and chondroitin sulfate on OA are reviewed within the context of evidence-based medicine. Almost every included trial has found the safety of these compounds to be equal to placebo. In the literature satisfying our inclusion criteria, glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain and improving joint function. Many studies confirmed OA pain relief with glucosamine and chondroitin sulfate use. The excellent safety profile of glucosamine and chondroitin sulfate therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients.
Key Words: Glucosamine sulfate; Glucosamine hydrochloride; Chondroitin sulfate; Knee osteoarthritis; nutritional supplement

24.01.2009, 22:49

As the most common musculoskeletal disease in the United States, osteoarthritis (OA) has long been a topic of intense research and debate. Knowledge about the biomechanical and biochemical progression of the disease continues to improve but remains deficient., , , and Even worse for the some 40 million Americans incurring pain and disability from the disease, research has resulted in only minimal advances in its treatment. and Symptomatic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) remains the status quo despite questionable efficacy and significant risks such as peptic ulcer disease, renal failure, and hemorrhage.7 With the prevalence of OA expected to double in the next 20 years and NSAID -related gastropathy currently the second most deadly rheumatic disease, and the investigation of disease-modifying treatment options for OA has become an important aspect of orthopedic care.
Glucosamine and chondroitin sulfate (CS), both components to the extracellular matrix of articular cartilage, have been used for medicinal purposes for nearly 40 years.9 After gaining popularity in Europe and Asia for the treatment of arthritis for the last 20 years, they gained popularity in the United States after the release of several lay publications in the late 1990s.10
One of the earliest studies to use glucosamine and CS for the treatment of the signs and symptoms of OA was a 1969 study by Vetter9 that showed a decrease in joint symptoms with topical application. In the following decades, numerous studies were designed to investigate the effects of glucosamine hydrochloride (GH), glucosamine sulfate (GS), and CS on outcomes such as joint space narrowing, functionality, and pain. Although many trials have been published showing significant treatment effects with these nutritional supplements, they have been largely ignored by the medical community in the United States because of their questionable quality.
Glucosamine and CS studies have been criticized for small sample sizes, confirmation of quality supplement, short length of therapy, potential bias because of manufacturer's sponsorship of the studies, inadequate masking of the study agent, and failure to adhere to the intention-to -treat principle Despite these weaknesses, meta-analyses have concluded that these supplements are likely to have some efficacy in treating the symptoms of OA with possible disease-modifying effects. medical circles and the public eye

24.01.2009, 22:50

The purpose of this review is to critically evaluate the evidence for the use of glucosamine and CS for OA with the goal of elucidating their indications for clinical use. It is necessary to evaluate each supplement independently (GS, GH, and CS) and jointly as a pair (glucosamine plus CS). Although placebo-controlled, “randomized,” double-blind studies date back 25 years, many of the older trials are difficult to analyze because of sponsorship from manufacturers and inadequate product concealment. Specifically, this review article focuses on double-blind, placebo-controlled, randomized controlled trials (RCTs) using glucosamine and CS for knee OA that have established established outcome measurement methods.
Specific Supplement Studies
Chondroitin Sulfate
In 1998 Bucsi and Poór11 evaluated the use of CS on OA symptoms (Table 1). They measured clinical symptoms via Lequesne's index, the occurrence of spontaneous joint pain, and 20-minute walk time in 80 OA patients who underwent 6 months of therapy with 800 mg of CS sulfate or placebo. A statistically significant improvement was shown in all 3 tested measurements over placebo with no difference in side effects. In this 3-month trial, Bourgeois et al.12 performed a similar study to determine whether the dosing schedule of CS had any impact on the efficacy of the treatment. 1,200 mg of CS (administered either as a single dose or as 3 equally divided doses) reduced Lequesne's index and spontaneous joint pain scores versus placebo (P< .01). Dosing schedules supported once-a-day administration. In a randomized clinical trial, Conrozier13 used an 800-mg dose in 104 patients treated for 1 year. Functional impairment recovered by approximately 50%, with significant improvement over placebo for all clinical criteria

