Treatment of joint syndromes in elderly patients

Differential diagnosis of articular syndrome

What are the differences between inflammatory synovitis and degenerative joint disease?

What are the clinical variants of the onset of arthritis in various diseases?

What laboratory tests are the most informative?

Articular syndrome is an almost universal manifestation of rheumatic diseases; its differential diagnosis underlies the determination of the nosological form, and therefore serves as a justification for the choice of therapeutic approach. In advanced stages of the disease, when there are organic changes in organs and tissues, the diagnostic problem is greatly simplified. Serious analysis is required at the onset, often represented exclusively by arthralgias.

Examination of patients complaining of arthralgia is aimed at identifying which structures of the musculoskeletal system are the source of pain or dysfunction. Joints are composed of surfaces of articular cartilage, bone, ligaments, and synovium. The joint space is not an unfilled space, as it seems to us when examining radiographs, but is represented by articular cartilage, transparent to X-rays; therefore, the degree of destruction of cartilage can be assessed radiographically by measuring the distance between two bone surfaces. Cartilage differs from bone in its more elastic composition, has a lower coefficient of friction and, most importantly, does not have the restorative abilities of bone. Therefore, cartilage damage must be considered as an irreversible process.

Cartilage defect or loss can occur in two ways:

• mechanical abrasion, as happens with osteoarthritis;
• erosion as a consequence of inflammatory synovitis in rheumatoid arthritis or other rheumatic diseases.

The synovium extends between the osteochondral borders on both sides and does not normally cover the articular cartilage. Its surface is represented by one or two layers of synoviocytes, capable of morphological adaptation, reflecting the function performed by the cell at the moment - synthetic or phagocytic. The histological picture of the initial stage of inflammatory synovitis is similar in most diseases. For example, it is impossible to distinguish ankylosing spondylitis from rheumatoid arthritis with a biopsy of the synovial membranes. Only in certain situations, for example in the case of tuberculous arthritis, can the diagnosis be based on biopsy findings.

As rheumatoid arthritis progresses, the process acquires the following characteristic features: erosive synovitis develops, corroding both cartilage and bone. Synovial villi, hypertrophied during the inflammatory process, are attached to the adjacent edge of the articular cartilage, creeping onto its surface. This inflammatory tissue replaces cartilage. This cartilage-replacing tissue is known as pannus and is composed of fibrous tissue infiltrated by chronic inflammatory cells, including mast cells. At the edge of the articular cartilage, the pannus replaces bone tissue, causing the occurrence of erosions detected by x-ray examination. Pannus can also penetrate the subchondral bone plate and grow in the subchondral bone.

Because cartilage is destroyed more quickly, progressive erosive synovitis appears on radiographs first as cartilage loss, then as periarticular bone erosion. It is important to note that persistent synovitis prevents the formation of osteophytes adjacent to the diminishing cartilage tissue. So, the radiological signs of chronic persistent synovitis are:

• loss of cartilage;
• Usuration of the bone adjacent to the places of thinning of the cartilaginous plates;
• no signs of osteophytes.

As the disease progresses, the vascularization of the synovium decreases (compared to earlier stages), which, on the one hand, is associated with fibrosis as a stage in the evolution of the disease, and on the other, with the immobility that develops as a result of fibrosis. The so-called “burnt-out rheumatoid arthritis” is formed. This expression can be considered unfortunate, since although physical examination reveals the absence of hyperthermia, effusion and hyperemia, the patients still have morning stiffness, an increase in ESR and, more importantly, with dynamic radiographic observation, bone usuration increases.

Degenerative joint diseases have completely different characteristics.

• No synovitis. (This, by the way, explains the low effectiveness of anti-inflammatory drugs for this disease.)
• The cartilage defect is localized in areas of mechanical damage. Often there is a juxtaposition of almost normal cartilage with areas where the cartilage is completely worn out.
• The appearance of osteophytes in the vicinity of areas of cartilage defects.

Only in the later stages of osteoarthritis can pain occur both during exercise and at rest and disturb night sleep. Since cartilage does not have a regenerative ability, once a symptom complex has arisen, it tends to progress. However, in cases of ordinary household loads, the cartilage wears out very gradually and the deterioration increases gradually, over the years. Symptoms of synovitis persist at rest and are only accentuated during exercise.

