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It is the restoration of homeostasis (stabilization of different physiological constants) and rheological properties (viscosity and elasticity) of a pathological synovial fluid by intra-articular injection of a "viscosupplementation" based on derivatives of hyaluronan.
In the 1960s, EA Balazs and colleagues develop the NIF-NaHA (non-inflammatory fraction of sodium hyaluronate), marketed in the late 1970s under the name HEALON used in ophthalmic surgery and HYLARTIL-VET used in the field veterinary. The first commercial in osteoarthritis back to the late 1980s in Japan. Hylan GF 20 (Synvisc) appears in 1995 in the European market and in 1997 the US market. Since September 2002 viscosupplementation is supported by social security on the basis of 114 euros, only the knee, at the rate of a year per knee treatment (3 injections), provided they are prescribed and directed by an orthopedic surgeon, rheumatologist or a physical medicine doctor.
To understand the importance of hyaluronan in joint function pathophysiological a recall is necessary.
The hyaline cartilage is a connective tissue containing neither nerves nor blood vessels. It is composed of an extracellular matrix and chondrocytes. Hyaline cartilage is composed of four layers. It ensures slippage between the joint parts during movements. It has a very low coefficient of friction and high pressure resistance. These properties depend on the structure and organization of the extracellular matrix. It consists of a dense network of collagen fibers and a very hydrophilic proteoglycans gel. This polymeric structure of proteoglycans is comprised of a hyaluronan chain to which are attached proteoglycan monomers. The cartilage homeostasis is ensured by the chondrocyte which regulates the synthesis and degradation of collagen and proteoglycans in the matrix, hyaluronan is mainly synthesized by chondrocytes.
The synovial tissue is a highly vascularized connective tissue that lines the inner surface of the joint capsule. It performs multiple functions including the secretion of hyaluronan which is a major component of synovial fluid playing a role in both the lubrication and trophism of the joint tissues.
The normal synovial fluid is viscous and colorless, is its high hyaluronan at a concentration and molecular weight sufficient, which gives it its elastic and viscous properties, transforming rough cartilage in effective bearing surfaces with a coefficient of friction very low. It also plays a role in transporting nutrients to the chondrocytes.
Hyaluronan endogenous has a molecular weight of about 4 to 5 million in the healthy synovial fluid, less than 4 million in OA synovial fluid. Its concentration in the healthy synovial fluid is from 2.5 to 4 mg / ml, it is less than 2 mg / ml in osteoarthritic liquid. The two essential properties of hyaluronan are viscosity, it covers protecting the tissues elasticity and shock absorbing. When its concentration and molecular weight decrease viscoelastic surface protection and tissue is no longer assured and the joint surfaces being degraded. The tangle of hyaluronan molecules also plays a role of "sieve", a real barrier between the synovial fluid and the intercellular matrix for large cells (macrophages and granulocytes) and mediators of inflammation. Finally, the hydrophilic properties of hyaluronan provide within the intercellular matrix mechanical protection chondrocytes nociceptors and soft tissue.
Osteoarthritis seems to be the consequence of an imbalance between the synthesis and degradation of the components of the cartilage matrix. The hypertension is seeking the cartilage that simultaneously increases the synthesis of products of the matrix and degradation enzymes. Everything happens then as if the chondrocyte ended up running out, the synthesis of degradative enzymes taking precedence over that of the matrix products. At the osteoarthritic synovial fluid quantitative and qualitative changes in hyaluronan are constant. Its concentration and its molecular weight is lowered.
Hyaluronic acid (HA) injected intra-articularly has a mechanical effect. It improves elastoviscous properties of synovial fluid, protects against shocks and filter pro-inflammatory molecules. This is not a drug but a medical device (therapeutic effect exerted by means of a physical and mechanical action, not a pharmacological action). But the effects of HA occurs and continues long after it disappeared from the joint (the mean half-life of HA in the joint is 12 hours). Experimental studies show that viscosupplementation is at the synoviocyte quantitatively and qualitatively improving the synthesis of endogenous hyaluronan. It would have also a pharmacological action of self-induction.