24.01.2009, 22:50

In a study by Mazieres et al.14 published in 2001, 130 patients were randomized to receive 1,000 mg of CS daily for 3 months and were followed up for an additional 3 months after therapy. Lequesne's index significantly improved (P = .02) and remained elevated for 1 month after treatment. These findings did not reach significance when the results were viewed with an intention-to-treat analysis. Mazieres et al.15 also evaluated 307 patients with knee OA for 6 months using CS.
Uebelhart et al.16 randomized 120 patients to receive placebo or 800 mg of CS for two 3-month periods during a period of 1 year. They showed a 36% improvement in Lequesne's index scores in the CS group whereas the placebo group only improved by 26%. This significant decrease in pain with improved function showed a long-term benefit with intermittent CS therapy.
Mathieu,17 in a double-blind prospective study of 300 patients in 2002, showed that over a 2-year period, CS reduced the radiographic progression of OA when compared with controls. In the CS group the radiological parameters remained stable. These results were further supported by the 2005 study of Michel et al.,18 which also showed a retardation of joint space narrowing in patients who received the same nutritional supplement for a 2-year period. Together, these studies suggest a disease-modifying role of CS.
Michel et al.18 performed an RCT in 300 patients with OA, testing 800 mg of CS against placebo for 2 years. They evaluated joint space narrowing as a primary outcome, with pain and function as secondary outcomes. They found no significant symptomatic effects between the treatment groups and concluded that CS may retard radiographic progression in patients with OA of the knee. Future evaluation of these structural observations was recommended. However, large well-designed studies are necessary to prove such an effect, especially with respect to the reproducibility and consistent measurement of joint space narrowing.
Glucosamine Sulfate
GS is one of the most studied dietary supplements available today (Table 2). In the last 30 years, many trials have been conducted and published on the effects of glucosamine on the signs and symptoms of OA

24.01.2009, 22:51

Müller and colleagues19 evaluated the short-term 4-week effects of 1,200 mg of GS using Lequesne's severity index and looked at the relative risks of side effects in the GS group versus the ibuprofen group. In this short 1-month study, GS was as effective as ibuprofen and significantly better tolerated (P< .001). Only 6% of patients taking GS reported adverse events, whereas 35% of ibuprofen users had an adverse event (mainly gastrointestinal in origin).
Noack et al.20 published a 4-week study comparing GS with placebo rather than ibuprofen. This short study of 252 patients showed that GS was more effective than placebo in improving OA symptomatology. Patients in the GS arm of the trial enjoyed a 3.3-point drop in Lequesne's severity index, whereas those taking the placebo improved by 2.0 points. A 6-week study by Reichelt et al.21 showed GS to decrease Lequesne's index over placebo in 155 patients. Unfortunately, these studies are too short to make significant long-term conclusions.
In 2001 Reginster et al.22 published the results of a trial in which 212 patients were randomized to receive placebo or GS daily for 3 years. Glucosamine was shown to protect the joint space from the narrowing effects of OA. A trend towards improving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores was seen without any statistically significant change.
A similar study by Pavelká et al.23 supported the findings of Reginster et al.,22 proving statistically significant effects of glucosamine on both radiographic progression and WOMAC scores.
Bruyere et al.24 used the same outcome measures of joint space narrowing and WOMAC scores to prove that the disease-modifying seen in the study of Pavelká et al.23 were also found in the older postmenopausal female population. Bruyere et al.25 investigated joint space narrowing in 212 knee OA patients at 3 years. Patients with less severe radiographic knee OA had the most dramatic disease progression as seen by joint space narrowing. The GS group, compared with the placebo group, showed a nonstatistical trend in significant reduction of joint space narrowing.
Cibere et al.26 tested GS in a 4-center 6-month randomized, double-blind, placebo-controlled study. No differences were found in the severity of disease pain episodes (flare-ups) or other secondary outcomes between placebo- and glucosamine-treated patients. They concluded that there was no evidence of symptomatic benefits from continued GS use from this 6-month study.
Herrero-Beaumont et al.27 evaluated 318 patients with knee OA in an RCT comparing GS, acetaminophen (Tylenol; McNeil Consumer Healthcare, a division of Johnson & Johnson, Guelph, Ontario, Canada), and placebo. After 6 months, 1,500 mg of GS was found to be better than placebo and acetaminophen by use of Lequesne's index and the WOMAC.
Hughes and Carr28 performed a randomized clinical trial with GS in 80 OA patients for 24 weeks. They found a 33% placebo response rate and no statistical improvement over placebo as a symptom modifier.
Collectively, these GS studies showed that GS as an individual agent may have some effect on the progression of the disease and was as safe as placebo at a dose of 1,200 to 1,500 mg/d for up to 3 years. Many studies had a short-term follow-up, and the evidence inconsistently supported the use of glucosamine as an effective alternative to higher-risk medications such as NSAIDs and cyclooxygenase II inhibitors for knee OA