Morning stiffness, characteristic of rheumatoid arthritis, ankylosing spondylitis and other systemic diseases, usually lasts for at least two hours. This symptom is associated with a physiological drop in the level of corticosteroids in the blood in the pre-dawn hours and with the accumulation of cytokines from the inflammatory fluid during sleep. Morning stiffness with osteoarthritis is transient, lasts no more than 20 minutes and does not coincide with objective symptoms. The duration of morning stiffness in systemic rheumatic diseases is directly dependent on the severity of inflammatory reactions. For example, one of the important criteria for remission of rheumatoid arthritis is the complete disappearance of morning stiffness.

With the exception of gout, synovitis is a manifestation of systemic diseases; patients show signs of a generalized process. Osteoporosis, on the contrary, is formed due to local mechanical effects and, naturally, is not accompanied by systemic effects.

Osteoarthritis affects almost exclusively the joints that experience weight bearing - the hip, knee, and first metatarsophalangeal. Polyarthrosis, as a rule, is familial in nature and is caused by genetic inferiority of cartilage and ligamentous apparatus. The appearance of deformations in the elbows, metacarpophalangeal, and wrist joints should be considered as a manifestation of inflammatory reactions.

As soon as degenerative joint damage begins to manifest itself clinically, its typical signs can also be detected on radiographs. At the same time, the initial stages of synovitis are X-ray negative. Usuration of bones is visible only when the process is advanced. Differential diagnostic characteristics of articular syndrome in osteoarthritis and systemic synovitis are presented in the table.

For many systemic diseases, the diagnosis becomes obvious only after a few months, when the classic symptom complex is formed. Significant diagnostic difficulties always arise in the early stages. However, there are certain characteristic opening options:

• acute monoarthritis,
• migratory arthritis,
• intermittent arthritis,
• spreading arthritis.

Acute monoarthritis most often occurs with septic lesions and synovitis, with microcrystalline arthritis. Both diagnoses can be verified quite easily using a diagnostic puncture and cultural or crystallographic analysis of synovial fluid.

The term “migratory” arthritis is used in cases where the inflammation in the initially affected joint completely subsides and the process resumes in the next ones. This option is quite rare and is characteristic of rheumatism and gonococcal arthritis.

Intermittent outbreaks of arthritis after a long period of remission occur in gout, spondylitis, psoriatic arthritis and arthritis associated with intestinal infection.

Spreading arthritis is the most nonspecific: in this case, with persistent inflammation in the initially affected joint, more and more joints are involved in the process.

When making a diagnosis, it is very important to take into account family history, for example, information about the presence of Heberden's nodes, gout, spondylitis, SLE, and hemochromatosis in the family.

When physically examining joints, three parameters must be taken into account: pain (sensitivity), swelling, and mobility. Synovitis is characterized by pain (sensitivity) throughout the entire joint. If the pain is localized only in a certain area (point) of the joint, you should think about a local, local cause of its occurrence, such as bursitis, tenosynovitis or fracture. Bone crepitus and osteophyte formation are cardinal features of degenerative joint disease. While effusion and thickening of the synovium are typical for synovitis. It is important to remember that soft tissue swelling is not detected on physical examination of axial joints and is rarely detected in proximal joints such as the shoulder or hip. In addition to the range of motion protocol, it can be noted whether there is a significant difference between passive and active range of motion. This difference indicates that the lesion is due to muscle weakness, tendon rupture, or neurological pathology, but not to bone blockage.

Analysis of the involvement of a specific joint in the process can be very important, since some joints are never affected in certain diseases and, on the contrary, for many nosologies there are typical localizations.

The temporomandibular joint, for example, is often involved in rheumatoid arthritis but is never involved in gout. The cervical spine is often affected in RA, spondylitis and osteoarthritis, but never in gonococcal arthritis or gout. The laryngeal joints are affected in a third of all cases of rheumatoid arthritis and are extremely rare in other types of inflammatory joint lesions. Characteristic symptoms of inflammation of the joints of the larynx are pain in the throat, localized in the larynx and accompanied by a change in voice. Both symptoms may only be evident for a few hours in the morning. Synovitis usually develops in non-weight-bearing joints of the upper extremities, whereas osteoporosis does not occur in the elbow, metacarpal, or wrist joints. Spondylitis, as a rule, progresses from the sacroilial joint up the spine, the location of which may vary. Rheumatoid arthritis, in turn, affects only the cervical region and does not cause lower back pain.

It has been observed that some joints are never affected at the onset of rheumatoid arthritis. These are the so-called articular exceptions - distal interphalangeal joint, metacarpophalangeal joint of the thumb, proximal interphalangeal joint of the fifth finger.

