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Jun22
Hyaluronic acid in osteoarthritis
Hyaluronic acid in osteoarthritis
Osteoarthritis(OA) is a degenerative joint disease and is thought to be wear and tear of joint as part of an aging process.There are 2 types of OA,primary and secondary.Primary OA occurs in a joint de novo.It occurs in elderly and mostly in weight-bearing joints such as knee and hip.This is more common.Secondary OA occurs due to an underlying primary disease of the joint which leads to the degeneration of the joint.It can occur at any age and occurs commonly at the hip. Osteoarthritis is characterized by a loss of articular cartilage, which has a highly limited capacity to heal itself. Along with these cartilage changes, a reduction in the elastic and viscous properties of the synovial fluid occurs. The molecular weight and concentration of the naturally occurring hyaluronic acid decreases. Theoretically, this loss of elastoviscosity decreases the lubrication and protection of the joint tissues and is one postulated mechanism of pain production in osteoarthritis.1,2 Pharmacologic treatment generally consists of analgesics and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Physical therapy can be used, with exercises to maintain range of motion and strength. Intra-articular corticosteroid injections are often used for transient symptom relief. When conservative measures fail, surgical treatments limited to arthroscopic debridement, osteotomies to redistribute load and total joint replacements have been the only options until recently.
Intraarticular injections of hyaluronic acid is a viscosupplementation that is newly available options for patients with symptomatic knee osteoarthritis.The increase in viscoelasticity of the synovial fluid seems to play a role.The indications for viscosupplementation can be considered for use in patients who have significant residual symptoms despite traditional nonpharmacologic and pharmacologic treatments.Patients who are intolerant of traditional treatments can be considered these injections.
Viscosupplementation
The concept of viscosupplementation is based on pathologic changes of synovial fluid hyaluronic acid with its decrease molecular weight and supplementation.Two hyaluronic acid products are currently available in the United States: naturally occurring hyaluronan (Hyalgan) and synthetic hylan G-F 20 (Synvisc). Hylans are cross-linked hyaluronic acids, which gives them a higher molecular weight and increased elastoviscous properties. The higher molecular weight of hylan may make it more efficacious than hyaluronic acid because of its enhanced elastoviscous properties and its longer period of residence in the joint space (i.e., slower resorption)3. The exact mechanism of action of viscosupplementation is not well known. Although restoration of the elastoviscous properties of synovial fluid seems to be the most logical explanation, other mechanisms must exist. The actual period that the injected hyaluronic acid product stays within the joint space is on the order of hours to days, but the time of clinical efficacy is often on the order of months.4 Other possible mechanisms to explain the long-lasting effect of viscosupplementation include anti-inflammatory and antinociceptive properties, or stimulation of in vivo hyaluronic acid synthesis by the exogenously injected hyaluronic acid.5
Clinical studies of hyaluronan
Multiple studies have been conducted to assess the efficacy of intra-articular hyaluronan injections. Initial studies6-8 in the 1970s and 1980s demonstrated benefits for hyaluronan-injected knees. More recently, Dahlberg and colleagues,9 and Henderson and coworkers,10 in randomized, double-blind placebo-controlled trials found no benefit from intra-articular hyaluronan over placebo. Lohmander and associates11 similarly found no significant differences between overall treatment and placebo groups; however, a subgroup analysis of patients more than 60 years of age with more severe symptoms revealed beneficial effects from the hyaluronan injections. In contrast to these recent trials, which demonstrated no or minimal beneficial effects from intra-articular hyaluronan, other randomized controlled studies12-14 suggest overall beneficial effects of hyaluronan over placebo. Another study15 demonstrated efficacy of hyaluronan in a randomized blinded trial, with the treatment group showing more improvement than the placebo group and a group taking oral naproxen.
Clinical studies of cross-linked hylan
A summary of four clinical trials performed in Germany using cross-linked hylan16 demonstrated excellent results in 71 percent of hylan-treated patients, compared with 29 percent of placebo-treated patients. After six months, 53 percent of hylan-treated patients still reported excellent pain relief, compared with 22 percent of the placebo-treated patients. In a double-blind, randomized placebo-controlled trial using hylan,17 it was found that 39 to 71 percent of hylan-treated patients were symptom free at 26 weeks compared with 13 to 45 percent of placebo-treated patients. Another study18 compared intra-articular hylan with NSAID therapy in a randomized blinded trial. Hylan was found to be as effective as NSAID therapy at 12 weeks and was superior to NSAID therapy at 26 weeks. In addition, findings from a clinical practice19 showed that 80 percent of 458 knees injected with hylan had a positive response, and the average duration of efficacy was 8.2 months.