24.01.2009, 22:52

Glucosamine Hydrochloride
The hydrochloride salt of glucosamine is a common glucosamine product, yet it has received relatively little attention from researchers (Table 3). Houpt et al.29 were unable to show statistically significant changes in the WOMAC pain score subset versus placebo after a short period of therapy with GH (8 weeks). All tested parameters tended to show improvement, and GH did significantly reduce the daily pain reported by patients (P = .018) and improved findings on clinical knee examination (P = .026). GH was shown to be as safe as placebo. Though failing to prove its primary outcome measure, this study suggested that GH benefited some patients with OA without the side effects of other treatment modalities. McAlindon et al.30 performed a 12-week GH study on 205 patients recruited over the Internet. By use of the WOMAC as the primary outcome, GH was safe but no more effective than placebo in treating symptoms of knee arthritis

24.01.2009, 22:52

Glucosamine and CS
The highly publicized Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was published in the New England Journal of Medicine early in 2006 (Table 4).31 The multicenter trial assigned 1,583 patients to randomly receive 1,500 mg glucosamine; 1,200 mg CS; both GH and CS; 200 mg of celecoxib (Celebrex; Pfizer, New York, NY); or placebo for 24 weeks. Patients were allowed to take up to 4,000 mg of acetaminophen for rescue analgesia daily (no pain medications were taken within 24 hours of clinical examination). All patients in the study were aged at least 40 years, had both clinical evidence (knee pain for most days of the month for ≥6 months) and radiographic evidence of OA (osteophytes ≥1 mm), and WOMAC scores from 125 to 400. The primary outcome measure was a 20% decrease in the summed score for the WOMAC pain subscale from baseline to week 24. Over 40 secondary outcome measures were included in the study
In the subgroup of 79 patients with moderate to severe pain (determined by a score of 300-400 on the WOMAC pain scale), GH and CS significantly reduced knee pain. In this subgroup of patients receiving GH and CS, 79% showed a 20% reduction in knee pain, whereas only 54.3% of the placebo group showed this improvement. However, GH and CS were not found to be significantly better than placebo in reducing knee pain by 20% from baseline in the pooled analysis of patients. Adverse effects were mild, infrequent, and evenly distributed across all groups tested, supporting the safety of these nutritional supplements.
Celecoxib was found to yield a statistically significant decrease in pain scores in the combined mild pain and moderate/severe pain subgroups but failed to have a significant effect on the pain scores in the moderate/severe pain subgroup. Celecoxib was also found to yield a faster decrease in pain scores, showing substantial decreases in pain scores at 4 weeks of treatment. Overall, celecoxib was found to have a significant effect on 6 of the 42 outcome measures followed in the study, whereas glucosamine and CS were found to have a significant effect on 14 of the 42 outcome measures.
This study, the largest and most rigorous of its kind, showed that GH and CS had a significant effect on patients with more severe OA. Questions remain about the usefulness of glucosamine and CS in mild OA and their effect on other parameters such as joint function, stiffness, and joint space narrowing. Limitations of the study noted by the authors were the high rate of response to placebo (60%) and the relatively mild degree of OA pain among the participants. Concomitant treatments, such as physical therapy, were not clarified. These limitations decreased the ability of the study to detect the benefits of treatment. Studies with alternative medical therapies have shown a higher placebo response rate.32 Celecoxib at 200 mg/d had noticeably effects smaller in the GAIT study compared with earlier studies.

