How does glucosamine work in the body?
Active glucosamine from the intestines enters the blood vessels and then into the cartilage. Its main task is to maintain chondrocyte function. Chondrocytes are special cells that work like mini factories. They produce building material for cartilage: collagen, hyaluronic acid, chondroitin sulfate and other important substances.
Therefore, adding glucosamine to the diet helps activate our internal “building factories” that restore cartilage joints, thereby relieving us of joint pain.
Glucosamine chondroitin complex Ultra caps 0.4g N90 (Pharmacor)
For prevention purposes, a person needs to introduce into his diet foods that are beneficial for cartilage and joints. Even ancient healers were well aware that strong, rich broths, as well as jellied meat, poultry and various types of fish, had healing powers. They also noticed that if tendons, bones, and cartilage are not removed from such dishes, their positive effects are further enhanced.
To this day, the most useful dishes for the prevention of joint and cartilage diseases are considered to be various strong broths and jellied meats, poultry, and fish. Strong broths and jellied meats contain substances - polysaccharides, which are part of the coating of the periosteum, cartilage and ligaments, and also take part in the synthesis of intra-articular fluid, which plays the role of a lubricant. If there is a lack of this fluid, a person experiences pain in the joints. It is polysaccharides that provide the elasticity of cartilage tissue. Therefore, by consuming rich broths and jellied meats, a person introduces these beneficial compounds into his body.
Proper nutrition and consumption of substances and plants that nourish cartilage and joints will allow a person to avoid diseases of the joints and cartilage, maintain health and performance.
Glucosamine
is a substance that is found in small quantities in food (in mollusk shells, as well as animal bones or bone marrow, some types of mushrooms). In addition, it is produced by cartilage cells of the human body. Glucosamine stimulates the production of long chains of sugars (glucosaminoglucans) necessary to maintain healthy human cartilage tissue.
Chondroitin
- is a high molecular weight polysaccharide and a structural analogue of human cartilage tissue. Contained in the skin, tendons and cartilage of animal origin and in fish (especially salmon, salmon). Chondroitin improves metabolic processes in cartilage tissue and prevents its destruction.
Methylsulfonylmethane (MSM)
is an organic sulfur-containing compound, tasteless and odorless, which is a source of sulfur of natural origin in a bioavailable form, and is usually found in various fruits, vegetables, cereals, and meat. In addition, MSM is found in the cells of the human body. In the body, sulfur is necessary for the formation of muscles, connective tissue, nails, hair and skin. Since sulfur plays an important role in human life, it must be present in the diet.
Boswellia extract
obtained from the resin of the Boswellia serrata tree, better known in Russia as the incense tree. The resin, obtained by cutting the tree trunk from where the milky sap appears, hardens and turns into yellowish balls. Frankincense tree resin has antiseptic properties, a pleasant smell, is chewed, and in small quantities crushed into powder is added to food.
Has the healing effect of glucosamine been proven in humans?
The first studies of glucosamine were carried out in the 80s of the last century in Italy. Clinical studies found that with long-term oral use of glucosamine, it reduced pain and improved joint movement, and slowed the progression of osteoarthritis. Most patients noticed a significant reduction in pain after just a month of taking glucosamine. The results were also confirmed when studying X-rays of patients after a course of glucosamine: a slowdown in joint destruction was noted. Subsequent experiments confirmed the data obtained and even showed an increase in the effect when combined with glucosamine and chondroitin.
In addition, it should be mentioned that glucosamine is recommended by the European Society for the Clinical and Economic Aspects of Osteoporosis and Osteoarthritis as first-line therapy for osteoarthritis and other degenerative joint diseases due to its ability to control pain and slow the progression of structural changes in the joints.
At the same time, glucosamine with another chondroprotective substance, chondroitin sulfate, showed particularly high effectiveness in osteoarthritis. The effectiveness of the combined use of these substances has been well studied in various comparative studies. It has been shown that in terms of effectiveness against the symptoms of osteoarthritis - pain, joint dysfunction - the combination of glucosamine and chondroitin, when used systematically, is not inferior to the most modern non-steroidal anti-inflammatory drugs and at the same time has a positive effect on the structure of joint tissues. In this case, one should take into account the doses of glucosamine and chondroitin, which were used in the largest foreign studies and are currently considered sufficient or therapeutic. For example, a therapeutic daily dose of glucosamine (1500 mg) and chondroitin (1200 mg) is contained in 3 capsules of the Teraflex drug and is therefore recommended for use in the first 3 weeks of treatment.
