I. Topical drugs.
1. Capsaicin: Capsaicin is a stimulating ingredient found in red pepper, and its mechanism of action is: reversible depletion of substance P (the neurotransmitter that causes peripheral pain sensation) by selectively stimulating C-type unmyelinated afferent nerves to cause the release of substance P. Double-blind controlled clinical trials have demonstrated the effectiveness of capsaicin in the treatment of hand and knee osteoarthritis.
2., NSAIDs: Topical topical preparations of NSAIDs can reduce joint pain with few adverse effects, but such preparations still suffer from poor absorption and pain relief.
II. Systemic medications.
1. Non-opioid analgesics: Because the elderly are prone to adverse reactions to NSAIDs and synovitis in OA is not a major factor in the early stages of the disease, general analgesics can be used for a short time as the drug of choice in mild cases, such as acetaminophen, 0.3-0.6 g per dose, taken orally two to three times daily, at a daily dose of no more than 4 g. The main adverse effects are gastrointestinal symptoms and hepatotoxicity.
A meta-analysis of 10 randomized controlled studies found that acetaminophen was significantly effective in relieving symptoms of osteoarthritis pain, but had little effect in improving patients’ pain indices, suggesting a limited role for acetaminophen in reducing morning stiffness and improving function. Patients taking acetaminophen must be aware of any concomitant alcohol consumption or other over-the-counter medications containing acetaminophen, which can increase the hepatotoxic metabolic load and cause liver damage.
2, NSAIDs: NSAIDs have both pain-relieving and anti-inflammatory effects, is the most commonly used class of drugs to control OA symptoms, mainly through the inhibition of cyclooxygenase activity, reduce prostaglandin synthesis, play a role in reducing pain and swelling caused by joint inflammation, improve joint movement. The main adverse effects include gastrointestinal symptoms, renal or hepatic impairment, effects on platelet function, and an increased risk of cardiovascular adverse events.
NSAIDs should be used at the lowest effective dose for a short course of treatment; selective cyclooxygenase (COX)-2 inhibitors or non-selective NSAIDs + misoprostol (200ug, 3/day) or proton pump inhibitors should be used for those with gastrointestinal risk factors. In conclusion, the choice of drug type and dose should be individualized, taking into account the individual patient’s underlying conditions, and attention should be paid to the dual cardiovascular and gastrointestinal risks in elderly patients.
3, opioid analgesics: for patients with acute pain episodes, when acetaminophen and NSAIDs cannot adequately relieve pain or when there are contraindications to the use of drugs and no additional causes of pain, consider using weak opioids, which are better tolerated and less addictive. For example, oral codeine or tramadol have no significant adverse effects on the gastrointestinal mucosa because tramadol does not inhibit prostaglandin synthesis.
These preparations should be started at low doses and slowly increase the dose every few days to reduce adverse effects. Extended-release opioid analgesics have been validated in clinical trials for the treatment of osteoarthritis. The aim of such attempts is to reduce the peak plasma concentration of opioid analgesics. One extended-release tablet – once-daily tramadol – relieves pain in knee and hip osteoarthritis. z Morphine ketone extended-release tablets administered twice daily relieves pain in patients with moderate-to-severe knee and hip osteoarthritis. Also, transdermal fentanyl patches, an opioid analgesic that relieves pain and improves function, have been used to treat moderate-to-severe knee and hip osteoarthritis.
III. Intra-articular injectable drugs.
1. Glucocorticoids: Osteoarthritis treatment usually does not require systemic application of glucocorticoids, but local intra-articular injections of glucocorticoids have a long history. Glucocorticoids can downregulate the expression of adhesion molecules and therefore reduce cellular leakage into the joint cavity and the subsequent inflammation. Glucocorticoid injections reduce the infiltration of macrophage-like cells in the synovial membrane of osteoarthritis. The amount of glucocorticoid injected depends on the volume of the joint being injected, with larger joints such as the knee requiring a larger dose of injection.
With proper methodology and technique, the risk of intra-articular infection is low, but post-injection corticosteroid crystalloid synovitis may occur. A review has shown that intra-articular glucocorticoid injections in patients with osteoarthritis can improve patient symptoms in the short term with few adverse effects, but it has not been demonstrated whether long-term improvement in patient symptoms can be achieved. The choice of specific glucocorticoid formulation, frequency of injection, and other factors associated with intra-articular glucocorticoid injections in patients with osteoarthritis are highly variable and are also influenced by the operator’s training and competence. In conclusion, glucocorticoid injections are more effective in patients with osteoarthritis with inflammation or with exudation. Considering the possible adverse effects, the number of glucocorticoid injections per year should not exceed four per single joint.
2. Hyaluronic acid (vitreous acid) derivatives: Both synthetic and natural hyaluronic acid derivatives can be used for intra-articular injections. In the United States, Hyalgan and Synvisc have been approved for the treatment of osteoarthritis of the knee. Synvisc requires three injections per course of treatment, while Hyalgan requires five injections. Although these two drugs are often mentioned as a drug to improve the structure of the joint, they are actually currently used only as drugs to control the condition.
They provide longer-term pain relief and improved joint mobility. There is evidence suggesting anti-inflammatory effects and short-lived lubrication, as well as analgesic effects through direct buffering of synovial nerve endings and normal hyaluronic acid production through stimulation of synovial lining cells. In one study, intra-articular injections of hyaluronic acid once a week for three weeks in patients with osteoarthritis provided relatively good pain relief. At the one-week follow-up, the effect was found to be comparable to intra-articular injections of glucocorticoids; at the 45-day follow-up, the effect was superior to that of glucocorticoids. In a Canadian study, 102 patients with osteoarthritis of the knee were randomized to 3 groups for 3 weeks with weekly intra-articular injections of either Synvicor, or Synvicor plus an NSAID, or an NSAID.