24.01.2009, 22:53

The GAIT study was designed to include 1,588 patients to provide the study with statistical power to detect 1 or more clinically meaningful differences based on an assumed placebo response rate of 35%. When this placebo response rate nearly doubled, the number of participants needed to obtain a similar statistical power increased substantially. With far too few patients given its placebo response rate, the data were barely able to prove its control (celecoxib) in the primary outcome measure (P = .04) and was unable to do so in the moderate/severe pain subgroup. Furthermore, the choice of the product tested (GH) has been called into question given the fact that GS has been more rigorously studied in the literature. The GAIT authors also chose less sophisticated methods for dealing with missing data, using the last observation–carried forward method rather than the multiple imputation method.
Alekseeva et al.33 examined 90 women aged between 40 and 75 years with Kellgren-Lawrence stage II or III knee OA who had pain after 40 minutes of walking and regularly took NSAIDs for pain relief. The patients were randomly selected either to receive 500 mg of the glucosamine and CS supplements with optional diclofenac (50 mg) or to receive a placebo and optional diclofenac for a total of 3 months. The results were measured by the WOMAC, daily need for NSAIDs, and evaluation of efficacy by the patient and the physician after 1 and 3 months of treatment and again 3 months after the oral supplementation had been stopped. The true WOMAC score decreased after 3 months of therapy and 3 months after the supplementation had been stopped (P< .03). At the end of the 3 months of therapy, the study group exhibited decreases in pain scores (P = .008) and increases in subjective functional ability. The patients taking the glucosamine and CS supplementation required less diclofenac. After 1 month of therapy, 4.5% stopped taking diclofenac and nearly 40% stopped taking it by the end of the study. Although limited by its size and the small subgroup that was studied (older women), this study showed that combined medications offer significant safety and effective pain relief in the short term with long-lasting effects.
Messier et al.,34 in a double-blind 12-month GH/CS study with 80 patients, incorporated 6 months of exercise after 6 months of a non-exercising treatment. The primary end-point was the WOMAC and functional measures such as the 6-minute walk. At 12 months, there was no difference between groups for the 6-minute walk, knee strength, mobility, and function over the placebo treatment.
Meta-Analyses of Glucosamine and CS Studies
Several important meta-analyses have been published in recent years about the efficacy of glucosamine and CS therapy. By performing exhaustive searches in the literature and applying systematic quality assessment of these studies, these meta-analyses provided pooled information from the many pre-existing small studies.
McAlindon et al.35 examined 15 double-blind, randomized, placebo-controlled trials of 4 weeks" duration or longer for their impact on the symptoms of hip and/or knee OA. They included studies of glucosamine and CS with various routes of administration , including oral, intramuscular, intravenous, and intra-articular. Very few of the examined studies described adequate allocation concealment or use of an intention-to-treat analysis. They also found evidence of significant publication bias, likely because of manufacturer's sponsorship of trials and the financial interests of the authors. When only the larger high-quality studies were evaluated, the effects of glucosamine and CS persisted, although they were noticeably diminished. This study also suggested that the full therapeutic benefit of these supplements likely did not occur in the first 4 weeks and that longer studies would be of significant value.
Richy et al.36 examined both structural and symptomatic efficacy of CS and glucosamine. By examining structural changes via radiographic progression of joint space narrowing, this analysis was the first to evaluate the disease-modifying effects of these supplements. Evaluating the results of 15 studies that included data from 1,775 patients, the authors showed a statistically significant improvement in symptom scores with both glucosamine and CS therapy. They were also able to show a significant effect of glucosamine on the progression of joint space narrowing over a 3-year period, suggesting a disease-modifying effect of the compound (no such studies existed for CS). Importantly, the tolerance for these supplements was again shown to be equal to that of placebo.
Bjoral et al.37 reviewed 63 RCTs using opioids, NSAIDs, glucosamine, CS, and acetaminophen (Tylenol; McNeil Consumer Healthcare) for knee OA including some 14,060 total patients. Acetaminophen, GS, and CS had maximum efficacies at 1 to 4 weeks with mild pain improvements. Overall clinical effects from these knee pharmacologic arthritic interventions were found to be small and limited to the first 2 to 3 weeks after the start of treatment.
Distler and Angueloouch38 reviewed clinical evidence for glucosamine and CS studies analyzing RCTs. Their results were inconclusive regarding the continuous use of these nutraceuticals because of weak research design