Glucosamine powder for the preparation of oral solution 1500 mg in bags No. 10
Name
Glucosamine.
Release form
Powder for the preparation of solution for oral administration.
Dosage
1.5 g 3.5 g. Quantity per package: 10 pcs.
Manufacturer
Amantismed LLC.
INN
Glucosamine.
FTG
Npvp.
Description
Powder consisting of particles of varying degrees of grinding, from white to white with a yellowish or white with a grayish tint.
Compound
Each package contains: active substance: glucosamine hydrochloride - 1500 mg; excipients: macrogol 4000, anhydrous citric acid, sorbitol.
Pharmacotherapeutic group
Other nonsteroidal anti-inflammatory and antirheumatic drugs. ATX code: M01AX05
pharmachologic effect
Glucosamine hydrochloride is a salt of the aminomonosaccharide glucosamine, which is an endogenous component and preferred substrate for the synthesis of glycosaminoglycans and proteoglycans in articular cartilage and synovial fluid. Glucosamine inhibits the activity of interleukin-1-β and other inflammatory mediators. Clinical efficacy and tolerability. The safety and effectiveness of glucosamine have been confirmed in clinical trials with treatment durations of up to three years. Short- and medium-term clinical studies have shown that the effectiveness of glucosamine in relation to the symptoms of osteoarthritis is observed after 2-3 weeks of its use. However, unlike NSAIDs, glucosamine has a long-lasting effect, lasting from 6 months to 3 years. Clinical studies with daily glucosamine supplementation for up to 3 years have shown gradual improvement in disease symptoms and slower structural changes in the joint, as demonstrated by plain radiography. Glucosamine has demonstrated good tolerability in both short- and long-term courses of treatment. Evidence of the drug's effectiveness was demonstrated when taken for three months, with residual effects for two months after its discontinuation. The safety and effectiveness of the drug have also been confirmed in clinical trials for up to three years. Continuous treatment for more than 3 years is not recommended, since there are no safety data when taking glucosamine for more than 3 years.
Indications for use
Relief of symptoms (mild to moderate pain) of adequately diagnosed osteoarthritis of the knee.
Directions for use and dosage
Orally, one packet (1500 mg) 1 time per day, preferably with meals. The contents of one package should be dissolved in a glass of water boiled and cooled to room temperature. Glucosamine is not intended for the treatment of acute pain symptoms. Symptom relief (especially pain relief) may only occur after several weeks of use, and sometimes longer. If symptom relief does not occur after 2-3 months of taking glucosamine, treatment should be reconsidered. Patients should consult a doctor if pain worsens after starting glucosamine. Dosage regimen for different categories of patients Elderly patients No dosage adjustment is required in elderly patients. Patients with impaired renal and/or hepatic function Glucosamine has not been studied in patients with impaired renal and/or hepatic function and therefore there are no dosing recommendations for these patients. Children and adolescents Glucosamine should not be used in children and adolescents under the age of 18 years, since there is no data on the safety and effectiveness of glucosamine in this category of patients.
Side effect
The frequency of development of adverse events is given in the following gradation: very often (≥ 1/10); often (≥ 1/100,
Contraindications
Hypersensitivity to glucosamine or any of the excipients. Powder for oral solution contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this drug. The drug should not be taken by patients who are allergic to shellfish, because The active ingredient (glucosamine) is obtained from mollusks and crustaceans. Pregnancy and breastfeeding period.
Overdose
There are no known cases of accidental or intentional overdose. In case of overdose, glucosamine should be discontinued, treatment is symptomatic, aimed at restoring water and electrolyte balance.