Adverse effects of intraarticular hyaluronic acid
Rates of adverse reaction has been low.The most frequent adverse reaction to this treatment is transient localised pain or effusion which is resolved within one to three days.There were no systemic effects attributed to hyaluronic acid.There are also reports on cases of induced pseudogout20.No long term side effects have been reported21.
Indications
Intra-articular hyaluronic acid injections should be considered in patients with significantly symptomatic osteoarthritis who have not responded adequately to standard nonpharmacologic and pharmacologic treatments or are intolerant of these therapies (e.g., gastrointestinal problems related to anti-inflammatory medications).2,14,15 Patients who are not candidates for total knee replacement or who have failed previous knee surgery for their arthritis, such as arthroscopic debridement, may also be candidates for viscosupplementation. Total knee replacement in younger patients may be delayed with the use of hyaluronic acid22.
Injection technique
Hyalgan is supplied in 2-mL vials (one injection per vial) or prefilled syringes, and Synvisc is supplied in 2-mL prefilled syringes. The recommended injection schedule is one injection per week for five weeks for Hyalgan, and one injection per week for three weeks for Synvisc. Repeat courses of viscosupplementation can be performed after six months. A knee joint can be injected several ways. One approach is to have the patient lie supine on the examination table with the knee flexed 90 degrees. In this position, the anterior portions of the medial and lateral joint lines can easily be palpated as dimples just medial or lateral to the inferior pole of the patella. Often, the medial joint line is easier to palpate and define and can be chosen as the site of injection. Alternatively, the knee joint can be approached with the knee extended, again with the patient lying supin. Most commonly the superolateral edge of the patella is the site of injection, but other quadrants of the knee near the patellar edges can also be chosen. With this approach (knee in extended position), the needle is generally aimed under the patella.
Actual injection site can be marked with a fingernail imprint or the barrel of a pen. Next, sterile preparation with a povidone iodine preparation (Betadine) and alcohol can be performed. A 22- to 25-gauge needle can be used for the injection. Local anesthesia with lidocaine before the injection can be used, but with a small gauge needle this is not always necessary. Alternatively, an ethyl chloride spray can be used for local anesthesia. Following puncture through the skin and into the joint space, the injection is accomplished. If resistance is encountered, redirection of the needle may be necessary.
If effusion is present, aspiration of the joint is recommended before the injection to prevent dilution of the injected hyaluronic acid. The aspiration can be performed at the same site as the injection, as previously described. The same needle can be left in place and used for the aspiration and the injection. Aspiration may require a larger bore needle, such as an 18- or 20-gauge needle. Following local anesthesia with intradermal lidocaine or ethyl chloride spray, the needle can be placed into the joint for aspiration. When aspiration is completed, hemostat clamps can be used to grasp and stabilize the needle, while the aspiration syringe is detached from the needle. The syringe containing hyaluronic acid can then be attached to the same stabilized needle followed by injection. No excessive weight-bearing physical activity should take place for one to two days following injection.

References:

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3. Wobig M, Bach G, Beks P, Dickhut A, Runzheimer J, Schwieger G, et al. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan. Clin Ther 1999;21:1549-62.
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18. Adams ME, Atkinson MH, Lussier AJ, Schulz JI, Siminovitch KA, Wade JP, et al. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cart 1995;3:213-25.
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20. Disla E, Infante R, Fahmy A, Karten I, Cuppari GG. Recurrent acute calcium pyrophosphate dihydrate arthritis following intraarticular hyaluronate injection. Arthritis Rheum 1999;42:1302-3.
21. Maheu E. Hyaluronan in knee osteoarthritis: a review of the clinical trials with hyalgan. Eur J Rheumatol Inflamm 1995;15:17-24.
22. Red book. Montvale, N.J.: Medical Economics Data, 1999.


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