24.01.2009, 22:53

Reichenbach et al.39 performed a meta-analysis of CS for OA of the knee or hip in 20 trials involving 3,846 patients. After analyzing the small and large studies, they found the trial quality to generally be low. They concluded that with the large-scale, methodologically sound trials, CS had minimal to nonexistent symptomatic benefit. They discouraged CS use by itself in routine clinical practice.
Leeb et al.40 performed a meta-analysis of 7 trials of CS including 372 patients. They cited the difficulties in design with co-mixing of medications in several studies using the visual analog scale and Lequesne's index. The findings in the CS groups were significantly superior to those in the placebo groups. They called for better and longer time periods for symptom-modifying evaluations.
The Cochrane Review is perhaps the most thorough of the meta-analyses performed on glucosamine's effect on OA.41 Updated in January 2005, this meta-analysis followed 3 selection criteria: they were RCTs, they were either placebo controlled or comparative, and they were blinded (single or double were both accepted). use of Lequesne's index. In 8 articles that showed adequate allocation concealment, glucosamine failed to show a benefit for either pain or function. The Cochrane Review confirmed the safety findings of the incorporated studies, finding glucosamine to have adverse events equal to the placebo. Although these conclusions were significant for the number of studies they incorporate, they did have their limitations. This review was designed to include a broad selection of clinical trials, accepting short-term studies, comparative control studies, and single-blind studies. In accepting these lower-quality articles, the power of the pooled results was negatively impacted.
Other Sulfur-Containing Compounds
S-adenosylmethionine (SAMe) and methylsulfonylmethane (MSM) are market leaders among the sulfur-containing compounds advertised for joint health. Despite the public interest in these compounds, few well-designed studies have been completed. An open-label study in 1987 showed that SAMe increased joint mobility with no evaluation of pain or function.42 Subsequent double-blind placebo-controlled studies have supported the use of SAMe and shown it was effective as many anti-inflammatory and pain-relieving drugs., and
In 2004 Najm et al.46 compared the efficacy of SAMe with Celebrex (Pfizer) for the symptoms of OA. In the first month of their 4-month study, celecoxib showed significantly more reduction in subjective pain reports by the participants (P = .024). By the second month, both study arms were equally effective in reducing pain (P< .01). This study noted increased functional health measures and increasing joint mobility in both treatment groups, without significant differences in side effects. These trends were not shown to be statistically significant.
Despite the presence of several studies suggesting the efficacy of MSM in reducing joint pain and enhancing mobility, and the literature on MSM is deficient. With a paucity of research, as well as the short length of follow-up, it is difficult to recommend MSM at this time as an efficacious therapy for OA. Kim et al.49 showed significant decreases in WOMAC pain (decrease of 25% from baseline) and physical function subcategories with MSM versus placebo. Improved performance of MSM users was seen in activities of daily life as measured by the Short Form 36 score (P = .05), but this study found no significant improvement in the total aggregate WOMAC score at 3 months.

24.01.2009, 22:54

Discussion
This review looked at the current research on the sulfur-containing nutraceuticals and their effects on proven outcome measures. In the literature satisfying our inclusion criteria, GS and CS have shown an inconsistent yet overall positive efficacy in decreasing OA pain and improving joint function. Most trials found the safety of these compounds to be equal to that of placebo. The literature on GH, GS, or CS as an individual supplement suggests a therapeutic value but falls short of proving a role for its independent use.
Although the study by Clegg et al.31 called into question the efficacy of GH and CS in mild OA, it showed the effectiveness of these supplements in the moderate/severe pain subgroup. Their study lacked the size to make up for a placebo response rate of over 60% and the relatively mild disease state of the study participants. When considered within the context of the other studies reviewed, it serves as another study to confirm the safety profile of glucosamine and CS and shows a reduction in pain scores with consistent use.
The scant literature on the sulfur-containing compounds SAM-e and MSM shows trends towards decreased pain and increased function with consistent use but fall short of proving any therapeutic benefit. However, they have a documented 3-month safety profile; there is a need for more randomized clinical trials.
Perhaps the most important trend seen in the current literature on nutraceutical use for OA is the importance of length of therapy. Although some studies have shown significant improvement in OA symptoms during a short time period, these studies involved the use of concomitant pain relievers, were poorly concealed for allocation, or were monetarily supported by manufacturers. In the more rigorous and lengthy studies comparing these compounds, effectiveness was not seen until several months into therapy. For example, in studies on CS significant effects were not seen until 3 to 6 months of treatment. In other studies the effectiveness of CS was not shown until month 9 of the treatment phase or month 4 of the post-treatment phase. In glucosamine studies a similar trend can be noted because treatment effects can be delayed until post-treatment follow-up. These findings support the need for more long-term trials and the importance of consistent use in patients who select these compounds as treatment for OA pain and disability.50
It is important to understand that many of these glucosamine and CS studies have been financed and sponsored by industry and specific manufacturers. Not all studies document this well, and financial relationships with industry, scientific investigators, and academic institutions are widespread. These potential conflicts influence research and have been well studied.51
When considering the use of vitamin or nutrient supplementation, it is important to realize that the supplements tested in trials are not necessarily the same as the supplements sold in stores.52 To reduce any potential complicating factors, clinical trials must use products that have been rigorously tested with regard to the purity and quantity of the supplements. Products available in stores are not adhered to these same specifications by the Food and Drug Administration (FDA) because they do not undergo federal testing for actual content. According to the Dietary Supplement Health and Education Act of 1994, the manufacturer is responsible for determining that the supplement is present in the advertised purity and amount and that any claims made about it are adequately substantiated.53
The FDA allows dietary supplement labels to include information describing the supplement's effect on the body and its biologic functions. These types of claims are referred to as structure/function claims. To make such claims, manufacturers must have some scientific data to substantiate them and not overstate the science.The FDA has the authority to declare a product mislabeled if its labeling is false or misleading. , and composition of dietary supplements.54 In the interim the industry has instituted its own good manufacturing practices to ensure quality products for the consumer.55 Reputable companies provide consumers with carefully formulated supplements that are accurately labeled. materials is laboratory tested for purity and potency.
For the consumer, it is important to purchase glucosamine and CS supplements that provide the efficacious amount of each ingredient as declared by the label. Several reputable companies, both national and store brands, have been shown to sell products that contain the labeled amount of glucosamine and CS at affordable prices. As a physician, it is important to recommend a brand name that has consistently shown itself to meet or exceed its claims on content quality and quantity in the