Precautionary measures
Before using glucosamine, you should consult your doctor to rule out the presence of joint diseases for which other treatment methods are prescribed. Cases of exacerbation of bronchial asthma symptoms have been described after starting to take glucosamine. Patients suffering from bronchial asthma should be informed about the possible worsening of symptoms of the disease. Patients with impaired glucose tolerance should use caution when taking glucosamine. For patients with diabetes mellitus, it is recommended to monitor glycemic levels and determine insulin requirements before and periodically during treatment. Sorbitol, which is part of the drug, can cause osmotic diarrhea. No special studies have been conducted in patients with impaired renal and/or liver function. According to toxicological and pharmacokinetic studies of glucosamine, such patients should not be dose limited. However, the use of glucosamine in patients with severe hepatic or renal impairment should be under medical supervision.
Use during pregnancy and lactation
There have been no studies on the effectiveness and safety of glucosamine in pregnant and lactating women, and therefore, taking the drug is not recommended for women during pregnancy and breastfeeding.
Impact on the ability to drive vehicles and other potentially dangerous mechanisms
There have been no studies of the effect of glucosamine on the ability to drive vehicles and other potentially dangerous mechanisms. You should refrain from driving vehicles or using other machinery if you develop drowsiness, dizziness, fatigue, headache or blurred vision.
Interaction with other drugs
Special studies on the interaction of glucosamine with other drugs have not been conducted. There are reports of an enhanced effect of coumarin anticoagulants, so more careful monitoring of coagulation parameters is necessary in patients concomitantly taking coumarin anticoagulants (for example, warfarin or acenocoumarol). Oral administration of glucosamine may increase the absorption of tetracyclines from the gastrointestinal tract, but the clinical significance of this interaction is small. The drug is compatible with non-steroidal anti-inflammatory drugs and glucocorticosteroids.
Storage conditions
In a place protected from moisture and light at a temperature not exceeding 25° C. Keep out of the reach of children.
Best before date
2 years. Do not use after the expiration date stated on the packaging.
Package
3500 mg (1500 mg of active substance) in bags made of multilayer packaging material (polyethylene terephthalate film / polypropylene film / aluminum foil / polyethylene film). 10 or 20 packets along with instructions for medical use in a cardboard pack.
Conditions for dispensing from pharmacies
Without a doctor's prescription.
Buy Glucosamine por.d/prig.d-ra for pr.vn.1500 mg in pack No. 10 in a pharmacy
Price for Glucosamine por.d/prig.d-ra for sq.vn.1500mg in package in unitary enterprise No. 10
Instructions for use for Glucosamine por.d/prig.sul.
Indications for use
Glucosamine has proven effective and indispensable in the treatment of many joint diseases. It is actively used for osteochondrosis, arthrosis, arthritis and other diseases. You just need to remember that the effects of glucosamine, as well as chondroitin sulfate, develop gradually. Therefore, the main indications for use are various manifestations of osteoarthritis:
- Pain
- Stiffness
- Crunching (characteristic sound when bending limbs)
- Swelling in the joint area
- Bone outgrowths (in case of advanced osteoarthritis)
Treatment or prevention?
Based on the above, we can conclude that glucosamine can be used not only to treat joint diseases, but also to prevent further progression of cartilage destruction. In order to curb dystrophic changes, the drug is prescribed when the first signs of the disease appear, as a rule, to athletes and people over 40, since these groups are most susceptible to the development of joint diseases. Glucosamine has established itself as an excellent substance in terms of effectiveness and safety profile, which has been popular for several decades.
The effectiveness of taking glucosamine in maintaining joint health has also been proven in combination with chondroitin. The combination of these substances promotes the restoration of cartilage tissue, increases the cartilage’s resistance to destruction and helps reduce pain1.
This combination is presented in the line of drugs “Teraflex” and “Teraflex Advance”, which helps reduce pain due to the presence of ibuprofen (a non-steroidal anti-inflammatory drug) in the composition, and the combination of glucosamine and chondroitin simultaneously begins to stimulate the renewal of cartilage tissue.
History of discovery and many years of experience in using glucosamine sulfate in clinical practice
The article discusses the current state of the problem of the effectiveness and safety of treatment of osteoarthritis with a focus on glucosamine sulfate. The history of the discovery of the compound, including its stabilized form, on the basis of which the prescription drug DONA (crystalline glucosamine sulfate) was created, is presented. The main pharmacokinetic indicators that determine its uniqueness, effectiveness and safety profile are outlined. Evidence is provided of the effectiveness and safety of glucosamine sulfate and crystalline glucosamine sulfate DONA in in vitro and in vivo studies. The contribution of Russian scientists to obtaining evidence of the effectiveness and safety of DONA in various treatment regimens for osteoarthritis of the knee joint is noted. The inclusion of the drug in the ESCEO treatment algorithm is justified.