Study of the olecranon region is often very fruitful in the evaluation of rheumatic diseases, since rheumatoid nodules, gouty tophi or psoriatic plaques are most often localized here. Rheumatoid nodules are also often located in the iliac region, on the ears, along the spine and may be indistinguishable from tophy on physical examination. However, rheumatoid nodules can be detected already in the early stages of the disease, are very characteristic of the initial outbreak and tend to decrease in size over time. Tophi often occur earlier than several years after the patient is given a clinically obvious diagnosis. Sometimes specific diagnosis requires biopsy of the nodule or aspiration of the tophi to identify crystals. Gout is clearly diagnosed by detecting uric acid crystals in synovial fluid aspirated from the inflamed joint. Serum uric acid levels can only indicate susceptibility to gout.

When conducting an X-ray examination, it should be remembered that: 1) osteoporosis is nonspecific and is often a consequence of immobility associated with pain; 2) narrowing of the joint space indicates loss of cartilage; 3) new bone growths indicate osteosclerosis, are a sign of osteophytes and the absence of synovitis; 4) soft tissue swelling is best diagnosed by physical examination.

It is important to remember that x-rays show the condition of the bones, not the cartilage or synovium, and since the destruction of cartilage takes time, the x-ray usually lags the clinical picture by several weeks. More specific information appears after three to four years, when erosion (usuration) of the articular cartilage occurs with granulation connective tissue - pannus.

The most informative laboratory test for rheumatoid arthritis is the latex test, aimed at identifying rheumatoid factor.

What is the diagnostic value of the latex test?

About 5% of healthy young people and 15% of older people have a positive latex test. Since rheumatoid arthritis affects approximately 1% of the population, it can be stated that only 15-20% of seropositive people suffer from rheumatoid arthritis. Only 85% of patients with an established diagnosis are seropositive. Thus, it is obvious that the latex test does not confirm or exclude the presence of the disease. The latex test is also often positive in other systemic connective tissue diseases, as well as in some chronic inflammations such as tuberculosis, gout, and bacterial endocarditis.

Once a positive titer of rheumatoid factor is detected, it persists throughout the disease. Therefore, there is no particular need for repeat studies in patients with obvious rheumatoid arthritis. However, serological tests are usually negative in the initial stages and become positive as the disease progresses.

This reaction has prognostic significance. In general, in seropositive patients the process is unfavorable; subcutaneous rheumatoid nodules are often involved. It should be noted that the detection of rheumatoid factor increases with age. In general, the classic debut of the disease, manifested by a typical symptom complex and a high titer of rheumatoid factor, is characteristic of patients aged 55-65 years. In this group of patients, the process progresses rapidly, and erosion of the articular surfaces develops early.

Negative results of a study of rheumatoid factor during long-term observation of a seriously ill patient force us to look for another disease that occurs with rheumatoid-like joint syndrome.