24.01.2009, 22:54

Conclusions
In the literature satisfying our inclusion criteria, GS, GH, and CS have individually shown inconsistent efficacy in decreasing OA pain and improving joint function. Many studies confirmed OA pain relief with glucosamine and CS use. The excellent safety profile of glucosamine and CS therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients.
References
1 N. Adachi, M. Ochi, M. Deie, Y. Ito and Y. Izuta, Lateral compartment osteoarthritis of the knee after meniscectomy treated by the transplantation of tissue-engineered cartilage and osteochondral plug, Arthroscopy 22 (2006), pp. 107–112. abstract | View Record in Scopus | Cited By in Scopus (6)
2 G. Spahn, T. Mückley, E. Kahl and G.O. Hofmann, Factors affecting the outcome of arthroscopy in medial-compartment osteoarthritis of the knee, Arthroscopy 22 (2006), pp. 1233–1240. abstract | View Record in Scopus | Cited By in Scopus (7)
3 M. Ikeuchi, T. Takahashi and T. Tani, Localized synovial hypertrophy in the anteromedial compartment of the osteoarthritic knee, Arthroscopy 21 (2005), pp. 1457–1461 abstract | View Record in Scopus | Cited By in Scopus (6)
4 D.K. Bae, K.H. Yoon and S.J. Song, Cartilage healing after microfracture in osteoarthritic knees, Arthroscopy 22 (2006), pp. 367–374. abstract | View Record in Scopus | Cited By in Scopus (13)
5 M.J. Stuart and J.H. Lubowitz, What, if any, are the indications for arthroscopic debridement of the osteoarthritic knee?, Arthroscopy 22 (2006), pp. 238–239. abstract | View Record in Scopus | Cited By in Scopus (8)
6 US Senate Committee on Health, Education, Labor and Pensions, Subcommittee on Aging, Center for Disease Control's role in combating the burden of arthritis, Department of Health & Human Services, Washington, DC (2004).
7 J.F. Fries, C.A. Williams, D.A. Block and B.A. Michel, Nonsteroidal anti-inflammatory drug-associated gastropathy: Incidence and risk factor models, Am J Med 91 (1991), pp. 213–222. abstract | View Record in Scopus | Cited By in Scopus (229)
8 J.J. Deeks, L.A. Smith and M.D. Bradley, Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: Systematic review of randomised controlled trials, BMJ 325 (2002), p. 619. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (210)
9 G. Vetter, Topical therapy of arthrosis with glucosamine (Dona 200), Munch Med Wochenschr 11 (1969), pp. 1499-1502 (in German). View Record in Scopus | Cited By in Scopus (5)
10 J. Theodasksi, B. Adderly and B. Fox, The arthritis cure, St Martin's, New York, NY (1997).
11 L. Bucsi and G. Poór, Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis, Osteoarthritis Cartilage 6 (suppl A) (1998), pp. 31–36. abstract | PDF (444K) | View Record in Scopus | Cited By in Scopus (81)
12 P. Bourgeois, G. Chales, J. Dehais, B. Delcambre, J.L. Kuntz and S. Rozenberg, Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 × 400 mg/day vs placebo, Osteoarthritis Cartilage 6 (1998), pp. 25-30. abstract | PDF (433K) | View Record in Scopus | Cited By in Scopus (76)
13 T. Conrozier, Anti-arthrosis treatments: Efficacy and tolerance of chondroitin sulfates (CS 4&6), Presse Med 27 (1998), pp. 1862–1865 (in French). View Record in Scopus | Cited By in Scopus (24)
14 B. Mazieres, B. Combe, A. Phan Van, J. Tondut and M. Grynfeltt, Chondroitin sulfate in osteoarthritis of the knee: A prospective, double blind, placebo controlled multicenter clinical study, J Rheumatol 28 (2001), pp . 173–181. View Record in Scopus | Cited By in Scopus (45)
15 B. Mazieres, M. Hucher, M. Zaim and P. Garnero, Effect of chondroitin sulfate in symptomatic knee osteoarthritis: A multicentre, randomised, double-blind, placebo-controlled study, Ann Rheum Dis 66 (2007), pp. 639–645. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9)
16 D. Uebelhart, M. Malaise and R. Marcolongo et al., Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: A one year, randomized, double-blind, multicenter study versus placebo, Osteoarthritis Cartilage 12 (2004), pp. 269–276. article | PDF (123K) | View Record in Scopus | Cited By in Scopus (66)
17 P. Mathieu, Radiological progression of internal femoro-tibial osteoarthritis in gonarthrosis: Chondro-protective effect of chondroitin sulfates ACS4-ACS6, Presse Med 31 (2002), pp. 1386-1390 (in French). View Record in Scopus | Cited By in Scopus (9)