Discovery of glucosamine
The history of the discovery of glucosamine is associated with the name of a German surgeon, professor at the University of Strasbourg, Georg Ledderhos. The substance was obtained in 1876 by hydrolysis of chitin and hydrochloric acid. 60 years later, in 1939, the English biochemist Walter Haworth presented the stereochemistry of this compound, after which other researchers joined the study of glucosamine. The main efforts were focused on studying the properties of the molecule, the beneficial qualities of the substance and the possibility of its use in clinical practice [1–3].
Endogenous and exogenous glucosamine
Glucosamine (2-amino-deoxyglucose) is an aminomonosaccharide that is endogenously synthesized in animals and humans by amination of glucose at position 2. The molecular weight of glucosamine is 179.17. The substance is soluble in water, sparingly soluble in methanol and ethanol, and practically insoluble in ether or chloroform. Its pKa is 7.52 at 20 °C and 6.91 at 37 °C [4, 5].
In 1971, it was found that glucosamine promotes the restoration of glycosaminoglycans, which are the basis of proteoglycans (a component of the cartilage matrix). The latter play a critical role in the synthesis of cartilage and bone tissue and provide compression resistance of cartilage [6]. It should be noted that glucosamine can also be obtained from food, mainly in seafood and fish.
With excessive stress and injuries, as age increases, or against the background of chronic diseases and a sedentary lifestyle, the body stops producing glucosamine in the required amount. Insufficient formation and supply of glucosamine is accompanied by impaired joint function and the occurrence of osteoarthritis (OA). Therefore, dietary supplements or medications containing it are used as an additional source of glucosamine to prevent or treat joint dysfunction.
Exogenous glucosamine has a direct effect on cartilage tissue and chondrocytes in OA [7–9]. It affects the expression of cartilage tissue genes, has anti-catabolic activity [10], reduces the production of prostaglandin E2 and prevents the activation of the nuclear factor kappa B signaling pathway, thereby inhibiting the intracellular cascade of signaling cytokines in chondrocytes and synovial cells, which is confirmed in in vitro
[8, 10–13].
Glucosamine prevents the activation of the proinflammatory and degenerative effects of interleukin 1β (IL-1β), which is produced in large quantities in OA joints [8]. IL-1β is not only a potent proinflammatory cytokine, but also a trigger for the expression of inflammatory factors such as cyclooxygenase 2, inducible nitric oxide synthase, IL-6, and tumor necrosis factor α (TNF-α). Helps increase the production of cartilage matrix degradation factors, primarily metalloproteinase (MMP) and disintegrin. Glucosamine reduces the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase and microsomal prostaglandin E synthase 1, the synthesis of prostaglandin E2 after stimulation with IL-1β, and is able to control the inflammatory cascade [14]. Long-term administration of glucosamine sulfate has been found to reduce cartilage destruction and MMP-3 mRNA expression in in vitro
[15].
These effects have been demonstrated in in vitro
for most glucosamine salts and glucosamine-based products.
The most common form of glucosamine is glucosamine hydrochloride. In a number of countries this product is registered as a food additive. The effectiveness of the compound has not been proven, and there is no certainty regarding pharmacokinetics.
Glucosamine hydrochloride is often used in combination with chondroitin sulfate. However, this complicates the assessment of the pharmacokinetic profile of such combinations. Chondroitin sulfate inhibits the absorption of glucosamine, as a result, the peak concentration of the latter decreases [5].
The use of glucosamine sulfate is accompanied by an increase in the concentration of sulfates, which makes it possible to compensate for the deficiency of inorganic sulfur in the body caused by low consumption of dietary proteins necessary for the synthesis of proteoglycans [16, 17].
In animals with surgically induced OA, the use of glucosamine sulfate significantly reduced the severity of synovitis (by 60%) compared to controls [18, 19]. However, surgically induced OA may not reflect all aspects of spontaneous idiopathic OA in humans. Studies in a human OA explant model have shown that glucosamine sulfate is a more potent inhibitor of gene expression than glucosamine hydrochloride when administered at comparable doses [20].