Treatment of joint syndromes in elderly patients

The widespread use of NSAIDs raises the issue of the safety of these drugs, especially in elderly patients. This is due to the presence of concomitant diseases in most of them and the need for concomitant therapy, which is a risk factor for the development of complications of anti-inflammatory drugs. This primarily applies to rheumatic diseases, which are more common in older people (OA, degenerative diseases of the spine). OA is the most common articular pathology, the share of which among rheumatic diseases is 60% [2,3]. OA occupies one of the first places among the causes of disability, and among people over 60 years of age, every third person has manifestations of OA [4]. The problem of comorbidity in OA always worries clinicians. In recent years, more and more new data have emerged on the frequency of concomitant pathologies in patients with diseases of the musculoskeletal system, primarily in patients with OA. Indeed, growing demographic shifts towards a significant increase in the number of elderly and senile people urgently dictate the need for the development and introduction of new drugs. This trend is especially clearly visible in relation to NSAIDs. The side effects of NSAIDs are well known: complications from the gastrointestinal tract, kidneys, arterial hypertension, bronchial asthma [5]. Frequent side effects have prompted the search for new drugs that simultaneously effectively reduce pain and inflammation and are well tolerated. A prerequisite for the creation of safer NSAIDs was the discovery in the early 90s of the last century of two isoforms of cyclooxygenase (COX) - the constitutional (physiological) isoenzyme COX-1, which catalyzes the formation of prostaglandins (PGs), involved in the implementation of physiological reactions, and the “pathological” one. isoenzyme – COX-2, the expression of which under the influence of pathogenic stimuli leads to the production of mediators and modulators of inflammatory and pain reactions. The practical result of these studies was the introduction into clinical practice of drugs that primarily suppress the production of COX-2, an isoenzyme that catalyzes the synthesis of PGs involved in the inflammatory process. These are so-called selective and specific NSAIDs, the use of which can significantly reduce the incidence of side effects (mainly gastropathy and nephropathy) [6]. Subsequently, it was revealed that not only COX-2, but also COX-1 is involved in the development of inflammation and pain, and COX-2 is involved in the synthesis of prostaglandins, which play an important role in the healing of ulcers of the upper gastrointestinal tract, as well as in the synthesis prostacyclin by vascular endothelial cells, which enhances the antithrombotic effect. This circumstance is especially important in relation to patients with concomitant cardiovascular pathology. In this regard, in recent years, the assumption has been substantiated that “standard” non-selective COX inhibitors in some cases may have an advantage over specific COX-2 inhibitors (coxibs) in the long-term treatment of OA in elderly people with diseases of the cardiovascular system. Moreover, recently new facts have been identified that cast doubt on the higher safety of specific COX-2 inhibitors, including in relation to the gastrointestinal tract. Thus, in a number of large-scale studies comparing standard and specific COX-2 inhibitors, an insignificant difference in ulcerative complications in the comparison groups was revealed, and the incidence of myocardial infarction was 4 times higher in the group of specific COX-2 inhibitors. Drugs in this group also increased the incidence of thrombotic cardiovascular events, which makes their use in elderly patients problematic [7,8]. Thus, highly selective (specific) COX-2 inhibitors are characterized by a low risk of gastrointestinal complications and an increased risk of thrombotic cardiovascular complications; non-selective NSAIDs - a high risk of gastrointestinal and hypervolemic cardiovascular complications (sodium and water retention, edema, increased blood pressure). In this regard, the “golden mean” can be considered drugs with a predominantly selective effect on COX-2. One of the first such NSAIDs to receive widespread practical use was meloxicam (Movix). Movix exhibits significantly higher inhibitory activity against COX-2 (about 12 times) compared to COX-1. As a result, the synthesis of prostaglandins is reduced in the inflammation site to a much greater extent than in the gastric mucosa and kidneys. This is a significant advantage of Movix over other NSAIDs. In addition to influencing the synthesis of prostaglandins, meloxicam (Movix) inhibits lipid peroxidation, reduces the formation of free oxygen radicals, platelet activating factor, tumor necrosis factor-alpha, proteinases and other inflammatory mediators. Preclinical data have demonstrated that meloxicam exhibits significant anti-inflammatory activity and a good gastrointestinal and renal tolerability profile. Does not show mutagenic, clastogenic and oncogenic potential in animal experiments. Experimental data suggest that meloxicam has a favorable safety profile. Meloxicam (Movix) has favorable pharmacokinetic properties. The long half-life (20 hours) allows the drug to be taken once a day, which makes it convenient for use and promotes strict patient compliance with the treatment regimen. Meloxicam is metabolized into inactive metabolites, which are excreted in half proportions in feces and urine. At the same time, taking meloxicam practically does not aggravate liver and kidney failure. Plasma concentrations of meloxicam in older men are similar to those in younger adults, but may be slightly increased in older women. The advantage of meloxicam is its compatibility with antacids, cimetidine, acetylsalicylic acid (ASA), methotrexate, warfarin, furosemide - drugs