24.01.2009, 22:55

18 B.A. Michel, G. Stucki and D. Frey et al., Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: A randomized, controlled trial, Arthritis Rheum 52 (2005), pp. 779–786. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (73)
19 D.A. Rothenfluh, D. Reedwisch, U. Müller, R. Ganz, A. Tennant and M. Leunig et al., Construct validity of a 12-item WOMAC for assessment of femoro-acetabular impingement and osteoarthritis of the hip, Osteoarthritis Cartilage 16 ( 2008), pp. 1032–1038. article | PDF (184K) | View Record in Scopus | Cited By in Scopus (1)
20 W. Noack, M. Fischer, K.K. Forster, L.C. Rovati and I. Setnikar, Glucosamine sulfate in osteoarthritis of the knee, Osteoarthritis Cartilage 2 (1994), pp. 51–59. abstract | View Record in Scopus | Cited By in Scopus (113)
21 A. Reichelt, K.K. Forster, M. Fischer, L.C. Rovati and I. Setnikar, Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee: A randomised, placebo controlled, double-blind study, Arzneimittelforschung 44 (1994), pp. 75–80. View Record in Scopus | Cited By in Scopus (79)
22 J.Y. Reginster, R. Derolsy and L.C. Rovati et al., Long-term effects of glucosamine sulfate on osteoarthritis progression: A randomized, placebo-controlled clinical trial, Lancet 357 (2001), pp. 251–256. article | PDF (94K) | View Record in Scopus | Cited By in Scopus (507)
23 K. Pavelká, J. Gatterová and M. Olejarová et al., Glucosamine sulfate use and delay of progression of knee osteoarthritis, Arch Intern Med 162 (2002), pp. 2113–2123. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (246)
24 O. Bruyere, K. Pavelka and L.C. Rovati et al., Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: Evidence from two 3 year studies, Menopause 11 (2004), pp. 138–143. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (40)
25 O. Bruyere, A. Honore and O. Ethgen et al., Correlation between radiographic severity of knee osteoarthritis and future disease progression: Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate, Osteoarthritis Cartilage 11 (2003), pp. 1–5. abstract | PDF (89K) | View Record in Scopus | Cited By in Scopus (34)
26 J. Cibere, J.A. Kopec and A. Thorne et al., Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis, Arthritis Rheum 51 (2004), pp. 738–745. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (51)
27 G. Herrero-Beaumont, J.A. Ivorra and M. Del Carmen Trabada et al., Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: A randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator, Arthritis Rheum 56 (2007), pp. 555–567. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (33)
28 R. Hughes and A. Carr, A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee, Rheumatology (Oxford) 41 (2002), pp. 279–284. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (70)
29 J.B. Houpt, R. McMillan, C. Wein and S.D. Paget-Dellio, Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee, J Rheumatol 26 (1999), pp. 2423–2430. View Record in Scopus | Cited By in Scopus (97)
30 T.E. McAlindon, M. Formica, M. LaValley, M. Lehmer and K. Kabbara, Effectiveness of glucosamine for symptoms of knee osteoarthritis: Results from an internet-based randomized double-blind controlled trial, Am J Med 117 (2004), pp. 643–649. article | PDF (118K) | View Record in Scopus | Cited By in Scopus (47)
31 D. Clegg, D.J. Reda and C.L. Harris et al., Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis, N Engl J Med 354 (2006), pp. 795–808. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (226)
32 T.J. Kaptchuk, The placebo effect in alternative medicine: Can the performance of the healing ritual have clinical significance?, Ann Intern Med 136 (2002), pp. 817–825. View Record in Scopus | Cited By in Scopus (104)
33 L.I. Alekseeva, N.V. Chichasova, L.I. Benevolenskaia, E.L. Nasonov and O.I. Mendel", Combined medication ARTRA in the treatment of osteoarthrosis, Ter Arkh 77 (2005), pp. 69–75 (in Russian). View Record in Scopus | Cited By in Scopus (1)