Crystalline glucosamine sulfate: study of efficacy and safety
In clinical practice, stable crystalline glucosamine sulfate (cGA-sulfate) is used. The pharmacokinetics and clinical effectiveness of this compound have been well studied.
The crystalline glucosamine sulfate molecule contains two sodium chloride molecules, which impart stability to the compound. This stabilized form was developed by , which subsequently created and introduced into clinical practice the prescription drug and the DONA brand. Other glucosamine sulfate preparations may differ from the original one. The composition may not contain the required amount of active substance, their effectiveness has not been adequately studied.
Crystalline glucosamine sulfate (DONA) is a prescription drug. It is registered in most European countries, as well as in the USA, Australia, Asia and Africa.
When dissolved in water or biological fluids, kHA sulfate forms a clear solution in which glucosamine, sulfate, chloride and sodium ions are present in a stoichiometric ratio of 2:1:2:2.
It is unknown whether the above effects of glucosamine in vitro
with therapeutic effects observed in clinical studies. However, it was found that cGA sulfate suppresses IL-1-stimulated gene expression of degeneration mediators in human chondrocytes at concentrations in the range of 10 μM, similar to those observed in the blood plasma and synovial fluid of the knee joint of patients with OA after the use of cGA sulfate at a therapeutic dose of 1500 mg/day [11]. The dose-dependent effect of kGA sulfate on IL-1β-induced gene expression of the matrix degradation factors MMP-3 (stromelysin 1) and ADAM-TS5 (aggrecanase 2) was confirmed [11]. Thus, kHA-sulfate at a dose of 1500 mg/day provides an acceptable therapeutic level of the substance in the blood - 8.9 μM/ml.
The half-life of kGA sulfate is 15 hours, which is sufficient for the drug to penetrate into the joint tissue and develop a therapeutic effect. Glucosamine hydrochloride, both when administered at a dose of 1500 mg/day and when administered at a dose of 500 mg three times a day, does not provide the required and clinically significant level of glucosamine in the blood (3.0 and 1.2 μM/ml, respectively). The half-life is also extremely short - 3.3 and 3.9 hours. Due to the rapid removal of glucosamine hydrochloride from the blood, it does not have time to penetrate the joint tissue and have a therapeutic effect.
The difference in therapeutic efficacy of different forms of glucosamine was confirmed in the most comprehensive meta-analysis on the use of glucosamine in OA and included in the latest edition of the Cochrane review (2009). It was first published in 2001 and updated in 2005 [21]. A 2009 Cochrane review analyzed data from 4963 patients from 25 clinical trials. The average age of study participants was 60.7 years. Of these, 69% are women. 1905 patients were randomized to treatment with glucosamine and 3058 to comparator drugs (placebo or active comparator). Most studies have been conducted with glucosamine sulfate (including cGA sulfate) and in patients with knee OA. A pooled analysis of placebo-controlled studies suggested a moderate analgesic effect (0.47), but results were inconsistent. The reason for this is the difference not only in the design/quality of the study, but also in the glucosamine salts used, their dosage forms and doses [8, 22].
Sensitivity analysis of methods and subgroups in a Cochrane review suggested that treatment effectiveness was demonstrated only in studies using crystalline glucosamine sulfate. Pooled results from studies using other products did not support positive results regarding pain and joint function. At the same time, studies using cHA sulfate (DONA) have established its superiority over placebo in the treatment of pain and functional disorders in OA.
A number of comparative studies have been carried out on the analgesic properties of cGA sulfate (DONA) and nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, a randomized, controlled, double-blind, multicenter, prospective study in parallel groups included 100 patients with knee OA who received cGA sulfate at a dose of 1500 mg/day, and 99 patients who received ibuprofen at a dose of 1200 mg/day. After four weeks of treatment, the Lequesne index decreased by approximately 40% in both groups. In the cGA-sulfate group, 48% responded to therapy, in the ibuprofen group - 52% (p = 0.67). Although the onset of action of ibuprofen was faster than that of HA-sulfate, the positive effect of the latter was observed after two weeks of treatment and was similar to the effect of NSAIDs.