At 26 weeks, both groups receiving intra-articular injections of Synvaco were significantly more effective than the NSAID group alone. The efficacy of intra-articular hyaluronic acid injections for symptomatic relief has been successively demonstrated in randomized trials of osteoarthritis of the ankle, shoulder, and hip joints. A multicenter, randomized, double-blind study evaluated the effect of hyaluronic acid in improving the condition. Patients received three courses of three intra-articular knee injections of hyaluronic acid or saline each over a one-year period. A joint space width (JSW) was assessed using a standing weight-bearing tablet. 273 patients completed the trial and data collection was completed. The trial failed to confirm a palliative effect of hyaluronic acid, as the primary endpoint was not met. The study found no significant difference between the two groups in joint space comparisons
. Those with a JSW of 4.6 mm or greater at enrollment had less joint space narrowing with hyaluronic acid application compared with saline use (0.55 mm + 1.04 mm in the placebo group and 0.13 mm + 1.05 mm in the hyaluronic acid group; P = 0.02). Hyaluronic acid products have also been used in osteoarthritis of the shoulder joint, local inflammation of the periarticular area, and adhesive capsulitis.
IV. Nutritional drugs.
1. Glucosamine: In the urine of patients with osteoarthritis, glucosamine can be detected and its excretion is increased. Amino glucose is a natural amino monosaccharide, which is an important component necessary for the synthesis of proteoglycans in the matrix of human joint cartilage. It can improve the metabolism of articular cartilage, enhance the repair ability of articular cartilage, protect the damaged articular cartilage, relieve the pain symptoms of OA, improve joint function, and delay the pathological process and disease process of OA, thus it has both symptom modulating and structural modulating effects. The usual dose of glucosamine should not be less than 1500mg per day, otherwise the efficacy is poor. Divided into 2 to 3 times to last for more than 8 weeks to show the effect, the use of more than 1 year more stable efficacy, can be used in combination with NSAIDs.
2, chondroitin sulfate: chondroitin sulfate is an aminoglucan composed of sugar molecules (molecular weight 14000 or so), which can reduce the destruction of cartilage matrix and synovial fluid components by competitively inhibiting the activity of degradation enzymes; improve the blood circulation of synovial membrane and subchondral bone by reducing the formation of fibrin thrombus. It can effectively reduce the symptoms of OA, alleviate pain, improve joint function, and reduce the dosage of NSAIDs or other painkillers. Adults take 1200mg orally daily.
3, vitamin A, C, E, D: OA cartilage damage may be related to the role of oxygen free radicals, this year’s research found that vitamin A, C, E may be beneficial to the treatment of OA mainly through its antioxidant mechanism. Vitamin D plays a role in the treatment of OA through the impact on bone mineralization and cell differentiation.
4, other nutritional supplements: some other nutritional supplements such as cat’s claw, shark cartilage, ginger extract, oral avocado and soybean unsaponifiables, etc., still need more research to support their clinical use value.
V. Other therapeutic agents to improve the structure or delay the course of the disease.
1, doxycycline: doxycycline is a tetracycline derivative with matrix metalloproteinase inhibition, which can exert an anti-inflammatory effect, inhibit the production of nitric oxide and reduce bone resorption. It can reduce the cartilage destruction of OA. Each time 100mg, 1-2 times a day orally.
2, diacerein: diacerein and its active metabolite rhodizonate are related to senna complex. Clinical trials have proved that diacerein is an interleukin (IL)-1 inhibitor, which can inhibit cartilage degradation, promote cartilage synthesis and inhibit synovial inflammation. It can not only effectively improve the symptoms of osteoarthritis, reduce pain and improve joint function, but also has a follow-up effect, and the efficacy can last at least 1 month after stopping the drug after 3 months of continuous treatment; it can also slow down the progression of OA disease and has a structural modulating effect. The drug does not inhibit the synthesis of prostaglandins. Adult dosage: 50 mg twice daily with meals, usually taken for not less than 3 months. Diarrhea is the main side effect of this type of drugs.
3, Bisphosphonates: The main mechanism of action in OA treatment is to inhibit osteoclasts from dissolving minerals, while preventing mineral efflux, and also inhibit collagenase and prostaglandin E2, thus reducing bone formation.
4, growth factors and cytokine modulators: growth factors and cytokine modulators can also be used in the treatment of osteoarthritis. Cytokines IL-1 and TNF-a are produced by synovial cells and can contribute to the inflammatory response of osteoarthritis. In addition, chondrocytes from patients with OA under-express natural anti-inflammatory molecules such as IL-1Ra, and in some patients, high levels of nitric oxide production by articular chondrocytes can inhibit IL-1Ra synthesis. In a rabbit model of osteoarthritis, transfer of the IL-1Ra gene into the joint prevented the progression of osteoarthritis. In human osteoarthritis, the application of IL-1Ra to block IL-1 is currently under investigation. In animal studies, attempts to induce the repair of joint lesions by the timed release of transforming growth factor beta from liposomes have revealed an increase in the number of cells in the defect area. These cells were derived from mesenchymal cells of the synovium. The repaired articular cartilage resembled hyaline cartilage in appearance and its integrity was maintained up to one year after surgery.
VI. Chondrocyte and stem cell transplantation: Several trials have transplanted chondrocytes and stem cells into areas of articular cartilage defects. Experiments have been performed with chondrocytes that have been transfected with the β-galactosidase gene and human chondrocyte vectors cultured in vitro and found to survive for 45 days. Transfection of chondrocytes with the galactosidase gene before and after transplantation has been successful.
VII. Gene therapy: Gene therapy for osteoarthritis is still being tried.