that are most often taken by middle-aged and elderly patients suffering not only from joint diseases, but also from cardiovascular diseases, fluid disorders salt metabolism, tendency to hypercoagulation. Compatibility with methotrexate distinguishes meloxicam from other NSAIDs, the simultaneous use of which with methotrexate is often accompanied by toxic effects on the liver and gastrointestinal tract. The analgesic effect of meloxicam increases when combined with muscle relaxants, which is especially important for vertebrogenic pain syndromes. Unlike traditional NSAIDs, meloxicam does not have a damaging effect on articular cartilage. A study of the effect of NSAIDs on metabolic processes in cartilage in patients with osteoarthritis has demonstrated that many of them are capable of accelerating the destruction of cartilage in OA. Experimental studies have shown that, unlike traditional NSAIDs, meloxicam does not have a negative effect on the metabolism of proteoglycans in human osteoarthritis cartilage explants [9]. Meloxicam potentially inhibited PGE2 synthesis in cultured human chondrocytes, preventing chondrolysis. Meloxicam did not affect the processes of cartilage formation and DNA synthesis in cultured chondrocytes. Data demonstrating the role of chondrocyte apoptosis in the pathogenesis of OA also substantiate the advisability of using relatively safe NSAIDs, in particular meloxicam, in OA [10]. A number of studies have demonstrated not only a therapeutic effect, but also significant advantages in terms of tolerability of meloxicam compared to other NSAIDs in patients with OA [11–14]. A comparative study of the effectiveness and tolerability of meloxicam 7.5 mg per day and diclofenac 100 mg per day for OA, conducted during the double-blind randomized clinical trial MELISSA, involved about 10 thousand patients [9]. Meloxicam was not inferior to diclofenac in terms of its effect on the intensity of pain, objective signs of inflammation and the general condition of patients. Meloxicam was better tolerated: adverse events were noted in 13% of patients receiving meloxicam and in 19% receiving diclofenac. At the same time, severe complications from the gastrointestinal tract were observed less frequently in the meloxicam group, and treatment discontinuation due to side effects was observed less frequently in the meloxicam group (5.4 and 7.9%, respectively). Among the patients included in the study, there were more patients in the meloxicam group with a history of peptic ulcers, but tolerability was assessed by patients as good in 95% of patients taking meloxicam and in 86% of patients taking diclofenac. In a comparative evaluation of meloxicam 7.5 mg per day and piroxicam 20 mg per day for OA during a 4-week double-blind randomized study involving more than 8 thousand people, it turned out that both drugs were equally effective in relation to joint symptoms as assessed by doctors and patients [eleven]. Adverse reactions were significantly less frequently observed in the meloxicam group (22.5%) than in the piroxicam group (27.9%), and were manifested mainly by gastrointestinal disorders. Thus, studies in large groups of patients have shown better tolerability of meloxicam compared to other NSAIDs. Meloxicam has established itself as an effective and safe drug for relieving pain in osteoarthritis of the facet joints of the spine - spondyloarthrosis. Spondyloarthrosis is characterized by pain and stiffness of the spine, especially limited painful extension. Due to pain and protective muscle spasm, active and passive movements are significantly limited. A feature of spinal pain syndromes is a combination of reflex muscle-tonic and myofascial syndromes with changes in the emotional sphere, which contributes to the chronicity of pain. A key role in the formation of a pain impulse caused by inflammation, damage or ischemia is played by algogenic compounds - serotonin, histamine, prostaglandins, bradykinin. The prolonged release of inflammatory mediators leads to sensitization of nosoceptors and the formation of “secondary hyperalgesia” of damaged tissue, which leads to a chronic pathological process. Prostaglandins increase the sensitivity of nociceptors to various stimuli, and their accumulation correlates with the intensity of inflammation and hyperalgesia. Since the importance of COX-2 in the cascade of conversion of arachidonic acid to prostaglandins was shown, interest in its role in the development of a painful stimulus and the mechanism of pain reduction when COX-2 is suppressed has increased enormously. Special studies have shown that the activity of COX-2 plays a large role in the development of hyperalgesia, therefore inhibition of COX-2 is considered as one of the most important mechanisms of anti-inflammatory and analgesic activity. These data justify the use of COX-2 inhibitors in the complex treatment of vertebrogenic pain. This type of pain often occurs in patients of older age groups, who are more sensitive than others to the undesirable effects of medications. Therefore, it is important that the drug used to treat this form of pain syndrome is well tolerated during long-term use, necessary for chronic diseases, and is well combined with other drugs. Meloxicam meets these requirements, as was shown in a comparative study of the effectiveness and tolerability of meloxicam and diclofenac in patients with spondyloarthrosis [15]. The study involved more than 200 patients who were prescribed meloxicam at a dose of 7.5 mg per day or diclofenac at a dose of 100 mg per day. The result was assessed before the start of treatment, as well as after 3, 7 and 14 days of treatment. Both drugs demonstrated similar effectiveness: back pain during movement significantly decreased after 3 days of taking both drugs and remained at the achieved level by the 14th day. There were no statistically significant differences in the effectiveness of both