The results obtained were confirmed in a study with a similar design, but in relation to a different ethnic group (178 patients from China) [23, 24].
Another large, prospective, multicenter, randomized, placebo-controlled, parallel-group comparative study included 319 patients with knee OA [25]. The duration of treatment was 12 weeks, the observation period in the absence of therapy was eight weeks. According to the results of the study, after two weeks of administration, kGA-sulfate at a dose of 1500 mg/day and piroxicam 20 mg/day demonstrated a comparable analgesic effect. After three months, the effectiveness of piroxicam was less than that of kHA sulfate. However, both drugs were more effective than placebo (p
The widely cited GUIDE study compared the analgesic effects of cHA sulfate 1500 mg/day, acetaminophen 3 g/day, or placebo [26]. The duration of therapy was six months. The GUIDE study confirmed that in patients with knee OA, the symptomatic effect of cGA sulfate was significantly superior to placebo. The effect of acetaminophen was not always different from the effect of placebo. Subsequently, in two- and three-year studies, for the first time for any of the pharmacological interventions, a significant slowdown in the radiographic progression of OA (the amount of joint space narrowing) was shown [27, 28].
Thus, cHA sulfate has been proven to have a structure-modifying effect and can therefore be considered a disease-modifying agent [27].
After five years, all patients with OA who participated in randomized placebo-controlled trials by JY Reginster et al. (2001) and K. Pavelka et al. (2002) and receiving cHA-sulfate at a dose of 1500 mg/day for at least 12 months were analyzed to study the need for arthroplasty. Of the 340 patients, information was obtained on 275, including 131 patients receiving placebo and 144 receiving cGA sulfate. The rate of knee replacement was more than twice as high in the placebo group – 19/131 (14.5%) versus 9/144 (6.3%) (p = 0.024). The relative risk was 0.43 with a 95% confidence interval of 0.20–0.92, a 57% reduction compared with placebo. Kaplan–Meier/log-rank survival analysis confirmed a significant reduction (p = 0.026) in the cumulative incidence of knee arthroplasty in those previously treated with cGA sulfate. It was concluded that the use of cHA sulfate for 12 months to three years was able to prevent knee arthroplasty for five years after cessation of treatment [29].
The post-marketing real-world cohort study PEGASus, organized by an independent scientific council and steering committee in France, found that cGA sulfate reduced the need for NSAIDs and analgesics [30]. In a study by G. Herrero-Beaumont et al. it was shown that the need to take NSAIDs or analgesics for pain relief was noted in 91.2% of OA patients receiving placebo, 79.2% receiving paracetamol and 77.6% receiving cGA sulfate [31]. Over six months, the average duration of use of NSAIDs or analgesics was 35.2 days in the placebo group, 27.8 days in the paracetamol group and 28.1 days in the cHA-sulfate group. The optimal duration of treatment with hGA-sulfate to alleviate the symptoms of OA is at least 12 weeks. In addition, it was noted that the therapeutic effect can persist for two months after the end of the course of therapy. Therefore, the most optimal treatment regimen for hGA-sulfate is as follows: take the drug for three months, take a three-month break. Thus, during each year there will be two cycles of therapy of three months each and two breaks also of three months [32].
In all short-term (maintenance) clinical studies, the drug's safety profile was good when compared with placebo or NSAIDs.
Thus, W. Noack et al. found that the tolerability of the drug was comparable to that of placebo [33]. The incidence of minor adverse events in the cGA-sulfate group reached 6%, in the placebo group – 10%. Routine laboratory tests at study entry and completion did not show any clinically significant changes. Treatment with crystalline glucosamine sulfate was significantly better tolerated than treatment with ibuprofen. Adverse events were recorded in 6 and 35% of patients, respectively (p
According to a recent Cochrane review, the safety profile of glucosamine is excellent [23]. Most of the studies presented here used cHA sulfate. Of 1883 patients randomized to glucosamine treatment, only 62 discontinued treatment due to toxicities. The number of patients with adverse events during therapy was 436 (based on 21 randomized controlled trials, n = 1451). Of the 1482 participants randomized to placebo, 70 discontinued treatment prematurely due to toxicities and 418 reported adverse events (n = 1061). Thus, glucosamine was as safe as placebo. When glucosamine was compared with placebo for the number of patients reporting adverse events, the resulting relative risk (fixed effect model) for the 13 randomized controlled trials was 0.99.