A team from the Taiwan Hospital published in "Journal of the bone and joined surgery" in March 2004 a meta-analysis (1) studies performed between January 1966 and December 2001. They identified 665 studies published in English, all randomized controlled comparing the efficacy and / or tolerance in knee intra-articular injection of HA versus placebo. They selected 20 respondents studies to strict selection criteria, corresponding to an efficiency analysis for 1647 treated knees and tolerance for 2252 treated knees.
The authors conclude that HA in knee osteoarthritis significantly reduces pain and increases significantly the functional indices. Patients over 65 years and which is advanced osteoarthritis (total disappearance of joint space) are less benefit to this treatment. Adverse effects consisting of painful local reaction, are valued between 2 and 8% depending on the study.
The authors identify a number of weaknesses of the studies that are the heterogeneity of the patient population, the criteria for inclusion and exclusion, the type of HA, evaluating results, instruments to measure results and status of the studies.
A Canadian prospective study (2) on "visco-supplementation with Hylan GF 20 in the treatment of osteoarthritis," published in 1996 examined 336 patients, 458 lap, over a period of 2.5 years. The authors assessed the overall treatment response and activity. They conclude that an improvement or significant improvement in 77% of cases on pain and in 76% of the activity. Patients have significantly decreased their use of concomitant medications (analgesics, NSAIDs, corticosteroids, physical therapy, assistive devices). Efficiency is more important in the early stages of osteoarthritis and arthritis means that in the advanced stage. The average duration of benefits was 8.2 months. Local adverse events were 2.7% per injection.
The EULAR (european league contre rheumatism) in its recommendations in 2003 noted: "there are two types of intra-articular HA preparations, low molecular weight and high molecular weight (> 1 million). It has been defined as high molecular weight were more effective than low molecular weight "(randomized controlled trial over 12 weeks, 70 knees).
symptomatic knee osteoarthritis in all stages of joint disease resistant to medical treatment, a patient maintaining regular physical activity.
- Three injections a week apart (D0, D7 and D14).
- The injection should be done by intra-articular with strict aseptic technique.
- Infected joint.
- Large effusion.
- Venous or lymphatic stasis.
- Pain, swelling, effusion passenger.
- Large effusion and pain requiring therapeutic paracentesis and analyzing the liquid to eliminate an infectious or microcrystalline cause.
Viscosupplementation offers interesting prospects for the symptomatic treatment of knee osteoarthritis resistant to conventional medical treatment (paracetamol, NSAIDs ...). It seems more effective in the early and intermediate stages, but some studies have shown efficacy in very advanced arthritis, which may constitute a temporary solution before the prosthetic procedure. However, it is unclear define the profile of responders, it has no criteria to prejudge the effectiveness of HA in a patient. It exists on the market a wealth of AH, different in molecular weight, method of extraction and scientific record, but no obvious difference has really been demonstrated. After intra-articular injection of HA, his presence in the synovial fluid is only a few hours, so that its action is prolonged several months. The AH seems to act more by self-induction of endogenous synthesis of HA viscosupplementation by without its mode of action has not been demonstrated.
1) Ti Chen-Wang Jinn Lin Chee-Jen Chang Tsan-Yu Lin and Hou Sheng-moui.
Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials.
The Journal of Bone ant Joint Surgery, Volume 86-A, number 3, 2004 march.
2) Andr├ę Lussier, Alfred A. Cividino, Charles McFarlane A, Wojciech P. Olszynski, Wayne J. Potashner and Rinaldo De Medici.
Viscosupplementation with Hylan in the treatment of osteoarthritis: results of clinical experience in Canada.
The Journal of Rheumatology 1996, 23: 9.
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The aim of this operation is to achieve anatomic ACL reconstruction using autologous (patient's tendon) under arthroscopic control. The principle of TLS is to use a single hamstring tendon graft in short. Parameters of ACL reconstruction with hamstring TLS.