drugs, while the tolerability of meloxicam was significantly better than diclofenac as assessed by both patients and researchers. Meloxicam has been successfully used to treat lesions of the periarticular tissues of the shoulder L. Vidal et al. compared the effectiveness of two doses of meloxicam - 7.5 and 15 mg per day and piroxicam 20 mg per day in the treatment of inflammation of the soft periarticular tissues of the shoulder joint [16]. The effectiveness of treatment was assessed based on a survey of patients after 7 days of treatment. It turned out that both drugs were comparable in both effectiveness and tolerability, but the number of adverse events in those receiving meloxicam was lower, and no differences were detected between the two doses of meloxicam. Meloxicam has proven effective in treating not only degenerative but also inflammatory joint diseases. A number of studies have demonstrated that in patients with RA, meloxicam is no less effective than diclofenac, piroxicam and naproxen [11,17]. In a 6-month double-blind comparative trial of 7.5 mg/day meloxicam and 750 mg/day naproxen, the efficacy of both drugs was approximately the same, but meloxicam was better tolerated, particularly in relation to the gastrointestinal tract and kidneys [14]. In the meloxicam group, various gastrointestinal complications were noted in 30.3% of patients, while in the naproxen group – in 44.7%. Gastric ulcers developed in 2 patients treated with naproxen and none with meloxicam. The decrease in hemoglobin and increase in creatinine in the naproxen group was also significantly greater than in the meloxicam group. The work of English authors presents the results of long-term (18-month) treatment of 357 patients with RA with meloxicam at a dose of 15 mg per day [18]. By the end of follow-up, the overall visual analog scale (VAS) score for disease activity decreased from an average of 3.32 to 2.33 cm. Indicators such as morning stiffness, night pain, and Ritchie joint index also improved. Only 11.4% of patients interrupted treatment due to lack of effectiveness. The drug was well tolerated. Only 13.7% discontinued treatment due to side effects, which included gastrointestinal, musculoskeletal, skin and respiratory disorders. Severe side effects, such as ulcers with bleeding or perforation, were noted in only 3 patients (0.8%). Thus, in the long-term treatment of inflammatory joint diseases, meloxicam is not inferior in effectiveness to standard NSAIDs and is clearly superior to them in tolerability. It is known that most NSAIDs can provoke bronchospasm, as well as worsen the course of bronchial asthma and hay fever. These side effects are due to COX-1 inhibition, so it is reasonable to assume that selective COX-2 inhibitors will be acceptable for the treatment of this category of patients. In this regard, S. Bavbek et al. tried to answer the question of whether it is possible to use meloxicam in people predisposed to “aspirin-induced” bronchial asthma [19]. It turned out that of the 21 patients who took part in the study, only one developed bronchospasm during treatment with meloxicam at a dose of 7.5 mg per day. The study demonstrated that meloxicam 7.5 mg may be a safe alternative to standard NSAIDs in patients with asthma and hay fever. The problems of NSAID gastropathy are quite often discussed in the literature. Data on kidney complications are less frequently reported. Non-selective NSAIDs cause a decrease in the level of renal prostaglandins, which leads to impaired Na excretion, fluid retention, development of arterial hypertension or worsening of its course. At the same time, the effectiveness of antihypertensive drugs decreases, which dictates the need for careful monitoring of blood pressure and dose adjustment of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics. According to the results of pathological studies, interstitial nephritis is observed in 60–100% of patients with RA who are forced to take full therapeutic doses of non-selective NSAIDs for years. The development of acute renal failure (ARF) is possible. A thorough analysis of the risk of developing acute renal failure in elderly patients was carried out in the USA [22]. According to the program for assessing the effectiveness and safety of drugs prescribed between 1999 and 2004. in persons over 65 years of age, the side effects of NSAIDs were assessed when taken for 6 months or more. Of 183,446 patients with a mean age of 78 years, AKI leading to hospitalization occurred in 870 patients. It turned out that meloxicam had the lowest risk of developing acute renal failure among the selective and non-selective NSAIDs analyzed. In 2001, data were reported on a meta-analysis of the results of treatment with meloxicam in 27 thousand patients [20]. According to these data, the frequency of cardiovascular adverse reactions during treatment with meloxicam was no higher than when using non-selective NSAIDs. There is a report of a trial study of the use of meloxicam 15 mg intravenously for acute coronary syndrome in 60 patients receiving standard treatment with ASA and heparin, compared with 60 patients receiving the same doses of ASA and heparin without meloxicam. It turned out that the addition of meloxicam to standard therapy in the assessment of the outcomes of acute coronary syndrome (relapse of angina pectoris, myocardial infarction (NIM) or fatal outcome) led to a decrease in the frequency of negative outcomes from 38.3 to 15% during stay in the hospital and from 48.3.3.3.3.3.3.3 up to 26.7% 90 days after treatment [21]. Thus, meloxicam is an effective drug that is not inferior in terms of the severity of the anti -inflammatory and analgesic effect of many traditional NSAIDs and beneficial to them with good tolerance, which allows it to be used as therapy for the first row to treat inflammatory and degenerative joint diseases. 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