Due to the presence of sodium chloride in the kHA-sulfate molecule, the question arises about the risk of increased blood pressure during such therapy.
Blood pressure monitoring during six months of observation did not reveal an increase in either systolic or diastolic blood pressure in those using cGA sulfate [34]. No differences were noted with the placebo group. This allowed us to assert that taking kHA sulfate for a long period of time is not accompanied by an increase in blood pressure. According to the results of the VITAL prospective cohort study, which included 77,718 people of both sexes over 50 years of age, glucosamine intake was associated with a significant reduction not only in overall mortality (by 18%), but also in mortality due to malignant neoplasms (by 13%). Regular use of glucosamine reduced the risk of developing lung adenocarcinoma by 51%. Antiproliferative effects of glucosamine against malignantly transformed cells have been demonstrated in vitro
on different cell cultures [35–38].
In our country, interest in glucosamine is associated with the name of Academician V.A. Nasonova. Thanks to her efforts, several studies were initiated, approved and conducted that confirmed the effectiveness of cHA sulfate for knee OA. Thus, domestic scientists assessed the effectiveness and tolerability of two treatment regimens with cHA-sulfate. The first group received kHA-sulfate at a dose of 1500 mg per os (sachet) daily, the second group received kHA-sulfate at a dose of 1500 mg per os (sachet) daily and 400 mg intramuscularly three times a week in the first three weeks. An open randomized prospective study included 60 patients with knee OA. The duration of the study was eight weeks, including six weeks of treatment, two weeks of observation. The following parameters were assessed: pain intensity on a Likert scale, general disease activity (separately by the doctor and the patient), severity of pain, morning stiffness and functional activity on WOMAC (mm on a visual analogue scale), intensity of pain at rest, starting pain on the third, sixth , eighth week, the severity of synovitis, the time of onset of the effect of therapy. During treatment, pain in the analyzed knee joint decreased in both groups. In the second group, a significant reduction in pain at rest was recorded after three weeks of therapy (p
Another widely cited Russian study was devoted to the study of clinical and instrumental characteristics, assessing the effectiveness and tolerability of acetaminophen, cGA sulfate, chondroitin sulfate and meloxicam in 80 patients with knee OA [41]. The design was an open, randomized, prospective, parallel group comparative study. The duration of the study was 18 months. In addition to clinical parameters reflecting the course of the disease (WOMAC, Lequesne algofunctional index), modern instrumental examination methods were used, such as standardized radiography of the knee joints under weight-bearing conditions, ultrasound tomography, magnetic resonance imaging of the knee joints and arthroscopy. This made it possible to visualize structural changes in OA and objectify the assessment of pharmacotherapy. The study found that the anti-inflammatory activity of meloxicam in doses of 7.5–15 mg/day, kHA sulfate in a dose of 1500 mg/day and chondroitin sulfate in doses of 1000–1500 mg/day are comparable. The proportion of responders to treatment according to OMERACT-OARSI in the meloxicam group was higher than in the cHA-sulfate and chondroitin sulfate groups - 100, 90 and 90%, respectively. Among those receiving paracetamol up to 2 g/day, this was 75%. Thus, the anti-inflammatory effect of acetaminophen has not been confirmed. The analgesic effect was proven for all studied drugs. Analysis of the data obtained led to the conclusion that with long-term use, meloxicam, kHA-sulfate and chondroitin sulfate can slow down the progression of knee OA. In addition, those taking acetaminophen had a statistically significant decrease in the joint space in the medial part of the knee joint, which indicated progression of the disease. During the study, the average narrowing of the joint space was the smallest in the cHA-sulfate group (-0.07; p = 0.0002) when compared with chondroitin sulfate (-0.1; p = 0.004), meloxicam (-0.06; p = 0.006) and acetaminophen (-0.37). The proportion of patients without severe joint space narrowing (>0.5 mm) was the smallest in the cGA-sulfate group compared with the other three groups. Regardless of the therapy received by patients, stabilization of chondropathy and a significant decrease in signs of synovitis, according to magnetic resonance imaging, were noted in all analyzed areas of the knee joint. The positive effect of KHA-sulfate, chondroitin sulfate and meloxicam on articular cartilage was confirmed by the results of arthroscopy in the analysis of the quantitative assessment of chondropathy (SFA-score). After 18 months, stabilization of the SFA score was noted in these groups. No positive dynamics were noted in the acetaminophen group.
