Treatment of osteoarthritis: use of glucocorticosteroids

Systemic use of corticosteroids in osteoarthritis is not shown, but intraarticular and periarticular injections of prolonged (depot) forms of corticosteroids give a significant, albeit temporary, symptomatic effect.

The variety of NSAIDs in the modern pharmaceutical market and the abundance of often contradictory information about their pharmacodynamics, efficacy and safety make it difficult to choose a drug. It is not always possible to extrapolate the results of a multi-centered controlled efficacy study to a particular patient. As it was mentioned above, the main sign according to which NSAIDs differ among themselves is their tolerability.

Evidence of the advantages of some NSAIDs over others with regard to analgesic and anti-inflammatory properties are absent. In addition, in light of the recent discoveries of more complex mechanisms of COX-1 and COX-2 involvement in pathological and physiological processes, it becomes apparent that selective and even specific (coxib) COX-2 inhibitors are not "ideal" NSAIDs. In order to ensure effective and safe treatment, first of all, a thorough examination of the patient is necessary in order to eliminate the risk factors for the development of side effects. If a risk of developing gastropathy is found, it is rational to prescribe selective or specific inhibitors of COX-2. If a non-selective NSAID exhibits significant efficacy in a particular patient, it can be administered in combination with misoprostol, proton pump inhibitors, or H ₂ -receptor antagonists .

In the presence of signs of renal failure, it is not advisable to prescribe NSAIDs, but if NSAIDs are necessary, preference should be given to specific inhibitors of COX-2, while treatment should be carefully monitored for serum creatinine. Patients with a risk of thrombosis during treatment with COX-2 inhibitors should continue taking low-dose acetylsalicylic acid and carefully monitor the state of the digestive tract.

When choosing NSAIDs from a group of nonselective patients for the elderly, preference should be given to the derivatives of propionic acid, related to short-lived NSAIDs (quickly absorbed and eliminated) that do not accumulate when metabolic processes are disrupted. If the patient is not at risk of developing side effects, treatment can begin with both a non-selective and a selective or specific inhibitor of COX-2. If the inefficiency or insufficient effectiveness of the drug must be changed.

Basic preparations of depot forms of corticosteroids

A drug	The content of active substance in 1 ml of suspension
Kenalog 40	40 mg of triamcinolone acetonide
Diprospan	2 mg betamethasone disodium phosphate and 5 mg betamethasone dipropionate
Depot-Medrol	40 mg methylprednisolone acetate

A feature of corticosteroids used for intraarticular administration is a prolonged anti-inflammatory and analgesic effect. Given the duration of the effect of depot corticosteroids, you can arrange in the following order:

1. hydrocortisone acetate - is released in the form of a microcrystalline suspension in 5 ml vials (125 mg of the drug); when intra-articular injection from the cavity is practically not absorbed, the effect lasts from 3 to 7 days; in connection with a relatively weak and short effect in recent times is extremely rare; 
2. triamcinolone acetonide - is released in the form of an aqueous crystalline suspension, in ampoules of 1 and 5 ml (40 mg / ml); anti-inflammatory and analgesic effect occurs 1-2 days after the injection and lasts 2-3 (rarely 4) weeks; The main drawback is the frequent development of atrophy of the skin and subcutaneous fat, necrosis of tendons, ligaments or muscles at the injection site;
3. methylprednisolone acetate - is released in the form of an aqueous suspension, in ampoules of 1, 2 and 5 ml (40 mg / ml); the duration and severity of the effect almost does not differ from the preparation of triamcinolone acetonide; when used at recommended doses, the risk of atrophy and necrosis of soft tissues at the injection site is minimal; practically does not have mineralocorticoid activity;
4. Combined drug (trade names registered in Ukraine - Diprospan, Flosteron) containing 2 mg of betamethasone disodium phosphate (highly soluble quick-absorbing ether, provides a quick effect) and 5 mg of betamethasone dipropionate (a poorly soluble, slow-absorbing depot fraction, has a prolonged effect) , is issued in ampoules of 1 ml, the composition of the drug causes a rapid (within 2-3 hours after intraarticular administration) and prolonged (3-4 weeks) effect; The micronized structure of the suspension crystals ensures painless injections.