34 S.P. Messier, S. Mihalko and R.F. Loeser et al., Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: A preliminary study, Osteoarthritis Cartilage 15 (2007), pp. 1256–1266 article | PDF (238K) | View Record in Scopus | Cited By in Scopus (6)
35 T.E. McAlindon, M.P. LaValley and J.P. Gulin et al., Glucosamine and chondroitin for treatment of osteoarthritis: A systematic quality assessment and meta-analysis, JAMA 283 (2000), pp. 1469–1475 Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (375)
36 F. Richy, O. Bruyere, O. Ethgen, M. Cucherat, Y. Henrotin and J.Y. Reginster, Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: A comprehensive meta-analysis, Arch Intern Med 163 (2003), pp. 1514–1522 Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (144)
37 J.M. Bjoral, A. Kloving, A.E. Ljunggren and L. Slordal, Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomized placebo-controlled trials, Eur J Pain 11 (2007), pp. 125–138.
38 J. Distler and A. Angueloouch, Evidence-based practice: Review of clinical evidence on the efficacy of glucosamine and chondroitin in the treatment of arthritis, J Am Acad Nurse Pract 18 (2006), pp. 487–493. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (3)
39 S. Reichenbach, R. Sterchi and M. Scherer et al., Meta-analysis: Chondroitin for osteoarthritis of the knee or hip, Ann Intern Med 146 (2007), pp. 580–590. View Record in Scopus | Cited By in Scopus (39)
40 B.F. Leeb, H. Schweitzer, K. Montag and J.S. Smolen, A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis, J Rheumatol 27 (2000), pp. 205–211. View Record in Scopus | Cited By in Scopus (102)
41 T.E. Towheed, L. Maxwell and T.P. Anastassiades et al., Glucosamine therapy for treating osteoarthritis, Cochrane Database Syst Rev (2005) CD002946.
42 B. Konig, A long-term (two year) clinical trial with S-adenosylmethionine of the treatment of osteoarthritis, Am J Med 83 (1987), pp. 89–94. abstract | View Record in Scopus | Cited By in Scopus (19)
43 H. Muller-Fassbender, Double-blind clinical trial multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of osteoarthritis, Am J Med 83 (1987), pp. 1–4.
44 A. Maccagno, E.E. Di Giorgio, O.L. Caston and C.L. Sagasta, Double-blinded controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis, Am J Med 83 (1987), pp. 72–77. abstract | View Record in Scopus | Cited By in Scopus (18)
45 G. Vetter, Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis, Am J Med 83 (1987), pp. 78–80. abstract | View Record in Scopus | Cited By in Scopus (18)
46 W.I. Najm, S. Reinsch, F. Hoehler, J.S. Tobis and P.W. Harvey, S-adenosylmethionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial, BMC Musculoskelet Disord 5 (2004), p. 6. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (0)
47 S.W. Jacob and R. Herschler, Dimethyl sulfoxide after twenty years, Ann N Y Acad Sci 411 (1983), pp. 13–17.
48 P.R. Usha and M.U.R. Naida, Randomised, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis, Clin Drug Invest 24 (2004), pp. 353–363. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (18)
49 L.S. Kim, L.J. Axelrod, P. Howard, N. Buratovich and R.F. Waters, Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: A clinical pilot trial, Osteoarthritis Cartilage 14 (2006), pp. 286–294. article | PDF (193K) | View Record in Scopus | Cited By in Scopus (13)
50 S. Owens, P. Wagner and C.T. Vangsness Jr, Recent advances in glucosamine and chondroitin supplementation, J Knee Surg 17 (2004), pp. 185–193. View Record in Scopus | Cited By in Scopus (11)
51 J.E. Bekelman, Y. Li and C.P. Gross, Scope and impact of financial conflicts of interest in biomedical research: A systematic review, JAMA 289 (2003), pp. 454–465. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (372)
52 A.S. Russell, A. Aghazadeh-Habashi and F. Jamali, Active ingredient consistency of commercially available glucosamine sulfate products, J Rheumatol 29 (2002), pp. 2407–2409. View Record in Scopus | Cited By in Scopus (35)
53 Joint supplements: Brands to try and brands to avoid. consumer reports. June 2006