Another domestic study was devoted to assessing the role of therapy for knee OA of stages 2 and 3 according to the Kellgren-Lawrence classification in 96 patients in the postoperative period (local articular cartilage defects according to the Outerbridge classification corresponded to stages 3 and 4) [42]. All patients underwent mosaic autochondroplasty, which turned out to be effective for restoring local defects of the articular surface. After mosaicplasty, patients could receive cHA sulfate for two years or NSAID therapy to relieve symptoms. The use of kHA-sulfate in the postoperative period had a positive structural-modifying effect on the hyaline cartilage of the knee joint and its function, assessed by the IKDC scale, in the medium term. The mean IKDC score at two years was 50.5 ± 4.98 for mosaic grafting and KGA-sulfate and 42.33 ± 6.69 for mosaic grafting and NSAIDs.
Thus, the history of the study of glucosamine sulfate, a careful analysis of the evidence obtained from in vitro
and
in vivo
, many years of experience with the use of kHA-sulfate in real clinical practice suggest that the drug is effective in OA. It affects the main pathogenetic mechanisms of the disease. It has symptom-modifying, structure-modifying and disease-modifying effects.
Currently, crystalline glucosamine sulfate is included in national and international clinical guidelines for the treatment of OA.
Conclusion
According to domestic epidemiological studies, OA of the knee and/or hip joints affects 13% of the Russian population over 18 years of age [43]. In 2021, the total incidence of OA in our country was 4,285,464 cases, or 3646.3 cases per 100 thousand adults, and the primary incidence was 683.4 cases per 100 thousand adults [44]. Considering the forecast of experts regarding the increase in the number of patients with OA, and therefore the increase in costs for healthcare and social institutions, it becomes obvious that the search for adequate and effective treatments remains an urgent task.
The choice of treatment involves an analysis of risk factors for the disease, the age of the patients at the time of the development of the disease or treatment, the range of comorbid conditions, the location and severity of changes in the joint (joints), the evidence base for the effectiveness and safety of the drugs that are planned to be used, and much more.
Treatment should primarily be aimed at reducing pain and improving the functional state of the joints.
In 2014, experts from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) proposed a unified step-by-step algorithm for the treatment of OA, which was successfully implemented in many countries around the world, including Russia [44, 45]. The ESCEO algorithm allows you to update and adapt treatment guidelines (with a thorough analysis of evidence), determine the priority of activities depending on the clinical manifestations of the disease, the effectiveness of the treatment, and the presence of comorbid conditions. It should be noted that this is the first experience in creating a detailed algorithm that allows doctors of different specialties to navigate numerous methods of treating OA and choose adequate therapy at different stages of the disease.
In 2021, the ESCEO algorithm was revised in response to new data. In particular, we are talking about obtaining evidence that paracetamol is not the “analgesic of choice”, since it provides minimal, probably clinically insignificant benefits in patients with osteoarthritis of the hip or knee joint [46–48]. At the same time, glucosamine sulfate, the original preparation of kGA-sulfate, has taken a central place in the algorithm for the treatment of osteoarthritis.
The original kHA-sulfate (DONA) is available in the form of 1500 mg sachet, 2 ml solution for intramuscular administration and 750 mg tablets. When taken orally, the first option is to dissolve the contents of one sachet in 200 ml of water, take the sachet once a day, the second option is to take one tablet twice a day, preferably with meals, with a glass of water. The minimum course of therapy is six weeks. When administered intramuscularly, the kGA sulfate contained in the ampoule must be mixed with 1 ml of water for injection. The prepared solution is administered 3 ml once a day three times a week for four to six weeks.
Injections of the drug can be combined with oral administration (powder or tablets).
The symptomatic effect occurs two to three weeks from the start of therapy. If necessary, the course of treatment is repeated at intervals of two months.
The duration and treatment regimen are prescribed individually.