Local intra-articular administration of triampinolone hexacetonide caused a short-term reduction in pain in the knee joints affected by osteoarthritis; the results of treatment were the best in cases of preliminary aspiration of exudate from the joint cavity before injection. R.A. Dieppe et al (1980) demonstrated that local intra-articular corticosteroids lead to a more pronounced pain reduction than placebo.

The main indications for the use of corticosteroids in osteoarthritis are the persistence of synovitis against a background of conservative treatment, as well as the persistent inflammation of periarticular tissues (tendovaginitis, bursitis, etc.). Planning intrasynovial administration of prolonged glucocorticosteroids, it should be remembered that the drugs of this group are contraindicated in infectious arthritis of various etiologies, infection of the skin and subcutaneous fat or muscle in the zone of administration, sepsis, hemarthroses (hemophilia, trauma, etc.), intraarticular fractures. With a persistent pain syndrome and the absence of synovitis that is not controlled by conservative therapy, glucocorticosteroids should not be injected into the joint, it must be administered periarticularly. In the III-IV stages of Kellgren and Lawrence, intra-articular injections of glucocorticosteroids should be used very carefully, only in the case of ineffective conservative measures.

An important requirement for intraarticular injections is compliance with aseptic rules:

• the hands of the doctor should be clean, preferably in surgical gloves,
• Only disposable syringes are used,
• after dialing the drug in a syringe immediately before the introduction of the needle is changed to a sterile,
• the evacuation of the intra-articular fluid and the administration of the drug must be done with different syringes,
• the injection zone is treated with 5% alcohol solution of iodine, then 70% alcohol,
• after injection, the injection site is pressed with a cotton swab dipped in 70% alcohol and fixed with a bandage or bandage for at least 2 hours,
• When carrying out manipulation, the staff and the patient should not talk.

After insertion of the needle into the joint cavity, the maximum amount of joint fluid must be aspirated, which already contributes to some analgesic effect (intraarticular pressure decreases, synovial fluid from the cavity removes the mechanical and biochemical inducers of inflammation), and also frees the place for subsequent administration of the drug substance.

According to HJ Kreder and co-authors (1994), the negative effect of intra-articular injections of glucocorticosteroids in rabbits was potentiated by their motor activity. After intra-articular injection of depot forms of glucocorticosteroids, it is advisable for some time not to burden the joint, since the observance of the rest period after injection contributes to a more pronounced and long-lasting effect.

Since studies on animals have demonstrated the ability of glucocorticosteroids to damage articular cartilage, and frequent intra-articular injections of depot forms of glucocorticosteroids are associated with the destruction of intraarticular tissues, injections are not recommended to be performed more than 3-4 times a year. However N.W. Balch and co-authors (1977) who retrospectively assessed radiographs of joints after repeated injections for 4-15 years, argued that the rational use of repeated injections of these drugs does not lead to an acceleration in the progression of the disease due to radiography.

Complications of the local therapy of glucocorticosteroids can be divided into intraarticular and extraarticular:

intraarticular:

• ineffective intra-articular GCS-therapy due to the resistance of joint tissues to glucocorticosteroids is observed in 1-10% of patients. It is believed that the mechanism of this process is based on the lack of GC receptors in the inflamed synovial tissue,
• increased pain and swelling of the joint is observed in 2-3% of patients, which is associated with the development of phagocytosis of hydrocortisone crystals by leukocytes of synovial fluid;
• osteoporosis and bone-cartilage destruction. JL Hollander, analyzing the results of long-term treatment of 200 patients, along with a good clinical effect, observed rapid progression of osteoporosis in 16% of patients, articular cartilage erosion in 4% and an increase in bone destruction of articular surfaces in 3%
• hemarthrosis; G.P. Matveenkov and co-authors (1989) observed two cases of hemarthrosis with 19,000 joint punctures;
• infection of the joint cavity with the subsequent development of purulent arthritis; the most common infection occurs in the knee joint, as a rule, signs of inflammation appear 3 days after the injection.

extraarticular:

• Atrophy of the skin at the injection site occurs when the drug enters the extraarticular tissues and is noted mainly after injections of glucocorticosteroids into small joints: jaw, interphalangeal, metacarpophalangeal; describes atrophy of the skin after injections into the knee joint;
• linear hypopigmentation with proximal proliferation from the joint;
• periarticular calcification - can join the atrophy of the skin over the joints,
• tissue granulomatous reactions,
• ruptures of ligaments and tendons, pathological fractures of bones.